Schizophrenia

Overview

• Most debilitating and costly of all adult psychiatric illnesses

• ~25% of all psychiatric beds are occupied by persons with schizophrenia

• 2002 fiscal costs of schizophrenia was 62.7 billion

• Greatest burden is lost productivity

Schizophrenia

• Multisystem disease

• Often difficult to describe and understand

• No single feature is pathogonomic of Schizophrenia

• Associated with a constellation of signs and symptoms

• A disease that affects many domains of human functioningCOGNITIONEMOTIONINTERPERSONAL RELATIONSHIPSDebilitating: 25-60% live with relatives•10-20% are homeless -

Epidemiology

• 2.2 million people have schizophrenia at any given time• One year prevalence rates are 1-4.6%• Prevalence rates are roughly stable across a range of

populations and cultures• Persons with schizophrenia in developing countries may

have a better course and prognosis• Persons with schizophrenia are less likely to marry

(particularly males) and less likely to complete higher education

• Between 14-20% of those with schizophrenia are employed competitively

Onset and Course of Illness

• Onset typical in late adolescence or early adulthood• Prodromal period or changes in mood and behavior prior to first break

may last up to five years• Early versus late onset illness• Early signs date back to childhood

– Deficits in verbal memory– Deficits in attentional vigilance– Deficits in gross motor skills– May be additional interpersonal difficulties or other difficulties in

functioning– Early conduct disorder may also be prodromal– Early signs may be subtle, irregular, and graduate and more

apparent in adolscence

Factors Assoc. with Better Prognosis

• Good premorbid adjustment• Acute onset• Later afe at onset• Being female • Precipitating event• Associated mood disturbance• Brief duration of active phase symptoms• Good interepisode functioning• Minimum residual symptoms• Absence of structural brain abnormalities• No family history of schizophrenia

SchizophreniaA. Two or more of the following during 1- month period (or less if successfully treated): (1) delusions* (2) hallucinations* (3) disorganized speech (frequent derailment or incoherence) (4) grossly disorganized or catatonic behaviour (5) negative symptoms (affective flattening, alogia, avolition)

B. Social Occupational Dysfunction

C. Duration: at least 6 months, with 1 month of active phase symptoms (or less if successfully treated) May include Prodromal/Residual periods

Schizophrenia (con’t)

D. Schizoaffective and Mood Disorder exclusion

C. Substance/general medical condition exclusion

E. Relationship to a Pervasive Developmental Disorder

Specify course:Episodic with Interepisode Residual Symptoms - with prominent negative symptomsEpisodic with No Interepisode Residual Symptoms - continuous (prominent psychotic symptoms) - with prominent negative symptomsSingle Episode in Partial Remission - with prominent negative symptomsSingle Episode in Full RemissionOther or Unspecified Pattern

Differential Diagnosis of Psychosis

• Mood Disorder with Psychotic features

• Prolonged Substance Abuse

• Brain Damage

• Infections

• Neurohereditary Disorders

• Nutritional Abnormalities

Positive Symptoms

Positive Symptoms

Hallucinations Delusions

Auditory Visual Somatic Olfactory

Thought withdrawal Thought insertion Thought broadcasting Persecutory Grandiose Religious Somatic Reference Being controlled Mind reading Guilt or sin

Disorganized Symptoms

Disorganized Symptoms

Thinking & Speech Behavior

Derailment Tangentiality Incoherence Circumstantiality Pressure of speech

Distractible speech Clanging Illogicality

Clothing & Appearance Social & Sexual Aggressive & Agitated Ritualistic or Stereotyped

Negative Symptoms

Negative Symptoms

Primary Secondary

Alogia

Affective blunting/flattening

Avolition

Anhedonia

Attentional impairment

Side effects of neuroleptic drugs

Demoralization and depression

Chronic institutionalization

lack of stimulation - withdrawal & apathy

Withdrawal as a response to delusions and/or hallucinations

Schizophrenia Subtypes

• Can change over the course of the illness

• Catatonic Type

• Disorganized Type

• Paranoid Type

• Undifferentiated Type

• Residual Type

Catatonic Type

Clinical Picture is dominated by at least two of the following:

(1) motoric immobility as evidenced by catalepsy

(2) excessive motor activity

(3) extreme negativism

(4) peculiarities of voluntary movement

(5) echolalia or echopraxia

Disorganized Type

Following criteria are met:

A. All of the following are prominent:

(1) disorganized speech (2) disorganized behaviour (3) flat or inappropriate affect

B. The criteria are not met for Catatonic Type

Paranoid Type

Following criteria are met:

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

B. None of the following is prominent: disorganized speech disorganized or catatonic behaviour flat or inappropriate affect

Undifferentiated Type

Type of Schizophrenia where symptoms:

(1) Meet Criterion A

(2 Are not met for the Paranoid, Disorganized or Catatonic type

Residual Type

Following criteria are met:

A. Do not fit into an other categories

B. Evidence of a disturbance as indicated by: presence of negative symptoms or two or more symptoms listed in Criterion A

Schizophreniform Disorder

• Criteria A, D, and E of Schizophrenia are met

• An episode of the disorder (including prodromal, active and residual phases) lasts at least 1 month but less than 6 months. “Provisional” when without recovery

• Specify if: Without Good Prognostic Features With Good Prognostic Features

Schizoaffective Disorder• Uninterrupted period of illness where there is either: Major Depressive Episode, Manic or Mixed concurrent with symptoms meeting Criterion A for Schizophrenia Major depressive episode must meet A1 criterion

• During illness, two week period of delusions or hallucinations in absence of prominent mood symptoms

• Symptoms meeting criteria for mood episode present for substantial period of the total duration of illness

• Not better accounted for substance use or general medical condition

Specify Bipolar or Depressive Type

Delusional DisorderA. Nonbizarre delusions of at least 1 months duration

B. Criterion A for Schizophrenia has never been met

C. Functioning is not markedly impaired or bizarre

D. If there are mood episodes concurrent with delusions, their total duration is brief relative to periods of delusional periods.

E. Not due to effects of substance or a general medical condition

Delusional Disorder (con’t)Specify type:

• Erotomanic Type: another person, usually of higher status in love with the person

• Grandiose Type: inflated worth, power, knowledge, identity

• Jealous Type: unfaithful theme

• Persecutory Type: Conspiracy theme

• Somatic Type: Physical defect theme

• Mixed Type: more than one of the above

• Unspecified Type: cannot be determined

Comorbidity

• Depression is very common with a comorbidity rate of 45%• Approximately 10% of those with schizophrenia die from the

illness though more recent estimates have lowered this to 4-5.6%

• Suicide risk is greater with mood and substance use disorders• Anxiety disorders have a high rate of comorbidity (43%) and

may prompt the formation and maintenance of persecutory delusions and hallucinations

• Lifetime comorbidity for substance use disorders is 50%• Associated symptoms also include anger, hostility, and social

avoidance

Violence and Associated Issues

• Rates of violence for persons with schizophrenia are lower than rates for persons with depression or bipolar disorder

• If violence occurs it is typically a result of the co-occuring substance use

• Rates of victimization risk can be very high• 34%-54% report childhood sexual or physical

abuse• 43%-81% report some type of lifetime

victimization

Sex differences in Illness Course

• Women have later age at onset

• Women have better premorbid histories

• Women express more affective symptomatology

• Women exhibit more benign course in terms of hospitalizations and social functioning

• Women appear to have less structural brain damage

• Males appear to have a higher incidence of the illness

Importance of Estrogen

• Pregnancy confers protective advantage

• Postpartum increased risk for psychotic symptoms

• Psychotic symptoms increase when estrogen levels are lowest during menstrual cycle

• Hormone supplements appear to offset psychotic symptoms during the menstrual cycle

ETIOLOGY

Biological

• Genetics

• Linkage Analysis

• Genetic Markers

• Heritability

• Twin Studies

• Adoption Studies

Brain Abnormalities

• Enlarged Ventricles

• Frontal Lobe

• Hypofrontality

• Temporal Lobe

• Neurochemical

Brain Abnormalities

Structural Brain Abnormalities Functional Brain

Abnormalites

CT and MRI image brain anatomy in living subjects.

Enlarged ventricles suggest brain tissue volume is reduced.

Reduced brain volume and cortical grey matter volume

Reduction of thalamus

Enlargement of the basal ganglia

SPECT and PET image brain physiology in living subjects.

Hypofrontality

Brain circuitry involved in hallucinations

Inactivity of cingulate cortex while performing a language task

Psychological Factors

Expressed Emotion: Jill Hooley

-Concerns the degree to which family members are either critical of a recently hospitalized patient, hostile, or express overinvolved and overprotective attitudes toward the patient. This construct is thought to reflect disturbances in the organization, emotional climate, and transactional patterns of the entire family system

-Assessed in the Camberwell Family Interview and usually takes 1-2 hours

-Most important element of EE is criticism-EE is a reliable risk factor for relapse in schizophrenia

Diathesis/Personality/Stress: Schizophrenia

DiathesisHeterogeneity within the etiology

DA involvement but complex; DA receptor sensitivity?

Enlargement of Ventricles, particularly for males

Polygenic vulnerability

Hypofrontality, particularly for negative symptoms

Severe birth complications

Viral infections

PersonalityPsychoticism historically but New data on Neuroticism

Schizotypal personality

In childhood lower scores on intelligence and ach

In childhood less responsive in social situations

In childhood more diff with motor dev

Escalating adjustment diff, dep, social withdrawal, irritability, noncompliance

Stressor

> Family based communication deviance

Expressed emotion assoc with increased risk of relapse; critical and overinvolved (effect size .31)

Severe prolonged stressors studied

High rates of criterion A stressors