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Verbal fluency as a familial trait marker in schizophrenia: a twin fMRI study
NeuroImage
13, Number
6,2OOl,
Part 2 of 2 Parts 1 D Ealw
PSYCHIATRY
Verbal Fluency as a familial trait marker in schizophrenia: a twin fMRI study Marco M. Picchioni*, Vivienne A. Curtis*, Cynthia H.Y. Fu*, Farooq Ahmad?, Xavier Chit&*, Tiiothea Toulopoulou*, Nanda Vythelingum”, Chris Andrew*, Steven C.R. Williams*, Robin M. Murray*, Philip K. McGuire* *Institute of Psychiatry, De Crespigny Park, London, U.K. 7Brooklands Mental Health NHS Trust, Birmingham, U.K. Introduction: Twin studies provide a unique natural opportunity to quantify the relative influence of genetic and environmental factors on the aetiology of schizophrenia. Several functional imaging studies of word generation tasks have revealed abnormal fronto-temporal activation in people with schizophrenia. Word generation deficits have been investigated clinically as a familial trait marker in schizophrenia and demonstrated to be present in those at high genetic risk of the illness. We investigated genetic and non-genetic influences on these abnormalities by studying h4Z twin pairs varying in their concordance for schizophrenia with functional MRI.
Method: Twin pairs discordant for schizophrenia and healthy control twins were compared using a paced verbal fluency paradigm. Word generation cued by letters was contrasted with repetition of the word ‘Rest’ in a blocked AB design. T2* weighted images were acquired in 12 non-contiguous axial planes on a 1.5 Tesla GE Signa System with EPI capability. Overt responses were made during silent portions of the compressed acquisition sequence using TR=4OOOms. Activation maps in Talairach space were generated using established nonparametric methods.
Results: Compared to control twins, twins with schizophrenia demonstrated significantly attenuated activation in the superior and medial prefrontal cortex, the cingnlate gyrus, fusiform gyms and cerebellum. When the well twins (with a schizophrenic co-twin) were compared to control twins they demonstrated attenuated activation in the inferior temporal lobe and parahippocampal gyrus, the insula, caudate, cingulate gyrus and cerebellum. However, there were no differences in medial frontal activation. Comparison within discordant twin pairs showed surprisingly few differences in activation except in the cingulate gyms.
Conclusion: These initial results suggest that the expression of schizophrenia is associated with abnormal fronto-temporal activation during word generation, but that there may also be functional abnormalities in those at high genetic risk of the disorder. These abnormalities may represent non-psychotic or trait markers of the schizophrenia genotype. Other abnormalities, such as attenuated medial prefrontal activation, may represent abnormalities in schizophrenia that are more related to the phenotypic expression of the disorder.
S1086
13, Number
6,2OOl,
Part 2 of 2 Parts 1 D Ealw
PSYCHIATRY
Verbal Fluency as a familial trait marker in schizophrenia: a twin fMRI study Marco M. Picchioni*, Vivienne A. Curtis*, Cynthia H.Y. Fu*, Farooq Ahmad?, Xavier Chit&*, Tiiothea Toulopoulou*, Nanda Vythelingum”, Chris Andrew*, Steven C.R. Williams*, Robin M. Murray*, Philip K. McGuire* *Institute of Psychiatry, De Crespigny Park, London, U.K. 7Brooklands Mental Health NHS Trust, Birmingham, U.K. Introduction: Twin studies provide a unique natural opportunity to quantify the relative influence of genetic and environmental factors on the aetiology of schizophrenia. Several functional imaging studies of word generation tasks have revealed abnormal fronto-temporal activation in people with schizophrenia. Word generation deficits have been investigated clinically as a familial trait marker in schizophrenia and demonstrated to be present in those at high genetic risk of the illness. We investigated genetic and non-genetic influences on these abnormalities by studying h4Z twin pairs varying in their concordance for schizophrenia with functional MRI.
Method: Twin pairs discordant for schizophrenia and healthy control twins were compared using a paced verbal fluency paradigm. Word generation cued by letters was contrasted with repetition of the word ‘Rest’ in a blocked AB design. T2* weighted images were acquired in 12 non-contiguous axial planes on a 1.5 Tesla GE Signa System with EPI capability. Overt responses were made during silent portions of the compressed acquisition sequence using TR=4OOOms. Activation maps in Talairach space were generated using established nonparametric methods.
Results: Compared to control twins, twins with schizophrenia demonstrated significantly attenuated activation in the superior and medial prefrontal cortex, the cingnlate gyrus, fusiform gyms and cerebellum. When the well twins (with a schizophrenic co-twin) were compared to control twins they demonstrated attenuated activation in the inferior temporal lobe and parahippocampal gyrus, the insula, caudate, cingulate gyrus and cerebellum. However, there were no differences in medial frontal activation. Comparison within discordant twin pairs showed surprisingly few differences in activation except in the cingulate gyms.
Conclusion: These initial results suggest that the expression of schizophrenia is associated with abnormal fronto-temporal activation during word generation, but that there may also be functional abnormalities in those at high genetic risk of the disorder. These abnormalities may represent non-psychotic or trait markers of the schizophrenia genotype. Other abnormalities, such as attenuated medial prefrontal activation, may represent abnormalities in schizophrenia that are more related to the phenotypic expression of the disorder.
S1086