Schizophrenia and other psychotic disorders

1. Schizophrenia and other psychotic disorders Schizophrenia Schizophreniform Disorder Schizoaffective Disorder Delusional Disorder

2. 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.

3. Eugen Bleuler: Disturbances in process of the schizophrenias,1908 • Scizw, schism or split, + frenos, 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

4. 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

5. 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

6. 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

7. 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

8. Prodrome Active Phase Residual Phase Prodrome Active Phase Residual Phase Pro- drome Active Phase Residual Phase The syndrome duration • Total duration must be at least 6 months The active phase must last at least 1 month

9. 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

10. 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

11. 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

12. Two more types • Undifferentiated • Residual

13. 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.

14. 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)

15. Etiological factors • Inherited susceptibility or several genes are involved • Retrospective strangeness in childhood behavior • A stress trigger is implicated.

16. 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.

17. The Genain Quadruplets (Rosenthal, 1963) (Genain means dire birth) Hester, Nora, Myra, and Iris: NIMH

18. 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

19. 0 Evidence of brain damage

20. 0 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

21. 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.

22. 0 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

23. 0 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)

24. 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

25. 0 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)

26. 0 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

27. Other etiologies • Family causation • Psychoanalysis • Sociological theories • Labelling • Social degradation/social drift • Double bind hypothesis • R.D. Laing

28. 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

29. 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

30. Brief Psychotic Disorder The schizophrenias Schizo- phrenia Schizophreniform Disorder 1 2 3 4 5 6 >6 Months duration of symptoms

31. 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

32. Subtypes of Delusional Disorder • Erotomanic • Grandiose • Jealous • Persecutory • Somatic • Mixed

33. 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

34. A variant dopamine hypothesis

35. 0 Brain structures in schizophrenia Substantia nigra Nucleus accumbens (VTA)

36. Neurodevelopmental model (Weinberger, 1995) Prefrontal Cortex Basal ganglia (Limbic system) Mesocortical pathway Mesolimbic pathway Ventral Tegmental Area

37. Disorganized speech • aka Formal thought disorder • Incoherence • Loose associations • Derailment/distractibility • Perseveration

38. 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.”

39. 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.”

40. 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.”

41. 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.

42. Grossly disorganized or catatonic symptoms • “Other symptoms” (Davison & Neale) • Inappropriate affect • Bizarre behavior • Social blunders/residual rule-breaking • Treasuring trash • Immobility • Waxy flexibility

43. Negative symptoms • Behavioral deficits: • Avolition • Alogia • Poverty of speech • Poverty of speech content • Anhedonia • Flattened affect • Monotone; less facial expression of emotion • Asociality

44. 0 The brain with schizophrenia • MRI scans: • The left brain is normal, while the right brain is damaged.