Epidemiological and genetic theories of schizophrenia. Who global burden o disease family studies, twin and molecular studies. kretschmer body build theory and risk of schizophrenia

1. DR OLANIYI A.C
REGISTRAR,
MENTAL HEALTH DEPARTMENT, OAUTHC ILE-FE.

2. Introduction
Epidemiology
Incidence
Prevalence
Epidemiological differences and similarities. Developing vs
developed nations
Morbidity, mortality burden
Genetics
Conclusion

3. What is epidemiology
Schizophrenia – low incidence, high prevalence.
0.16 – 1 / 1000 population – incicendence
Prevalence – 1% in general population
BUT : incidence – higher in – developed nations than
developing.
 reason – migration from developing to developed.

4. low
Annual incidence - 0.16 to 1.0 / 1000
Mcgrath et al (2008) & kirkbride (2012) - showed a skew in
incidence. More in specific population group.(Migrant).
This finding contradicts JABLENSKY et al 1992 conclusion
from WHO ten country study -- INCIDENCE & PREVALENCE
are similar in all population group.
Current meta-analysis (Mcgrath et al) - incidence is higher in
developed nation than developing.

5. High, very low complete recovery.
1% in general population
Lifetime prevalence (simeone et al 2015) 5/1000 population.

6. All life stages. Childhood - old age.
Common between 15years - 54years. less likely < 5years
Early onset in males, late onset in females (Oestrogen
protective effect)
2 peaks : 20years and 33years
Median age of onset. 28years - male; female 32years
Male : Female - 1.4 : 1

7. Fertility – Decreased – both gender.
Reason – difficulty initiating, maintaining intimate
relationship. Why? – deficit theory of mind– makes reciprocal
social interaction and communication difficult.
2. social isolation, instituitionalization.
3. hyper-prolactinemia due to antipsychotics esp atypicals
and haloperidol
 Erectile and sexual dysfunction.--- antipsychotics.

8. DEVELOPING VS DEVELOPED CULTURE
Cultural diff in aetiology
Cultural diff in outcome
Aetiology – developing nation – infectious dx/ nutritional
disorder inclination
Developed nation – aetiology – unknown

9.  2 WHO studies.
 A. IPSS – (Nigeria Colombia india) studied developing nations .
Compared to developed nation, Esp- Europe.
 Result – Developing nations – better outcome > developed
nations.
 CRITICS : - developed nation had facilities so might have over-
captured chronic cases.
 While developing nations captured acute cases since they
wouldn’t have admitted lots of chronic cases.

10. So; Anoda study done – WHO ten country study.
Confounding factors – eliminated. : BY
1. They capture only first episode
2. cases didn’t met diagnostic criteria, excluded.
E.g first episode < 1month, substance use, comorbid physical
illness.
All captured ptx (developing and developed) – followed up.

11. RESULT – Developing – better outcome > developed
countries.
Observed factors responsible for this better outcome in
developing nations/culture.
1. being married/cohabiting with a partner
2. access to supportive network esp friends and
extended/compound family type.
3. kinship relationship. Etc

12. Observed negative factor across all cultures – EE.
Yet this is more pervasive in developed cultures esp western
world.

13. 1990 WHO – GBD study – DALY = disability-adjusted life
year.
1 DALY = 1yr of health lost due to a disease in a population
from 1. disability 2. mortality 3. handicapping. Caused by the
disease.
GBD shows – Schiz has the 3rd highest DALY.
Comorbidities – Communicable and Non communicable

14. Communicable – HIV, TB, Hb
Non communicable – CVD, diabetes, metabolic syndrome,
Depression and suicide.
Mortality – currently due to – CVD – Suicide – Accident.

15. GENETIC STUDIES
Family studies
Twin studies
Adoption studies
Molecular genetic studies
GWAS
CNV

16. Rudin (kraepelins student) - first significant family
study.
Dementia praecox more common in relatives of
probands.
Recent study (Gottesman et al 1991): metanalysis of
diff family study. Concluded - symptoms present in
different levels/class of relatives of probands.

18. Observed familiar distributuin of schizophrenia + disorder
with schizophrenial-like psychosis among diff classes of
relatives.
This reinforces the idea - Schizophrenia spectrum disorder.

19. First significant study - 1920s by LUXENBERGER.
Findings: MZ > DZ concordance.
inkeepin with Gottesman 40-50% heritability
MZ/DZ co-twin with no expression. Show the expression in
their offsping. Confirming heritability.
Inaddition the risk of schizophrenia is shared equally among
these offspring
non expression in the co-twin may be related to
environmental factors.

20. Heston 1966; followed up 47 babies born to parent(s) with
schizophrenia and separated from them at 3rd day of life. to
a different family with no family history of schizophrenia.
Findings, at 36years of age- about 10% developed
schizophrenia.
Peterson & sorenson 2011 published findings from Danish
study of 1960.
Adoptees with schizophrenia and control were studied for
schizophrenia in biological parents. Result were consistent
with 1966 Heston study.

21. Currently no particular gene has been directly link to causing
schizophrenia
But evidence suggest multiple genes(hundreds-thousands)
with small effects.
3 types of genetic variations now applicable to schizophrenia :
Single nucleotide polymorphism
Copy Number variants
Rare Variants

22. Responsible for many of the gentic risk for schizophrenia
Currently 108 genetic loci identified to be of signicficant
causal relation to schizophrenia.(2014 psychiatry genomic
consortium).
these SNPs involve genes coding for Dopamine D2,
glutamate receptors and Serotonine transporter.

23.  Are either deletion or duplication of part of chromosomes of genetic
material of at least 1kb in size.
 1st CNV deletion found – Chr 22q11.2 1976 == velocardioacial
syndrome, digeorge and sphintzen syndrome.
 Currently – 12 CNV identified.
 Compared to SNPs, CNVs carry more risk significance if present.
 NB:: CNV PENETRANCE???

25.  About 1/2 of CNV associated schizophrenia are inherited.
 Others are acquired de novo e.g in life. i.e parents of such
schizophrenia had no CNVs.
 This usually due to sporadic mutation.And such individal illness has
not been inherited.
 However development of his CNV/schizophrenia increases
heritability by offspring by 50%.
 NB: presence of CNVs for schizophrenia increases the risk for other
illness with psychosis.But with an exception Bipolar disorder.

26. These are SNPs or dinucleotide polymorphism in
individual genes.
There presence confers greater risk.
Identified till date is SETD1A mutation

27. Disrupted in schizophrenia 1 gene DISC-1 :
Translocation between chromosomes 1 and 11.
Dystrobrevin binding protein-1 Dysbindin P-1.
Neuregulin gene
Regulator of G-protein signaling-4

28. Study how these SNPs, CNVs and Rare variants
affect the brain neurochemistry and structure, to
ultimately culminate in the development of
schizophrenia.
1.Affectation of NMDA receptor mediated signalling,
synaptic plasticity, immune functioning.

29. The NMDA abnormality linked to dysregulation of
immune fuctioning. Evidence for this - mutation in
major histocompatibity complex on chr-6. lead to
autoimmune disorders and wide spread inflammation
observerd in some schiozphrenia.
2.CNVs deletion - reduced/impaired expression of the
affected gene. WHILE;
Duplication - Over/Excessive expression

30. Schizophrenia; epidemiologially is a chronic disorder
evidence by high prevalence, caused by reduce
likelihood of complete recovery.
Highly familiar, though no specific gene has been
directly linked as the sole aetiology.
Multiple genes of small effect but with greater
summating effects.