schizophrenia: epidemiology and aetiological theories mrcpsych lep module: psychosis-1
TRANSCRIPT
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Schizophrenia: Epidemiology and Aetiological theories
MRCPSYCH LEP MODULE: PSYCHOSIS-1
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Contents
o Epidemiologyo Methodological problems
o Epidemiological statistics
o Aetiological theorieso Current hypotheses
o Genetics
o References & Further reading
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Epidemiology – methodological problemso 1st: Lack of diagnostic uniformity.
o Improved with the advent on DSM-IV & ICD-10 combined with standardised interview e.g. Present State Examination (PSE), etc.
o Good reliability but issues with validity.
o 2nd: Case finding
o Most common- clinical case detection from hospital admission data, population surveys and follow-up studies of birth cohorts
o Various biases, pros and cons of each method
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Epidemiologyo Schizophrenia is a disorder with a low incidence but a relatively high prevalence. It is fairly
evenly distributed around the globe.
oAnnual incidence – between 0.17 and 0.54 / 100 population {using broad definition}
- 2 to 3 times lower using DSM-IV or ICD-10 criteria
oAge of onset: usually 15-45 yrs (but may start at any age)
o Occurs equally in men and women but mean age of onset is about 5 years earlier in men. Peak onset in men is 20-24 age group but female onset is more common with increasing age.
o Prevalence: 1.4-4.6 /1000 of the population at risk (Data from 23 prevalence studies between 1931-1999, Jablensky 2003)
o Worldwide lifetime prevalence is approximately 1%
[Shorter Oxford Textbook of Psychiatry, 4th Ed. & Seminar Series, General Adult Psychiatry, 2nd Ed]
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Epidemiologyo The literature is divided on the question of whether lower socio-economic group
is a risk factor for Schizophrenia.
o Current literature emphasises a true urban effect: a high proportion of patients are born in inner cities or deprived areas and they do not merely drift into them.
o Urban effect is a complex interplay of factors related to genes, selective migration into and out of cities, possibly over several generations, cultural and socio-economic factors e.g. higher rates of social deprivation and dysfunctional families within urban areas; the interplay possibly occurs early in life or even in utero rather than at the time of illness onset.
o Studies from different countries show that immigrants tend to have a higher risk of Schizophrenia than the general population of either their native or their adopted country.
[Seminar Series, General Adult Psychiatry, 2nd Ed]
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Epidemiology Family member affected Risk
Identical twin 46%
One sibling/ fraternal twin 12-15%
Both parents 40%
One parent 12-15%
One grandparent 6%
No relatives affected 0.5-1%
Schizophrenia liability based on affected relatives
[Oxford Handbook of Psychiatry, 2nd Ed]
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Mortality
o SUICIDE is the most common cause of premature death in Schizophrenia- 10-38% of all deaths in Schizophrenia.
oHighest risk probably in the year after 1st presentation
[Oxford Handbook of Psychiatry, 2nd Ed]
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Aetiological theories
oNo ‘unified theory’ of Schizophrenia yet
oNeurodevelopmental hypothesis
oNeurochemical abnormality hypothesis
oDisconnection hypothesis
oThere are other (historical) theories as well but they lack scientific evidence
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Neurodevelopmental hypothesis
oExcess of obstetric complications
oMotor and cognitive problems precede the onset
oAbnormal cerebral structure at first presentation
oDermatoglyphic and dysmorphic features
oPossibly acquired in utero – abnormal brain but absent gliosis
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Neurochemical abnormality hypothesisoNot fully attributable to any single neurotransmitter abnormality
oDopaminergic overactivity
oGlutaminergic hypoactivity
oSerotonergic (5HT) overactivity
oAlpha- adrenergic overactivity
oGABA hypoactivity
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Disconnection hypothesisoSPET, PET, fMRI scans
oWidespread reduction of grey matter (particularly temporal lobe)
oDisorder of memory and frontal lobe function on a background of widespread cognitive abnormalities.
oReduced correlation between frontal and temporal blood flow on specific cognitive tasks
oReduction in white matter integrity in tracts connecting the frontal and temporal lobes
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Genetics o Linkage studies - family based analyses that utilize genetic markers and the information from
multiple affected individuals present in a given family to identify linked regions of the genome that is, regions co-inherited or segregating with the disease.
o Candidate gene association studies [Hypothesis: common diseases are a result of interactive contribution of common variants with small effect sizes and the susceptibility alleles will be shared by a significant proportion of unrelated affected individuals].
o GWAS – Genome wide association studies (with individual genotyping or using DNA pooling) to identify SNPs (Single Nucleotide Polymorphisms)
o Studies to identify CNVs (Copy Number Variations)- submicroscopic deletions or duplications stretching from a few kilobases to several megabases covering several or many genes. E.g. velocardiofacial/DiGeorge (VCFS) syndrome region (22q11)
o GxE studies: Gene-environment interaction studies
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Major Schizophrenia candidate genes
Gene Locus Function Meta-analysisCOMT 22q11 Catecholamine metabolism ++DAOA (G72) 13q32-34 D-serine metabolism ++DISC1 1q42 Neurodevelopment and synaptic function +++DRD2 11q23 Dopamine signalling ++DTNBP1 6p22 Neurodevelopment and synaptic function +++++GABRB2 5q32 GABA signalling ++++GRIN2B 12p12 Glutamate signalling ++NOTCH4 6p21.3 Neurodevelopment +++COMT= Catechol-O-methyltransferase; DAOA (G72) = D-amino acid oxidase activator; DISC-1=Disrupted in schizophrenia 1; DRD2= Dopamine receptor 2; DTNBP1=Dystrobrevin binding protein 1; GABRB2=Gamma-aminobutyric acid (GABA) A receptor, beta 2; GRIN2B=Glutamate receptor, ionotropic, N-methyl D-aspartate 2B; NOTCH4= Notch homolog 4 (Drosophila); ‘+’ indicates strength of association.
Tiwari AK, et al (2010)
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References & Further Reading
o Gelder M, Andreason N, Lopez-Ibor J, Geddes J (Eds.) 2012. New Oxford textbook of Psychiatry. Oxford University Press.
o Stein G & Wilkinson G (Eds.) 2007. Seminars in General Adult Psychiatry (2nd Ed). The Royal College of Psychiatrists. Gaskell, London.
o Semple D & Smyth R (Eds.) 2013. Oxford Handbook of Psychiatry. Oxford University Press.
o Tiwari AK, Zai CC, Muller DJ, Kennedy JL (2010) Genetics in Schizophrenia: where are we and what next? Dialogues Clin Neurosci 12(3) 289-303.