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Schizophrenia and Related Psychotic Disorders Diana O. Perkins, MD, MPH Associate Professor of Psychiatry Director, Schizophrenia Treatment and Evaluation Program Schizophrenia and Related Psychotic Disorders Clinical characteristics Epidemiology Etiology Psychotic Disorders Clinical Characteristics Schizophrenia is Heterogeneous... A syndrome defined by a constellation of clinical symptoms With multiple causes, that are similarly expressed Show video tape Schizophrenia: Clinical Features Positive Symptoms a distortion or excess of normal function Negative Symptoms a decrease or loss in normal function Disorganization of thoughts and behavior Cognitive Impairments Mood Symptoms Features of Schizophrenia Positive symptoms Negative symptoms Functional Impairments Work Interpersonal relationships Self-care Cognitive deficits Mood symptoms Disorganization Positive Symptoms (Psychosis) Disturbance of Perception (Hallucinations) Disturbance (Delusions) of Thought Content Positive Symptoms Disturbance of Perception may effect any sensory modality Positive Symptoms: Hallucinations Auditory Hallucinations • involve voices or sounds • single or multiple • familiar or unfamiliar • may make insulting remarks or be pleasant • may comment on behavior • may command person to perform acts Positive Symptoms: Hallucinations Other Sensory Modalities • Tactile: may involve electrical, tingling, or burning sensations • Visual • Gustatory • Olfactory Positive Symptoms: Delusions Delusions • fixed false beliefs • examples: - persecutory delusions delusions of reference delusions of being controlled thought broadcasting/insertion/withdrawal grandiose religious nihilistic somatic Features of Schizophrenia Positive symptoms - Hallucinations - Delusions Negative symptoms Functional Impairments Work Interpersonal relationships Self-care Cognitive deficits Mood symptoms Disorganization Negative Symptoms Negative symptoms include: decreased expression of feelings diminished emotional range poverty of speech decreased interests diminished sense of purpose diminished social drive Differential Diagnosis of Negative Symptoms Negative Symptoms primary to schizophrenia: The “Deficit Syndrome”: primary and enduring negative symptoms in individuals with schizophrenia • The Deficit Syndrome occurs in about 20% of treated patients Differential Diagnosis of Negative Symptoms Negative Symptoms may be secondary to: antipsychotic EPS side effects - decreased emotional expression and apathy may be due to Parkinsonian side effects - lack of initiation of activity may be due to bradykinesia psychosis depression or anxiety demoralization Features of Schizophrenia Positive symptoms - Delusions - Hallucinations - Disorganization Functional Impairments Work Interpersonal relationships Self-care Cognitive deficits Negative symptoms - emotional range - expression of emotion - motivation/drive - interests - social drive - poverty of speech Mood symptoms Disorganization Positive Symptoms: Disorganization • Disorganization of Speech – tangential or circumstantial speech – looseness of associations • Disorganization of Behavior – odd mannerisms – catatonic stupor Video Tape Positive symptoms: • Hallucinations • Delusions Disorganization • Speech • Behavior Negative symptoms: Features of Schizophrenia Positive symptoms - Delusions - Hallucinations - Disorganization Functional Impairments Work Interpersonal relationships Self-care Cognitive deficits Disorganization - speech - behavior Negative symptoms - emotional range - expression of emotion - motivation/drive - interests - social drive - poverty of speech Mood symptoms Cognitive Domains: Severe Impairment in Schizophrenia – – – – – Severe Impairments Serial learning Executive functioning Vigilance Motor speed Verbal Fluency – – – – – Moderate Impairment Delayed recall Distractibility Immediate memory span Visuomotor skills Working memory Working Memory – Aspects of Working Memory • Temporary storage and manipulation of information • “workspace” for holding items of information in mind as recalled, manipulated, and associated with other ideas and information – Tests • patients with schizophrenia tend to perform 1-2 standard deviations below the mean • Tests: visual, spatial, auditory working memory 12 Executive Function – Aspects of Executive Function • Focus attention • Distinguish the important aspect of a task or a situation from unimportant • Prioritize • Perform mental or physical activities proper sequence • Modulate behavior based on social cues – Tests: • Patients perform 2-3 standard deviations below mean • Examples: Trail Making Tests, Wisconsin Card Sort, Tower of London The Wisconsin Card Sorting Test The Wisconsin Card Sorting Test The Wisconsin Card Sorting Test The Wisconsin Card Sorting Test The Wisconsin Card Sorting Test The Wisconsin Card Sorting Test The Wisconsin Card Sorting Test The Wisconsin Card Sorting Test The Wisconsin Card Sorting Test The Wisconsin Card Sorting Test The Wisconsin Card Sorting Test Vigilance – Ability to monitor target stimuli over an extended duration of time • inability to attend to relevant stimuli and ignore irrelevant stimuli • inability to concentrate • increased susceptibility to distractions • inability to sustain effort and attention – Tests of Vigilance: • patients perform 2-3 standard deviations below the mean • example: CPT Cognitive Functions: Mild or No Impairment in Schizophrenia Mild Impairment No Impairment • Word recognition • Perceptual Skills • Delayed recognition • Long-term factual memory memory • Confrontation naming Features of Schizophrenia Positive symptoms - Delusions - Hallucinations - Disorganization Cognitive deficits - Attention - Memory - Verbal fluency - Motor function - Executive function Negative symptoms - Decreased experience and expression of emotions - Decreased motivation/drive Functional Impairments - Decreased initiative Work Interpersonal relationships - Social withdrawal Self-care Disorganization - speech - behavior Mood symptoms Mood Symptoms – Dsyphoric • anger, hostility, fear, irritability, depression, anxiety • high risk of suicide – Euphoric • sense of power, control, exhilaration Mood Symptoms – Primary to schizophrenia – “Reactive” • psychosis is frightening • reality of illness is demoralizing – Co-morbid disorder • major depressive episode Features of Schizophrenia Positive symptoms Delusions Hallucinations Disorganized speech Functional Impairments Work Interpersonal relationships Self-care Cognitive deficits Attention Memory Verbal fluency Executive function (eg, abstraction) Disorganization - speech - behavior Negative symptoms Anhedonia Affective flattening Avolition Social withdrawal Alogia Mood symptoms Depression/Anxiety Aggression/Hostility Suicidality Diagnosis of Schizophrenia Symptoms Severity/Impairment/Distress Duration Differential Diagnosis of Schizophrenia Significant psychotic symptoms for at least one week Continuous signs of the disturbance for at least six months Markedly impaired ability to function Without known etiology Differential Diagnosis of Schizophrenia Differential Diagnosis: related disorders Schizophreniform Disorder Brief Psychotic Disorder Delusional Disorder Schizoaffective Disorder Schizoid Personality Schizotypal Personality Disorder Paranoid Personality Disorder Differential Diagnosis of Schizophrenia Differential Diagnosis: Mood Disorders with Psychotic Features Major Depression Bipolar Disorder Differential Diagnosis of Schizophrenia Organic Mental Disorders substance induced (e.g. PCP, amphetamine, cocaine, hallucinogens, cannabis, alcohol, a variety of prescribed medications most diseases affecting the central nervous system case OVERVIEW Demographics: Vignette 1: Michael Michael is a 23 year old single male. He lives with his father. He completed some college and currently works at the shipping dock of a department store. Occupational History: Michael has worked for nearly a year at the shipping dock. He has had several other jobs that he quit when he felt “frustrated”. He has also been unemployed for several long periods. He calls in sick to work several times a month and is currently on probation at work. Status of Current Treatment: He is currently an outpatient in the psychiatric clinic. He was hospitalized for 4 days approximately two months ago. Chief Complaint and Description of Problem: Michael reports that he has trouble fitting in and believes that all his co-workers are “weird”. He reports feeling “a little confused” at work, but admits he usually goes to work “high” on marijuana or crack. History: Michael had been in his usual state of good health until approximately three years ago. At the time he was smoking crack cocaine and marijuana several times a week and reports several episodes where he thought that the police were following him and bugging his phone. All of the Vignette 1: Michael episode occurred after a heavy episode of drug use, and resolved after one or two days. He eventually went to the psychiatric clinic for help with the episodes of paranoia, but denied any substance use to the clinic staff. He was prescribed haloperidol, which he took for two days, and then stopped because the medication made him feel “weird”. Prior to three years ago, the patient had no history of mental illness. However, over the past 3 years he has frequently used crack and marijuana and during periods of heavy use he has consistently felt “more paranoid” and “cut-off from everyone”. There are no other major life changes and there have been no deaths of close friends or relatives. However, his relationship with this father is quite strained. His mother died over 10 years ago. About 2 months ago Michael was admitted to the hospital after becoming very aggressive towards his father. He accused his father of sabotaging his car, trying to kill him, and said he would “get dad before dad got me”. In the emergency room Michael was agitated, and was fearful that sirens were the police coming to arrest him. He also reported hearing “voices” telling him “bad stuff” while in the emergency room. Urine toxicology screen was positive for marijuana, PCP, and cocaine. His agitation and paranoid ideation, as well as the “voices” resolved by the third hospital day, without any medication treatment. Treatment History: Michael has had one prior substance abuse inpatient stay lasting 6 days, where, off substances and without medication, his psychotic symptoms resolved. Vignette 1: Michael Other Current Problems: He reports that he always feels “weird and anxious”. He smokes marijuana or crack 1-3 times a day and drinks “several beers” daily. Current Social Function: Michael has no close friends although he will socialize with co-workers occasionally while at work. He is estranged from his father who feels that he does not try hard enough to get better. Outside of work, he watches TV and listens to music. For the past several months, Michael has said he feels anxious and depressed most of the time, because he feels he has no life and no future. He says he never feels interested in anything, and he wishes that he were “more motivated”. His appetite is fine and he has had no change in weight. He reports that his sleep is “pretty good” and he is sleeping 6-8 hours a night. Vignette 1: Michael He denies motor changes (either periods of agitation or motor slowing), and his movements and rate of speech are normal during the SCID interview. He states his energy is “fine”. He feels hopeless about the future, specifically that he will never get a “good job” or have a “decent place to live” but denies feeling worthless or guilt. He blames his father for his current living and work situation. He states that his concentration is “fine”, and there is no evidence of impaired concentration during the interview. He denies recurrent thoughts of death or suicidal ideation. He denies any other periods of depression or loss of interest/motivation in the past five years. Michael denies any periods of time when he has felt euphoric or irritable. He denies thoughts that others take special notice of him. He acknowledges “feeling paranoid” at times when he smokes crack and marijuana. At these times he believes that the police are bugging his phone, and following him and trying to “get him”. He denies any other unusual beliefs. After smoking crack and marijuana he admits that he also occasionally hears muffled voices coming up from the floor, but the voices are indistinct. He admits to hearing the sirens in the emergency room, but he says “I think I was really hearing that”. He denies any other perceptual abnormalities. He states that the paranoid ideas or the “voices” have always resolved when he has stopped the drugs for a week or more, as is true during this hospitalization. On examination, he is reasonably well dressed and well groomed. His motor behavior is normal and well organized. He exhibits a full range and normal display of affect. His speech is normal in rate and rhythm, and his thought form is generally well-organized. He exhibits poor eye contact . watches TV and listens to music. Schizophrenia: Epidemiology Common disease: One in every 100 people develops schizophrenia Each year, 100,000 people are newly diagnosed with schizophrenia in the U.S. On any given day, 600,000 people are in active treatment for schizophrenia in the U.S. Etiology Risk Factors for Schizophrenia Genetic Vulnerability Factors Environmental Risk Factors • Obstetrical Trauma • In-utero events • Infectious Pathogens • Nutritional Factors • Substance Abuse • Stressful life events • College • Boot Camp Schizophrenia is a genetic neurodevelopmental disorder Schizophrenia Schizophrenia What does your baby’s future hold? occurs in all races all cultures all social classes and both sexes Schizophrenia can be treated but not cured …yet! Courtesy of Canadian Schizophrenia Society Genetic Loci Linked to Schizophrenia Schizophrenia: Course Age of onset may begin at any age typically begins in late adolescents and early adulthood late onset form males often have earlier age on onset than females Schizophrenia Course varies from recovery to severe disability in treatment settings commonly see more severe, chronic course Natural History Of Schizophrenia Stages Of Illness Premorbid Prodromal Onset/ Deterioration Residual/ Stable Healthy Worsening Severity Of Signs And Symptoms Gestation/Birth 10 20 30 Years 40 50 Natural History of Schizophrenia Stages of Illness premorbid prodromal residual/ stable onset/ deterioration Healthy Worsening Severity of Signs and Symptoms Gestation/Birth 10 20 30 40 50 Schizophrenia Course: Variable Complete recovery (~ 5-10%) Complete, or almost complete remission of symptoms, but with periodic exacerbations of illness symptoms Chronic symptoms, serious impact in function Schizophrenia Factors affecting prognosis: age of onset sex premorbid function abrupt versus insidious onset family history of mood disorder precipitating events duration of untreated illness substance abuse Prospective Study of First Episode Schizophrenia Percent of Patients Remitting 100 Time to Remission 80 60 40 20 Remission Rate 87% Median Time to Remission 11 wks 0 1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 Weeks of Treatment Robinson et al. 1999 First-Episode: Predictors of Treatment Response Duration of untreated illness : Mean Median Active psychosis: 52 wks 11 wks Prodrome: 151 wks The longer the duration of pre-treatment symptoms, the poorer the clinical outcome (r=.4, p=.0001) The longer the duration of pretreatment symptoms, the longer the time to respond to antipsychotic medication treatment (p=.03) Loebel et al. Am J Psychiatry 1992;149:1183-1188 Cumulative relapse rates by episode of illness 90 80 1st Relapse(104 patients at risk) 70 2nd Relapse (63 patients at risk) 60 3rd Relapse (20 patients at risk) 50 40 30 20 10 0 Year 1 Year 2 * Refers to year(s) after recovery from the previous episode Robinson et al 1999 Year 3 Year 4 Year 5 Mean Time to Response Successive Episodes Episode (N=40) 1 2 Episode (N=12) 1 2 3 0 20 40 60 80 Days to Therapeutic Response Lieberman JA. J Clin Psychiatry. 1996;57(suppl):68-71 100 120 Alternative Pathways to the Development of Residual Positive Symptoms in Schizophrenia: A Treatment Resistant Clinical Sub-type: Patients who have persistent positive symptoms despite treatment with antipsychotics early in the course of illness. Neuroprogressive Pathology: Symptoms that are initially treatment responsive and become unresponsive after subsequent episodes of illness.