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A. Essential features:

1. Psychotic features for at least one month (less if treated)

2. Functioning below highest (expected) level

3. Duration of six months, continuously (including prodromal or residual phases)

B. Active Phase: Two or more of the following, for one month:

1. Delusions

2. Hallucinations

3. Disorganized speech

4. Grossly disorganized or catatonic behavior

5. Negative symptoms

C. Prodromal or residual symptoms (from DSM IIIR)

1. Social isolation or withdrawal

2. Impairment in role functioning

3. Peculiar behavior

4. Impaired personal hygiene

5. Blunted or inappropriate affect

6. Abnormal speech (digressive, vague, over-elaborative)

7. Odd beliefs (superstitious, ESP, etc.)

8. Unusual perceptual experiences

9. Apathy

D. Subtypes:

1. Catatonic type

a. Catalepsy or stupor 

b. Negativism or mutism 

c. Excessive motor activity 

d. Peculiar voluntary movements (posturing, mannerism, stereopathy, grimacing) 

e. Echolalia or echopraxia

3. Disorganized type:

a. Disorganized speech 

b. Disorganized behavior 

c. Flat or inappropriate affect 

d. Does not meet criteria for catatonic type

4. Paranoid type

a. Preoccupation with one or more delusions or frequent auditory hallucinations 

b. Not prominent: disorganization, catatonia, inappropriate or fiat affect

5. Undifferentiated type

a. Active psychotic symptoms

b. Does not meet criteria for other types

6. Residual type

a. Not psychotic

b. Does not meet criteria for other types

E. Exclusionary Criteria

1. Mood disorder (if present, is of relatively brief duration)

a. Schizoaffective disorder (mood disorder is prominent, psychotic when euthymic) 

b. Bipolar disorder (psychosis only during manic or depressive phases) 

c. Psychotic depression

2. Organic etiology (substance abuse, seizure disorder, delirium, etc.)

F. Other related diagnoses:

1. Schizophreniform: duration less than six months

2. Brief reactive psychosis: duration less than one month

3. Schizotypal personality disorder.. Does not meet "Active Phase" criteria for schizophrenia

4. Delusional (Paranoid) disorders: Persistent, nonbizarre delusions only

G. Evaluation

1. Complete physical and neurological exam

2. Mental status exam-- neuropsychological testing as indicated

3. Full laboratory screen: lytes, BUN, creatinine, calcium, glucose, CBC, thyroid panel, liver enzymes, VDRL, B 12, folate, HIV when indicated

4. Toxic screen

5. Brain imaging (extremely low yield in absence of neurological signs)

6. EEG if clinically indicated

III. Onset and course

A. Prevalence

1.1% prevalence world-wide

2. Prevalence varies by region in the USA

3. Highest incidence among the urban poor

4. Incidence may be decreasing in Great Britain since 1950

B. Age of Onset

1. Typical: males 18-25 yrs, females 26-45 yrs

2. 10% of cases occur after age 40

C. Premorbid Deficits

1. Children at risk have lower scholastic test scores

2. Future schizophrenic children identified in home movies--abnormalities of affect and coordination

3. Evidence of thought disorder in children at risk

4. "Pandysmaturation": diffuse developmental abnormalities starting in infancy

D. Stress and age of onset

1. Army draftees: 8-fold higher incidence during first few months than during second year of service

2. College students: 44% of cases in first semester

3. Patients with self-reports of childhood abuse have earlier onset, poorer course

E. Gender differences

1. Lifetime risk is approximately equal (possibly higher for males)

2. Males have earlier onset, poorer course

3. Females' course may worsen after menopause

4. 90% of males, 25% of females develop illness before age 30

F. Perinatal Risk Factors

1. Modest increase in Spring and early Winter births

2. Increased incidence among cohorts exposed to influenza or famine during third trimester (sixth month)

3. Increased incidence following obstetrical complications

G. Course

1. Generally, poor outcome

2. Approximately 10% recover, 20% have "good outcome"

3. Outcome is better in underdeveloped countries

4. Suicide rate: 10-13%; attempts: 18-55%

5. Negative symptoms tend to worsen over time

H. Predictors of outcome

1. Poor outcome associated with: negative symptoms, poor premorbid function, insidious onset, no remissions (Chestnut Lodge Follow-up Study)

2. Outcome best correlates with initial medication response (NIMH Follow-up)

3. "Kraepelinian Schizophrenia": 5 years without remission, unable to live independently-- associated with unresponsiveness to medication 4. Outcome worse if pharmacotherapy delayed

I. Course: Paranoid type

1. Later age of onset

2. Rapid onset

3. Better prognosis

J. Course: Hebephrenic type 1. Earlier age of onset 2 Insidious onset

3. Continuous, but stable

K. Course: Undifferentiated tpe

1. Course similar to hebephrenic

2. Continuous, but stable

IV. Negative Symptoms

Anhedonia (inability to experience pleasure)

Associality (social isolation)

Affective flattening

Alogia (poverty of speech and thought)



A. Differential Diagnosis

1. Neuroleptic-induced akinesia

2. Depression

3. Frontal lobe injury

4. Idiopathic parkinsonism

5. Substance abuse (particularly post-stimulant)

6. Hypothyroidism

B. Deficit Syndrome: Primary, enduring negative symptom

C. Crow's Classification of Schizophrenia

  Type I      Type II
Prominent Symptoms Psychotic Symptoms Negative Symptoms
Cerebral ventricles Normal  Enlarged
Cognitive function Normal  Impaired
Medication response Good  Poor
Etiology  DA Hyperactivity Structural


D. Three Component Model

1. Negative symptoms

2. Reality distortion (delusions and hallucinations)

3. Disorganization (thought disorder and inappropriate affect)

E. Awareness of Illness

1. More than half of patients have moderate-to-severely impaired insight

2. Trait characteristic-- does not improve with treatment

3. May reflect frontal cortical dysfunction

V. Patterns of inheritance

A. Familial versus sporadic

B. Concordance rates: monozygotic twins 40-50%, dizygotic twins 15% 

C. Copenhagen study (1968): biological relatives 9% rate of schizophrenia versus 2% rate among adoptive relatives; adopted-away children 16% risk. 

D. Linkage studies have been negative, including studies of gene for D2 receptor

E. No single genetic pattern can be identified:

1. Several discreet diseases?

2. Multifactorial threshold model?

3. Partial penetrance?

VI. Biological abnormalities

A. Enlargement of cerebral ventricles

1. Lateral and third ventricles enlarged

2. Bilateral (L>R), of small magnitude

3. Present at time of diagnosis, usually static

4. Larger ventricles in affected discordant monozygotic twin

B. Histopathological changes

1. Decreased size of anteromedial temporal lobe

2. Cytoarchitectural abnormalities of parahippocampal gyms and hippocampus

3. Reduced neuronal density: prefrontal cortex, thalamus, cingulate gyms

4. Absence of gliosis-- suggests developmental abnormality

5. Evidence for abnormal cell migration in hippocampus and frontal cortex (Akbarian)

6. Caudate volume decreased in neuroleptic naive; increased with neuroleptic exposure

C. Hypofrontality

1. In resting state, may correlate with negative symptoms (inconsistent)

2. Failure to activate prefrontal cortex with Wisconsin Card Sorting Test

3. Not affected by neuroleptics

D. Neuropsychological functioning

1. Generalized deficits: attention, memory, learning, shifting sets 

2. Cognitive deficits present premorbidly, worsen over course of illness

3. Smooth pursuit eye movements (SPEM)

a. Abnormal in 50-85% of schizophrenic patients 

b. Abnormal in 45% of first degree family members 

c. Does not segregate with illness 

d. May be alternative expression of autosomal dominant gene 

e. Not specific-- occurs in mama (state dependent) and Parkinson's disease

4. Evoked potentials

a. P50 waveform decreased after second of paired stimuli in normals, not in patients with schizophrenia 

b. May reflect impairment of gating (filtering) auditory input 

c. Up to 50% of first degree relatives also have defect 

d. Impaired generation of P300 event-related potentials

E. Receptors and neurotransmitters

1. Dopamine D2 receptor density may be increased in striatum and nucleus accumbens (controversial)

2. Norepinephrine receptor density increased in nucleus accumbens?

3. Glutamate receptors: alterations in density and subunit composition in frontal cortex and hippocampus?

4. Inconsistent findings of altered serotonin activity

VII. Theories of etiology

A. Dopamine hyperactivity

1. Schizophrenia and acute psychosis associated with increased mesolimbic dopamine activity

2. May be mediated in part by mesocortical hypoactivity (prefrontal cortex)

3. Supporting evidence:

a. Dopamine agonists, such as amphetamine, produce psychosis 

b. All conventional antipsychotics are dopamine antagonists 

c. Affinity for D2 receptors correlates with antipsychotic potency

4. Evidence which complicates the dopamine model

a. Agents acting at other receptors also produce psychosis (LSD, PCP) 

b. Antipsychotic effect may follow a delay of 2-10 weeks after dopamine blockade initiated 

c. Inconsistent evidence of abnormalities of dopamine, its metabolites, or receptor densities in patients with schizophrenia 

d. Negative symptoms not clearly linked to dopamine

B. Serotonin dysfunction

1. LSD is serotonin agonist

2. MDMA toxicity produces chronic psychosis

3. Clozapine is active at 5HT2a and 5HTlc receptors

4. Evidence of serotonin abnormalities have been inconsistent

C. Phencyclidine (PCP) model

1. NMDA antagonists (PCP & ketamine) produce delusions, hallucinations, thought disorder, negative symptoms, frontal deficits and catatonia in normals

2. Ketamine selectively produces psychotic relapse in patients

3. PCP and ketamine block ion channel associated with NMDA-type glutamate receptor complex

4. Glutamate mediates dopamine activity

D. Viral hypothesis

1. May account for season of birth, decreasing incidence in Great Britain (immunizations)

2. Evidence for increased risk of schizophrenia if exposed to influenza during 6th month of pregnancy

E. Diathesis and stress model (Two-Hit model)

1. First factor: inherited vulnerability to schizophrenia, may be manifested by neuropsychological deficits (impaired auditory gating) 

2. Second factor. Environmental injury to hippocampus (obstetrical injury, infection, trauma, hypoxia)

F. "Schizophrenogenic Mother"-- Discredited

VIII. Violence (Taylor, 1995)

A. Elevated rate of violence

B. Homicide best studied, may be increased by 10-fold compared to general population, but still less than 1%

C. Highest risk: paranoid subtype with delusions which promote violence 

D. Auditory command hallucinations only risk factor within context of delusional system

IX. Psychosocial treatment

A. Acutely:

1. Containment, reduce stimulation, develop alliance

2. Avoid medication side effects

3. Educate, support family

B. Long term:

1. Individual treatment

Supportive, problem solving therapy

Emphasis on medication compliance, social skills 

Adaptation to illness 

Assertive Case Management 

Cognitive Behavioral approaches

2. Family work

Educational, supportive, moderation of "Expressed Emotion" 

Emphasis on understanding illness, realistic expectations 

Family groups following psychoeducation model

C. Outcome

1. Family education and individual social skills training reduced relapse by 50% at one year (Hogarty et al)

2. Expressed emotion (criticism and over-involvement) predicts relapse: patients in high EE households have 3.7-fold higher rate of relapse

3. Individual supportive therapy may be less effective than family~ based approaches at two-year follow-up

4. Programs for Assertive Community Treatment (PACT) models have demonstrated efficacy for patients at high risk for hospitalization 5. Preliminary evidence that cognitive-behavioral approaches may improve outcome in