Schizophrenia and other psychotic disorders

Schizophrenia

Schizophreniform Disorder

Schizoaffective Disorder

Delusional Disorder

Schizophrenia

Different from other disorders in that there is no essential feature.

Variety due to historical development of the diagnosis

Benedict Morel (1852): démence précoce Emil Kraepelin: Deteriorating course of

dementia praecox (1898)– Kraepelin grouped together dementia paranoides,

catatonia, and hebephrenia.

Eugen Bleuler: Disturbances in process of the schizophrenias,1908

, schism or split, + , mind. Bleuler emphasized the breaking of

associative threads, lack of purposeful direction, and distractibility

Observed that there was not always early onset or deteriorating course

More history of diagnosis

Kurt Schneider: Pathognomic symptoms– Emphasized the importance of

hallucinations and delusions in diagnosis Adolf Meyer (1917) and the American

experience– A more flexible approach with subtypes– Emphasized the process-reactive

dimension

A history of overdiagnosis

Hoch (1949, 1955) added pseudoneurotic schizophrenia and pseudopsychopathic schizophrenia.

Schizophrenia became a catch-all diagnosis, much more commonly diagnosed in the United States than in Great Britain.

DSM-III (1980) began to narrow the diagnostic criteria

DSM-IV diagnostic criteria

A screening test– http://www.schizophrenia.com/sztest/survey2.php

At least two characteristic symptoms:– +Delusions *– +Hallucinations *

* Only one symptom required if it is bizarre delusions or continually commenting or conversing auditory hallucinations

– +Disorganized speech– +Grossly disorganized or catatonic behavior– Negative symptoms

More diagnostic criteria

Significantly long-lasting marked impairment of social or occupational functioning or self-care.

Lasts for six continuous months, including at least one month of active phase symptoms

No major depressive, manic, or mixed mood episodes

The syndrome duration

Total duration must be at least 6 months

ProdromeProdrome Active PhaseActive Phase Residual PhaseResidual Phase

ProdromeProdrome Active PhaseActive Phase Residual PhaseResidual Phase

Pro-drome

Pro-drome Active PhaseActive Phase Residual PhaseResidual Phase

The active phase must last at least 1 month

Subtypes of schizophrenia

Five types: Paranoid, disorganized, catatonic, undifferentiated, residual

Paranoid type– Preoccupied with one or more delusions,

or– Frequent auditory hallucinations– Speech, behavior, and affect are not

prominently impaired

Disorganized type (formerly hebephrenic) Behavior and speech are disorganized

– Clang associations and neologisms– Complete neglect of appearance

Flat or rapidly changing inappropriate emotion

Not paranoid type

Catatonic type At least two of

– Motor immobility• Catalepsy• Waxy flexibility• Stupor

– Purposeless excess movement– Extreme negativism: Motiveless resistance,

rigidity, mutism– Strange movements: posturing,

stereotyped movements, grimacing– Echolalia or echopraxia

Not paranoid or disorganized type

Two more types

Undifferentiated Residual

Critique of DSM-IV types

Low diagnostic reliability Little predictive validity Considerable overlap Possible improvements:

– Positive/negative/mixed symptom types– Positive/negative/disorganized symptoms– It is easier to distinguish between types of

symptoms than types of patients.

Etiologies of schizophrenia

The etiology may be complex, due to– Broad set of symptoms– Positive and negative symptoms

Genetic factors in etiology– 1% of general population– 10% in first-degree relatives of probands– 45% in identical twins of probands– Same rate in children of probands (16.8%) as

in children of their non-schizophrenic identical twins (17.4%) (Gottesman and Bertelsen, 1989)

Etiological factors

Inherited susceptibility or several genes are involved

Retrospective strangeness in childhood behavior

A stress trigger is implicated.

What are the genes?

Dopamine hyperactivity is found in schizophrenia, but the genes for the five types of DA receptors found so far are not linked to schizophrenia (Coon et al., 1993)

However, Akil et al. (2003) found a link to the COMT genotype.– The COMT gene is polymorphic: met-met, val-met, and val-

val.– The val-val variant is associated with poor prefrontal

functioning.– The prefrontal cortex DA system normally inhibits the corpus

striatum DA.– Uninhibited, striatal DA produces the positive symptoms of

schizophrenia.

The Genain Quadruplets (Rosenthal, 1963) (Genain means dire birth)

Hester, Nora, Myra, and Iris: NIMH

Environmental factors in etiology

We will see that dopamine hyperactivity relates to the positive symptoms of schizophrenia.

The negative symptoms may be due to brain damage: Some people with no family history of schizophrenia or any related disorder develop schizophrenia

Evidence of brain damage

Prenatal damage factors: Epidemiology Incidence of schizophrenia increases

with:– season of birth: late winter/early spring– viral epidemics in second trimester

(Tsuang, 2000)– population density and latitude– malnutrition or refeeding after thiamine

deficiency (cf. Korsakoff’s syndrome)– prenatal stress: WW II widows’ offspring

More on brain damage

Cellular migration errors Monochorionic monozygotic twins

– More likely to be mirror-image twins– Monochorionic concordance: 60%– Dichorionic MZ concordance: 10.7%– DZ dichorionic concordance: 10%

Concordant MZ twins have nearly identical fingerprints and palm prints; non-concordant MZ twins do not.

Evidence of brain damage in schizophrenia Neurological symptoms

– Catatonia and facial dyskinesias– Unusual rates of blinking, staring– Avoidance of eye contact– No blink reflex to a tap on the forehead– Stopped speech w/ looking away, esp. to right– Jerky eye movements and poor visual

tracking– Interdependence of eye and head

movements– Impaired reaction of pupils to light changes

More evidence of brain damage

Structural symptoms– Doubling of size of lateral ventricles– Abnormalities in temporal and frontal lobes and in

medial diencephalon– Smaller anterior hippocampus: smaller neurons– Decreased gray matter in left temporal lobe– Damage to left temporal lobe in adults may

produce schizophrenia de novo– Low activity in prefrontal cortex (hypofrontality)

And still more evidence…

Abnormal cell pruning after puberty (Keshevan, Anderson & Pettegrew, 1994)– Excessive pruning in the prefrontal cortex (negative

symptoms)– Failure of pruning in some subcortical structures

(positive symptoms) Higher incidence of schizophrenia in people

who experienced birth complications: – Oxygen deprivation, drugs, infections, endocrine

disorders

Variant dopamine hypothesis

Hypofrontality lowers sustained release of DA in nucleus accumbens

Nucleus accumbens DA receptors become hypersensitive

Normal DA activity from VTA triggers positive symptoms of schizophrenia

Drugs which treat schizophrenia lower DA activity; increase Parkinsonism

D2 receptors are supersensitive in 70% of people with schizophrenia (Grandy, 2005)

Evaluation of the dopamine hypothesis Why is the antischizophrenic effect of

drugs delayed? Why do DA levels have to be reduced

below normal to treat schizophrenia? Some newer antischizophrenia drugs

affect serotonin and GABA More neurochemicals are probably

involved in such a complex disorder

Other etiologies

Family causation Psychoanalysis Sociological theories

– Labelling– Social degradation/social drift– Double bind hypothesis

R.D. Laing

Schizophreniform Disorder

Same symptoms as Schizophrenia, but lasts from 1 to 6 months

No decline in functioning is required for this diagnosis

If the symptoms last less than one month but more than one day, diagnose Brief Psychotic Disorder

Schizoaffective Disorder

A mood episode coincides with the active phase of schizophrenia

Hallucinations or delusions occur for at least two weeks before or after the mood episode

The schizophrenias

1 2 3 4 5 6 >6Months duration of symptoms

BriefPsychotic Disorder

BriefPsychotic Disorder

Schizophreniform Disorder Schizo-phrenia

Delusional Disorder

Non-bizarre delusions for at least one month

None of the other symptoms of schizophrenia

Behavior not directly affected by the delusions is normal

Subtypes of Delusional Disorder

Erotomanic Grandiose Jealous Persecutory Somatic Mixed

Shared Psychotic Disorder

An otherwise unaffected person shares the delusional beliefs of a person with a psychotic disorder

Usually found only in long-term relationships of dominant-passive partners

Social isolation seems to be a necessary feature

A variant dopamine hypothesis

Brain structures in schizophrenia

Nucleus accumbens(VTA)

Substantia nigra

Neurodevelopmental model (Weinberger, 1995)

Prefrontal

Cortex

Ventral Tegmental Area

Basal ganglia(Limbic system)Mesocortical

pathway

Mesolimbicpathway

Disorganized speech

aka Formal thought disorder Incoherence Loose associations Derailment/distractibility Perseveration

Disorganized speech 1

“Takes less place. Cat didn’t know what Mouse did and Mouse didn’t know what Cat did Cat represented more on the suspicious side than the mouse. Dumbo was a good guy. He saw what the cat did, put himself with the cat so people wouldn’t look at them as comedians. Cat and Dumbo are one and alike, but Cat didn’t know what Dumbo did and neither did the mouse.”

Disorganized speech 2

“Everyone should have a good laugh. Don’t cry over it. Don’t tell anyone -- they will tell someone. Appreciate it without criticism. A word like milk shouldn’t be mentioned.”

Disorganized speech 3

“So to beseech you as full as for it. Exactly or as kings. Shutters shut and open so do queens. Shutters shut and shutters and so shutters shut and shutters and so and so shutters and so shutters shut and so shutters shut and shutters and. So and so shutters shut and so and also. And also and so and so and also.”

Disorganized speech credits

Disorganized speech 1 and 2 are from a person with schizophrenia, quoted in Zimbardo’s Instructor’s manual for Psychology and Life.

Disorganized speech 3 is from a poem by Gertrude Stein.

Grossly disorganized or catatonic symptoms “Other symptoms” (Davison & Neale)

– Inappropriate affect– Bizarre behavior

• Social blunders/residual rule-breaking• Treasuring trash

– Immobility – Waxy flexibility

Negative symptoms

Behavioral deficits:– Avolition– Alogia

• Poverty of speech• Poverty of speech content

– Anhedonia– Flattened affect

• Monotone; less facial expression of emotion

– Asociality

The brain with schizophrenia

MRI scans: The left brain

is normal, while the right brain is damaged.