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Arch Gen Psychiatry. 2004 Oct;61(10):974-84.

Association of genetic risks for schizophrenia and bipolar disorder with specific and generic brain structural endophenotypes.

Author information

  • 1Division of Psychological Medicine, Institute of Psychiatry, London. c.mcdonald@iop.kcl.ac.uk

Abstract

CONTEXT:

For more than a century, it has been uncertain whether or not the major diagnostic categories of psychosis--schizophrenia and bipolar disorder--are distinct disease entities with specific genetic causes and neuroanatomical substrates.

OBJECTIVE:

To investigate the relationship between genetic risk and structural variation throughout the entire brain in patients and their unaffected relatives sampled from multiply affected families with schizophrenia or bipolar disorder.

DESIGN:

Analysis of the association between genetic risk and variation in tissue volume on magnetic resonance images.

SETTING:

Psychiatric research center.

PARTICIPANTS:

Subjects comprised 25 patients with schizophrenia, 36 of their unaffected first-degree relatives, 37 patients with bipolar 1 disorder who experienced psychotic symptoms during illness exacerbation, and 50 of their unaffected first-degree relatives.

MAIN OUTCOME MEASURES:

We used computational morphometric techniques to map significant associations between a continuous measure of genetic liability for each subject and variation in gray or white matter volume.

RESULTS:

Genetic risk for schizophrenia was specifically associated with distributed gray matter volume deficits in the bilateral fronto-striato-thalamic and left lateral temporal regions, whereas genetic risk for bipolar disorder was specifically associated with gray matter deficits only in the right anterior cingulate gyrus and ventral striatum. A generic association between genetic risk for both disorders and white matter volume reduction in the left frontal and temporoparietal regions was consistent with left frontotemporal disconnectivity as a genetically controlled brain structural abnormality common to both psychotic disorders.

CONCLUSIONS:

Genetic risks for schizophrenia and bipolar disorder are associated with specific gray matter but generic white matter endophenotypes. Thus, Emil Kraepelin's pivotal distinction was neither wholly right nor wholly wrong: the 2 major psychoses show both distinctive and similar patterns of brain structural abnormality related to variable genetic risk.

PMID:
15466670
[PubMed - indexed for MEDLINE]
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