Chapter 11:Schizophrenia and the Psychosis

Spectrum

Hanan D. Trotman

Vijay Mittal

Kevin D. Tessner

Elaine F. Walker

DSM-5 Criteria for Schizophrenia

Two or more of these symptoms must be present for at least one month (can be less if being successfully treated)

And at least one symptom must be either (1), (2), or (3)(1) Hallucinations (2) Delusions (can be either bizarre or nonbizarre)(3) Disorganized speech (e.g., frequent derailment or incoherence)(4) Grossly disorganized or catatonic behavior(5) Negative symptoms (e g., affective flattening, alogia or avolition).

Continuous disturbance for 6 months (attenuated symptoms, residual symptoms)

Social or occupational dysfunction (or both) for significant portion of the time

Notes: Catatonia can also be used as a specifier for any other diagnosis

DSM-5: Other Schizophrenia Spectrum Disorders

Schizophreniform disorder- Symptoms do not meet the six-month criterion. This is frequently met prior to the diagnosis of schizophrenia

Schizoaffective disorder- Hybrid between mood disorders and schizophreniaAt some points, meets for both mood episode and main schizophrenia

symptomsDelusions and/or hallucination present without mood episode for 2 or

more weeks over lifetimeMood episode symptoms present majority of the time

Delusional Disorder-in DSM-5 delusions need not be

bizarre

Diagnosis: Other Schizophrenia Spectrum Disorders

Schizophreniform disorder- Symptoms do not meet the six-month criterion. This is frequently met prior to the diagnosis of schizophrenia

Schizoaffective disorder- Hybrid between mood disorders and schizophreniaAt some points, meets for both mood episode and main schizophrenia

symptomsDelusions and/or hallucination present without mood episode for 2 or

more weeks over lifetimeMood episode symptoms present majority of the time

Delusional Disorder-in DSM-5 delusions need not be

bizarre

Diagnosis: Other Schizophrenia Spectrum Disorders

Schizophreniform disorder- Symptoms do not meet the six-month criterion. This is frequently met prior to the diagnosis of schizophrenia

Schizoaffective disorder- Hybrid between mood disorders and schizophreniaAt some points, meets for both mood episode and main schizophrenia

symptomsDelusions and/or hallucination present without mood episode for 2 or

more weeks over lifetimeMood episode symptoms present majority of the time

Delusional Disorder-in DSM-5 delusions need not be

bizarre

Diagnosis: Comorbidity

Majority experience episodes of major depression before onset

Substance abuse: ~47% of patients in the community and ~90% in prison settings meet lifetime criteria

Schizotypal Personality Disorder (SPD): no change in DSM-5

Symptoms: Social anxiety and withdrawal, affective abnormalities, eccentric behavior, unusual ideas (e.g., belief in ESP), and unusual sensory experiences (e.g., confusing noises with people’s voices)

Unusual ideas and perceptions are not severe or persistent enough to be delusions or hallucinationsHowever, recurring and atypical of the person’s culture

Increased risk for developing schizophrenia

Symptoms: Positive Versus Negative Symptoms

Positive symptoms: Involve an excess of ideas, sensory experiences, or behavior. Psychotic symptoms, hallucinations, delusions, and bizarre behaviors

Negative symptoms: Involve a decrease in behavior, such as blunted or flat affect, alogia and avolition 

Probably involve different neural mechanisms

Symptoms: Cognitive Deficits

Deficits on a broad range of mental tasksSimple sensory processingAttentionAbstract thinking

Cognitive deficits may be the core feature of the illness

Symptoms: Social Cognitive Deficits

Pervasive and persistent impairment in comprehending and solving social problems

Less able to label facial expressions of emotion

Basic cognitive impairments correlated, but do they not fully explain social deficits

Epidemiology

Usually first diagnosed between 20 and 25 years of ageMales about 4 years earlier than females

Lifetime prevalence of schizophrenia around 1% in both industrialized and nonindustrialized societies

Prognosis

Schizophrenia is among the most debilitating of mental illnessesThe majority experience repeated episodes of illness even with

treatment 20% to 30% able to live independently and/or maintain a job Higher rate of early morbidity than the general population Suicide is leading cause of death: 25%–50% attempt suicide and

4%–13% successfully commit suicide 

Negative predictors: More severe negative symptoms, longer duration of untreated psychosis, being male, gradual onset, early age of onset, poor premorbid functioning, and a family history of schizophrenia

Etiology: Childhood

Children who later develop schizophrenia usually have childhood deficits in several areas

Cognitive Score worse on tests of intelligence and achievement Poorer grades in school

Social Less responsive in social situations Exhibit less positive emotion Abnormal gestural behavior Poorer social adjustment

Motor Delays and abnormalities in motor development Late acquisition of early motor milestones such as bimanual manipulation and

walking Mood

Feelings of depression, social withdrawal, irritability, and noncompliance 

Etiology: Premorbid Period

Behavioral risk indicators often exist prior to the onset of schizophrenia Subclinical positive and negative symptomsFunctional decline (e.g., impaired attention, depressed mood,

and decreased school performance)

~20%–40% of individuals meeting prodromal syndrome criteria develop a psychotic illness within 3 years

The onset of the first episode of schizophrenia may be sudden or gradual

Etiology- Diathesis Stress Model

Development of the disorder requires a preexisting constitutional diathesis with subsequent exposure to stressors

Diathesis- Both inherited and acquired factorsInherited factors are genetically determined

characteristics of the brain that influence its structure and function.

Acquired vulnerabilities result from genetic mutations or prenatal events and delivery complications that compromise fetal brain development

Etiology- Diatheses

Obstetric Complications (OCs)Toxemia, preeclampsia, and labor + delivery

complicationsOCs associated with oxygen deprivation most strongly

linked with later schizophrenia

Psychosocial Stress during PregnancyStressful events during pregnancy are associated with

greater risk or schizophrenia and other psychiatric disorders in adult offspring.

Prenatal stress triggers the release of maternal stress hormones, which can disturb fetal neurodevelopment

Etiology- Diatheses

Risk elevated for individuals born shortly after a flu epidemic or prenatally exposed to rubella

Critical period between the fourth and sixth months of pregnancy. Nutritional deficiency during this period increases risk

Season-of-birth effect- disproportionate number born during the winter monthsMay be explained by increased viral exposure

Etiology- Stressors

Stressors- Influence the expression of the vulnerability. Some brain maturational processes after puberty play

important roles in triggering the clinical expression of latent vulnerability to schizophrenia

Examples of stressors include:Psychosocial stressor (e.g., death of a loved one)Cannabis useSocial/Cultural Discrimination

Etiology- Family Factors

Expressed emotion (EE)- communications that are critical, negative, or emotionally over-involved

Schizophrenia patients who live with family members who express high levels of EE are more likely to relapseE.g., 9 month relapse rate: 50% patients returning to high

EE vs. 15% low EE

Etiology- Neuropathology

While many structural and functional brain abnormalities have been found, none are:Unique to schizophrenia or Characterize all schizophrenia patients

Neurocircuitry dysfunction resulting from abnormalities in connectivity among brain regions may be the substrate for psychotic symptoms

Etiology- Neuropathology

Enlarged brain ventricles, especially the lateral ventricles

Decreased volume in frontal and temporal lobes, thalamus, hippocampus, and whole brainThalamus and hippocampus changes appear to be

progressive in nature beginning prior to illness onsetDiffusion Tensor Imagery (DTI)- measures the

strength and direction of water diffusion in white matter. Suggests axonal damage or demyelination in individuals

with and at risk for schizophrenia

Etiology: Heritability

The genetically closer the biological relative with schizophrenia, the greater the riskConcordance rate of monozygotic (MZ) twins: 30%-50% Rate of dizygotic (DZ) twins:12% to 17 %

Adopted children whose biological parents have schizophrenia have higher rates of schizophreniaCannot be explained by “schizophrenogenic mother” or

other similar hypotheses

Etiology: Genetic Hypotheses

Common disease common variant hypothesis: Schizophrenia arises from common genetic variationNo single gene or allele has a major impact on risk status

Mutation hypothesis: Schizophrenia may result from multiple rare variants that can arise from spontaneous, or de novo, mutations not present in the biological mother or father, especially copy number variations

Epigenetics: Potentially heritable changes in gene expression that are not due to changes in DNA sequenceEpigenetic profiles differentiate psychotic patients from controls

Etiology: Dopamine Hypothesis

Initial support for the role of dopamine in schizophreniaDrugs that reduce dopamine activity (e.g., antipsychotics)

also serve to diminish psychotic symptomsDrugs that heighten dopamine activity (e.g., cocaine)

exacerbate or trigger psychotic symptoms

Dopamine is used widely in the brain Used especially in the circuits that link subcortical with

cortical brain regionsAntipsychotic drugs work by the D2 dopamine receptor

subtype prevalent in subcortical regions of the brain

Etiology: Glutamate Hypothesis

There is diminished glutamate signaling in schizophrenia patients

Blockade of NMDA receptors (a type of glutamate receptor) produces symptoms in normal subjects, including negative symptoms and cognitive impairments not seen with dopamine agonistsPhencyclidine (PCP) and ketamineDrugs that indirectly enhance NMDA receptor function

can reduce negative symptoms and improve cognitive functioning in schizophrenia patients

Etiology: Hybrid Neurochemical Theories

There are reciprocal connections between forebrain dopamine projections and systems that use glutamate

Dysregulation of one system would be expected to alter neurotransmission in the other

Etiology: Cannabis

D-9-tetrahydrocannabinol (C-9-THC): Principal active ingredient of cannabis Increases risk for psychosis by augmenting dopamine

neurotransmission and stress hormone releaseMechanism for how it causes biological effects currently

unknown

Treatments: First-Generation Antipsychotics

Primary biological treatment of schizophrenia is antipsychotic medication

Typical antipsychotics act by decreasing dopamine activity via receptor blockadeThey can also induce movement disorders—most notably

tardive dyskinesia

Treatments: Second-Generation Antipsychotics

All block dopamine neurotransmission to some extent, however, they vary in the extent to which they affect serotonin, glutamate, and other neurotransmitters

Efficacy with positive symptoms at least as good as first generation antipsychotics typicalMixed evidence about whether more effective for

negative symptoms and cognitive impairments

Treatments: Second-Generation Antipsychotics

Significant side effects: Metabolic syndrome, substantial weight gain/obesity, new onset or worsening of diabetes mellitus, and lipid abnormalitiesLower risk of movement problemsUse during schizophrenia prodrome is controversial

Clozapine is effective for treatment-resistant schizophrenia; however, it has unique and significant side effects (e.g., agranulocytosis and seizures)

Treatments: Medication Compliance

60% of first episode patients relapse after 1 year without receiving active treatment

Injectable, long-lasting (depot) antipsychotic medication may be administered every 2 to 4 weeks Decreased rates of relapse especially evident for first

episode patients.

Psychosocial Treatment: Family Therapy (FFT) and CBT

FFT: Improves family members’ knowledge of and coping with schizophreniaTeaches communication techniques to reduce negative EEReduces relapse rates by as much as 50%

CBT: Uses standard CBT techniques during nonpsychotic periods to deal directly with symptomsChallenge positive symptoms and promote functional

behaviorsReduces symptom severity, though less effective with

long-term/chronic patients