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) NOT caused by bad parenting NOT curable (but can improve)

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

Positive Symptoms

Additions to normal function Delusions Hallucinations Distorted language/communication Disorganised speech / behaviour Catatonic behaviour Agitation

Negative Symptoms

Losses of normal function -Affective flattening -Alogia -Avolition -Anhedonia -Attentional impairment

Blunted affect, emotional withdrawal, poor rapport, passivity, apathetic, social withdrawal

Cognitive Symptoms

Thought disorder Odd use of language

incoherence, loose associations, neologisms

Impaired attention / cognitionreduced verbal fluencylearning/memoryexecutive functions

Subtypes of schizophrenia

Paranoid Disorganized Catatonic Undifferentiated Residual

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

Etiology of schizophrenia

Genetic Structural brain changes Functional brain changes Dopamine hypothesis

Genetic Risk

Structural changes in brain

Larger ventricles Subgroup: inverse correlation

between ventricle size and response to drugs

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

Structural changes in brain

Increased loss of gray matter in adolescence

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

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

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.

Brain Dopamine Pathways

Nigrostriataldegenerates in Parkinson’s disease

Mesolimbicpositive symptoms of schizophrenia

Mesocorticalnegative symptoms of schizophrenia

Tuberoinfundibular

Mesolimbic DA Hypothesis

Hyperactivity of mesolimbic DA mediates positive symptoms of psychosis

Accounts for these psychotic symptoms whether in SZ or other disorders

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

Treatment of Schizophrenia

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

First generation antipsychotic

side-effects

Extrapyramidal side-effects – Parkinson symptoms, dystonia, restlessness

Sedation Weight gain Dry mouth, constipation Cardiac toxicity Postural hypotension

Second generation antipsychotic side-effects

Weight gain Increase blood sugar – diabetes Increased lipids Sedation

Non-pharmacologic treatments for schizophrenia

Psychotherapy – supportive Social skills training Family Therapy – expressed

emotion Psychosocial rehabilitation

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.