Genetics (4)The results of adoption studiesThe rate for Schizophrenia is greater among the2oftheSchizophreniabiologicalrelatives4Adoptees than among the relatives of control.-The finding supports the genetic hypothesis16
16 Genetics (4) The results of adoption studies – The rate for Schizophrenia is greater among the biological relatives of the Schizophrenia Adoptees than among the relatives of control. – The finding supports the genetic hypothesis
Molecular genetic studiesTwomainapproaches:1.linkageanalysisIt is applied to multiply affected families, but nolinkagemarkers havebeen clearlyidentified.2. Candidate gene approachesGenes for biological mechanisms that may beinvolved in Schizophrenia have been localized andcloned. Using this technique, a number of genescoding for DA and 5-HT receptors have beenexcluded from linkage to Schizophrenia in variouspedigrees17
17 Molecular genetic studies Two main approaches: 1. linkage analysis It is applied to multiply affected families, but no linkage markers have been clearly identified. 2. Candidate gene approaches Genes for biological mechanisms that may be involved in Schizophrenia have been localized and cloned. Using this technique, a number of genes coding for DA and 5-HT receptors have been excluded from linkage to Schizophrenia in various pedigrees
The neurodevelopmental hypothesisTheneurodevelopmentalhypothesissuggested that schizophrenia in which thepathological changes of the disorder are laiddown early in life, presumably through geneticinfluences, and then modified by maturational andenvironmentalfactors(Murray et al, weinberger 1987)18
18 The neurodevelopmental hypothesis The neurodevelopmental hypothesis suggested that schizophrenia in which the pathological changes of the disorder are laid down early in life, presumably through genetic influences, and then modified by maturational and environmental factors (Murray et al, weinberger 1987)
Some findings compatible with the neurodevelopmenthypothesis of schizophreniaNon-progressivestructuralbrainlesionsNon-progressivecognitiveimpairmentCytoarchitectural disturbances without gliosisCognitive and social impairments in childhood‘Soft'neurologicalsignsExcessofwinterbirths19
19 Some findings compatible with the neurodevelopment hypothesis of schizophrenia • Non-progressive structural brain lesions • Non-progressive cognitive impairment • Cytoarchitectural disturbances without gliosis • Cognitive and social impairments in childhood • ‘Soft’ neurological signs • Excess of winter births
Chang in brain structure in schizophreniaPost-mortemThe patient's brains are lighter and somewhat smaller*There is consistent enlargement of the lateral ventricle,particularly in the anterior and temporal horns this means areduction in volume of medial temporalstructures such as the hippocampus and parahippocampalgyrus.CT scan:enlarged cerebralventricles.MRl:reduction in the volume of temporalI lobe.Abnormalities have been found in frontal lobes, basalganglia,andthalamusSPECT20PET
20 Chang in brain structure in schizophrenia ❖Post-mortem ❖The patient’s brains are lighter and somewhat smaller ❖There is consistent enlargement of the lateral ventricle, particularly in the anterior and temporal horns ❖ this means a reduction in volume of medial temporal structures such as the hippocampus and parahippocampal gyrus. ❖CT scan：enlarged cerebral ventricles. ❖MRI: reduction in the volume of temporal lobe. Abnormalities have been found in frontal lobes, basal ganglia, and thalamus. ❖SPECT ❖PET