Psych 119U Final

Religious Delusions in Psychosis

- 46.8% of Schizophrenia cases found to have Religious Delusions - This figure varies significantly by study - Also prominent in Bipolar Disorder with psychosis - Common delusions include religious themes such as sin and punishment, supernatural forces, etc. - Religious delusions held with more pervasiveness/conviction than other delusions - Creates a stigma against the association between Schizophrenia and Religion

Substance Abuse and Bipolar Disorder

- 60% of patients with type 1 bipolar disorder had a substance abuse disorder in their lifetime. - Cannabis is the most abused drug among bipolar patients - Up to 40% of people have a dual diagnosis of both bipolar disorder and substance abuse. - The exact reasons why the rates of bipolar disorder and substance abuse are so high are unknown. - Some possible reasons: - Using substances in order to self medicate and treat their bipolar disorder symptoms. - Psychosocial stress might be a factor that causes both disorders to co-occur. - During the manic episodes they have feelings of grandiosity and therefore want to have those feelings more so they seek out drugs that will give them that high and euphoric feeling.

Marijuana use among Bipolar disorder?

- Against - May decrease psychotic threshold - Leads to earlier onset of disorder - Associated with lower treatment compliance - Increased duration and/or severity of mania - Overall higher rates of negative outcomes - For - Low dose of THC can have antidepressive effects - CBD serves as a fast-acting mood stabilizer - Self-medication with less side effects - Overall, Bipolar Disorder is a very complex disease that varies from person to person and what may work for one by no means works for all. Endocannabinoid Model - Plays role in mood, appetite, memory - Marajuana - Delta -9-Tetrahydrocannabinol (THC) - CB1 receptor agonist - Effects on dopamine - Mimics positive, negative and cognitive symptoms - Cannabidiol (CBD) - Blocks CB1 and CB2 receptor - Antipsychotic and anxiolytic - Higher CBD leads to less psychotic symptoms

Why is religious coping beneficial?

- Behavioral - Religion associated with better day-to-day practices - Social - Support system for members of religious communities - Psychological - Beliefs about God, held by most patients and often used to justify illness - Physiological - Relaxation response in the body due to religious participation - More research is needed into the relative importance of these factors - Overall, seems to have a positive effect on quality of life

Parkinson's and Huntington's and Psychosis

- Both of these diseases cause breakdown of nerve cells primarily in the basal ganglia - The basal ganglia is primarily involved in motor movement and cognitive function - It is hypothesized that the dysfunction in the basal ganglia is one of the markers for schizophrenia and these diseases involve a breakdown in basal ganglia functioning. Parkinson's Disease - Psychosis may affect 1 in 5 patients with Parkinson's Disease - These primarily manifest as visual hallucinations (different from schizophrenia in which auditory are most common) - Delusions often arise as well in Parkinson's patients - While the medication taken for Parkinson's may contribute to the onset of psychosis, it is also possible that it is the disease itself that is causing this by its neurodegenerative nature - If it is the medication that is causing psychosis in Parkinson's patients, it is important to understand which part of the medication would be responsible - Believed that it is the increase in dopamine from this medication which improves motor function - This contributes to the dopaminergic model of psychosis - Parkinson's psychosis involves paranoia, hallucinations and overall diminishment of quality of life - Caregiver even states that it is easier to handle the physical as opposed to mental symptoms of the disease Huntington's Disease ● Inherited neurodegenerative disease characterized by chorea and cognitive decline. ● Common psychiatric symptoms include the presence of dysphoria, agitation, irritability, apathy, & anxiety. ○ Symptoms occur in any stage, but more common in later stages of the disease. ● Psychosis: delusions and hallucinations are less common in HD than other psychiatric symptoms ○ 3% delusions, 3% auditory hallucinations, 2% tactile hallucinations, no visual hallucinations ● Paranoid schizophrenia-like symptoms occur in 3% to 11% of cases. ● Further research is needed in order to clarify the links between genetic loading and the emergence of psychotic symptoms in Huntington's disease

Dementia and Psychosis

- Deficits of Acetylcholine transfer and location of pathology of patients with dementia (disruption to posterior part of the brain which relates to vision) make them particularly susceptible to visual hallucinations - Delusions also relatively common and can be persecutory in nature - Capgras has also been seen in patients with dementia - Imposter syndrome where they believe somebody they know is not who they say they are

Epilepsy and Psychosis

- Epilepsy: also known as "seizure disorder"; characterized by unpredictable seizures that can cause other health problems - Schizophrenia-like psychosis: very rare; occurs in 2-8% of patients with intractable epilepsy - Schizophrenia-like states in epilepsy include: - an intact affect - unimpaired ability to relate to others - relative absence of negative symptoms (i.e., flat affect, lack of initiative) - rare deterioration of the patients' personality - absence of psychosis in the patient's family - absence of premorbid schizoid traits and better premorbid day-to-day function - psychosis marked by ideas of reference, paranoid delusions, and hallucinations - May be due to the adverse effects of AEDs (antiepileptic drugs)

Current Treatment options of bipolar disorder

- Mood Stabilizers - Ex.) Lithium - Used in order to stabilize mood - One of the first lines of treatment given to bipolar patients - Antipsychotics - Usually given to manage mania episodes in addition to lithium medication - Interpersonal Therapy - Cognitive Behavioral Therapy (CBT) - Group Psychotherapy - May help patients adhere to treatment plans since most bipolar patients don't like treatment due to lack of insight into their disorder and they sometimes like their mania episodes since they feel a sense of euphoria

Does the age of onset change for bipolar disorder?

- The average age for overall onset of bipolar is said to be 25 years old - Younger than 25 is considered "early onset" - Average age of onset without use of cannabis - First manic episode: 25.1 years - First depressive episode: 24.4 years - Average age of onset with cannabis use - First manic episode: 19.5 years - First depressive episode: 18.5 years

Cognitive Behavioral Therapy and Substance Use Disorder

- Used to help treat use of stimulants, marijuana, alcohol, opioids - Licensed clinician leads 12-16 sessions - Three main goals: - Identify and recognize the problem - Avoid reusing the drug - Coping with it - Key Components: - Functional Analysis - Aims to identify: triggers, thoughts and feelings, behavior, positive and negative consequences - Skills Training - Teaches you how to: learn coping skills for dealing with everyday stressors, focus on your interpersonal and intrapersonal skills, problem solving, relapse prevention

Religious practice among psychotic patients

-91% engage in some form of private religious participation -68% in public religious services or activities -according to some studies, more likely to participate in religious practice (especially privately) than the general population -worth seriously considering how religion can affect treatment/prognosis - 295 participants from a mental health center in Lithuania - Questionnaires- 63.3% reported having religious delusions - women= belief that they were saints - men= belief that they were gods - religious content of delusions not influenced by personal religiosity- related to marital status and education! - Limits: Lithuanian population, cross-sectional design, no verification of diagnoses

Difficulty diagnosing COS

-Article gave overall view on COS -Diagnosed using same criteria as Adult Schizophrenia with the "exception of Criteria B. Criteria B states that the afflicted individual's level of functioning must be diminished. However, as this is difficult to assess in children, they instead must fail to meet the expected level of functioning for a child according to their age". -Clinicians are very reluctant to diagnose COS- one of the main confusions and difficulties in this disorder is differentiating between delusion and hallucinations and child's imaginative play. Additionally, children are in the midst of developing which is a unique process to every single child -In cases of COS, there are often disturbances in the child's psychosocial functioning prior to the onset of the illness, which are referred to as premorbid abnormalities -Presentation is extremely different from child to child -Current literature suggests that COS is misdiagnosed when other disorders, such as Bipolar Disorder or Autism Spectrum disorder should be used -Difficult because if you misdiagnose someone the child will suffer from mismedication. But if you hold back a diagnosis, they are being denied treatment and medication that they otherwise could have started

Adjunctive Psychosocial Treatments for Schizophrenia

-Cognitive Behavioural Therapy (CBT) - Focus: reduction of symptoms, relapse, increased functionality, increased coping methods, informing patient about disease and role of medication - Positive Outcomes: consistent in reducing positive and negative symptoms, may also improve adherence - Limitations: requires a lot of training, timing is important to effectiveness - Family Intervention Therapy (FIT) - Focus: help the family members involved with caring for the patient to indirectly help the schizophrenic, lowering relapse by lowering resentment from family, crisis management - Positive Outcomes: reductions in relapse and duration of hospitalization, increased medical adherence and social functioning - Limitations: limited effectiveness in combating the symptoms of the disorder -Social Skills Therapy (SST) - Focus: improving skills for everyday use, e.g. self care, use of meds, vocational and recreational skills - Positive Outcomes: slight improvement in symptoms, improve employment outcomes enhancing interview skills - Limitations: more research is required to determine effectiveness with adherence, reduction of relapse - Cognitive Remediation Therapy (CRT) - Focus: compensate for cognitive functional loss, focuses on positive reinforcement - Positive Outcomes: improves performance on neurological tests that mark for indices in memory, attention, and executive function - Limitations: measure of overall functioning is unclear

Is religion a problem?

-Contradictory studies on whether or not religiosity increases religious delusions -Christian patients seem to be more likely to experience religious delusions (may suggest association) -Patients with religious delusions are often worse in terms of cognitive deficits, general outcome -No obvious connection between religious delusions and religious participation

Areas of current gender difference studies

-Gender Differences in Medication and Symptom Profiles ● The Estrogen Hypothesis

Neural basis? of religious coping

-Generally, found that hallucinations and delusions= excess of DA in brain - Poorer prognosis - But, religious behavior also linked to activating DA systems in the brain - Better prognosis if positive style coping - How can the excess of dopamine in brain lead to both better or poorer prognoses? - Greater medial temporal lobe activation in individuals with above average beliefs - +0.69 correlation score between temporal lobe signals and paranormal thinking scores - Ventromedial corticolimbic pathways vs dorsally mediated serotonergic and noradrenergic pathways - Not much found on laterality - However, older study by Bear and Fedio (1977) says hyperreligiosity activation more likely to occur in left sided.

Psychosis X Alzheimer's: Medications

-Haloperidol has mild to moderate efficacy in AD+P patients (reduces delusions) -Olaznapine and Risperidone - significanlty effective for improving behavioral symptoms -Lower rates of motor side effects in patients with AD + P -Aripiprazole acts as a "stabilizer" of DA/5HT system -partial agonist at D2 and 5HT1A receptors and antagnoist at 5HT2A receptor Cholinergic Therapy Hypothesis - AD studies show cholinergic hypofunction - Xanomeline tartrate is an M1 and M4 selective muscarinic receptor agonist that has been shown to improve symptoms of AD. - Behavioral symptoms were reduced or prevented in the treatment group. With a significant, dose-dependent reduction noted in vocal outbursts, suspiciousness, delusions, agitation, hallucinations, wandering, fearfulness, compulsiveness, tearfulness, mood swings, and threatening behavior.

Brain Tumors

-In rare cases, the removal of brain tumors can cure psychosis in patients - It would be useful to study these patients to see what the brain tumor was doing to cause the psychosis in the first place - One such patient had auditory hallucinations and persecutory delusions (both consistent with schizophrenia) and both of these symptoms ceased following the removal of his tumor in the left lateral ventricle and septum pellucidum. He also had hydrocephalus of both lateral ventricles. - Enlarged ventricles have been shown in schizophrenia patients - More studies of psychosis from brain tumors and lesions would be useful in revealing the areas of the brain that are most implicated in psychosis and possibly aid in the discovery of more effective treatment

Genetic and environmental factors of COS

-Many presumed genetic and environmental factors found to correlate with COS, however, nothing is completely proven (as with adult onset schizophrenia) -Familial factors include childhood neglect, being ignored associated with negative symptoms -Childhood abuse and mistreatment, such as physical or sexual abuse, associated with positive symptoms -Pre-natal infection thought to be associated with childhood onset schizophrenia and adult onset schizophrenia -Complications at birth -Age of paternal parent also thought to be a risk factor for schizophrenia -Nature of genetics is poorly understood but clear there is some factor of it in this disorder

Art as a therapy add-on for schizophrenia

-allows for exploration of the inner world in anon-threatening way valuable for 3 reasions 1. act as a catalyst in facillitating verbailzation in a nonverbal patient 2. more closely duplicates the patient's primary process view of himself and his world 3. helpful in monitoring the patient's progress in the hospital and act as confirmatory clincal evidence of change -helps complete treatment but no significant effects on social functioning measures

Neural parallels of creativity and psychosis

-divergent thinking was associated with bilateral activation of PFC -Schizotypal individuals had muchg reater acitivtation of right prefrontal cortex -creativity has been shown to be positively correlated with the strength of resting-state functional connectivity between the medial PFC and the middle temporal gyrus (mTG)

Sue Morgan

-hallucinations and delusions are her primary symptoms but she has organized speech -relaxed by drawing the repetitive black lines; art as a form of expression and therapy

Yayoi Kusama's "Meditation

-main symptoms: -visual and some auditory hallucinations -fear of contact w/ others, social isolation -several reported delusions and paranoia

Neurodevelopmental model of cos

-outlines the various structural, pathological and functional nuances of the brain that are associated with this illness, as well as the resulting cognitive implications -in normal development,brain develops excess neural connections that we begin to prune out as we develop . Patients who have COS may have an abnormal amount of neural connections such that there is a greater reduction of them which leads to abnormal connectivity and activity Another article- Rapoport (2011) Childhood-onset Schizophrenia Support For a Progressive Neurodevelopmental Disorder -COS patients exhibit a gradual loss of gray matter, delayed and disrupted white matter growth, and a progressive decline in cerebellar volume (Rapoport et al., 2011) -dysfunction in frontal lobe linked to dysfunction and development of negative symptoms -dysfunction in temporal lobe may be linked to positive symptoms -causes for all of these abnormalities in the brain is unknown!

schizo-affective disorder and creativity

-ppl in scientific and artistic occupations were not more likely to suffer from psychiatric disorders -siblings of patients with autism and the first-degree relatives of patients with schizophrenia were significantly overrepresented in creative professions (hypothesis of the inheritance of a watered-down version of the mental illness conducive to creativity whilavoiding the aspects that are debilitating -schizo element of schizo-affective disorder is closely related to creativity, not the affective element both creativity and mental illness involve deviations from normative modes of thought -mental illness symptoms deviate in stereotyped ways whereas creativity inolves novel and different results -euphoria can be present in either case -suffering seen in mental illness less so with creatives -creativity is more strongly correlated to positive psychosis symptomsthan negative

Religion = better clinical outcomes?

-reduced suicide attempts -reduced smoking -better quality of life -increased social integration/reduction of negative symptoms -many of these studies are correlational or self-report -semi-structured interviews with 115 outpatients with psychotic illness -all subjective responses; questions guided based on patient response -71% said religion/spirituality added meaning or purpose to lives -increased social integration in 28% (decreased in 3%) -reduced risk of suicide attempts in 33% (increased in 10%) - - 1,824 subjects recruited based on DSM-IV definition of the disorder self report measures of religiousness and spirituality (0-4) - Religiousness= having a community + beliefs, emotions, and practices in relation to higher power - Spirituality= thinking about self as part of larger spiritual force Significant association between religiousness and well-being and symptoms

Stimulants

1. Merriam-Webster Dictionary: an agent (such as a drug) that produces a temporary increase of the functional activity or efficiency of an organism or any of its parts1 2. Stimulants act in the brain to increase the levels of monoamines (dopamine [DA] and norepinephrine [NE]) within the synaptic cleft therefore increasing neural transmission rates5 3. Induce feelings of euphoria when taken in a non-medical context (for enhanced performance above baseline)5 4. Most stimulants classified in the US as Schedule II Drugs (providing positive medicinal effects with potential for abuse) 5. Increase blood pressure, heart rate, constrict blood vessels, increase blood glucose, and open up breathing passages5 6. Act mainly on the central nervous system (CNS)5

Religion and Treatment Adherance

103 participants from Geneva, Switzerland psychiatric facility - Medication adherance measured by questionnaire and blood sample - Hypothesis confirmed that religious involvement lead to better medication treatment adherance Clinical Implications -Important to reduce stigma against religion and take its benefits seriously -Further studies necessary to understand factors at play -In therapy paradigms, patients should be asked about their spiritual beliefs as a method of validating them -Encourage religious exploration/group participation (potentially)

Major Depressive Episode

5 or more of the following are present and must include a and b. Present during the same 2-week period a. depressed mood most of the day almost every day b. markedly diminished interest or pleasure in all ormost activities most of the time almost every day c. significant weight loss or gain d. insomnia or hypersomnia nearly every day e. restlessness or being "slowed down" noticibely f. fatigue or loss of energy nearly every day g. feeling wortlhess or having excessive guilt even for long past actions or subtle mistakes h. dificulty thinking and/or concentrating or indecisiveness i. recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation

CoMoRbidity in COS

82 children, ages 4-15 years old diagnosed with childhood onset schizophrenia or schizoaffective disorder -99% (81 of these children!) had at least one other comorbid illness: attention deficit hyperactivity disorder (84%), oppositional defiant disorder (43%), depression (30%), and separation anxiety disorder (25%) were the most common comorbid conditions identified -This article was published in 2006, using criteria of the DSM-4 for these diagnoses-- may not be the most recent literature on COS but definitely provides us with some insight on comorbid diagnoses -Many symptoms of these disorders overlap -Begs for more research on childhood mental disorders versus adult mental disorders -Raises the question on if we should completely rely on the DSM in order to diagnose these illnesses -Another setback may also be the manifestation of a mental disorder, when a change in biological, psychological, or developmental functioning results in a youth's enduring behavioral, cognitive, or emotional impairment

Music therapy and schizophrenia

A clinical method that utilizes music to help accomplish an individual's goals. Used to help emotional, cognitive, and social needs of the patient. Involves singing, composing and/or listening to music. Patients use their learned abilities and apply them to different aspects of their lives. Help patients communicate and express themselves through a nonverbal medium that is more comfortable than what the world presents.

Nihilistic delusions

A conviction that a major catastrophe will occur. common, something horrible is going to happen, is happening, we have to get ready What about ex in social psych?

Alcohol Use Disorder

A problematic pattern of alcohol use leading to clinically significant impairment or distressed marked by at least two of the following occurring within a 12-month period: 2-3 symptoms = mild, 4-5 moderate, 6+ severe Diagnostic includes: ➔ Social/ Interpersonal problems arise ➔ ingesting alcohol in larger ➔ amounts/longer periods of time ➔ ➔ Persistent but unsuccessful effort to control their consumption ➔ Time WASTED trying to obtain, use and ➔ quit ➔ ➔ CRAVINGS become overwhelming ➔ FAILINGS in life [obligations, responsibilities] following use of alcohol REDUCED social, occupation activities Continued use despite physical or psychological problem cause/exacerbated by alcohol use Tolerance Withdrawal Neurotransmitter effects: »INC GABA »INC Endogenous opioids »INC Dopamine and Serotonin »DEC Glutamate receptors Long Term Effects »Malnutrition »Amnestic syndrome »Cirrhosis of the liver »Damage to endocrine glands and pancreas »Heart failure, Stroke »Capillary hemorrhages »Erectile dysfunction »Hypertension »Facial swelling and redness »Destruction of brain cells

Opioid Use Disorder

A problematic pattern of opioid use leading to clinically significant impairment or distressed marked by at least two of the following occurring within a 12-month period: Diagnostic includes: ➔ Consuming opioids in larger amounts/longer periods of time ➔ Persistent but unsuccessful effort to control their consumption ➔ Time WASTED trying to obtain, use and recover ➔ CRAVINGS become overwhelming ➔ FAILINGS in life [obligations, responsibilities] following opioid use ➔ Important social, occupational, or recreational activities are given up or reduced because of opioid use. ➔ Recurrent opioid use in situations in which it is physically hazardous. ➔ Continued opioid use despite knowledge physical/psychological problems ➔ Tolerance ➔ Withdrawal »Opium, Morphine,Heroin,Codeine, Vicodin, Zydone, and Lortab, OxyContin, Percodan, & Tylox. Based on DSM-5, 21.7% of patients met criteria for moderate and 13.2% for severe opioid-use disorder, respectively (Boscarino, 2011) Effects: »Euphoria, drowsiness, reverie » DEC inhibition / INC self-confidence » Severe "comedown" after about 4 to 6 hours » INC Endogenous opioid system » INC Endorphins and enkephalins » Lack of coordination » Infectious diseases via shared needles » DEATH » Symptoms of tolerance/ withdrawal: muscle soreness and twitching Tearfulness, yawning Cramps, chills/sweating increase in HR and BP, insomnia, & vomiting

Continuum of Care (CoC)

A program committed to ending homelessness by quickly rehousing homeless individuals and families 1. Outreach 2. Treatment and transitional housing 3. Permanent supportive housing "Housing Readiness" Reaching sobriety and compliance with psychiatric treatment are considered essential for successful transition to housing CoC--possible issues Assumes that individuals with psychiatric disabilities cannot maintain individual housing before their clinical status is stabilized Seen as a series of hurdles--many are unable or unwilling to overcome Housing is a fundamental need, maybe they need this addressed first in order to tackle their mental illness or substance abuse problems? Other strategies: "Housing First" approach: homeless individuals are put into housing first, then their ailments are treated Permanent-supportive housing: couples housing with counseling and access to meds *Studies have disproved the prior idea that certain people can't be housed What is needed in a more successful intervention? Research shows that the best interventions for psychotic homeless people include: Stressing the maintenance of stable, durable housing over time Provision of food and clothing Addressing physical health problems and securing treatment Training individuals to minimize their risk of victimization Interventions that decrease depressive symptoms may also improve the quality of life in homeless psychotic patients Treatment of substance abuse has been reported to improve outcomes in homeless persons with dual diagnoses of mental illness + substance abuse

reduction in restraint-use is possible without an increase in assaults

A recent study by Godfrey et al (2014) evaluated efforts to reduce the use of mechanical restraints at a psychiatric hospital in North Carolina. ○ Over three years, the hospital initiating de-escalation technique training for the staff members and employed a response team for crisis situations, as well as added a requirement of advanced approval for the use of mechanical restraints. ○ 98% reduction in mechanical restraint use with no increase in assaults or injuries ● Another study by Knox & Holloman (2012) concluded that a reduction in the use of restraints necessarily includes strong leadership, policy and procedural change, staff training, consumer debriefing, and regular feedback ● It appears that the most important step to make toward reducing the use of mechanical restraints is a change in culture surrounding their practice -Data from past incidents should be analyzed to inform future practices and policies ● Institutions should look to incorporate preventive measures ○ Patient assessment to determine medical and psychological risks ○ Daily, meaningful, and engaging treatment activities ○ Finding emotional triggers ● Debriefing ○ Immediately after the incident and is to confirm the patient's safety and review the situation and try to turn the environment back to the way it was before the incident ○ Occurs a few days later and requires the collaborative efforts of the treatment team, attending psychiatrist, and a representative from facility's management team to find the source of the problem and find ways to avoid future incidents

Psychosis X Alzheimer's: Genes

APOE gene - a well - known risk factor for late-onset AD -overall, APOE does not seem to contribute to risk of psychosis in AD HTR2A and HT2RC (5-HT Reeptor subtypes) may be associated with AD+P -Single SNP results in a T102C substituition -> lower levels of HTR2A mRNA -However, different groups have obtained conflicting results -associated between 5-HT system and AD+P remains unclear possible association between dopamine receptors and AD+P -several studies suggest a small but significant association between DRD3 gene and risk of psychosis -> results are conflicting for AD+P, however A mutation in COMT, an enzyme responsible for degrading and inactivating DA, could lead to psychosis -single SNP results in a V to M substituion -Numerous studies have found a significant association of COMT haplotypes for psychosis in AD

Neurodevelopmental Effects and Childhood Maltreatment

Abnormalities in some neurodevelopmental processes have been hypothesized to originate from early traumatic events that occur during childhood When faced with early and severe stress, researchers have found a dysregulation of the HPA axis due to chronic stress-induced release of glucocorticoid Researchers have hypothesized that the dysregulation of the HPA axis may underlie the dopaminergic abnormalities found in the brains of those who suffer from schizophrenia but further studies have to be conducted in order to be able to support that hypothesis

Negative Symptoms

Account for a large portion of morbidity/disability associated with schizophrenia. Diminished emotional expressions (flat affect) Reductions in the expression of emotions in the face Reduced eye contact Reduced prosody (intonations or speech) Movements of the hand, head, and face that give emphasis to emotion and speech Avolition Decrease in motivated self-initiated purposeful activities Alogia Diminished speech output (not seen in videos) Anhedonia Decreased ability to experience pleasure or recall previous pleasurable events or activities Asociality Lack of interest in social interactions, May be actually due to limited opportunities for social interactions If have lot of negative symptoms.. Outlook is not good Poorer social, academic, work outcome More likely to have hospitalization Flat effect: we don't think their actual experience of emotion is different, but their outward expression is flat Inappropriate eye contact, no variation in voice, speech is monotone Movement is also reduced, and not connected with speech Avolition: red flag early on, when someone is developing psychosis they stop bathing and take care of themselves Cant gather energy to go through fuss, also don't care Don't clean, wash themselves (red flag) Anhedonia: don't experience pleasure very much, don't get as much spice out of life (differs from depression) Asociality: due to lack of opportunities to socialize (cant because of situtaion) or just don't care for it 1/3 have no response, 1/3 have good response, 1 Nothing treats negative symptoms Positive symptoms are much easier to knock out Ask about serotonin?

Identification of a Common Neurobiological Substrate for Mental Illness (Goodkind)

Aim is to explore whether different psychiatric disorders have common or different neural substrates Meta analysis method of 193 studies with 15,892 individuals 6 diagnostic groups were tested Schizophrenia Bipolar disorder Depression Addiction OCD Anxiety (other than OCD) Panel A shows pooled data of all patient groups Panel B has Psychotic and Non-Psychotic disorders separated. Panel C shows areas common to all patient groups The bilateral insula and midline structures, basal ganglia especially the Anterior Cingulate Cortex are identified in panel A. The Psychotic patients had the same areas involved as the non psychotic patients but with greater magnitude of effect and a larger area of involvement-in psychotic group you see same areas but with greater extent, larger effect (mostly a larger level of impact on the same areas) more decrease grey matter and wider area of effect psychotic group: drives caudate area involvement (basal ganglia) Additionally, the psychotic patients had increased area in the striatum - a common finding in schizophrenia, believed to be a correlate of medication 3 areas showed common patterns in all groups. Left and Right Insula, and dorsal Anterior Cingulate Cortex. -anterior cingulate and insula makes sense for they are important for emotional cognition Results from the three common areas divided by diagnosis. What you see is that the only group that is different from the rest is the schizophrenia group Some but not all scientists include bipolar in the psychosis category. These didn't. -quantified level of effect in these 3 areas -showed schizo group had greatest level of deficit -common pattern amongst all disorders except anxiaty did not have anterior cingulate involvement Comparison of the 3 areas (bilateral insula and dACC) with activation networks in healthys Shows that these 3 areas are major components of both task induced and resting networks -what does loss of grey matter potentially mean? -what's missing? -could be neurons are gone (neurogenerative diseases) -less dendritic branching *** seen in schizophrenia -cell bodies still there, just get pruned down to bear bone structures -cortical thinning: loss of dendritic arbor, pruning, loss of synapses, not actual loss of neurons -what does that do to cell density in remaining cortex -density of neurons increase -not a good thing, densely packed b/c loss of synpases -study compared 3 core areas (bilateral insula, anterior cingulate with activation pattern maps) -essentially saw that they created a consistent network of activation, not just random 3 areas, they work together doing similar kinds of things with similar time courses Level of gray matter loss correlated with task performance. The greater gray matter loss, the worse participants performed on executive function tasks There was a small trend for attention and no relationship for general processing speed. -analyzed 3 kinds of cognitive tests: executive function, attention, general cognitive speed (not as frontal lobe dependent) -correlated with executive function, attention but not overall processing speed -study important because sends a message about biological boundaries and if they exist

Medicare guidelines for restrains and seclusion

All patients have the right to be free from restraint or seclusion, of any form, imposed as a means of coercion, discipline, convenience, or retaliation by staff. ● Restraint or seclusion may not be used unless the use of restraint or seclusion is necessary to ensure the immediate physical safety of the patient, a staff member, or others. ● The use of restraint or seclusion must be discontinued as soon as possible based on an individualized patient assessment and re-evaluation. A violation of any of these patients' rights constitutes an inappropriate use of restraint or seclusion and would be subject to a condition level deficiency. ● The decision to use a restraint or seclusion is not driven by diagnosis, but by a comprehensive individual patient assessment. ● For a given patient at a particular point in time, this comprehensive individualized patient assessment is used to determine whether the use of less restrictive measures poses a greater risk than the risk of using a restraint or seclusion.

Schizoaffective Disorder

An undisturbed period of illness when there is a major mood episode concurrent with schizophrenia symptoms. Delusions or hallucinations for 2 or more weeks in the absence of a major mood episode. Meaning that the mood and psychotic disorders are not ALWAYS happening at the same time. Lifetime prevalence is 0.3% Higher rates than suicide than schizophrenia Not a perfect overlap, period of psychosis without mood disorder

Nucleus Accumbens and manic psychosis

Anterior Cingulate Cortex (ACC) communicates with the nucleus accumbens which is involved with the reward system & situated between the caudate and putamen. Dopamine neurons project from the ventral tegmental area (VTA) to the nucleus accumbens & this pathway is activated in association with rewards. The same mesolimbic dopamine pathway that evokes feelings of reward, motivation, and euphoria can also result in risk-taking behavior. Dopamine release in the nucleus accumbens reinforces behavior and influences risky choices in manic individuals.

Treatment of schizophrenia with psychostimulants

Antipsychotics and Stimulants ● Opposing mechanisms ● Stimulants increase D2 receptors and Antipsychotics decrease D2 receptors ● Little impact Negative symptoms (NSS) ● DA agonists may improve NSS without worsening positive symptoms in selected patients ● methylphenidate, amphetamine, and modafinil or armodafinil ● Varying degrees of success ● Some patients improve, some patients have exacerbated psychotic symptoms ● Underactivity in Meso-cortico pathway vs. overactivity in Meso-limbic dopamine system

Treatment of Violence and Psychosis

Antipsychotics typically are one first line of treatment • Clozapine, a second-generation antipsychotic has been shown to reduce aggression, hostility, violent behavior, and hallucinations • Others include risperidone, olanzapine • Mechanism of Action: • Serotonin 5-HT2A and D4 receptor antagonist, together with weak D2 blocking properties contribute to most of the advantageous effects of the drug • Two year study of 229 schizophrenia spectrum patients found second-generation antipsychotics such as clozapine significantly reduced risk of violence, while typical antipsychotics did not have any significant effect

Progressive brain structural changes mapped as psychosis develops in 'at risk' individuals (Sun)

As the field moves toward the early intervention and prevention rout, studies started coming out assessing those in the prodromal state around the time of conversion to full psychosis (or not). This is the first study (with significant results) to compare the brains of those identified as prodromal who go on to develop psychosis (converters) and those that do not (non-converters) Non-converters are of two types; those that go on to develop another psychiatric illness and those that go on and don't receive any diagnosis. Qualitatively, you see across the entire frontal lobe and much of the rest of the brain, those who convert have greater cortical contraction than those who do not convert. Approximately 2mm for non-converters and 4mm for converters. The one area that survives statistical correction is the right prefrontal cortex (remember?), primarily the superior and middle frontal gyrus

Delusional Disorder:

At least 1 month of one or more delusions but no other psychotic symptoms. Hallucinations are mild if present at all. No odd or bizarre behavior. Not purely associated with manic or major depression. Lifetime prevalence 0.2% Family friend: checks under the bed to find the guy sleeping with his wife Delusion is I know you're cheating, I'm going to catch it

Referential delusions

Belief that certain gestures, comments, environmental cues, etc. are directed at oneself.

Persecutory delusions

Belief that one is going to be harmed, harassed, etc. by an individual, organization or group. (paranoid..)

Bizarre vs. "Normal" delusions

Bizarre delusions are those that are clearly implausible and not understandable even to same-culture peers and do not derive from ordinary life experiences. OR any delusions that express a loss of control over mind or body. Example: an outside force has removed his or her internal organs and replaced them with someone else's organs without leaving any wounds or scars. Example: my thoughts have been removed and/or alien thoughts have been put into my mind. Normal delusions are theoretically plausible though are clearly not supported by any evidence. Example: the police have me under surveillance

Prevalence of COS in U.S.

COS is a rare and debilitating illness that appears to be continuous with the adult onset disorder Based on observations from the National Institutes of Mental Health (NIMH) cohort, its incidence is less than 0.04% Approximately 30-50% of children with affective or other atypical psychotic symptoms are misdiagnosed as COS

Catatonia

Can occur in the context of many other disorders. 3 or more of 12 psychomotor features -Stupor: no psychomotor activity or not actively relating to environment -Catalepsy: Passive induction of a posture held against gravity -Waxy flexibility: slight, even resistance to positioning by examiner -Mutism: little or no verbal response -Negativism: opposition or no response to instructions or external stimuli -Posturing: spontaneous and active maintenance of a posture against gravity -Mannerism: odd, circumstantial caricature of normal actions -Stereotypy: repetitive, abnormally frequent, non-goal-directed movements -Agitation -Grimacing -Echolalia: mimicking another's speech -Echopraxia: mimicking another's movements In Family of psychotic spectrum disorders Catalepsy -like a statue Not in in of itself a psychotic disorder, lots of conditions can have cataonic effects Can be psychotic but doesn't have to

Ethic Case Study- Charlie

Charlie is a 55 year-old man and has been able to live a stable and functioning life for more than a decade without the use of antipsychotic medications. In the past when Charlie took antipsychotic medications he hated them because he felt sluggish and gained a lot of weight. However, under the supervision of his psychiatrist and with the support of his family he was able to stop taking antipsychotic medications. As a result of discontinuing the antipsychotics, he felt healthier and he repeatedly expressed that he wanted to avoid all medication treatment in the future. Recently, Charlie's symptoms got way worse and he was involuntarily hospitalized after experienced paranoid delusions and attacking his daughter because he thought she was an imposter. Due to his desire to never take medication for his psychosis, the medical staff did their best to treat him without antipsychotics. However, after a couple of weeks in treatment, his symptoms worsened and he continued to be a risk to others. Because he was hospitalized involuntarily and is not in state to make decisions for himself, his wife legally holds the executive decision of whether or not to provide temporary antipsychotic medications to stabilize Charlie's symptoms. Dilemma: Whether or not to provide pharmacological treatment for Charlie Doctors know that providing antipsychotics for Charlie would stabilize his systems -- however he has repeatedly expressed that he never wants to go back on medication Paternalism is = doing good for the patient even if it is something that they don't want for themselves This means that by giving Charlie antipsychotics to stabilize his symptoms the Doctor following a paternalistic practice

Childhood Neglect vs. Childhood Abuse

Childhood Maltreatment is undoubtedly associated with earlier development of schizophrenia, as well as an increase in severity of symptoms Upon further research we see that neglect, more so than abuse, is more correlated with the severity of negative symptoms. In general, there is average of 5-6 time fold of cases of reported childhood maltreatment in Schizo/psychotic patients in comparison to the general population. Sexual abuse (a form of physical abuse) is correlated highly with schizotypal symptoms and positive symptoms Childhood maltreatment is not only associated with Schizophrenia but also with other dissociative psychotic disorders, such as: PTSD Dissociative Identity Disorder (DID) Depression Anxiety Substance Abuse

Stimulants and Child Development

Children with ADHD have lower levels of tonic dopamine, so they are prescribed stimulants ○ Cause increases in dopamine, similar to psychosis, in areas including the prefrontal cortex ○ Dosage-based for acute psychosis Child Development ○ Neurotoxicity from Adderall ○ Sensitization ○ Adolescent brain is undergoing constant development ○ Field is unclear about long-term effects

Future Research on COS

Clinical presentation of schizophrenia at this unusually early age of onset has been associated with premorbid developmental abnormalities, poor response to neuroleptic treatment, greater admission rates, and poor prognosis -Combining antipsychotic treatment with psychotherapeutic intervention may be a more comprehensive treatment strategy -There is a dire need for early characterization of symptoms and biomarkers, better understanding of the pathophysiology and progression of the illness -Recent advances in neuroimaging methodologies, particularly those that provide a window into brain functioning and circuitry, may provide a blueprint for identification of novel biomarkers for schizophrenia. -Research and implementation of novel treatments coupled with advances in genome-wide microarray technology may lead to the identification of genes that are relevant not only in the pathophysiology of schizophrenia, but also in providing an insight into treatment response, or course prediction

What are the Psychotic Disorders?

Currently considered a spectrum disorder with a set of disorders ranging in severity. This is new for DSM-5 Schizotypal personality disorder Not a classic Psychotic Disorder. This is a personality disorder that is beginning to be considered a milder but stable variation of psychosis. Does not involve full symptoms in any of the domains. This is a pervasive pattern (long term and unchanging) of social and interpersonal deficits, including reduced capacity for close relationships. Involves cognitive or perceptual distortions and eccentricities of behavior. Begins in childhood or early adulthood. Autism is also a spectrum disorder DSM is an attempt to try to describe a mountain fo people with symptoms Cluster A personality disorders... Not classic shizophrenia disorder Schizotypal personality disorder Not mild schizophrenia Difficuly with close relationships -> odd in appearance, interests MAGICAL THINKING - high in this Refers to thinking the world has underlying weird special unexplained things going on, hidden forces, auras, energies, high on conspiracy theories much more than what you can see Governent gassing us theory -> I think it could be possible..different than delusional

What is childhood onset schizophrenia (cos)?

DSM-5 diagnostic criteria for schizophrenia requires at least two of the following five symptoms to be present for a month. [1] At least one of these must be (1), (2), or (3): 1. Delusions 2. Hallucinations 3. Disorganized speech 4. Grossly disorganized or catatonic behavior 5. Negative symptoms Other criteria include a markedly lower level of functioning in one or more major areas, such as work, interpersonal relations or self-care; persistence of continuous signs of disturbance for at least 6 months; the ruling out of schizoaffective disorder; and the exclusion of substance abuse or another medical condition that may be causing the disturbance. "Childhood-onset schizophrenia is a severe form of psychotic disorder that occurs at age 12 years or younger and is often chronic and persistently debilitating"

What is Substance Use Disorder?

DSM-5 differences from DSM-IV: ○ no longer uses the terms substance abuse and substance dependence ○ Substance Use DIsorder classification is defined as mild, moderate, or severe to indicate the level of severity ○ The diagnosis is based on evidence of impaired control, social impairment, risky use, and pharmacological criteria. ● Defined as: ○ Recurrent use of alcohol and/or drugs causes clinically and functionally significant impairment, such as health problems, disability, & failure to meet major responsibilities at work, school, or home.

Cannabis Use Disorder

DSM-V defines it as: - A problematic pattern of cannabis use leading to clinically significant impairment or distress, as manifested by at least two of the following within a 12 month period: - Cannabis is taken in larger amounts than intended - Persistent desire to cut down use - A lot of time dedicated to obtain, use, or recover from its effects - Craving - Failure to fulfill obligations at work, school, or home - Continued use despite persistent problems - Reduced involvement in social, occupational, or recreational activities - Recurrent use in physically hazardous situations - Continued use despite knowing it causes physical or psychological - Tolerance - Withdrawal - Brief history: - 2700BC: first documented in central Asia and China - 1937: Marijuana Tax Act made it illegal to possess or transfer it - 1990's: medical legalization - Current Day: recreationally legal in WA, OR, CA, NV, AK, ME, MA, CO - Drug of abuse: marijuana - Three types of strains - Ruderalis, Sativa, Indica - Endogenous Neurotransmitter System - Involved in mood, pain, appetite, and energy regulation - Receptors: CB1 in the CNS, and CB2 primarily in PNS

Stimulant Use Disorder

DSM-V defines it as: continued use of amphetamine-type substances, cocaine, or other stimulants leading to clinically significant impairment or distress, from mild to severe - Primary drugs of abuse: caffeine, cocaine, amphetamines (methamphetamine) - Brief history: - Alkaloid is derived from coca plant leaves - Until 1906, cocaine used to be an active ingredient in coca cola - 1887: amphetamine was first synthesized - 1919: methamphetamine was first synthesized in Japan - World War II: given to soldiers to enhance performance - caffeine: least potent, mild tolerance, withdrawal is mild but long-lasting - withdrawal symptoms: nausea, headaches, fatigue, poor concentration - cocaine: powerful, short-acting CNS stimulant - intensity and duration depends on route of administration - 17-18% of all users become dependent - inhibits dopamine transporter - amphetamines: synthetic, strong stimulant - excite dopamine transporters and VMAT Amphetamines - Used in a binge pattern - Acute Effects - Euphoria, increased energy, higher self confidence, decreased appetite, increased libido, increased blood pressure, chronic inflammation - Chronic Effects - Tolerance to euphoric effects, anorectic, cardiovascular effects, degeneration of DA and 5-HT receptors, psychotic episodes with delusions or hallucinations - Symptoms usually clear up after going through withdrawal - Withdrawal - Depression, anxiety, cravings, fatigue, hyperphagia, insomnia, anhedonia - Pharmacological Treatments - Currently none have been approved by the FDA

Delusional syndromes in partner of individual with delusional disorder

Delusional material from the dominant partner provides content for delusional belief by the individual who may not otherwise entirely meet criteria for delusional disorder

Disorganized Thinking (speech)

Derail from questions Tangential answers Come in an out of focus Makes 0 sense at all, cant make sense of it Picture having headache AKA Formal Thought Disorder Switching from one topic to another (derailment or loose associations). Answers to questions may only be slightly related to the question, if at all. Rarely speech is nearly incomprehensible and can resemble aphasia or "word salad".

Bipolar Disorder and Pregnancy

Difficult clinical challenge to protect the mother from mood instability and potential consequences and to ensure the infant's health • Studies are not possible to conduct due to ethical reasons • Stopping drug therapy is shown to be associated with twice the risk of mood episode relapse and bipolar symptoms throughout 40% of the pregnancy • Depressive episodes can also lead to poor prenatal care and nutrition and trouble with attachment • However some medications are associated with congenital heart defects, neural defects, and developmental delay Women who are responsive to lithium are recommended to continue lithium treatment during pregnancy ⚫ Protection from mood instability • Teratogenic, cardiac anomalies due to neonatal toxicity • No association with neurodevelopmental deficits • Late pregnancy: associated with neonatal adaptation syndrome • Breastfeeding: can rise quickly into toxic range, possible with physician supervision

Euphoric States Experienced in Manic Psychosis

Disorder tends to lead to feelings of euphoria, as well as extreme confidence & self-esteem. Grandiose beliefs and amplified behaviors Manic psychosis can be experienced in a euphoric or irritable manner. Can eventually lead to risk-taking behavior related to the surge of dopamine release Excess dopamine can produce euphoria & initiate a manic event, whereas low amounts of dopamine can contribute to the depressive symptoms of BPD

Manic Episode

Distinct period of abnormally and persistently elevated, expansive, or irritable mood. 3 or more of the following (4 if the mood is only irritable) are present and must include a and b. Lasting at least 1 week. a. inflated self-esteem or grandiosity b. decreased need for sleep (feels rested after 3 hours of sleep) c. more talkative than usual: pressure to keep talking d. racing thoughts or "flight of ideas" e. extremely distractible f. markedly increased activity (socially, work, school, sexual etc.) g. excessive involvement in pleasurable activities that have high potential for painful consequences. Buying sprees, sexual indiscretions or foolish business investments. Grandiosity God comes into play, I am god, I am talking to God, healing for him, religiosity is a common occurance Start a lot of projects but complete very few Point g gets people with bipolar into trouble Doing cocaine sleeping around Buying gifts for others Because of a. Schizophrenics don't like taking medication Disease tells them you are trying to kill them with drugs Don't think they are sick Bipolar hate treatment because they love how mania feels especially if they have had depression Weary of forcing treatment on people

Duration of Untreated Psychosis in First-Episode Schizophrenia: Marker or Determinant of Course? (McGlashan)

Duration of untreated psychosis (DUP) is thought to be extremely important. There is evidence that the longer a person goes without treatment, the worse their lifetime outcome. However, some argue about what this means It could be that those who do not seek treatment might have a less aggressive form of the disorder. It could also be that there is something about bing in a psychtic state that does lasting damage. General findings show large heterogeneity in outcome for schizophrenia patients. However most commonly, you see a marked drop in functioning in the first months following onset with a plateau with some smaller ups and downs. The presence of affective and depressive symptoms seems to predict a slightly better outcome Positive response to initial medication treatment strongly predict better long term outcome The presence of negative symptoms predicts a worse long term outcome -longer you are psychotic not getting treatment, the worse you are long term -hospital readmittion greater -work less likely -social outcomes not as good -suicides more likely -important to note that this is just correlation -there are other interpretations -could be that ppl with shorter untreated psychosis are different than those with longer untreated psychosis -might have different variant of conditions -could be longer you are actively psychotic more destruction you have in life and that will have a secondary efect -what professor was told: seems something is neurotoxic about brain under psychosis, maybe neural inflammation, brain in this state makes them have power outcomes long term DUP is typically between 1-2 years. Two subgroups. One has DUP of weeks to a few months, the other has a DUP of 1+ years. Longer DUP may be due to worse symptoms (primarily paranoia) Longer DUP may be due to worse premorbid functioning. Early intervention via early identification and education seems to be an effective public health approach reducing DUP from 2 years to about 4-5 months. While longer DUP is associated with poorer outcome, it is believed that most of the deterioration happens very early in the course of the disease. Vey early intervention may be able to halt some of the deterioration in neural and functional status. -duration of untreated psychosis is 1-2 years -last 15 years big push for early identification and prevention -2 sub groups -1. untreated psychosis weeks - months -2. much longer untreated psychosis -maybe those who didn't get help until 2 years started off at a very high functioning level and took them longer to get to lower functioning level -prodromal research prevention model - McGloshan -dropped 2 years to 4-5 months -prodromal model: most interesting model

Differences Between BPD and SZ

Estimated that during manic episodes only 70% of people experience some form of psychosis. BPD psychosis is always attached to mania or depression, unlike schizophrenia. If disorganized thought is present it tends to be less severe in BPD. Antidepressants can precipitate manic psychosis in patients with BPD. (Same phenomenon is not common in SZ) Delusions tend to be more goal directed in BPD.

Prefrontal Cortex and Executive Functioning in Manic Psychosis

Executive functioning depends on the prefrontal cortex and is responsible for directing attention, cognitive flexibility, strategy shifting, & inhibitory/impulse control. The ACC is localized in the prefrontal cortex and interacts with the amygdala which is a region critical to emotional responsiveness. Disrupted connectivity between the amygdala and ACC is most likely accountable for the risky choices seen in manic psychosis because the amygdala, which is crucial for fear recognition, is unable to communicate properly. People in the manic state can behave unethically because their prefrontal cortex receives distorted evaluations of the repercussions associated with their actions

Treatment of Schizophrenia

Existing antipsychotic medications have their main effect through blockade of dopamine D2 receptors. These are most prominent in the striatum Approximately 30% of patients respond very well and go into remission Approximately 30% of patients have partial response with ongoing issues that are somewhat milder than the original episode The rest of patients do not seem to respond well at all. These patients may have a different neurobiological abnormality leading to their psychosis. These drugs have often serious and powerful side-effects Original antipsychotics could cause movement disorders that could be permanent and disabling Current, so called atypical antipsychotics cause a variety of metabolic side-effects and can lead to significant weight gain and even type 2 diabetes Long term compliance is a challenge even in those patients that respond well. Either due to side effects, cost, or increasing symptoms that conflict with compliance (i.e. paranoia and somatic delusions) Even in those who respond well, current treatments only reduce positive symptoms, especially delusions and hallucinations. Remember that it is the negative and cognitive symptoms that are most predictive of long term social functioning and disability. Moved away from lobotomy because discovery of thorozine - first antipsychotic drug First generation of atypical antipsychotic drugs Current treatment is medication Dopamine antagonists (all medication is this) Blocks dopamine D2 receptors Harsh reality is: approx. 30% of patients respond very well, 30% will respond ok partial response still have milder symptoms, the rest of patients won't respond at all Most powerful psychiatric mediation = tremendous side effects Half patients discontinue treatment because of this Feeling slowed down, robotic Antipsychotics = neurolethics = major tranquilizer Strong sedative effects Significant weight gain Up to 80 pounds Gynacomastia = breat in males Can develop type 2 diabetes Gain of cholesterol Biggest problems with drugs - even when they go well they only treat positive symptoms No treatment for negative symptoms yet

Schizoid personality disorder

Far less than 1% have this Characterized by person lacking any social needs Highly unusual Counter to our evolutionary past no sexual drive Suspiciousness does not rise to the level of delusion Default position of me against the world

Fetal Hypoxia and Structural Brain Abnormalities in Schizophrenic Patients, Their Siblings, and Controls (Cannon)

Fetal hypoxia is one of the known factors associated with a higher risk of psychotic disorders. Authors wanted to investigate the interaction of this "environmental" factor and genetic factors by studying patients and their healthy siblings compared to controls in how hypoxia affects the brain. They looked at hypoxia as well as another somewhat related factor; low birth weight/prematurity. Conducted MRI imaging and analyzed gray matter, white matter, ventricle size and sulcus volume. Note whole brain gray matter effects in patients and siblings and NOT controls Note NO White Matter effects (newer technologies have largely contradicted this) Note Ventricular effects only in patients. Note Sulcus volume effects primarily in patients but also in the temporal lobe in siblings. Effects are strongest in temporal lobe: Is this surprising? Control brains are resilient to hypoxia AND low birth weight. What does this mean? Siblings look VERY similar to patients except when there is hypoxia AND low birth weight.

Positive Symptoms/ Delusions

Fixed beliefs that are not amenable to change in light of conflicting evidence. Persecutory delusions: Belief that one is going to be harmed, harassed, etc. by an individual, organization or group. (paranoid..) Referential delusions: Belief that certain gestures, comments, environmental cues, etc. are directed at oneself. Grandiose delusions: When an individual believes that he or she has exceptional abilities, wealth, or fame. Positive: Gain of function Above and beyond normalness Erotomanic delusions: When an individual falsely believes that another person is in love with him or her. Nihilistic delusions: A conviction that a major catastrophe will occur. Somatic delusions: focus on preoccupations regarding health or organ function Jealous delusions: partner is cheating. No evidence at all or the person believes they have bits of evidence they believe add up to proof.

Ethics and restrains

Four principles: ● Autonomy-freedom and choice of an individual ● Beneficence-obligation of caregivers to give patient the best care ● Nonmaleficence-do no harm, promote good ● Justice-equal and fair access to resources Conflicts...Restraints: ● Restrict patient's movement and doesn't take into consideration their opinion ● Are restraints the best option? ● Restraints can cause physical harm and emotional stress ● Use of restraints typically due to inadequate resources available (not enough trained staff)

Lobotomy:

Freeman father of lobotomy Administered electric or insulin shock Electric usually because of "familiarity to psychiatry" What is transorbital lobotomy doing? Disconnecting frontal lobe from thalamaus Disrupt frontal lobe to make decision Makes person docile, passive Voluntary behavior is diminished Are they actually happier, better? No They can still speak? Yes, had reduced self awareness of negative emotional states, how they felt, didn't care about those 65 - 70 years ago

Significant treatment effect of adjunct music therapy to standard treatment on the positive, negative, and mood symptoms of schizophrenic patients: a meta-analysis

Gap in Knowledge: Music therapy used to treat positive symptoms is inconclusive due to lack of evidence Purpose: Evaluate the treatment effect of music therapy on the specific subscale symptoms of SZ, including the overall disease severity of schizophrenia, positive symptoms, negative symptoms, psychopathology, and mood symptoms. Methods: Meta-analysis of SZ patients w/ standard treatment with and without adjunct MT Results: Treatment effect significantly better in patients who received adjunct MT than those who did not, in both negative and positive symptoms.

What are the psychotic disorders?

Generally thought of as a disordered state where a person begins to lose touch with reality and begins to exhibit odd behavior. Psychosis defined as having symptoms in one or more of the following 5 areas. Delusions Hallucinations Disorganized thinking Grossly disorganized or abnormal motor behavior Negative symptoms

Gender Differences in 1st Onset

Goal: ""Explore gender differences in symptom profiles, family adversities, pathways to care, and characteristics of inpatient treatment at the time of first diagnosed schizophrenia spectrum disorder among adolescents" (Talonen et al., 2017). ○ Took teenagers ages 13-17 ○ Schizophrenia spectrum disorder: schizophrenia, schizoaffective, schizotypal personality, delusional, brief psychotic, etc. Findings: ○ Girls = more self-harming behavior and depression ○ Boys = more aggression ■ Theorized that this aggression explains why the male population of this study was more often hospitalized involuntarily ○ For family adversities: girls had more recorded stressors (parental substance abuse or mental health issues, domestic violence, death in the family, financial difficulties, etc.) ■ Females more vulnerable to stressors as a triggering factor in schizophrenia spectrum disorders ■ Possible explanation: varying rates of maturation in adolescents and increasing dimorphism of the CNS ● Overall there are somewhat gendered profiles of symptoms, however, this is similar to the gender differences found in the normal population

Altered cortical maturation in adolescent cannabis users with and without schizophrenia

Goals: During late adolescence, progressive cortical thinning occurs in heteromodal association cortex (HASC) that is thought to subserve cognitive development. However, the impact of cannabis use disorder (CUD) upon cortical gray matter development in both healthy adolescents and adolescents with early-onset schizophrenia (EOS) is unclear. Main method: T1-weighted magnetic resonance images were acquired from 79 adolescents at baseline and after an 18-month follow-up: 17 with EOS, 17 with CUD, 11 with EOS + CUD, and 34 healthy controls (HC). Mean age at baseline was 16.4 years (CUD+) and 17.0 years (CUD−). Using FreeSurfer, measures of cortical thickness for ROIs within HASC were obtained. A 2 (EOS versus no EOS) × 2 (CUD versus no CUD) multivariate analysis of covariance was applied to change scores from baseline to follow-up to test for main effects of EOS and CUD and an interaction effect. Primary finding: After adjusting for covariates, a significant main effect of CUD was observed. Adoles- cents with CUD showed an attenuated loss of cortical thickness in the left and right supramarginal, left and right inferior parietal, right pars triangularis, left pars opercularis, left superior frontal, and left superior temporal regions compared to non-using subjects. Stepwise linear regression analysis indicated that greater cumulative cannabis exposure predicted greater cortical thickness in both the left (p = .008) and right (p = .04) superior frontal gyri at study endpoint after adjusting for baseline cortical thickness for the entire sample. T Disc: These prelim- inary longitudinal data demonstrate an atypical pattern of cortical development in HASC in adolescents with CUD relative to non-using subjects, across diagnostic groups. Additional studies are needed to replicate these data and to clarify the clinical significance of these findings. To our knowledge, this is the first longitudinal study to examine the effects of CUD on nonpsychotic adolescents and adolescents with EOS. Our findings provide a snapshot of the effects of CUD on brain structure during late adolescence, suggesting that cannabis exposure during this developmental stage may attenuate normative age-dependent cortical thinning. The effects of cannabis exposure during other life stages, for example, during early adolescence or adulthood, may be very different. Longitudinal developmental studies, with scanning at multiple time points, are needed to fully characterize the effects of cannabis on the de- veloping brain in both nonpsychotic adolescents and adolescents with schizophrenia.

areas of brain where healthy individuals have the thickest cortex followed by DZ healthy co twin followed by monozygotic healthy cotwin

Here we see data from the analysis of genetic liability. These analyses ask the question "which areas show the following pattern where Control twins have larger cortical thickness than DZ co-twins (healthy twins) who in turn had more cortical thickness than MZ co-twins. Controls >DZ>MZ In other terms, it asked for a linear effect of genetic closeness to a schizophrenic person where controls = 0%, DZ co-twin = 50%, MZ co-twin = 100% Genetic liability map reveals significant correlations with cortical thickness mostly in frontal polar areas and lateral prefrontal areas -consistent finding with disease maps -some differences -greatest genetic = ffrontal and prefrontal, losses might be disease specific -less invovlement of parietal and temporal These analyses are arguably less relevant Here, we are looking at what are called inter-class-correlations ICC. They are showing that in healthy twins, MZ twins have very similar cortical thickness throughout the brain and DZ twins have far less similar cortical thickness patterns. They also show that in twins where one is affected by schizophrenia (discordant twins), there is comparably less twin-to-twin similarity in cortical thickness. Not surprising given the fact that one twin is suffering from a significant brain disorder. -interclass correlations -parts of the brain that are highly similar thickness when you look at one identical twin vs. other -strongly influenced by brain -in healthy invidiauls, cortical thickness is very genetically driven Discordant MZ (one schizo one doesn't)

Reward Salience and Manic Psychosis

Higher activation in nucleus accumbens leads to larger responses to gain and diminished responses to losses. Overall reinforcing effect on any "rewarded" behavior. Imbalance can be so severe, people lose touch with reality.

Childhood maltreatment and the Prodromal Period

Higher levels of emotional abuse and neglect has been shown to lead to shorter prodromal periods. Contrary to the belief that they would have longer periods since they have no-one to care for them ● This has been attributed to the relation between more flamboyant symptoms expressed in those that have experiences emotional and physical neglect. ● The emphasis of the symptoms thus leads to hyper-awareness of the individual from others around them.

Homelessness and psychosis

Higher rates of psychosis are found in younger persons and the chronically homeless. Homeless persons with mental illness are significantly more likely to be white, to be high school graduates, to have a lifetime diagnosis of substance dependence, and to be married. According Treatment Advocacy Center: Approximately 33 percent of the homeless are individuals with serious mental illnesses that are untreated; Many of these people suffer from schizophrenia, schizoaffective disorder, bipolar disorder or major depression. Studies from the 1990s show people with serious mental illness were reported to be 10 to 20 times more likely than the general population to become homeless.

Patterns of cortical thinning in different subgroups of schizophrenia

In DSM-IV, we had "subtype" specifications for patients with schizophrenia. Paranoid Disorganized Catatonic Residual Undifferentiated These were dropped in DSM-5 This study involved structural imaging of schizophrenia patients divided into the following subtypes: Paranoid Symptoms, Negative Symptoms, and Disorganized Symptoms If there are significant biological differences as well as clinical differences, then maybe dropping these subtypes was premature. Widespread cortical thinning seen when all subtypes were combined Separating the groups reveals clear evidence that the effect in the combined group is driven primarily by the negative symptom dominant group. Negative Subgroup: Prefrontal, Temporal and Parietal areas highly significant thinning Paranoid Subgroup: Some prefrontal areas, temporal areas but much less than in the negative group. Disorganized Subgroup: Least cortical thinning of all the subgroups. Superior and Middle Prefrontal and some temporal areas.

Causes for Increase in negative symptoms related to childhood maltreatment

In studies assessing the WHY factor behind the increase in negative symptoms as well as other comorbid disorders reveal the importance of the regulation of the HPA Axis. ● Participants of sexual abuse were shown to have a dysregulated HPA Axis ● This dysregulation is caused by the hypersecretion of corticotropin releasing factor (CRF) ● The dysregulation can be attributed in hyperactivity of the HPA axis due to the prolonged stress of neglect, such as the distress felt of not knowing where one is going to sleep or what to wear, especially when resources are limited for children/ lack of autonomy and control.

Dopamine and Manic Psychosis

Increased D2/3 receptor density In the caudate and putamen. Stimulation of subthalamic nucleus in patient with Parkinson's disease induced psychotic symptoms. Treatment with high dose antipsychotic Ended psychosis but lead to severe depression. Are There Different Types of Psychosis? Dopamine has been implemented in both SZ and BPD. Many affected regions of the brain overlap particularly cortical regions. Differences in not always entirely clear. (Schizoaffective Disorder)

What is the purpose of bioethics?

It answers questions about: Basic human values such as the rights to life and health Rightness or wrongness of developments in healthcare, technology and medicine Society's responsibility for the life and health of its members Health professionals ought to act with their patients to maximize patient autonomy

Personality disorder

Life long Pervasive, hits every aspect of person's life Maladaptive, cannot elieviate underlying urges and behaviors Very little insight

Outcomes of COS

Long-term course of 76 patients with suspected diagnosis of childhood onset schizophrenia -1920-1961, only 50% were confirmed with diagnosis of schizophrenia from original sample -Follow-up investigation conducted and outcome was overall poor or everyone Clemmensen et al. (2012) A systematic review of long-term outcome of early onset schizophrenia -Conducted in 1980 identified a total of 21 studies, which included 716 patients who were either suffering from early onset schizophrenia (EOS) or both EOS and other psychotic disorders (MIX). -In general, the outcome in studies with EOS is worse than the outcome in MIX studies. Only 15.4% of the patients in EOS studies versus 19.6% of the patients in MIX studies experienced a "good" outcome. In contrast, 24.5% of the patients in EOS studies versus 33.6% in MIX studies experienced a "moderate" outcome, and 60.1% in EOS studies versus 46.8% in MIX studies experienced a "poor" outcome. -Early manifestation is associated with a particularly poor prognosis -Although these studies are old, they study long-term outcomes of schizophrenic patients. We should take this data with a grain of salt knowing that the quality of life for schizophrenia patients is very low and being diagnosed with childhood onset schizophrenia is associated with a poorer quality of life than adult onset schizophrenia

Antiepileptic drugs (AED) for pregnant women

Lower the rate of firing in the brain to treat epilepsy • At first, AEDs were only prescribed for those who did not respond to lithium ⚫ Can be prescribed as monotherapy, in combination with lithium or an antipsychotic to treat mania • Three main AEDs prescribed for bipolar disorder: Lamotrigine (Lamictal), Carbamazepine (Tegretol), and Valproic acid (Depakene, Depakote) • No statistical difference in PP between mothers treated with lamotrigine and lithium • Carbamazepine and valproic acid are associated with neural defects such as spina bifida ⚫ Late pregnancy: Valproic acid has an increased risk of neonatal toxicity syndrome and lower mean IQ scores • Breastfeeding: all possible with physician's supervision

Grossly Disorganized or Abnormal Motor Behavior

May manifest in many ways Childlike silliness Unpredictable Agitation Can affect any or all goal directed behavior, leading to difficulties in daily living. Catatonic type: marked decrease in reactivity to the environment. negativism: resistance to instructions Rigid, inappropriate or bizarre posture Mutism and stupor: complete lack of verbal and motor responses Catatonic excitement: purposeless and excessive motor activity without obvious cause or goal. Repeated stereotyped movements Grimacing, staring Echoing of speech

A Multimodal Analysis of Antipsychotic Effects on Brain Structure and Function in First-Episode Schizophrenia (Lesh)

Medication effects have long been a thorn in the side of psychiatric neuroscience research It is unclear which findings are influenced or outright due to treatment with antipsychotic medication Lesh et al decided to very directly test the effects of medication on first episode psychosis First episode is defined as the first appearance of major symptoms. Often with a stay at a psychiatric hospital -another imporant issue is medication effects -for practical and ethical reasons, studies are done on patients on medication -hard to study those unmedicated -unethical to keep patients off medication so you can study them -duration of untreated illness is quite toxic for the brain -Lesh looked for participants who were first episode psychosis (first time they had break) and also untreated -wanted to do brain study on them before they medicated them - Structural Imaging: Gray Matter Differences Data strongly indicate that group differences are driven primarily by the medicated group. WTF? Authors discuss that there is increasing evidence that there is neuro-inflammation in schizophrenic brains and that antipsychotic drugs might reduce this inflammation. Reduced inflammation would appear as reduced gray matter in medicated patients. However: key group is missing (impossible to do). Which group is this? -look at grey matter thickness -top images: all schizophrenics, medicated, regular first episode schizo, unmedicated -controls have more brain matter in certain parts of frontal lobe and tempo -separated medicated vs. control -greatest group difference -greatest gray matter loss in medicated first ep. schizo -separate unmedicated vs. control -differences much much smaller -medicated vs. unmedicated -medicated have less cortex -looks like drugs are hurting them -lots of discussion in paper and field about this -neural inflimmation -pretty sure that brains of people with schizophrenia are inflammed, swollen -Lesh thinks what these medications are doing is reducing inflammation and looks like reduced grey matter, loss of synpases already happened but brain is swollen, so what should have lookedl ike thinner cortex looks swollen, masked by neural inflammation in untreated patients -it's not that medication creates loss of synapse, they get rid of neural inflammation which unmasks damage done by disease -markers of neural inflammation rising in schizo, alzheimer patients -problem with study: -super important group we can't have that would support inflammation idea: medicated controls to see what if anything the drugs do to brains without schizophrenia Functional Imaging AX-CPT task used to evaluate activation patterns Task is to press a button when an X follows an A A->X trials made up 70% of trials Hardest trials were B->X where participant must NOT press the button to X A->Y were also difficult because a participant get ready to press the button when they see the A but must resist even though the Y looks similar to the X -coemmision: shouldnot have pushed, but you pushed -A followed by something else (ADHD people are bad at this - inattentivity, impulsitivity) -good test of frontal lobe function Results strongly suggest that the medicated group has neural activity somewhere between the control and the unmedicated group. Unmedicated group does the worst. Additional analyses show that the level of gray matter differences do not correlate with the level of activation. This shows that the increased activation is not solely due to cortical thinning (remember that thinning might be a good thing the view of the authors in this context) -Axcpt: medicated group is in between control and unmedicated -worst of is unmedicated -a little better is medicated -best control -what they found in terms of activaion -thinner non-inflammed cortex is better than bigger inflammed cortex

Family Intervention in schizophrenia

Method: - BFT consists of one on one interviews with family members, psychoeducational class about schizophrenia, markers for possible signs of relapse, training for crisis management, social skills training - All delivered in 2-3 hour sessions once a month - Contrast group receives conventional family support from outpatient physicians, learn about warning signs of emergency psychotic episode and information about schizophrenia, much less training intensive - 8-10, 20 minute sessions a month much less detailed training - Self assessments taken on day of admission into ward, 4-5 weeks after admission, lastly on day of or day after discharge of patient Predictions? 1. BFT will reduce familial burden for caretaking 2. BFT will have a positive impact on attitude towards taking care of schizophrenic family member Findings - Attitude of family to take care of patient upon discharge much more positive than contrast group - Contrast group has 13 instances of relapse, BFT Group has 1 instance of relapse after 1 year follow up - FIT consists of 13 relative group sessions, 90 mins long, 1st session within 1st month of program, the rest occurring monthly - Relatives able to vent about emotions - Deliver info about disorder management - Offer hope for psychotic relative to get better - Assist relative to reduce patient criticism and let them be more independent - Help relative reprioritize and put selves first - Learning coping methods Individual training 5hrs/5 days a week - Learning vocational skills -Social skills training -Place to vent feelings - Family intervention therapy with individual treatment vs. individual treatment alone 1. FIT + individual treatment produce stronger benefits for clinical and social prognosis of schizophrenia than individual treatment alone 2. FIT + individual treatment produce ability to reduce high-expressed emotion in family members or schizophrenic patient Combined treatment effective for the first year of follow up, but not the second - Presence of dropouts from the study affected the statistical analysis (suicide, dropout, and loss of motivation to stay with program) - There was low relapse and rehospitalization overall - Treatment was equivocal - Differences declined by 2nd year follow up -One third of high-EE reversed to low-EE - But not entirely significant - Study was effective in normalizing relatives' attitudes - Needs to be more group sessions/family sessions next time

How is potential danger determined in psychotic patients?

Multiple clinical assessments are used as a measure of potential violent behavior • Assessments such as S-RAMM, GAF, and PANSS scales are a few that have served well to predict future violent behavior • These scales also serve as predictors of future self-harm • Research has shown there is an overlap between risk factors for future violence and future self-harm • Historical Clinical Risk Management-20 (HCR-20) is a common tool to assess violence risk • Includes 20 risk factors from historical, clinical, and risk management domains • Threatening or intent of violent action • Presence of persecutory delusions • Command auditory hallucinations, which may direct an individual to commit acts of violence • Age • Highest rates of violence occurring during adolescence and early adulthood • Risk decreases sharply after age 40 • Previous history of violence

What is ethics?

Not the law or moral compass "Ethics refers to the well-founded standards of right and wrong that prescribe what humans ought to do, usually in terms of rights, obligations, benefits to society, fairness, or specific virtues." "Bioethics is an application of ethics to the field of medicine and healthcare"

Treatment of Cos

Once a diagnosis is confirmed, aggressive medication treatment, usually with Clozapine an atypical antipsychotic, combined with family education and individual psychotherapy is used Overall findings indicate that COS patients may be more responsive to Clozapine, relative to other antipsychotics, in addition to Clozapine having higher efficacy in COS than in adult onset schizophrenia patients Clozapine has severe side effects including those affecting the hematopoietic system (agranulocytosis), cardiovascular system (myocarditis), central nervous system (seizures, akinesia, myoclonic jerks), and liver function, along with other side effects such as severe movement disorders, hypersalivation, hyperglycemia, diabetes, and weight gain, which are particularly problematic for children and young adults Although antipsychotic treatment and psychotherapeutic interventions provide some symptom relief, there is still a very high percentage of residual psychotic symptoms and cognitive deficits

Is paternalism ever justified?

One exception when it is justified is when the person poses as high probability of substantial harm and it infringes on the rights of others "It must be necessary to avert significant risk, first, in the judgment of health officials but, ultimately, to the satisfaction of a judge," and "[The intervention] must be well tailored to address the risk and not going beyond what is necessary in the situation" (Buchanan, 2008). In Charlie's case, medication should be provided if his symptoms worsen, if he poses a threat to others but it would have to be at the minimum dosage in order to stabilize his symptoms

Cannon et al 2002a Summary and Limitations

One of the unique qualities of this study is the sulcul and gyral tracing pattern. This study shows us that there are partially non overlapping areas that show disease specific deficits compared to those that show a genetic liability pattern. Genetic liability identifies much of the frontal lobe as being affected. Disease specific areas affect a subset of the frontal lobe, primarily in middle frontal gyrus. Additionally, parietal and temporal association areas were identified as being disease specific areas. Major limitation is that this method is blind to non-surface gray matter including areas that are CLEARLY important to psychiatric illness. Cingulate, insula, parahippocampal gyrus, hippocampus, amygdala, basal ganglia

Effects of listening to music on auditory hallucination and psychiatric symptoms in schizophrenia

PURPOSE: The purpose of this study was to explore the effects of listening to music in patients diagnosed with schizophrenia, on their auditory hallucinations, and positive and negative symptoms. METHODS: They split patients up into 2 groups: In Group AB, 11 patients listened to music followed by a wash out period (to prevent carry-over effects) and then a usual care period, and 12 patients in Group BA had a usual care period followed by a wash out period and then listened to music. For one week, those who were in the experimental period listened to individualized music using an MP3 player whenever they had an auditory hallucination. And data was collected through CAHQ and PANSS. RESULTS: The results showed that there was a statistically significant decrease in the frequency of auditory hallucinations after listening to the music. There was also a decrease in the mean scores for positive symptoms, negative symptoms, and general psychopathology after listening to music, but only negative symptoms showed a statistically significant decrease. The treatment effects on scores for positive symptoms, negative symptoms, and general psychopathology were greater in Group BA (where they listened to music later) than in Group AB. CONCLUSION: These results suggest that listening to music may be useful for managing auditory hallucinations in schizophrenics.

Ethics Concepts

Paternalism Paternalism is described as an action performed with the intent of promoting another's good but occurring against the other's will or without the other's consent. In medicine this is the acts of authority by the physician in directing care and distribution of resources to patients. Coercion Coercion is defined as the practice of forcing another party to act in an involuntary manner by the use of intimidation or threats or some other form of pressure or force. This is often used on patients who refuse to willingly take their medication

Hallucinations

Perception-like experiences that occur without external stimulus. They are vivid and clear, with the full force and impact of normal perceptions, and not under voluntary control Any sense may be involved but auditory hallucinations are the most common Perceived as clearly distinct from a persons own thoughts or "self talk" Does not include hallucinations that only happen right before (hypnagogic) or right after sleep (hypnopompic). Caveat: hallucinations may be considered "normal" in some cultures when part of religious experiences. perception in absence of sensory information Or milder level hallucinations or distortions Raw input is transformed Like I see a face that's aging in front of my eyes Could be very vivid or not, wispy, fully formed.. Whispers or people yelling at you Hallucinations are nasty.. Smell feces, burning hair, death Voices are not saying good things... bad things Ex. I have bugs on me, my arm is burning, I have snake inside me, bugs under skin.. Auditory are most common!! Usually voices Report that their own inner voice is different than the voice they hear (it is the same system) There is also distinction between scary level auditory hallucination.. Have 2 voices that talk to each other: mire sever case Also reach higher level severity if voice has running commentary on what you are doing (constant voice) Patients with mood symptoms (depression) could have more insight Not all ppl with tis disorder have depressions

Paranoid personanility distorder

Person's primary motivation is not if people will screw them, it's when How are you going to backstab them Current president might have this

Childhood Maltreatment History in Schizophrenics

Physical Abuse- Physical harm or injury on the child, either through malicious intent or severe discipline (e.g. spanking, whipping, punching, etc.) Physical Neglect- Failure to provide the basic necessities for the child to live (e.g., food, clothes, water, shelter, etc.) Emotional Abuse- AKA Psychological Abuse, the deliberate act of shaming or insulting someone (e.g., Name calling, threats, isolation, blaming the victim, etc.). Emotional Neglect- Failure to provide emotional support for the child (e.g., feelings of worth, caring, warmth, etc.)

Voxel-based morphometry study of the insular cortex in bipolar depression (Li-Rong Tang)

Picking up from the last study, these folks wanted to zoom into the insula to dissect sub-regional effects in the insula. They separated the insula into 3 areas Ventral anterior - involved in affective regulation and processing Dorsal anterior- involved in higher order cognitive processing Posterior - involved in interceptive processing Note a few things Great variation in the posterior insula Relatively small effects Lithium seems to have a protective effect

Factors that Increase the Risk of Psychosis

Predisposition Predisposition is an increased likelihood of developing a particular disease based on a person's genetic makeup Implications: ● Development of acute psychosis or psychotic symptoms in the context of cannabis increases with genetic predisposition to psychosis Doing cannabis at a young age Young cannabis users are considered 18 and younger. Regular cannabis users are those who smoke a few days a week. A heavy cannabis user smokes multiple times a day. Implications: ● The earlier someone starts smoking, the more likely the more likely they will develop a psychotic disorder. Predisposition for psychotic symptoms were assessed using "paranoid ideation" & Psychoticism subscales - Determined if they were "cannabis exposed" - Cannabis exposed was defined as "lifetime cannabis use of five times or more and frequency of use (once a month; three to four times a month; once to twice a week; three to four times a week; almost daily)" - Baseline measures of psychosis were taken initially during the experiment and compared to a follow-up measure four years later. - 320 participants were reported as cannabis exposed initially and 361 reported being cannabis exposed during the follow-up. - 17.4% experience one psychotic symptoms - 7.1% reported two or more psychotic symptoms. - Significantly higher with those having a predisposition and only moderate increase in those with no predisposition - This suggested that the development of acute psychosis in the context of cannabis may be associated with genetic predisposition to schizophrenia. - It also supports the notion that cannabis use may trigger the development of a psychosis in predisposed individuals, rather than producing a specific "cannabis psychosis"

Substance/Medication-Induced Psychotic Disorder

Presence of one or both of the following symptoms Delusions Hallucinations There is evidence from history, exam, or lab testing of The symptoms developing during or soon after substance intoxication or withdrawal or after exposure to a medication. The involved substance/medication is capable of producing the symptoms. Happens soon after stopping or starting medication Medication is changing importanct chemistry in the body? Drug use is stressor

Brief Psychotic Disorder

Presence of one or more of the following: at least one of these must be 1, 2, or 3. 1. Delusions 2. Hallucinations 3. Disorganized speech 4. Grossly disorganized or catatonic behavior. Duration of episode is 1 day to 1 month only with return to full level of functioning. Specify if following marked stressor or if postpartum (during pregnancy or within 4 weeks) High rates of relapse If you just have hallucinations for 1 day is it brief psychotic disorder? Yes? Postpartumdepression: 1st month after delivery, the mom can have significant depression, can't handle situation, maybe psychotic symptoms, postpartum psychosis - mgith injure, kill baby Lasts 1 day to 1 month but repeats a lot

HIV- Associated Psychosis

Prevalence rates of severe and chronic mental illness in HIV-infected patients (historically encompassing schizophrenia and bipolar disorder) are estimated to range from 4-19% - No evidence suggests that HIV causes schizophrenia, but data do support that schizophrenia contributes to high-risk behavior associated with HIV infection. -Schizophrenia and psychosis tend to be diagnosed only after HIV had been diagnosed - Other clinical features of Hiv-associated psychosis: - Delusions (87% of patients) - Hallucinations (61%) - Mood symptoms (81%) - When psychosis occurs in patients with HIV-associated dementia, it is characterized by prominent agitation, irritability, and delusions and is often part of a manic syndrome that has been called "AIDS mania." - In contrast to mania in bipolar disorder, AIDS mania is associated with a worse prognosis, greater number of symptoms, more chronic course, and infrequent spontaneous remissions. - AIDS mania patients are commonly irritable and infrequently hyper-talkative or euphoric - A frequent manifestation of AIDS mania, either early or late, is the delusional belief that the patient has either been cured of HIV or has discovered the cure. - Results in resumption of high-risk behavior and medication nonadherence

Schizophrenia, Suicide, and Substance Abuse and Childhood Maltreatment

Previous studies have found that people who have been diagnosed with schizophrenia and experienced childhood trauma (sexual abuse, physical abuse, or emotional abuse, but NOT physical neglect) are at a higher risk for suicide attempt than schizophrenics who did not experience childhood trauma. This may be due to the increase feelings of hopelessness, unsuccessful in coping with their experiences, and neurodevelopmental effects. Researchers have found that severity of childhood trauma may play a role in patients with schizophrenia developing substance abuse. Drugs may help these patients in coping with stressful situations and temporarily feel euphoric, but further studies are needed to form a causal link between schizophrenia and substance abuse.

Alzheimer's Disease

Primarily thought of as a form of dementia and associated with memory loss AD psychosis is characterized by hallucinations or delusions for one month or more that were not present before onset of AD Atypical antipsychotics are usually used as treatment Enlarged ventricles in the brain are consistent in both Alzheimer's and Schizophrenia The onset of psychosis in many patients diagnosed with Alzheimer's suggests similarities between the brain chemistry and structure of those with schizophrenia and those with Alzheimer's - Additionally, both are associated with cognitive deficits with Alzheimer's primarily being memory loss - A popular theory regarding the onset of Alzheimer's involves the production of amyloid oligomers which disrupts neurotransmission pathway - Some suggestion that these affect not only the acetylcholine pathways but also dopamine - There has also been some success in using D2 agonists as treatment for cognitive symptoms of Alzheimer's just as typical antipsychotics tend to be D2 agonists. - It is important to look at the similarities between the onset of the two diseases and see if further associations can be made between them

Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia (Cannon)

Purpose of the study was to determine which areas of gray matter are perturbed by disease and which are affected by genetic factors. Authors utilized discordant MZ and DZ twins as well as control twins to pursue their questions. Conducted surface based cortical thickness mapping using high resolution MRI images. Each participants brain was meticulously traced to identify key known sulci and gyri. -Done in order to deal with the major problem of heterogeneity in brain gyrification. -how genetically similar are you to a person w/ schizophrenia -big problem in neuroimaging -tremendous variability in brains, size, shape, in gyral and sullcul patterns -we have for the most part same gyri and sulci -linear morphing -early neuroimaging = pull and smush to get brains into a standardized space -nonlinear morphing - pull each area with finer tunedadjustments In this study -per brain/ undergraduates drew all sulci of brain and labeled them -precise studies of cortical thickness, there aren't a lot of good options Problems: all cortical based b/c of methodology we don't go into subcortical structures such as hippocampus These maps compare cortical maps of the schizophrenic patients to THEIR healthy MZ co-twin. Shows areas where there is a disease specific effect because all effects of genetics are removed here. Areas that show up as significantly different between patients and their genetic matched controls tend to be in "association", "secondary" or "higher" areas of cortex. Dorsolateral Prefrontal Cortex Superior Temporal Cortex Superior Parietal Cortex -comparison b/w schizo participant and healthy co-twin MZ -genetically the same, differences we say are ascribed to disease and environment Correlations between deficits in regional cortical thickness and symptom and cognitive function Note significant correlations with negative symptoms and thinning of frontal and temporal areas Note Lack of significance in any occipital regions. Note significant correlations between cognitive functions and thinning of all cortex except occipital. -quantitatively -diff lobes with different locations -negative symptoms see significant correlation with frontal lobe and temporal lobe -greater loss = worse -cognitive f(x) that have been shown many times to be sensitive to schizophrenia -positive symptoms - no significant correlations = lvl of positive symptoms don't match up very well with cortex b/c from basal ganglia -cognitive effects correlated w/ everything except occipital lobe

Dose-response relationship in music therapy for people with serious mental disorders

Purpose: Examine the influence study design (RCT vs. CCT vs. pre-post study), type of disorder (psychotic vs. non-psychotic), and number of sessions Methods: Meta-analysis; all participants were also on traditional treatment (no music-only trials were tested). Ratings were collected through self-report or by an independent (blindfolded) rater, no therapist ratings were excluded Music therapy was offered between one and six times per week over a period of one to six months. Results: Therapy "dosage" was the only strong and significant predictor of the effect of music therapy compared to standard care for both groups tested. Stephan, a 14-year-old boy, was unwilling to speak with anyone except his family since the age of 7 He is described as initially stubborn, lost his temper, did not play, never worked at anything. And had been under psychiatric care for years without any results. Changing the music tempo the therapist gained a sense of mood control By the end of 2-month therapy he had begun talking and socializing with other children and began to function at a higher level in areas like school Discussion Adjunct MT improved negative as well as positive symptoms compared to those who did not receive MT regardless of duration, frequency, number of sessions, or duration of each session. However, the effects of MT increase with increasing amounts of sessions MT decreases frequency of auditory hallucinations Cognitive deficits also improve Overall, important additional treatment option for symptoms medication cannot improve and for its side effects

Neural Correlates of Delusion in Bipolar Depression (Radaelli)

Remember that not all patients with Bipolar Disorder will show psychotic symptoms. This study wanted to compare those that do show psychotic delusions vs. those that do not show delusion. Pretty simple study using historical delusions NOT current delusions.

Neurological Effect of Different Drugs

Reward and Acute Addiction: Driven by Dopamine and Endogenous Opioids End-stage addiction: Neuroplasticity in the anterior cingulate and orbitofrontal glutamatergic projections to the nucleus accumbens. Reduced capacity of PFC to exercise executive control over drug seeking.

Serotonin and Norepinephrine Neurotransmitters and Manic Psychosis

Serotonin begins in the brainstem and travels throughout various areas of the brain, including the prefrontal cortex and basal ganglia. Serotonin is involved in mood regulation: A deficit in the serotonin neurotransmitter is implicated in mania. Occasionally, an SSRI is prescribed with a mood stabilizer in order to treat BPD. The norepinephrine neurotransmitter is released during the activation of the sympathetic nervous system (i.e. fight-or-flight response), and high levels of norepinephrine is a component for manic psychosis.

atypical antipsychotics for pregnant women

Side effects causing weight gain also affect the developing infant ⚫ Association with gestational diabetes • Not associated with major congenital defects • Associated with motor deficits, respiratory distress, seizures, and transient neurodevelopmental delay -breastfeeding: possible with physician supervision

Cognitive symptoms in Schizo

Stable and lifelong, often prodromal ** ➢ After first episode, scores of global cognition range from between 1-2 standard deviations BELOW those of healthy cohorts ❖ Do not remit ❖ Unresponsive to teaching or cognitive rehabilitation ❖ Have been found to correlate with degree of structural brain abnormalities ➢ Increased ventricular size ➢ Reduced medial temporal lobe volumes ❖ Deficits are moderate to severe across several domains, including: ➢ General Intelligence ➢ Working Memory ➢ Attention/Vigilance ➢ Verbal Learning and Memory ➢ Executive Functions ➢ Social Cognition ➢ Speed of Processing

hypotheses connecting amphetamine use and psychosis

Stress Vulnerability Model ● Combination of genetics and environmental ● factors, including drug abuse, traumatizing ● events, medications, etc., can influence our susceptibility to developing a mental disorder. ● Stimulants are considered stressors to people's mental state ● ● Increased use of stimulants can increase an individual's vulnerability to psychotic symptoms Sensitization ● Acute psychotic episodes Sensitization to drugs has been successfully proved in animal models due to increased dopaminergic sensitivity and upregulation Higher prevalence of relapsing into psychosis after first psychotic episode Constant stimulant use can lead to a toxic response and develop into a serious chronic mental illness

Age & Cannabis Studies

Study #1 - Longitudinal Study Used Swedish Conscripts to demonstrate an association between early life cannabis use and schizophrenia. - Subjects that reported previous use of cannabis use at the time of conscription were significantly more likely to be diagnosed with schizophrenia later in life. - Conducted in multiple studies Study #2 - Animal Study - Animals studies conducted on rats. - Rats that were exposed to cannabinoids early in life had increased schizoaffective-like phenotypes - Had decreased prepulse inhibition ( model of schizophrenia). - Acute administration of haloperidol normalize the prepulse inhibition.

Stroke Psychosis

Study found two cases of acute onset of psychosis in two different patients: - 1) Case 1: acute basal ganglia hemorrhagic stroke - 2) Case 2: acute midbrain ischemic stroke - Case 1 patient reported fixed false beliefs related to his new physical impairment on the right side of his body (nurses had injured him), auditory hallucinations (right side was dead), & nihilistic somatic delusions (right side and tooth was rotting) - Lesions in basal ganglia caused disruption in frontal subcortical circuits along with structures such as the external capsule, thalamus, and posterior limb of the internal limb - Case 2 patient reported both visual and auditory hallucinations of seeing/hearing her dead uncle. However, she demonstrated preserved insight (she was aware the hallucinations were not real). - Brain magnetic resonance imaging showed acute infarcts in the thalami, left cerebral peduncle, and midbrain.

Progressive Reduction in Cortical Thickness as Psychosis Develops: A Multisite Longitudinal Neuroimaging Study of Youth at Elevated Clinical Risk (Cannon)

Study from a massive multi-site study of prodromal schizophrenia. Identified youth at clinical high risk for psychosis - mild/attenuated symptoms. Conducted a baseline scan and a scan at 12 months OR when patients converted to full psychosis. 274 cases, 35 of whom converted to psychosis and 135 controls. They additionally collected blood to conduct cytokine analysis to look into the possibility of neuro inflammation. This is a rate of brain change analysis, not a baseline analysis trying to predict who will convert. Importantly, in this study, there were no baseline differences in cortical thickness. On the left we see Converters vs Controls, on the right we see Converters vs. Nonconverters The difference to zoom into is the FDR corrected map revealing Right superior frontal, middle frontal, and medial orbitofrontal regions (holy crap! Again?) showing increased thinning in the converters compared to both the controls and the non-converters. There were NO differences between the rate of change between controls and nonconverters. An additional area showed greater change in the converters than the others. The 3rd ventricle showed greater expansion in the converters than the others. Here we see analyses of medication effects We see that the patients receiving antipsychotic medication had greater LOSS of gray matter in the Right Prefrontal Cortex and Greater EXPANSION of the 3rd ventricle. Think back to the Lesh et al study Inflammation??.....YES Proinflammatory cytokines were strongly correlated with gray matter loss in the right PFC in Converters.. Less so in NonConverters, and not in controls What about those with shorter vs. longer prodromal phases? Well, huge effects. Those with shorter prodromal phases had significantly greater gray matter loss in Right Pre Frontal Cortex and greater increase in 3rd ventricle volume between scans.

Folsom et al.: Prevalence and Risk Factors for Homelessness and Utilization of Mental Health Services Among 10340 Patients with Serious Mental Illness in a Large Public Mental Health System

Study of 10,340 people treated for schizophrenia, bipolar disorder, and major depression over a one year period Used computer records of patients in a large public mental health system Goal 1: to calculate the factors that are associated with a greater risk of homelessness amongst mentally ill subjects Goal 2: to understand the utilization of mental health services by homeless versus not homeless patients Mental Illness Effects 20% of schizophrenic subjects were homeless 17% of bipolar patients were homeless 9% of depressed patients were homeless Compared to 2.8% homelessness in non-mentally ill populations Utilization of Mental Health Services Homeless patients were more likely to use emergency and inpatient treatment Homeless patients were less likely to use outpatient treatment facilities Increased chance of homelessness associated with: Male African American Substance Abuse Disorder More than four times as likely to be homeless Lack of Medicaid insurance Poorer Functioning Decreased chance of homelessness associated with: Latinos and Asian Americans No effect of: Level of education Age, contrary to prior studies

Estrogen Hypothesis Study:

Study: Fluctuation of Latent Inhibition Along the Estrous Cycle in the Rat: Modeling the Cyclicity of Symptoms in Schizophrenic Women? ● Latent Inhibition was used as a model for attentional impairment in schizophrenia ○ Latent Inhibition - a selective-attention phenomenon manifested as a poorer conditioning of stimuli that had been experiences as irrelevant prior to conditioning his study tested: ○ Whether expression of latent inhibition would oscillate in correspondence to the hormonal fluctuations of the estrous cycle ○ If these fluctuations would be "pro-psychotic" with the loss of latent inhibition ● Broad Methods: ○ Vaginal smears of female rats (3-4 months) were taken each morning ○ Rats needed to demonstrate 2 regular estrous cycles of 4 consecutive days to be used for behavioral training ○ Latent Inhibition was measured by a conditioned emotional response motivated by thirst and two-way active avoidance Results: ● Latent inhibition was seen in rats in the pre-exposure stage of estrus, but not the remaining three estrous cycle phases (those with the most estrogen present) ← fluctuations were present ● Latent inhibition was seen as associated with both high and low levels of estrogen ○ Suggests that hormonal fluctuations (not hormonal amounts) are the critical aspects triggering the latent inhibition abnormality ● Dopaminergic activity was observed as higher during pro-estrous and early estrous cycles ○ Both cycles follow surges of estrogen ○ Disruption of latent inhibition may be facilitated by increased dopaminergic transmission as well

Cortical Thinning, Functional Connectivity, and Mood -Related Impulsivity in Schizophrenia; Relationship to Aggressive Attitudes and Behavior (Hoptman)

The authors are tackling a troubling fact - there is a slightly higher incidence of aggression in psychotic patients. They theorize that aggression is related to some other psychological constructs. Primarily they talk about positive and negative urgency. Urgency and aggression are associated with failure of inhibition. Inhibition is primarily achieved by the frontal lobe primarily oribital frontal and frontal polar regions. Authors did structural and functional connectivity analyses to determine the neural correlates of aggression and urgency. This analysis basically demonstrated the construct validity of urgency, particularly negative urgency being related to aggression Positive Urgency = Tendency to rash action in the context of strong positive affect Negative Urgency = Tendency to rash action in the context of strong negative affect Example: When I feel bad I will often do things I later regret in order to make myself feel better now. Is there a problem here in how patients vs controls may interpret the question and their own internal states in order to answer this question? Patients are significantly elevated in positive and negative urgency Caveat: these are self report measures. Self report measures are inherently limited. Particularly problematic here is the potential for different self report effects in patients vs. controls. Gray matter correlates of self reported urgency Patients displayed reduced cortical thickness across the frontal lobe. Unclear if they ignored the rest of the brain or if cortical thickness was only affected in the frontal lobe. Negative urgency showed a negative correlation with Right frontal pole and Right orbital frontal cortex but only in patients. Surprised me Positive urgency negatively correlated with left rostral anterior cingulate and right frontal pole but again only in patients. Surprised me again! In patients, reduced connectivity was seen between right frontal pole and rostral anterior cingulate with increased positive urgency. Increased connectivity was seen between left frontal pole and right middle occipital gyrus.?? In patients, reduced connectivity was seen between a) left lateral orbitofrontal gyrus and left middle frontal gyrus, b) left midial orbitofrontal gyrus and left superior frontal gyrus and right ristral anterior cingulate, and c) left rostral anterior cingulate and left superior/middle frontal gyrus. Increased connectivity was seen between the left lateral orbitofrontal cortex and right inferior/middle frontal gyrus and left cingulate, b) left middle orbitofrontal gyrus with precuneus, c) left frontal pole and right superior parietal lobule, d) right medial orbitofrontal gyrus with cuneus. ???? Dysfunction in neural systems controlling affective regulation including the identified system (orbitofrontal, anterior cingulate, amygdala) predispose one to aggression. Both structural abnormalities (cortical thinning) and functional disconnection was observed in ventral prefrontal and limbic/cognitive control regions, particularly the rostral anterior cingulate and orbitofrontal cortex.

Psychological Impact of childhood trauma

The early onset of schizophrenia and other dissociative disorders are caused by the impact of childhood trauma. ● The increased levels of exposure to traumatic events makes schizo patients more prone to be hospitalized at an earlier age as well as increase their positive symptoms. ● The amount of abuse underwent is positively correlated with the amount of hallucinations and delusions they experience. ● An increase of early trauma is also associated with a rise in negative schemas. This is triggered by emotional abuse and physical neglect, instilling hopelessness and lack of self worth

Smoking and schizophrenia

The frequency of smoking behavior in schizophrenics is not only higher than the normal population, but also higher than any other psychiatric condition Having schizophrenia increases your risk of being a smoker by at least a factor of 2 At least 70% of schizophrenia patients smoke (Leon, 1996). In one study, only 8% of schizophrenic males quit smoking compared to the 31% of people from the local general population Cigarette smoking is a risk factor for dyskinesias, a movement disorder characterized by involuntary muscle movements, similar to tics Increased morbidity and mortality in chronic schizophrenia have been linked to tardive dyskinesia Hypothesis: smoking among family members in families with genetic loading for schizophrenia may be a marker for those at risk of developing schizophrenia Alpha-bungarotoxin Labels neurons with a specific type of nicotinic receptor alpha-Bungarotoxin is a sensitive hippocampal nicotinic receptor channel and has a high calcium permeability may be smaller in the brains of schizophrenia patients Supported by initial study from Freedman et. al. 1995 which suggests that schizophrenic patients have fewer nicotinic receptors in the hippocampus, a condition which may lead to failure of cholinergic activation of inhibitory interneurons In non-affected relatives of patients with schizophrenia, nicotine administration can briefly reverse this abnormality, suggesting a genetic linkage between nicotinic function and schizophrenia. Nicotine delivered by ad lib smoking transiently reversed the P50 auditory evoked response gating deficit in smokers with schizophrenia. found that the alpha-7 nicotinic receptor gene mediates the release of gamma-aminobutyric acid (GABA) during the inhibitory process of repetitive auditory stimulation The enhanced release of GABA activates GABAB receptors that decrease the release of glutamate, thus preventing hippocampal neurons from responding to the second stimulus in the sensory gating paradigm This gene plays an essential role in mediating interactions between GABA and glutamate neurons and is proposed to also influence the neuronal functioning within the hippocampus and cortex The schizophrenia population has an unusually high number of people with single nucleotide polymorphisms of the promoter region in this gene decreased alpha-7 nicotinic receptor binding in the reticular nucleus of the thalamus, hippocampus, cingulate cortex, and frontal lobe regions of schizophrenia patients may contribute to psychotic symptoms Decreased alpha4/beta2 nicotinic receptor binding in the hippocampus , cortex, and striatum , and increased levels of binding in the caudate and putamen nicotine affects the glutamatergic and dopaminergic systems, which may relieve negative symptoms. Smoking influences nicotinic cholinergic receptors, increasing firing of dopamine neurons and enhancing dopamine release in the nucleus accumbens and prefrontal cortex Participants who took typical antipsychotic medications smoked more cigarettes per day (avg = 41.7) and had greater session CO boosts (avg = 9.1) than not only smokers without psychopathology but also those taking atypical antipsychotics (29.9 cigarettes/day and 2.3 CO boosts) How is clozapine like nicotine? Able to counteract auditory sensory gating impairment through alpha-7 nicotinic receptor mechanisms even with repeated dosings

Risk factors for homelessness among people with psychotic disorders

The study, which took place in the UK looked in medical records and conducted interviews with psychotic individuals who have and never have experienced homelessness. A number of social and behavioral risk factors were identified, including: Loss of contact with childhood carers; cases were significantly more likely to have lost contact with all childhood carers for 6 months or more, and this remained true for the pre-homeless period. Discontinuity of childhood care; cases were significantly more likely to have been placed juvenile detention facilities or children's homes Substance use; cases were more likely than controls to have a lifetime diagnosis of a substance use disorder

Lack of Accessibility to Treatment Homeless people are "a minority neglected by medicine in general and psychiatry in particular"

There is a failure of the community mental health care system to meet their needs Once homeless, it can be even more difficult to stick with a support program or treatment; they will have a harder time getting medication, and if they do, they won't have the proper supervision to take it correctly. There is a correlation between states closing down psychiatric facilities and an increasing number of individuals with serious mental illness who are homeless At any given time, there are more people with untreated severe psychiatric illnesses living on America's streets than are receiving care in hospitals. Consequences Once homeless, schizophrenics may suffer from lack of sleep, poor hygiene and vulnerability to becoming a victim of violence, all of which can make a psychotic episode more likely. The mortality rates for homeless people with schizophrenia are four times that of the general population and more than twice that of people with schizophrenia who are not homeless Homeless individuals with mental illness fare significantly worse in terms of physical health, incarceration, level of subsistence needs met, victimization (being physically assaulted, sexually assaulted, or robbed) and subjective quality of life than those who are not mentally ill. Without any treatment or support, reversing homelessness for schizophrenics is very difficult.

Structural brain alterations in subjects t high-risk of psychosis: A voxel-based morphometric study (Meisenzahl)

These scientists were among the first to look at the brains of peopled considered to be in the "at risk mental state" or at High-Risk for psychosis. Patients included for one of three reasons. Presence of prodromal symptoms: Thought interferences, though perseveration, though pressure, thought blockages, disturbances of receptive language, decreased ability to discriminate between ideas and perception, unstable ideas of reference, derealization, visual perception disturbances, acoustic perception disturbances. Attenuated Psychotic Symp. or Brief limited psychotic symptoms MRI scans were done as well as clinical evaluation with the Positive and Negative Syndrome Scale (PANSS) The PANSS data were used to find areas in the brain where symptoms correlated with cortical thickness. They found widespread cortical thinning in the frontal, insular, and temporal cortices. Cluster 1: Large prefrontal area involving dorsomedial, ventromedial, bilateral dorsolateral and right ventrolateral, orbitofrontal, and anterior cingulate. Greatest reduction was seen in the Right Prefrontal (keep this in mind) Cluster 2: Further left prefrontal areas. Cluster 3: Further left prefrontal AND Left Insula Cluster 4: left middle and superior temporal gyrus. Cluster 5: Right inferior, middle and superior temporal gyrus, and right insula These analyses looked at the correlation of positive (warm colors) and negative (cool colors) symptoms with gray matter volume. Positive symptoms were correlated with medial prefrontal and ACC gray matter volume. Negative symptoms had much wider correlations Cluster 1: A medial prefontal cluster including ACC and orbitofrontal Cluster 2 and 3: Left VLPFC and DLPFC and OFC. Highest correlation was with DLPFC Consistent with prior study showing that negative symptomology is associated with the greatest cortical abnormalities.

Bipolar Disorder

This is a serious condition that includes both manic episodes and depressive episodes. There are several disorders under this category. Bipolar Type I Full manic episodes and full depressive episodes Bipolar Type II Hypomanic episodes and full depressive episodes Cyclothymic Disorder Two years (1 for children) of hypomanic and depressive symptoms without meeting full criteria for either Not always psychotic Bipolar is one of the most misunderstood conditions Mistaken for Extreme moodiness Condition has both major depressive episodes and manic episodes Ifference between type 1 and 2 Type 1: full manic episodes Type II: hypomanic episodes Cyclothymic Euthymia = normal Bipolar type 1 is a sin curve Bipolar type 2 is a sin curve with lower humps Dysthymia Person has persistantly low mood but not severe enough to be depression

Ethics Case Study- Tina

Tina is an eighteen-year old college freshman who goes to a medical clinic to treat depression that she believes she has: She reports that she has low moods, crying spells, and a profound lack of energy making it hard for her to complete basic daily tasks. She wants to be treated because she is scared of failing out of school. She had a friend in highschool who was prescribed sertraline and had good results so she wants to be prescribed that medication. Tina reports that she had no change in mood, appetite, or behavior and did not feel worthlessness or guilt. When asked about the past month at college, she answered that she felt fabulous and was getting A's and had a great social life. She does not express impulsivity, grandiosity, or psychosis She also notes that both her father and her older sister have been diagnosed with bipolar disorder but does not want to be diagnosed with it because "she's not crazy and irresponsible like them" and she sees the way that people look at them when they are aware of their diagnosis Tina's physician suspects that she may be suffering from a depressive episode that is in relation to type II bipolar disorder but Tina is adamant that she only has depression and wants to take a Selective Serotonin Reuptake inhibitor as treatment. Tina's family history shows that if she were to take the SSRI there is a high chance that she would have a bad reaction. After further discussion, Tina agrees to take Lurasidone as long as her doctor does not put bipolar disorder on her health records. Is it ethical for the doctor to adhere to Tina's wishes although she has family history of bipolar disorder? If Tina does not fully qualify for bipolar disorder is it ethical to prescribe her Lurasidone for depression? This drug is mainly used for bipolar treatment and may raise some red flags if she is being prescribed it for depression. Is it more important to adhere to patient privacy or promote accurate diagnostic and treatment practices?

Schizophreniform Disorder

Two or more of the following each present for a significant portion of time during a 1-month period. At least 1 of them must be 1 2 or 3. 1 Delusions 2 Hallucinations 3 Disorganized speech 4 Grossly disorganized or catatonic behavior 5 Negative symptoms Lasts for 1-6 months Note that the diagnostic criteria are almost the same as for schizophrenia except for the duration. Schizophreniform is the first 6 months of schizophrenia but it may not last longer than 6 months in which case it is not changed to schizophrenia Schizophreniform does not require impaired social and occupational functioning like schizophrenia does. Place holder diagnosis Vast majority of these people will be diagnosed with schizophrenia 2 symptoms for most of the month then on and off for the rest of the months Difference from schiozphernia Place holrder, first 6 months Does not require imparied social and occupational functioning

Schizophrenia

Two or more of the following each present for a significant portion of time during a 1-month period. At least 1 of them must be 1 2 or 3. 1 Delusions 2 Hallucinations 3 Disorganized speech 4 Grossly disorganized or catatonic behavior 5 Negative symptoms Persists for at least 6 months Drop in at least one important area of functioning Not part of diagnosis but important associated feature is impaired cognitive function. Not part of the diagnosis but important associated feature is anosognosia or a lack of insight or awareness of the presence of the illness. Lifetime prevalence is 0.5-1% Graduating from schizophrenaform Impaired cognitive function: Why is this not part of diagnosis> Average psychologist isn't going to sit there and do cognitive tests Anosognosia In other disorder substance abuse, schizophrenia Pre-schizophrenia -> schizophrenia: they go from maybe it's not real to it being their world SLIGHTLY HIGHER INCIDENCE IN URBAN RURAL AREAS Due to toxins? Stressors Further away from equator, slightly higher the incidence b/c social discunftion Is a big deal and they like to be alone, schizophrenics move north and south? Maybee theory Why do females get psychosis a year or 2 later Hormonal factor? Neuroprotective feature of estrogen

"Seclusion and restraint are not treatment modalities but treatment failures."

Up to 150 restraint-related deaths occur in the United States every year, with strangulation, aspiration, suffocation, and heart attacks the most common causes. ● Closely examined 61 restraint-related deaths: dearth of safe practices and an overuse of the 'treatment' ● While only 26% of the deaths were in psychiatric settings, nearly 75% of the patients that died had a psychiatric history, with the most common disorder being schizophrenia and other psychotic disorders. ● Many of the deaths occurred from illegal use of restraints, such that in one-third of the cases they failed to meet the legal standard for use, and of those restrained to prevent aggressive behavior, almost half still did not meet the legal standard. F ● Finally, in almost all of the cases that had information on less restrictive interventions, the staff failed to use alternative treatments as well as failed to explain why such alternatives were not used Schizophrenia study ● Patients treated at Centre of Psychiatry Weissenau ● 56 men, 61 women; 79.5% diagnosed with schizophrenia, 12% with schizoaffective disorder, 8.5% with delusional or other psychotic disorder ● 1 in 6 patients were subjected to restraints or seclusion ● Aggressive behavior and hostility were associated with use of restraints or seclusion ● 57 patients (48.7%) experience a traumatic event or before or during their stay Increased probability by 7 folds (no past study to their knowledge found this) Bipolar study ● 400 bipolar patients; 229 (57.2%) females; median age was 32 yrs ● 260 (65%) have been physically restrained regardless of the setting (home, hospital, or both) ● Sex, use of antipsychotic drugs and Khat, comorbidity, and having more than one episode were associated with use of restraints ● Made them two times more likely than people who did not exhibit these characteristics

Amphetamines

Vyvanse (lisdexamfetamine dimesylate)2 - Long-acting (one pill/day) - Also used to treat binge eating disorder (BED) - Side effects: nausea, vomiting, constipation, weight loss, headache, emotional dysregulation - 7th most commonly prescribed drug in the US with an average of 10.4 million monthly prescriptions - Rx ranging from 10-70 mg - Adderall (amphetamine, dextroamphetamine, mixed salts)2 - Both long (XR) and short-acting (IR) (multiple pills/day) prescriptions - Side effects: loss of appetite, weight loss, dry mouth, stomach pain/upset, nausea, dizziness, headache, fever, trouble sleeping, nervousness - Rx ranging from 5-30 mg Approximately 5%-35% of US students MISUSE Amphetamines at one point during their undergraduate career

Grandiose delusions

When an individual believes that he or she has exceptional abilities, wealth, or fame.

Erotomanic delusions

When an individual falsely believes that another person is in love with him or her. not as common, this person wants me

Controversy of Results of Childhood Maltreatment

While some findings show strong evidence of physical neglect being the biggest predictor of negative symptoms in schizophrenic patients, others show that sexual abuse is the biggest predictor Other data also shows that physical abuse and not neglect is a predictor of positive symptoms, such as delusions and hallucinations. Most studies make clear that there is little research done on neglect in general as most studies have focused on the abuse factor of maltreatment. More recent studies are now geared toward an emphasis on both physical and emotional abuse.

The Methamphetamine Model

Why Methamphetamine (MA)? ● Inhibits or reverses DAT, NET, SERT -> more DA, NE and 5-HT in synapse ○ Also an agonist of alpha-2 adrenergic receptors, and inhibits VMAT and MAO ● Similar to amphetamine, but much stronger and longer lasting, due to being highly lipophilic

Somatic delusion

focus on preoccupations regarding health or organ function (different than sensory) fears about body being very sick, organ has gone missing, is rotting away

What types of 'religious coping' are positive?

limited studies on the subject -seeking support, guidance, collaboration associated with positive outcomes -religious coping is perhaps the main predictor of psychological well-being according to some studies - important to distinguish from negative religious coping (which has worse outcomes) -negative coping includes reappraisal of God's powers, spiritual discontent, etc

in general, are there sex differences in schizophrenia?

no

Reduced Latent inhibition and the shared vulnerability model

normal precuneus activatino highest when at rest -in creative individuals MPFC/precneus is active at abnormal times -hyperactivation/hyperconnectivity o f devault network may contribute to disturbances of thought in schizophrenia -Parallel features of creativity and psychosis: -cognitive disinhibition or low latent inhibition -attention driven by novelty -neural hyperconnectivity dopaminergic and serotonergic systems invovled -glutamatergic system dysfunction also potentially related to low latent inhibition Inverted U hypothesis of creativity and psychopathy: once an individual's creative potential threshold has been exceeded is when they are susceptible to excess hyperactivity and positive psychotic symptoms

Persistent auditory hallucinations:

occur in the absence of any other features.

Jealous delusions

partner is cheating. No evidence at all or the person believes they have bits of evidence they believe add up to proof.

Schizophrenia, art, and creativity

positive relationship b/w creativity and schizotypy -well known artistic figures diagnosed with mental illnesses -schizo score higherthan controls on divergent thinking -creativity and psychoticism are highly correlated -explanations of the association between creativity and mental illnesses (especially sz) -increased loading? - buffering effects?

Attenuated psychosis syndrome

psychotic-like symptoms that are below a threshold for full psychosis. Less severe or come and go AND insight is relatively maintained. prodromal (symptoms that come before full blown disease, episode right before full blown disease

Pathography

study of the life of an individual with regard to the influence of a particular disease or psychological disorder

Genetic factors which may contribute to violence

• Aggressive behavior is known to have heritable components, mediated by multiple alleles at many loci • Low concentration of serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in CSF is associated with an increased propensity for aggressive behavior in psychiatric patients • Polymorphism in the catechol O-methyltransferase gene has been associated with significantly higher levels of hostility in schizophrenia patients

Bipolar Disorder and Postpartum Psychosis

• Bipolar disorders: serious brain illnesses marked by extreme shifts in mood, energy, and ability to function in everyday life ⚫ Bipolar I, II, and cyclothymia • Postpartum psychosis (PP): marked by hallucinations, mood swings, strange beliefs, cognitive impairment, disorganized behavior, and lack of insight occurring in the first 1-4 weeks after childbirth • These disturbances and lack of insight can put both the mother and infant in danger • Women with a family history of bipolar disorder or PP are at risk for PP ⚫ >50% risk: for mothers with bipolar disorder and one past episode of PP

Why might psychosis lead to violent behavior?

• Certain studies show that the presence of persecutory delusions in psychotic individuals was associated with an increase in aggressive behavior • There is evidence that persecutory delusions are significantly more likely to be acted upon than other types of principal delusions • Untreated schizophrenia was associated with the emergence of persecutory delusions at follow up (odds ratio = 3.52, 95% CI = 2.44-5.55) • Schizophrenia was associated with violence but only in absence of treatment (odds ratio = 3.76, 95% Cl = 1.39 -10.19) • Results indicate that the emergence of persecutory delusions in untreated schizophrenia may explain violent behavior • Delusions containing threat or control-override (TCO) symptoms were also noted to increase the risk of violence • Threat: being followed, poisoned, watched, etc • Control override: losing control to an external source (e.g. one's mind being controlled by an outsider) • Patients experiencing TCO symptoms were approximately twice as likely to be aggressive than those experiencing other psychotic symptoms, according to one study • The violent behavior of psychotic individuals is sometimes consistent with the content and themes of current delusions/hallucinations • Violent behavior therefore may then be a rational response to irrational beliefs and perceptions

Violence and psychosis

• Mental illness is commonly pointed to as a cause of violent behavior • Many people have an attitude of fear toward psychotic individuals, creating a stigma surrounding mental illness • However, violence is typically an uncommon result of mental illness or psychosis • Most patients with psychosis are not violent, though psychotic patients are 4-5x more likely to engage in violent behavior than the rest of the population • Psychotic patients are also more likely than the general population to be victims of violence • Violent behavior appears to be associated in particular with persecutory or threatening delusions • A survey of the records of a total prison intake of 2,743 men remanded in the Brixton prison on criminal charges over four months • 1,241 prisoners yielded a high prevalence of psychiatric disorder • 237 men (8.7%) psychotic • 166 men (70%) schizophrenic • Violence among men with schizophrenia was high • 9% of non-fatal assaults, 21% offences of damage to property, homicide (five (11%) ) and arson (six (30%) ) were committed by men with schizophrenia • Higher prevalence of schizophrenia than would be expected in the general population of Greater London (0.1-0.4%)

Environmental factors which contribute to risk of violence

• Patients with psychosis are significantly more likely to be the targets of violence than the perpetrators • Studies have shown individuals with psychosis are 2.3 - 140 times more likely to be the victims of violence than the general population • Childhood abuse and exposure to violence are commonly associated with violent behavior later in life • Rates of aggression and conduct disorder are highest among children who have both family history of antisocial behavior and grew up in a disturbed environment • Gene-environment interaction • Aggregate study of 45,533 individuals found a strong association between violent behavior and a history of being violently victimized

Summary of violence and psychosis

• Persecutory delusions, command auditory hallucinations appear to play a role • Substance abuse • Environmental factors such as exposure to violence • History of violence • Treatment with second-generation antipsychotics may reduce violence • Removal of the stigma associated with psychosis and mental health treatment • No single variable or factor can explain violence in psychosis • Extensive research is needed to identify solid, reliable risk factors and contributions to violence

Violence in Bipolar Disorder

• Prior research has found that almost 50% of people diagnosed with bipolar disorder have a history of violent behavior • Bipolar patients are more likely to be agitated which may result in impulsive aggression during manic or mixed episodes • Depressed states which may produce intense feelings of dysphoria along with agitation and irritability also puts patients at risk of violent behavior • Impulsive aggression • Most common with bipolar and other affective disorders • Bipolar disorder is associated with high prevalence of childhood trauma as well as the possibility of aggressive and potentially violent behavior • Important for clinicians to consider historical and clinical information during assessment of patient's potential for violence • Violence history, substance abuse, childhood trauma, and impulsivity in addition to mood symptoms can help clinicians reach an accurate assessment • Recognizing the impact of early trauma on a patient can help improve the therapeutic alliance and lead to better treatment outcome

Risk factors for violence in psychosis

• Systematic review and meta-analysis regression of 110 studies • Aggregate study of 45,533 individuals with schizophrenia (88%) or other psychoses (12%) • Violence was strongly associated with a history of being violently victimized • Strongly associated with lack of insight • Strongly associated with history of polysubstance abuse, recent or comorbid substance abuse • Moderately associated with childhood physical or sexual abuse • Violence associated with nonadherence to treatment, poorer impulse control skills -No significant association between violence and intelligence or verbal scores on neuropsychological tests

Mindfulness Intervention for Psychosis

● Adjunct to pharmacotherapy ● Mindfulness Interventions ○ acceptance and non-judgement vs targeted symptom reduction ○ aimed to decrease distress from experience of psychosis as opposed to directly challenging delusions and hallucinations like CBTp ● Small to moderate effects on negative symptoms and quality of life ● None to small effects on positive symptoms ● There's been cases of meditation induced psychosis in some studies ● Heterogeneity of mindfulness interventions ○ Non-clinical variants of mindfulness lead to adverse effects ○ Meditations that focus on breathing and presentness are the ones related to improvements in negative symptoms ● Caution is highly advised for delivery, More empirical study required... but should it be pursued?

Risk Factors for Late-Onset Schizophrenia

● Age-associated psychosocial factors that may contribute the precipitation of schizophrenia symptoms later in life: ○ Retirement ○ Financial difficulties ○ Bereavement ○ Death of peers ○ Physical disabilities ● Many late-onset patients are reported to have had premorbid schizoid or paranoid personality traits that fell short of diagnostic criteria for personality disorders ● Relatives of late-onset probands have a lower morbid risk of schizophrenia vs relatives of early-onset schizophrenia patients ● Relatives of females or early-onset schizophrenia patients have an increased risk of schizophrenia compared to relatives or late-onset cases

Psychosis X Alzheimer's: Behavior

● Agitation and aggression are among the most common and troublesome behaviors ● Depressive symptoms, functional and cognitive impairment, increased mortality ● Common delusions in AD patients: delusions of persecution, infidelity, abandonment, or that deceased individuals (e.g. parents) are still living. Paranoid delusions of theft. ○ Beliefs that one's home is not one's home; that a family member is someone else, has been reduplicated, or is an imposter (Capgras Syndrome); the presence of phantom boarders; and that images on the television are actually people present in the house ○ Typically not bizarre or complex, and Schneiderian first-rank symptoms are rare (contrast with schizophrenia). ● Hallucinations in AD can occur in any sensory modality, but visual hallucinations are most common (contrast with schizophrenia). ● Comorbidity between delusions and hallucinations Agitation - "inappropriate verbal, vocal, or motor activity" (Cohen-Mansfield and colleagues) Physical vs. verbal Agressive vs. Non-agressive

What is Alzheimer's Disease (AD)?

● Alzheimer's is a progressive type of dementia that causes problems with memory, thinking and behavior. ● Destruction and death of nerve cells causes memory failure, personality changes, cognitive impairments, problems carrying out daily activities and other symptoms ● Alzheimer's is NOT a normal part of aging. ● About 270,000 Americans under the age of 65 have AD. Signs - Memory loss that disrupts daily life - Challenges in planning or Solving problems - Difficulty completing familiar tasks at home, work, or leisure - Confusion with time or place - Trouble understanding visual images and spatial relationships - New problems with words in speaking or writing - Misplacing things and losing the ability to retrace steps - Decreased or poor judgement - Withdrawal from work or social activities - Changes in mood and personality

Late-Onset Schizophrenia

● Because of the DSM-III, people weren't being diagnosed with schizophrenia ○ Instead, most commonly diagnosed with paraphrenia or dementia praecox Paraphrenia: used to describe "folly" in the 19th century, roughly equivalent to schizophrenia today ● Dementia Praecox ○ illness with chronic deterioration of mental processes responsible for emotion and volition Up until the DSM-III-R was published (1987), there was no acknowledgement of older people developing schizophrenia ows the same general criteria of early-onset schizophrenia ● International Late-Onset Schizophrenia Group wanted to overcome difficulties of nomenclature to allow for more efficient research and came up with two classifications: ○ Late-Onset Schizophrenia - Characterized as the onset of symptoms after the age of 40 up until 60 and considered a subtype of schizophrenia ■ Neurodevelopmental disorder ○ Very-Late-Onset Schizophrenia-Like Symptoms - Onset of symptoms after the age of 60 ■ Suggests more neurodegenerative components with brain abnormalities and neuropsychological deficits ● Proportion of schizophrenia patients whose illness first emerged after age 40 has been estimated to be 23.5% ● Prevalence rate of schizophrenia in individuals between ages 45 and 64 is 0.6% ● Likelihood of very-late onset schizophrenia-like psychosis increases by 11% with each 5-year increase in age

Efficacy of CBT; Positive Symptoms

● CBT primarily designed for positive symptoms ● Collaboration appropriate with patient's abilities ● Outpatient and Inpatient ● Effects, with small to moderate effect size.... ○ Positive effects holds in meta-analysis (Zimmerman et al, 2005) ○ Alleviation of positive symptoms when compared to non-active control groups with drug dosage considered- persisted over time (Sensky et al, 2000) ○ Accelerated remission (Lewis et al, 2002) ○ Lower rates of relapse (Gumley et al, 2003)

Psychosis X Alzheimer's: The Brain

● CT scans show right frontal lobe atrophy and changes in brain asymmetry ● MRI studies show decreased gray matter volumes, especially in frontal cortex. Parietal cortex was also affected. ○ Sex differences in AD + P with only female subjects showing reduced cortical thickness in left orbitofrontal, superior temporal, and insular regions (Whitehead) ○ Males with AD+P have hyperperfusion in right striatum ○ Females with AD+P have right insular, infero-lateral prefrontal cortex and inferior temporal hypoperfusion ● SPECT scan show reduced cerebral perfusion across cortical regions in AD+P ○ Mostly frontal cortex but also temporal and parietal ● PET scan showed greater hypometabolism in neocortex, primarily in bilateral frontal and prefrontal cortex ● PET scan showed that hallucinations in AD were associated with lower regional cerebral blood flow in the right parietal cortex. (Lopez) ● Higher striatal dopamine D2/D3 receptor availability was found Agitation in AD-Deficits in structure and function of frontal cortex, anterior cingulate cortex, posterior cingulate cortex, amygdala, and hippocampus. Associated with misinterpretation of threats and affective regulation. Apathy in AD-Deficits in frontal cortex, anterior cingulate cortex, posterior cingulate cortex, orbitofrontal cortex, inferior temporal cortex, and may be associated with avoidance behaviors. chosis X Alzheimer's: The Brain (Cont.) ● AD + P doesn't meant you have more severe plaques (or tangles) ● Plaques cause synapse impairments in AD, greater synaptic loss in AD ○ As synapse loss is the strongest correlate of cognitive decline in AD and the trajectory of decline is more severe in AD + P, synapse loss may be greater in AD + P. ● Superior temporal gyrus, dorsolateral prefrontal cortex, and inferior parietal cortex were most affected. ● Nucleus accumbens dopamine D3 receptor density is significantly higher in AD + P with no difference in receptor affinity (independent of antipsychotic use) ● Reduced serotonin (5-HT) in the ventral temporal cortex ○ The lower 5-HT levels could be related to lower cell counts in dorsal raphe nucleus in AD + P ● Higher muscarinic M2 receptor density in orbitofrontal gyrus of AD patients with delusions and in middle temporal gyrus of AD patients with hallucinations ● Increased norepinephrine in the substantia nigra ● frontal cortical regions, including dorsolateral prefrontal cortex, appear commonly affected in AD + P.

Relationship between ADHD and Schizophrenia

● Comorbidity between ADHD and schizophrenia (24- 40% of children with COS had ADHD-like symptoms before onset) ● Overlap and phenomenological representation of ADHD and COS, exacerbated by stimulant drugs that can cause psychotic symptoms ● Prodromal Symptoms ○ Acute psychotic symptoms ○ Loss of cognitive ability, difficulty concentrating, thought interference ○ Self-medicating with psychostimulants ● During Psychosis ○ Taking psychostimulants can increase psychotic symptoms in patients with schizophrenia Case Study ● 20 year old man with normal childhood and no behavioral or academic issues (aside from smoking marijuana regularly) ● Found it difficult to concentrate in college and decided to take Adderall ● Became acutely psychotic after smoking cannabis at a party ● Officially diagnosed with schizophrenia after lengthy hospitalization and relapse into symptoms after discontinuing aripiprazole (antipsychotic) ● Prodrome of schizophrenia is associated with cognitive deficits ("difficulty concentrating" → thought interference and disturbances of receptive language) ● People who are presenting with pseudo-ADHD may be actually in the prodrome of schizophrenia ● Sensitization and stimulants

Psychosis (P) & Alzheimer's (AD)

● Comorbidity: 50% ● Clinical Studies: median prevalence of AD + P was 41%, with a 3-year cumulative incidence approximating 50% ● Epidemiologic studies: prevalence of AD + P, closer to 25% ○ These differences may reflect that the rate of AD + P is dependent on AD stage, with low rates of psychosis in prodromal and early AD and higher rates in middle and later stages ● Cognitive decline increases risk for P ○ The more rapid cognition begins the fail, the higher the risk for developing psychosis. ○ AD+P patients have greater cognitive impairment than AD -P patients

Brain Findings Late-onset Schizo

● Comparing age-matched late onset schizophrenia patients and control subjects ○ late-onset schizophrenia patients have higher ventricle-to-brain ratios and third ventricle volume ● Volume reductions of the left temporal lobe or superior temporal gyrus mimic the changes seen in the brains of younger early-onset patients ● One difference from early-onset schizophrenia, though not significant from unaffected subjects, has been larger thalamic volume in late-onset patients compared to early-onset ● Very-late-onset patients show focal cerebrovascular abnormalities in the form of infarcts or areas of high signal intensity ○ These are based on studies that haven't carefully screened out people with organic cerebral disorders ● PET scan studies have shown both increases and no change in D2 receptor density in late-onset patients in relation to a comparable control ● ERP studies showed late-onset patients having significantly later N400 peaks when compared to normal control -matches the findings in early-onset patients

Behavioral/Dopamine Sensitization

● Drugs of abuse typically create tolerance in the user, that is the user must consume larger and larger amounts of the drug to achieve the same effect of euphoria. ● Research shows that in methamphetamine users, a cellular cascade is initiated by excess dopamine in the brain created by methamphetamine use. ● Typically, this results in less methamphetamine being needed in order to initiate a methamphetamine-induced psychosis in users user over time. ● Dr. Ujike's study on rats revealed this behavioral or "psychosis" sensitization ● Bottom line, as time passes, the high decreases with the same does of drug but undesirable consequences such as paranoid/psychotic symptoms are increased with the same dosage. (Ujike, 2002) ● More dopamine is released in the striatum/nucleus accumbens than the brain is used to. ● The "enhanced" dopamine in this area of the brain sets off multiple cascades as described in Ujike's study of rats and humans. ● Three cascades work in tandem: 1. D1 receptor/PKA/phospo-34Thr-DARPP-32 2. glutamate/NMDA/Cam-KII 3. Ras/MAPK ● What is the main take-away message? (Remember LS-2?) ● Long-term methamphetamine use causes long-term changes to genetic expression and therefore, brain function. ● Long-term stimulant use increased the amount of synaptic connections as well as the presence of more cortical neurons (similar to what is seen in schizophrenic patients). ● All three cascading events lead to long term changes in neural function and therefore sensitization to psychosis that is related to the dopaminergic model. This is due to downstream alterations to genetic expression through induction.

Electroconvulsive Therapy (ECT) and Postpartum Psychosis

● ECT is recommended if mother's symptoms do not improve with medication, especially if she has impairments in self-care and thoughts and judgment that threaten her safety ○ commonly used for catatonia (decrease in food intake or refusal to take medications) or suicidality ● Before ECT was popularized, 9/14 postpartum psychosis patients died; after it became standard practice, mortality rate decreased to 1/23 ● Although an overall effective therapy, needs more research since it's not as commonly used as medications

Known Risk Factors for Alzheimer's Disease

● Environment: Pollutants, lifestyle (Depression predicts an increased risk of developing AD) ● Age: Double risk every 5 years after 65. 50% chance after 85 ● Family history: Those who have a parent, brother or sister with Alzheimer's are more likely to develop the disease. The risk increases if more than one family member has the illness. ● Heredity: APOE-e4 (increases likelihood but does not guarantee), APP, PS-1 (early-onset), and PS-2 (early-onset) ● Stress on the brain (e.g. stroke, head collision)

The Estrogen Hypothesis

● Estrogen Hypothesis - suggests that estrogen provides protection from the onset of schizophrenia and also weakens the severity of some schizophrenic symptoms (especially negative symptoms) ● Estrogen is a gonadal hormone that affects behavior, mood, and cognition ● Estrogen enhances neurocognitive performance and attenuates symptoms ● Estrogen may play a role in the regulation of the dopaminergic system There are two peaks of schizophrenia onset ○ First Peak: after their first occurrence of menstruation ○ Second Peak: after the age of 40 (about the age of menopause onset) ● Psychotic symptoms vary over menstrual cycles ● Premenopausal schizophrenic women seem to experience smoother illness progressions with fewer negative symptoms than men do ● Women with schizophrenia are generally hypoestrogenic - they have lower levels of circulating estrogen and increased menstrual irregularities ● Alterations in the neuroprotective effect of estrogen in women with psychotic disorders impacted cortical gray matter, but not cortical white matter (measured by bone mineral density)

Gender differences in medication

● Goal: examine long term effects of repeated administration of antipsychotics and the possible sex and developmental differences due to treatment Aripiprazole (ARI) ○ ○ ○ 3rd generation antipsychotic Reported reduction inside effects Partial dopamine D2 agonist ● Looked for sensitization to ARI in adolescent rats and whether or not this sensitization could be transferred to olanzapine (OLZ) and/or clozapine (CLZ) ● Evaluated sensitization to ARI using two models: conditioned avoidance model and the phencyclidine(PCP)-induced hyperlocomotion model ● Significant results: ○ Long-term behavioral changes and a sex difference in response to ARI treatment in adolescence (shown in both CAR and PCP-induced hyperlocomotion models) ○ In the CAR model specifically: ""female rats made significantly more avoidances than males in both ARI and vehicle groups, indicating higher sensitivity to the acute and long-term effects of ARI" (Freeman et al., 2017). ○ Did find that sensitization was transferable to OLZ but this result was not significant ● Possible explanation: ○ Adolescence is a time of pruning and reorganization of the dopamine system ○ Normal sex differences that occur in developmental processes taking place during adolescence could potentially explain the sex difference found in this study

Methamphetamine disrupted PPI

● High dose MA can disrupt the prepulse inhibition (PPI) in mice ○ Not repaired by typical antipsychotics (D2 receptor antagonists) ○ Repaired by Clozapine ■ antagonist of 5-HT2A and D2 ■ increases binding to NMDA receptors in frontal cortex ■ Agonist of GABAB receptors ● Supports MA model ○ MA increases release of glutamate ○ Excess glutamate can cause excitotoxicity and impair AMPA and GABA signalling ○ Dysregulated GABA signalling = less downstream inhibition ○ Fits in with hypoglutamatergic and GABAergic models

Efficacy of CBT; Negative Symptoms

● Historically, a secondary target/ outcome of CBT ● Mixed results... ○ CBT resulted in improvements in negative symptoms, but no more significant than the effects of another cognitive therapy- cognitive remediation (Klingberg, 2011) ○ Recent meta-analysis shows none to small effect size on negative symptoms measures (Velhorst, 2015)

Differences between early-onset and late-onset

● Late onset schizophrenia patients are more likely to ○ Be female, ○ Have the paranoid subtype of schizophrenia, ○ Have lower levels of negative symptoms, ○ Have less impairment in learning, abstraction, and flexibility, ○ Have better premorbid functioning with respect to work and marriage. ● People who develop late-onset more often have hearing or visual deficits which we think may lead to a higher likelihood of paranoia ○ They also may have had before becoming ill, a tendency to have some paranoid ideas about people or to be more withdrawn than the average person ● Patients with late-onset are more likely to complain of visual, tactile, and olfactory hallucinations ○ Last week's lecture -- more likely to hallucinate with lack of stimuli ● Patients with late-onset are less likely to display formal thought disorder, affective flattening, or blunting ● When onset is after age 60, formal thought disorders and negative symptoms are very rare ● Neuropsychological Impairments: ○ Poor performance in measures of executive functioning, learning, motor skills, and verbal ability ○ Very-late-onset patients have similar patterns of impairment as do patients with dementia -- widespread functional deficits ● Cognitive deficits in learning, abstraction, and cognitive flexibility are milder in late-onset patients when compared to early-onset patients ○ These skills may already be concrete by a later age

why are women more likely to be patients of late-onset schizo

● MENOPAUSE! ○ Mid-adulthood drops in estrogen may expose females to a higher risk of developing schizophrenia ● Estrogen has an anti-dopaminergic effect that is a protecting factor against schizophrenia in early life -withdrawal may lead to increased sensitivity levels of dopamine receptors

Estrogen Therapy and Postpartum Psychosis

● Possible factor in onset of postpartum psychosis is the significant change in hormones after childbirth ○ decrease in estrogen ● In the past, it resulted in rapid and significant remission of mood, psychosis, and cognitive symptoms, restoring estrogen levels close to normal ○ A recent study didn't yield the same results, so this therapy is still under investigation

Psychoeducation and Psychotherapy

● Psychoeducation helps the patient and her family with expected outcomes, treatment strategies, and future prevention ● Affected mothers unfamiliar with the diagnosis fear they are untreatable and are ashamed of the mentally ill stigma ○ this illness is most treatable when symptoms are recognized early ● Cognitive behavior therapy, family-focused therapy, and interpersonal therapy help alleviate stress about role changes, relationship difficulties, and other environmental stressors

Genetics, Heritability and mRNA of SZ and Methamphetamine psychosis

● Shared genetic risk for schizophrenia (SZ) and MA psychosis ○ NOT MA use without psychosis ○ Only 7% of variance explained ● Family history of SZ, higher risk for MA psychosis. ○ Also bipolar and depression ○ NOT drug or alcohol abuse ○ Higher familial loading -> Higher risk for prolonged MA psychosis ● mRNA expression in prelimbic and orbitofrontal involved in GABAergic neuronal functioning and expression ○ Increased expression of mRNA in rats with behavioral sensitization to MA ○ Decreased expression of mRNA in SZ's ○ May point to differences in cognitive and negative symptoms

Postpartum Psychosis Influence on Suicide and Homicide

● Significant increase in suicide risk in first postpartum year ● In a clinical survey, 28-35% of women had delusions about their babies, but only 9% had thoughts of harming them ● Andrea Yates in 2001: women with postpartum depression and psychosis drowned her five children in a bathtub ○ Doctor did not keep her on antipsychotics due to worries about side effects ○ Husband left her alone with the children ○ During a taped session with a psychiatrist, reported that she didn't think it was wrong because her children would have been "tormented by Satan"s

Treatment for MA psychosis

● Similar response rate to antipsychotics as SZ's ○ Atypicals slightly better response ● Electroconvulsive therapy (ECT) ○ Preclinical: repair of sensorimotor gating, PPI and novel object recognition ○ Clinical: ~4 sessions to treat MA persistent psychosis ■ increased hippocampus, amygdala and insula after ECT in SZ's ○ Side effects can include headaches, nausea, muscle tension and short term memory loss ● Repetitive transcranial magnetic stimulation (rTMS) ○ Increased cognitive functioning in MA abusers ○ Decrease in negative symptoms in SZ's ○ Specifically, DLPFC for both groups ○ Very few adverse effects (scalp irritation)

Structural Similarities and Differences of Methamphetamine psychosis and SZ

● ● ● Similar prefrontal (PFC) and temporal cortex damage More blood oxygenation in DLPFC than SZ's ○ During verbal fluency task ○ Interestingly scores were similar Differences in parietal cortex? ○ Decreased grey matter BUT increased white matter in MA abusers ■ May be due to inflammation OR ■ Compensatory gliosis ○ SZ's reduced temporal lobe volume ● Subcortical ○ Similar hippocampal deficits to SZ ○ Similar cingulate cortex grey matter reduction to SZ ○ More amygdala deficits in MA psychosis than SZ

Symptoms of MethAmphetamine psychosis

●MA psychosis occurs in ~20-30%, persistent psychosis ~10% of users ○ Highly correlated with length of time and severity of use Most similar to paranoid SZ ○ Starts with paranoia > delusions > auditory hallucinations > visual hallucinations (severe use) ○ Progression of psychotic state similar to SZ, except more visual distortions in prodromal SZ ● Cognitive symptoms similar to SZ ○ Inhibition, selective attention, sustained attention visual search and memory ○ SZ's more severe scores on visual search and sustained attention ● Disorganized speech and thought, not as common in MA psychosis ● Conflicting evidence of negative symptoms ○ Most commonly alogia and flattened affect (~20%)

Verbal learning and memory and SZ

❖ One of the most consistent cognitive dysfunctions in SZ ➢ Poor retention of verbal information ➢ Poor recall of learned information ➢ Decreased ability to semantically encode (process information relating to meaning) ❖ Cited as a cause for another known deficit in long-term memory ❖ When given a list of words, healthy individuals demonstrate Pollyanna principle ❖ SZ patients tend to remember all words equally regardless of connotation, suggesting that the experience of anhedonia impairs semantic encoding of the words

Attention/Vigilance and SZ Links between ADHD and SZ

❖ Primary cognitive deficit in SZ ❖ SZ patients have poor ability to maintain attention even prior to the first psychotic episode ➢ Even those genetically predisposed to SZ have poor ability to maintain attention (Cornblatt et al, 1985) ❖ By the time of first episode, attentional impairments are typically already present and of moderate severity ❖ Cohort of 1037 New Zealanders (born 1972 -1973) ❖ By age 26, SZ spectrum diagnosis given to 35 individuals ➢ ~10 diagnosed with legit SZ, ~25 with schizophreniform disorder ➢ Adult schizophreniform disorder significantly associated with juvenile ADHD: 4.5% greater risk ❖ Examined comorbidity in 82 youths (ages 4-15) with childhood-onset SZ/schizoaffective disorder ❖ Comorbid ADHD found in 84% (N = 70: 54 boys, 16 girls) ➢ 38 (55%) = combined subtype ■ Not looking good for me ➢ 23 (33%) = predominantly inattentive subtype ➢ 2 (2%) = predominantly hyperactive-impulsive subtype ➢ 6 (7%) = ADHD not otherwise specified

Executive functions and SZ

❖ Purposeful, goal-directed behavior ❖ Consistently among best predictors of functional performance ➢ Self-care, social, interpersonal, community, and occupational functions are all associated ❖ Planning and problem-solving capacity significantly impaired ❖ Inflexible thinking ❖ Negatively associated with treatment interference ➢ Less engagement in therapy ➢ Less medication compliance ➢ Longer hospital stays

General Intelligence and SZ

❖ SZ Patients have lower IQ scores than general population ➢ Prior to and at first episode ➢ Further decline after diagnosis ❖ By 1st grade, children who eventually develop SZ already perform a full grade equivalent BELOW their peers ❖ Poor performance on processing speed subtest of the WISC often determines who later develops SZ spectrum disorders ❖ Nonverbal, verbal, and reading ability assessed at ages 8, 11, and 15 ❖ Arithmetic ability assessed at ages 11 and 15 ❖ Vocabulary assessed at ages 8 and 11 ❖ Children who later developed SZ showed significant deficits in: ➢ Nonverbal and verbal intelligence tests from the age of 8 ➢ Arithmetic/mathematic skills from the age of 11

Limits of Cognition Assessment tests

❖ SZ is heterogeneous disease, therefore cognitive dysfunctions as well as level of impairment within each domain is inconsistent across patients ❖ The time chosen to evaluate the abilities of the patient is also a limiting factor. ❖ Batteries of tests used in different studies are not standardized ❖ SPQ Test

Social Cognition and SZ

❖ SZ patients consistent impairment in: ➢ Representing and utilizing contextual social information ➢ Interpret social intent of others ➢ Identify facial affect of others ■ Hyperactivation/Hyperactivation (compensatory) ➢ Recognize emotion in social contexts ➢ Anticipate social sequences

Links between ASD and SZ

❖ Sasson et al (2007) ➢ ASD, SZ, HC presented situations where faces are included or digitally erased ➢ HC and SZ oriented to face regions faster when faces vs absent ➢ SZ slower in orienting to faces than HC ➢ ASD showed no difference in orientation to faces vs absent ➢ Hypothesis: ASD and SZ may share an abnormality in utilizing facial information for assessing emotional content in social scenes but differ in the ability to seek out socially relevant cues from complex stimuli ❖ Pinkham et al (2008) ➢ 12 ASD, P-SZ, NP-SZ, HC ➢ Rated faces on trustworthiness ➢ ASD and P-SZ showed significantly reduced activity in the R amygdala, R FFA, and L VLPFC compared to controls ➢ ASD and P-SZ showed significantly reduced activity in the L VLPFC compared to NP-SZ ➢ Hypothesis: well-defined neural substrates of social cognition and a specific neural mechanism that may underlie social cognitive impairments in both ASD and P-SZ

Working Memory and SZ

❖ The ability to hold in mind and mentally manipulate information over short periods of time ❖ Carries more of a "cognitive load" than simple attention ➢ Additional demands of manipulating information ❖ Verbal working memory (present in majority of patients) ➢ Ex. remembering and successfully following lengthy instructions ❖ Visuospatial working memory ➢ Ex. retention and manipulation of visuospatial information ❖ Non-verbal (object) working memory ➢ Ex. retain the identity of two objects for 3 sec

Verbal Fluency and SZ

❖ Verbal fluency tests assess ability to produce words from specific phonological or semantic category. Tests reveal: ➢ Difficulty producing speech on demand ➢ Poor storage of verbal information ➢ Inefficient retrieval of information from semantic networks ❖ Information stored is not always retrieved as a result of inability to properly access semantic networks ❖ VF deficits also associated with poor interpersonal functioning

A study of Amphetamines in Non-ADD/ADHD Persons

➔ Amphetamines utilize the same mechanisms in the impaired and non-impaired human brain (via utilizing the DAT to increase synaptic DA levels) ➔ Undergraduate users of nonprescription amphetamines were more likely to report increased involvement with alcohol, ecstasy, marijuana, risky sexual behavior, cocaine, and cigarettes. ➔ Very few studies show effects on cognitive enhancements due to nootropic use in non-ADD/ADHD persons -- fewer on positive correlations with academic achievement ➔ Sarah and Farah (2011) examined the effect of nootropics on 40 young adult subjects (aged 18-24) via tasked examining learning, cognitive control, and working memory. No benefits immediately following the learning task were recorded. Small, yet statistically significant benefits found in delayed recall and recognition (4 days - 2 weeks). ➔ Effect associated with increased DA signalling in the dorsal anterior cingulate cortex and inferior parietal lobe.

CBT for Psychosis

➔ CBT: Behavioral and Cognitive Interventions to disrupt cycle that contributes to pathology- it is COLLABORATIVE ➔ Highly recommended adjunct to antipsychotic medication in schizophrenia treatment ➔ "...getting better is functioning like other people," Aaron Beck ➔ Acceptance of Condition ➔ Examining triggers of acute episodes and early signs of relapse ➔ Critical analysis of origins of hallucinations ➔ Linking underlying beliefs behind delusions and recognizing delusional thoughts ➔ Treating co-existing anxiety or depression ➔ Interventions for cognitive disorder ➔ Stress reduction tools ➔ Social Skills Training 1. CBT + Treatment as usual (TAU) 2. Supportive Counseling (SC) + TAU 3. TAU alone - Phase 1 - Collect recovery data over 70 days - Phase 2 - 18 month follow-up psychiatric interview and medical record exam Predictions? - CBT Group would show ___ in comparison to other two groups 1. Decreased levels of symptoms at 18 months 2. Reduced rates of relapse 3. Reduced readmission to hospital 4. Shorter duration of admission 5. Longer duration of survival before relapse Findings - Medical compliance was good across all treatments - CBT significantly improves positive, negative, and general symptoms at the 18 month follow up according to Positive and Negative Syndrome Scale (PANSS) - No advantage to relapse or rehospitalization, delusions, or hallucinations - Little to no difference between SC and CBT, due to therapeutic focus, differing populations - Liverpool generated significant results, but not other two

Neural Mechanism of Amphetamines (based on ADD/ADHD persons)

➔ Current estimates show that approximately 2⁄3 of diagnosed ADD/ADHD patients are prescribed amphetamines ➔ Drugs block the dopamine transporter, DAT, within the brain, thus increasing levels of DA within the synaptic cleft ➔ See increased in DA in the ventral striatum, associated with reward and motivation - correlated with improvements in symptoms related to inattention. ➔ Little evidence found that amphetamine medications increase academic achievement in impaired subjects compared to controls - report significantly lower GPAs and showcase significantly smaller graduation rate percentages ➔ Medications believed to partially normalize cognitive impairments