PSY 183 Schizophrenia 2024 Lecture Notes PDF

Introduction to Psychopathology Alan J. Fridlund, Ph.D. NOTICE: These Lecture Notes © Copyright 2014, 2019, 2020, 2023, 2024, by Alan J. Fridlund, Ph.D. All Rights Reserved. They May Be Copied Freely for Internal Use by Students Currently Registered in UCSB Psych 183. For-Profit...

Introduction to Psychopathology Alan J. Fridlund, Ph.D. NOTICE: These Lecture Notes © Copyright 2014, 2019, 2020, 2023, 2024, by Alan J. Fridlund, Ph.D. All Rights Reserved. They May Be Copied Freely for Internal Use by Students Currently Registered in UCSB Psych 183. For-Profit Reproduction in Whole or In Part Without Written Permission of the Instructor Is a Violation of U.C. Regulations and the DMCA and Is Expressly Prohibited.  Notice All Course materials (class lectures and discussions, handouts, examinations, Web materials) and the intellectual content of the Course itself are protected by United States Federal Copyright Law, and the California Civil Code. UC Policy 102.23 expressly prohibits students (and all other persons) from recording lectures or discussions and from distributing or selling lectures notes and all other course materials without the prior written permission of the Instructor (See http://policy.ucop.edu/doc/2710530/PACAOS-100). Students are permitted to make notes solely for their own private educational use. Exceptions to accommodate students with disabilities may be granted with appropriate documentation. To be clear, in this class students are forbidden from completing study guides and selling them to any person or organization. The text has been approved by UC General Counsel.  DSM-5-TR “Schizophrenia Spectrum and Other Psychotic Disorders”  What Defines a “Psychotic Disorder”?* Psychotic Disorders often include: ⚫ Delusions – Fixed beliefs that are not amenable to change in light of conflicting evidence. They may be, for example, grandiose (special status or abilities), persecutory, somatic (one is rotting away or disfigured), religious (one has sinned against God, on a mission from God, or is the Devil), sexual (one is a pedophile or rapist, or that masturbation has caused their illness), or nihilistic (one is dead or the world does not exist). Delusions vary with culture. ⚫ Hallucinations – vivid perceptual experiences that seem real but occur without an external stimulus and outside of sleep, e.g., hearing voices (most common), seeing people or things, intense odors or tastes. ⚫ Disorganized thinking – “derailment” (loose associations), neologisms, tangentiality, incoherence or “word salad” ⚫ Disorganized motor behavior – chaotic or bizarre movements or postures, stereotyped repetitive movements. * Psychotic signs and symptoms can occur in many disorders (e.g., Major Depression and Bipolar Disorder, but they are not the defining features of those disorders.  Major Disorders within DSM-5-TR “Schizophrenia Spectrum and Other Disorders” ⚫ Schizotypal Personality Disorder (also included under Personality Disorders) ⚫ Delusional Disorder – having one or more delusions that persist for 1 month or longer without other psychotic signs/symptoms. ⚫ Brief Psychotic Disorder – presence of delusions, hallucinations, or disorganized speech or behavior, for < 1 month, and which is not a culturally sanctioned response or a medication/drug reaction. Half of people recover fully, but about half relapse and may progress toward a Schizophrenia diagnosis. ⚫ Schizoaffective Disorder – Diagnosed when individuals have a history of Major Depression and/or Mania/Hypomania along with an existing Schizophrenia diagnosis. ⚫ Substance/Medication Induced Psychotic Disorder – e.g., from bad reaction to cannabis, amphetamines, cocaine, hallucinogens, opiates, anti-Parkinson’s medications, and many other prescribed medications). Must always be excluded before diagnosing another Psychotic Disorder.  What is Schizophrenia? ⚫ Disorder in which psychotic signs/symptoms predominate ⚫ Affects ~1-2 % of population across cultures – Affects 24 million people worldwide, and 2.8 million in the U.S. Accounts for ½ of all psychiatric inpatients, ¼ of all 1st admissions to U. S. mental hospitals. – By historic estimates, schizophrenia accounted for 2/3 of all homeless in U.S. (probably overshadowed now by epidemic of drug/ETOH abuse). – Seriously disabling for most; about 30% attempt suicide, and ~10 % die by suicide (greatest among unemployed males with history of depression). ⚫ Known since the mid-19th century – Auguste Morel (1860) – démence précoce (“premature dementia”) Note: dementia is not a normal part of aging, and Schizophrenia does not resemble the most typical forms of dementia. – Emil Kraepelin (1898) – dementia praecox (Latinate form of Morel’s term) – Eugen Bleuler (1911) – schizo-phrenia (“shattered mind”) ⚫ Primary symptoms (thought disorder: breakdown of associations) ⚫ “Restitutional” symptoms (hallucinations and delusions - ways to restore a coherent inner world) ⚫ Not multiple or “split” personality (this is now known as Dissociative Identity Disorder) ⚫ One Schizophrenia or many kinds of Schizophrenia? The evidence is unclear. ⚫ Schizophrenia is probably the most-researched mental disorder, yet it remains a mystery and the treatments are still inadequate. A Case of Schizophrenia  Typical Features of Schizophrenia ⚫ Dramatic loss of previous level of functioning: – acute onset (“Schizophrenic break”) predicts a possibility of remission and a better prognosis. – gradual onset predicts a slow decline and a worse prognosis. ⚫ Disturbances of language and communication w/ “autistic” thinking and speech (full of private meanings; unrelated to Autistic Spectrum Disorder): – Tangential, incoherent, rambling speech – Flight of ideas or derailments (“going off the track”) ⚫ “Formal thought disorder” – Altered thought boundaries (thought broadcasting, insertion, removal) – Hallucinations – Delusions ⚫ Disordered emotionality: “flat,” “paranoid,” or “silly” affect ⚫ Disturbances of the will – inertia, followed by inertness and mutism as disorder progresses ⚫ Social withdrawal, purposeless wandering ⚫ Lapse in hygiene and other self-care ⚫ Motor abnormalities – Reduced spontaneity – Bizarre or stereotyped gestures – Catatonia (~ 10%) – frozen postures or episodic “frenzy,” stupor, mutism, echopraxia (repeating others’ movements), echolalia (repeating others’ speech) ⚫ These features are often labeled positive or negative symptoms, depending upon whether they represent added or deficient cognitions or behaviors. Risk Factors: Who Becomes Schizophrenic? ⚫ Not child-rearing – research disproves earlier theories that focused on deviant family interactions and communications ⚫ Genetic relatedness (consanguinity): – Odds of a child becoming schizophrenic are: ⚫ 15 % if one parent is schizophrenic (vs. 1-2 % base rate) ⚫ 46-48 % if both parents are schizophrenic (vs. 1-2 % base rate) – Above risk applies even if children are adopted early into new homes – Twin concordances ( MZ = ~.5, DZ = ~.15), which may speak to genetics, epigenetics, and/or intrauterine environment  Genetic Relatedness and Schizophrenia Genl Pop 1 Spouse 2 1st Cousin 2 Half Sib 6 Sib 9 1 Sc Parent 15 DZ Twins 17 2 Sc Parents 46 MZ Twins 48 0 10 20 30 40 50 60 % Concordance  Nongenetic Risk Factors in Schizophrenia ⚫ Birth complications (e.g., protracted labors, forceps deliveries) ⚫ Maternal malnutrition ⚫ Maternal exposure to influenza virus – Risk greatest at 6th month of gestation – Viral exposure may explain part of the MZ / DZ twin concordance difference ⚫ Seasonality of birth - 5-8% likelier (up to 15% in some studies) with December to May births, with peaks in February–March (6 months earlier in Southern Hemisphere); consistent with infection at 6th month of gestation. ⚫ Other maternal infectious agents may be involved: – Rubella virus (German measles) – leading vaccine-preventable cause of birth defects – Toxoplasmosis spores (“neuroteratogenic”): carried by cats and expelled in feces; greater prevalence of cat ownership among parents of children with Schizophrenia, and with childhood cat exposure. Research findings are inconsistent. – Endogenous retroviruses (e.g., herpes simplex II) ⚫ Older sperm (▲ mutations with age) - odds of having a child with Schizophrenia are: – About 1 in 200 if father is 25 – About 1 in 120 if father is 40 – About 1 in 70 if father is 50 ⚫ Cannabis – risk is enhanced with certain genotypes and is especially high in adolescent males. Do NOT use marijuana if it has given you a psychotic reaction, or if there is a history of psychosis in your family. Adolescent Cannabis Use and Later Schizophrenia Two Cases of Schizophrenia w/ Paranoid Features  What Is the Damage in Schizophrenia? ⚫ Early views (discredited): – Metabolic disorder (Kraepelin) – Double-binding mother (Freudians) ⚫ Structural brain damage (autopsy, CT scans) – Cellular derangement – Loss of gray matter with enlarged ventricles (loss is twice as fast with heavy and/or early cannabis use, especially in males) – Loss of prefrontal white matter (myelinated axons) ⚫ Disordered brain activity (PET & fMRI scans) – Frontal lobe and temporal lobe language areas – basal ganglia - responsible for smooth movements and shifts of attention – Cerebellum – responsible for balance, “automatic” motor skills, and timing of movements and thoughts ⚫ Neurotransmitter dysfunction – Dopamine hypothesis (too much DA turnover in certain brain areas) – Dopamine-serotonin interaction (too much DA turnover in certain brain areas, insufficient serotonin turnover in others) – Many other neurotransmitter systems are implicated. ⚫ Modern view: schizophrenia is a neurodevelopmental disorder which begins with fetal brain mis-wiring, possibly due to viral or other influences.  Positive vs. Negative Symptom -Predominant Schizophrenia* (Research Classification: Not in DSM-5-TR) ⚫ Later age of diagnosis (20-25) + ⚫ Females > Males Symptom- ⚫ Childhood oddity, irritability, aggressiveness Predominant ⚫ Frequent abnormal Dopamine-turnover findings Schizophrenia (Paranoia, delusions, ⚫ Good response to classical antipsychotic meds hallucinations, ⚫ Less chance of observable brain damage odd behaviors) ⚫ Better prognosis versus – ⚫ ⚫ Earlier age of diagnosis (16-18) Males > Females Symptom- ⚫ Childhood withdrawal, passivity Predominant ⚫ Infrequent abnormal Dopamine-turnover findings Schizophrenia (Social withdrawal, ⚫ Poor response to classical antipsychotic meds flat affect, inertia, ⚫ Greater chance of observable brain damage catatonia) ⚫ Worse prognosis * Some cases begin as + Symptom-Predominant Schizophrenia and become – Symptom-Predominant Schizophrenia over time.  Positive- Symptom Schizophrenia and Parkinson’s Disease: The Dopamine (DA) Seesaw ⚫ Drugs that increase brain DA turnover can cause a psychotic disorder that resembles + symptom Schizophrenia. ⚫ Classical antipsychotic medications lower brain DA turnover by “sitting on” and blocking DA receptors while being inert, and they induce motor signs/symptoms that resemble Parkinson’s disease (tremor, muscle rigidity, slow shuffling gait), which involves the loss of DA neurons in the basal ganglia. ⚫ Individuals (10 %) suffering from Parkinson’s disease, when taking medication to restore DA levels to reduce their Parkinson’s signs/symptoms, may suffer from a psychotic disorder that resembles + symptom Schizophrenia. ⚫ BUT the – symptoms in Schizophrenia seem to have more to do with serotonin (5-HT) turnover in the brain, and modern “second-generation antipsychotics” affect both DA and 5-HT. ⚫ Many other neurochemical systems besides DA and 5-HT are involved, and new medications are being devised to target them.  Treatments for Schizophrenia ⚫ Medication (Primary Treatment) – Acute goal – sedation and “chemical restraint” done at Emergency Room or as part of a voluntary or involuntary hospitalization – Long-term goal – normalization of cognition and behavior, reintegration to former life to the extent possible – BUT overall, med compliance < 30% (= Bipolar Disorder compliance) ⚫ Individual and Family Psychotherapy – Adjustment to illness ⚫ Family ⚫ Friends ⚫ Work ⚫ Love – Deal with patient’s depression, anxiety resulting from knowledge of primary diagnosis of Schizophrenia. – Symptom self-monitoring – Building compliance with medication ⚫ Supervised living or rehab experiences: Assisted Outpatient Treatment (“halfway house”, “supervised living”) and Day Hospital programs  Medication for Schizophrenia Typically called: Antipsychotics, Major Tranquilizers, or Neuroleptics You Do Not Need To Know Medication Names Classical Antipsychotics (Treat Mainly + Signs/Symptoms and Are Now Rarely Used) Haldol Prolixin Thorazine Mellaril Stelazine Second-generation (Atypical) Antipsychotics (Treat Both + and – Signs/Symptoms and are in wide use) Abilify Caplyta Clorazil Geodon Invega Latuda Rexulti Risperdal Seroquel Vraylar Zyprexa Clozaril is most effective current medication, especially with treatment- resistant Schizophrenia. It has the fewest side effects, and may curb suicide, but it carries the risk of a fatal blood disorder (neutropenia, the loss of white blood cells), which requires continual blood testing.  Cobenfy: A Major New Schizophrenia Medication Unlike previous antipsychotic medications, Cobenfy targets and stimulates brain “muscarinic” receptors for acetylcholine. Like the 2nd-generation antipsychotics, Cobenfy treats both + and – symptoms. It’s currently ~$2K/month, and it’s unclear whether it will prove superior to current medications in efficacy and side effects.  Side Effects of Antipsychotic Medications ⚫ Drowsiness / sedation occurs with most antipsychotics, and can be beneficial in agitated patients. Abilify and Latuda are exceptions. ⚫ Increased risk of “Metabolic syndrome” – Weight gain (often severe, especially in abdomen) – Elevated blood lipids (cholesterol & triglycerides), which increase risk of heart attack and stroke – Type 2 Diabetes (blood glucose dysregulation) which can lead to nerve damage and blindness – Patients are often prescribed other medications to reduce these effects. ⚫ Persistent movement side effects (much less problematic with second-generation antipsychotics): – Akathisia (“cruel restlessness”), e.g., rocking, “Thorazine shuffle” – Pseudoparkinsonism ⚫ Resting Tremor ⚫ Slowness of movements ⚫ Muscular rigidity – Tardive dyskinesia ⚫ Early lip-puckering “rabbit sign” ⚫ Eventually, tongue- and limb-writhing ⚫ New medications aid in minimizing TD for current sufferers Other Disorders In Which Antipsychotic Medications Are Sometimes Used: ⚫ Major Depression with psychotic features ⚫ Severe Generalized Anxiety Disorder that does not respond to usual anti-anxiety medications. ⚫ Bipolar Disorder (several antipsychotic medications such as Abilify are FDA-approved for both Schizophrenia and Bipolar Disorder) ⚫ Paranoid, Schizoid and Schizotypal Personality Disorders – for disordered, sometimes psychotic thinking ⚫ Borderline Personality Disorder – for transient psychotic episodes ⚫ Acute and Post-traumatic Stress Disorder – for paranoia ⚫ Disorders with transient psychotic features (e.g., Brief Psychotic Episodes, Depersonalization/Derealization Disorder, delirium, etc.) ⚫ Cannabis and other Substance/Medication Induced Psychotic Disorders ⚫ Agitation in the elderly (especially at nightfall: “Sundowner’s Syndrome”) ⚫ Severe insomnia (Seroquel especially) ⚫ Rage episodes in Autism Spectrum Disorder (Risperdal especially)  Is Schizophrenia a Violent Disorder? ⚫ People with Schizophrenia often act, dress and speak unusually, and it is natural for others is to be wary. ⚫ Unfortunately, Schizophrenia is often portrayed in the media as “multiple personalities” or a “split” personality, involving the takeover of one’s personality by violent forces. This is a total misconception. Schizophrenia is the disintegration of major aspects of normal functioning. ⚫ The best predictors of violence by anyone are: – Prior history of violence. – Drug and alcohol (ETOH) abuse. ⚫ For people with Schizophrenia, violence is likelier with: – Failure to take medication – quite common in Schizophrenia. – Presence of “command hallucinations” which order person to act violently. – Ongoing drug/ETOH abuse: odds of violence compared to Psycho non-Schiz population are 1.2 : 1 without substance abuse, and 4.4 : 1 with substance abuse. ≠ Schizophrenia ⚫ Most Schizophrenic violence is suicide, or violence toward family members, when person is off medication. ⚫ People w/Schizophrenia are 14 X likelier to be the victims of violence rather than the perpetrators.  Prognosis in Schizophrenia ⚫ Formerly, “Rule of thirds” – 1/3 improve, 1/3 stay same, 1/3 deteriorate – rule probably reflected cases of Bipolar Disorder historically misdiagnosed as Schizophrenia ⚫ Now, since Bipolar Disorder is (accurately) diagnosed more frequently, the prognosis is worse. On 30-year follow-up, of people with Schizophrenia diagnosis: – 20% show good adjustment – 54% had incapacitating symptoms, with most living at home or with relatives – 18% were institutionalized ⚫ Prognosis remains worse for – symptom Schizophrenia, although newer medications may be more effective at treating – symptoms and may improve prognosis ⚫ Good news: incidence of Schizophrenia appears to be declining world-wide, perhaps due to better prenatal and infant nutrition, less traumatic childbirth methods, and global introduction of the influenza vaccine. End  Hallucinations in Schizophrenia ⚫ Usually auditory: – Malevolent or taunting voices commenting on patient’s actions or character, often with sexual overtones – Voices ordering the patient to take certain actions (“command hallucinations”) – Two or more voices arguing with each other – Hearing one’s thoughts as though they are spoken out loud ⚫ Visual, tactile, or olfactory hallucinations suggest seizure disorder, drug abuse (e.g., opiates, hallucinogens, psychostimulants), or other organic condition (e.g., toxic encephalopathy) Seasonality of Births of Individuals Later Diagnosed with Schizophrenia (Northern Hemisphere)* Relative Risk Month of Birth Mortensen et al., New England J. of Medicine, 1999, Vol. 340, Pp. 603–608 *Six months earlier in Southern Hemisphere; no seasonality observed for equatorial locations.