Chief Dr H.T.O. LADAPO, MD (Ukraine) FMC Psych.., FWACP, FHAN, MPH ( Unilag )

1. Mental Health CareChallenges in Management of Schizophrenia and other non affective psychosispresented by Chief Dr H.T.O. LADAPO, MD (Ukraine) FMC Psych.., FWACP, FHAN, MPH (Unilag)

2. Introduction (1) • Early Greek physicians described delusions of grandeur, paranoia, and deterioration in cognitive functions and personality. • Schizophrenia did not emerge as a medical condition worthy of study and treatment until the eighteenth century.

3. Intoduction (2) • Emil Kraepelin delineated insanity: manic-depressive psychosis and dementia praecox (or dementia of the young) • In 1911 EugenBleuler suggested the term schizophrenia (splitting of the mind) for the disorder.

4. Intoduction (3) • He also described four primary symptoms (the four As): abnormal associations, autistic behavior and thinking, abnormal affect, and ambivalence.

5. Intoduction (4) • Nondisease models: -The societal reaction theory ("a sane reaction to an insane world") -Thomas Szasz's theory which states that schizophrenia is a myth enabling society to manage deviant behavior

7. Epidemiology (1) • Schizophrenia is a leading public health problem that exacts enormous personal and economic costs worldwide. • Schizophrenia affects just under 1 percent of the world's population (approximately 0.85 percent).

8. Epidemiology (2) • NIMH’s Epidemiologic Catchment Area (ECA) study – lifetime prevalence 1.5% • International Pilot Study of schizophrenia (IPSS) • Determinant of Outcome studies by WHO (12 countries)

9. Epidemiology (3) • A 1987 review of over 70 prevalence studies of schizophrenia published since 1948 identified point prevalence in various population groups ranging from 0.06 percent to 1.7 percent, with lower rates in developing countries.

10. Epidemiology (4) • Life time risk ranges from 0.7% to 1.3% • The prevalence rate is similar in different cultures when assessed using similar instrument ( Jablensky et al 1992) • Exceptions include Slovenia, Western Ireland, Catholics in Canada and Tamils of Southern India

11. Epidemiology (5) • Low rates have been reported in the Hutterrites and the Anabaptist sects in the USA • Onset usually between the ages of 15 and 45 • Peak age in men 15 - 25years • Peak age in women 25 – 35 years

12. Risk factors • Genetic Factors • Ethnicity and Racial Factors • Age • Sex • Season and Birth Order • Birth and Fetal Complications • Social Class: ”downward drift” and “social causation” theories

13. Risk factors • Marital Status • Immigration • Urbanization and Industrialization • Life Stressors • Infections • Suicide Risk

14. Aetilogy (1) • Cause is unknown • Results from a complex interplay of genetic, environmental and social factors

15. Aetiology (2) Neurobiological model Structural abnormalities include: • enlarged lateral ventricles • enlarged third ventricle, and • reduced volume of a number of structures, including hippocampus, amygdala, and frontal and temporal cortices.

16. Aetiology (3) Genetic factors • Family studies • Twin studies • Adoption studies

18. Aetiology (4) Genetic factors • Putative schizophrenia susceptibility loci yielding some evidence of confirmation include loci on chromosomes 6, 8, and 22.

19. Aetiology (5) Neurobiology • blood flow to several brain regions, including prefrontal and temporal areas, is altered in schizophrenia. These changes may be related to or may underlie positive and negative symptoms as well as some cognitive deficits.

20. Aetiology (6) Neurobiology Biochemical basis of schizophrenia • Dopamine • Serotonin • glutamate

21. Aetiology (7) Dopamine hypothesis: • It postulates a hyperactivity of dopamine transmission at the D2 receptors in the mensecephalic projection to the limbic striatum (Synder et al. 1974)

22. Aetiology (8) Evidence in support of dopamine hyp. • There is a tight correlation between the therapeutic doses of conventional antipsychotic drugs and their affinities for D2 receptors (Seeman, 1987) • Indirect dopamine agonists can induced psychosis in healthy subjects and at very low doses provoke psychotic symptoms in schizophrenia (Carlsson 1988)

23. Postmortem and PET studies have shown increased dopamine D2 receptor level in the brain of schizophrenic patients (Wing et al, 1986) • There is also emerging evidence for a presynapticdopaminergic abnormality in schizophrenia (Laruelle et al 1999). • Existing literature suggested heritable abnormalities of prefrontal dopamine function are prominent features of schizophrenia (Egan et al, 2001)

24. Serotonin • Serotonin receptors are involved in the psychotomimetic and psychotogenic properties of hallucinogens [e.g (LSD)]; • the number of cortical 5-HT 2A and 5-HT 1A receptors is altered in schizophrenic brains;

25. 5-HT 2A and 5-HT 1A receptors play a role in the therapeutic and/or side­ effect profiles of atypical antipsychotics (e.g., Clozapine); • certain polymorphisms of the 5-HT 2A receptor gene are associated with schizophrenia; • the trophic role of serotonin in neurodevelopment may be usurped in schizophrenia;

26. 5-HT 2A receptor-mediated activation of the prefrontal cortex may be impaired in some schizophrenics; • serotoninergic and dopaminergic systems are interdependent and may be simultaneously affected in schizophrenia (Liebermann et al. 1998, Harrison 1999).

27. Glutamate • Potent non-competitive antagonist of the NMDA subtype of glutamate receptor (NMDA-R), induce schizophrenia-like symptoms in healthy individuals and worsen some symptoms in Schizophrenia (Hirayasu et al. 2001; Andreasen 1997). • Postmortem studies of schizophrenic brains additionally indicate abnormalities in pre and postsynaptic glutamatergic indices.

28. NMDA-R hypofunction in the cortical association pathways could be responsible for a variety of cognitive and other negative symptoms (Carlsson et al 2000). • It has been proposed that NMDA-R antagonist can cause excess compensatory release of glutamate that can over activate unoccupied non-NMDA glutamate receptors. This might in part be responsible for their behavioural effects.

29. The effects of inhibiting NMDA-R may manifest through dopamine neurotransmission as dopamine and glutamate systems in the central nervous system have both anatomical and functional inter relationship. • Finally, NMDA-R hypo function may also produce abnormalities in the neuroplasticity of neurons by altering synaptic connectivity.

30. Aetiology (9) • Neurodevelopmental hypothesis: posits that insults occuring in-utero or shortly after birth are responsible for the structural abnormalities which manifest in symptoms later in adolescence/adulthood

31. Evidence in support includes • Absence of gliosis despite evidence of neuronal loss • Evidence of impaired maturation, migration and pruning of neurons in schizophrenic brains • Cytoarchitectural abnormalities in medial temporal lobe

32. Aetiology (10) Environmental factors: • maternal bonding • early rearing • Poverty • immigration status • Stress • viruses.

33. Aetiology (11) Social factors • Culture • Migration • Residence • Social isolation • Occupation and social class

34. Aetiology (12) Psychosocial stresses: • experiencing life event in the preceding six months doubles the risk of developing schizophrenia (Paykel 1978) • There is however, no evidence that schizophrenics experience more life events than the general population

35. Aetiology (13) Family • Deviant role relationship: “schizophrenogenic mother” • Lidzs & Lidzs (1948) described marital schism and marital skew • Bateston et al, 1956 described Disorder family communications (Double bind theory)

36. Aetiology (14) Psychodynamic factors Mainly of historical interest • Freud's theory of schizophrenia • Melanie Klein’s theory

38. CLINCAL FEATURES DIAGNOSTIC CRITERIA • Schneider • Langfelt • New Haven Schizophrenia Index • St. Louis Criteria • Research diagnostic Criteria • Present State Examination (PSE) • ICD-10 • DSM • Positive vs. Negative symptoms

39. SCHNEIDERIAN FIRST RANK SYMPTOMS • Audible thoughts • Voices arguing or discussing or both • Voices commenting • Somatic passivity experiences • Thought withdrawal and other experiences of influenced thought • Thought broadcasting • Delusional perceptions • All other experiences involving volition, made affects, and made impulses

40. Second rank symptoms • Other disorders of perception • Sudden delusional ideas • Perplexity • Depressive and euphoric mood changes • Feelings of emotional impoverishment • “And several others as well”

41. DSM IV and ICD 10

42. Types • Type I schizophrenia was characterized by predominantly positive symptoms, good premorbid functioning, sudden onset, normal brain structures by computed tomography (CT), good response to treatment, and a better long-term course.

43. Type II schizophrenia was characterized mainly by negative symptoms, an insidious onset, poor premorbid functioning, abnormalities on CT scans, a tendency to drug resistance, and a poorer long-term course and outcome, often resulting in behavioral deterioration. (Tim Crow)

44. Other types • Paranoid • Hebephrenic/disorganised • Catatonic • Simple • Residual • undifferentiated

45. TREATMENT • Pharmacotherapy • Psychosocial intervention

46. Factors Influencing Antipsychotic Drug Selection

47. Psychosocial intervention • Individual psychotherapy • Group therapy • Family Therapy • Psychiatric Rehabilitation • Social Skills Training • Vocational Rehabilitation • Residential Treatment And Housing Programs

48. Features Weighing Toward Good to Poor Prognosis in Schizophrenia Good Prognosis Poor Prognosis Late onset Young onset Obvious precipitating factors No precipitating factors Acute onset Insidious onset Good premorbid social, sexual, Poor premorbid social, sexual, and work histories and work histories Mood disorder symptoms Withdrawn, autistic behavior (especially depressive disorders) Married Single, divorced, or widowed Family history of mood disorders Family history of schizophrenia Good support systems Poor support systems Positive symptoms Negative symptoms

49. Other features of poor prognosis • Neurological signs and symptoms • History of perinatal trauma • No remissions in 3 years • Many relapses • History of assaultiveness

50. Other psychotic Disorders • Delusional Disorders • Schizophreniform Psychosis • Reactive Psychosis • Schizo-Affective • Atypical-Folie a Deaux, culture bound syndrome, Capgras,Cotard,Fregoli • Schizotypal personality disorder • Postpartum psychosis