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Schizophrenia Overview

Schizophrenia Overview. Irving Kuo, M.D. Central Arkansas Veterans Healthcare System. Schizophrenia is the most severe and debilitating mental illness in psychiatry and is a brain disorder. Myths about schizophrenia. NOT multiple personality disorder NOT dangerous (for the large majority)

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Schizophrenia Overview

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  1. Schizophrenia Overview Irving Kuo, M.D. Central Arkansas Veterans Healthcare System

  2. Schizophrenia is the most severe and debilitating mental illness in psychiatry and is a brain disorder

  3. Myths about schizophrenia • NOT multiple personality disorder • NOT dangerous (for the large majority) • NOT caused by bad parenting • NOT curable (but can improve)

  4. Diagnosis of Schizophrenia A. Characteristic symptoms -Delusions -Hallucinations -Disorganized speech -Grossly disorganized or catatonic behavior -Negative symptoms B. Social/occupational dysfunction C. Overall duration > 6 months D. Exclude mood disorders, drugs, pervasive developmental disorders

  5. Positive Symptoms • Additions to normal function • Delusions • Hallucinations • Distorted language/communication • Disorganised speech / behaviour • Catatonic behaviour • Agitation

  6. Negative Symptoms • Losses of normal function -Affective flattening -Alogia -Avolition -Anhedonia -Attentional impairment Blunted affect, emotional withdrawal, poor rapport, passivity, apathetic, social withdrawal

  7. Cognitive Symptoms • Thought disorder • Odd use of language incoherence, loose associations, neologisms • Impaired attention / cognition reduced verbal fluency learning/memory executive functions

  8. Subtypes of schizophrenia • Paranoid • Disorganized • Catatonic • Undifferentiated • Residual

  9. Epidemiology • 1% prevalence worldwide • Most begin in late adolescence to 20’s • M=F • Females age of onset is generally later – better outcome • Downward drift social-economically • Die younger – 10% suicide

  10. Etiology of schizophrenia • Genetic • Structural brain changes • Functional brain changes • Dopamine hypothesis

  11. Genetic Risk

  12. Structural changes in brain • Larger ventricles • Subgroup: inverse correlation between ventricle size and response to drugs

  13. Structural changes in brain • Hippocampus, amygdala, parahippocamp. • Smaller in affected twin • Disordered hippocampal pyramidal cells • Correlation between cell disorder and severity • May be due to maternal influenza in 2nd trimester • Also in entorhinal, cingulate, parahippocampal cortex

  14. Structural changes in brain • Increased loss of gray matter in adolescence

  15. Structural changes in brain • Shrinkage of cerebellar vermis • Thicker corpus callosum • Frontal lobes • Abnormal neuronal migration in one study • Dendrites have fewer spines • But no major structural abnormalities • Measures of frontal function impaired

  16. Functional changes in brain • Hypofrontality hypothesis • Discordant twins: low frontal blood flow only in affected twin • Wisconsin card sorting task • Schizophrenics can’t shift attention to other criterion • Functional imaging: frontal lobe activity lower at rest, esp. in right hemisphere, does not increase during task. • Drug treatment increased activation of frontal lobes

  17. Dopamine hypothesis • Amphetamine (very high doses)  paranoia, delusions, auditory hallucination • Amphetamines worsen schizophrenia symptoms • Effects blocked by dopamine antagonist chlorpromazine (Thorazine) • Typical antipsychotics block D2 receptors and alleviate positive symptoms.

  18. Brain Dopamine Pathways • Nigrostriatal degenerates in Parkinson’s disease • Mesolimbic positive symptoms of schizophrenia • Mesocortical negative symptoms of schizophrenia • Tuberoinfundibular

  19. Mesolimbic DA Hypothesis • Hyperactivity of mesolimbic DA mediates positive symptoms of psychosis • Accounts for these psychotic symptoms whether in SZ or other disorders

  20. Mesocortical DA Hypothesis • Deficit of mesocortical DA mediates negative and cognitive symptoms of psychosis - more controversial - degenerative in some SZ patients - may be primary deficit - may be secondary drug effect

  21. Treatment of Schizophrenia

  22. Medications for schizophrenia • Conventional antipsychotics - Haldol, Thorazine, Mellaril, etc. • Second generation antipsychotics -Risperidone, Zyprexa, Seroquel, Geodon, Abilify, Clozaril • Medications are better for positive symptoms than negative symptoms

  23. First generation antipsychotic side-effects • Extrapyramidal side-effects – Parkinson symptoms, dystonia, restlessness • Sedation • Weight gain • Dry mouth, constipation • Cardiac toxicity • Postural hypotension

  24. Second generation antipsychotic side-effects • Weight gain • Increase blood sugar – diabetes • Increased lipids • Sedation

  25. Non-pharmacologic treatments for schizophrenia • Psychotherapy – supportive • Social skills training • Family Therapy – expressed emotion • Psychosocial rehabilitation

  26. Future Directions in the Treatment of Schizophrenia • More optimistic view of outcome • Much stronger focus on early intervention and prevention e.g. early psychosis clinics and prodromal studies • Specific treatments for cognition in schizophrenia • Increased understanding of neurobiological basis beyond dopamine hypothesis with non-dopamine treatments • Renewed emphasis on rehabilitation, supported employment etc.

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