NIHR Biomedical Research Centre, Institute of Psychiatry (King's College London)/South London and Maudsley NHS Foundation Trust, London, UK.
Psychol Med. 2009 Nov;39(11):1783-97. doi: 10.1017/S0033291709990316. Epub 2009 Jul 2.
Morphometric endophenotypes which have been proposed for psychotic disorders include lateral ventricular enlargement and hippocampal volume reductions. Genetic epidemiological studies support an overlap between schizophrenia and bipolar disorder, and COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes have been implicated in the aetiology of both these disorders. This study examined associations between these candidate genes and morphometric endophenotypes for psychosis.
A total of 383 subjects (128 patients with psychosis, 194 of their unaffected relatives and 61 healthy controls) from the Maudsley Family Psychosis Study underwent structural magnetic resonance imaging and genotyping. The effect of candidate genes on brain morphometry was examined using linear regression models adjusting for clinical group, age, sex and correlations between members of the same family.
The results showed no evidence of association between variation in COMT genotype and lateral ventricular, and left or right hippocampal volumes. Neither was there any effect of the BDNF, 5-HTTLPR, NRG1 and DTNBP1 genotypes on these regional brain volumes.
Abnormal hippocampal and lateral ventricular volumes are among the most replicated endophenotypes for psychosis; however, the influences of COMT, BDNF, 5-HTT, NRG1 and DTNBP1 genes on these key brain regions must be very subtle if at all present.
精神分裂症和双相情感障碍存在重叠，这得到了遗传流行病学研究的支持。此外，COMT、BDNF、5-HTT、NRG1 和 DTNBP1 等基因可能与这两种疾病的发病机制有关。本研究旨在探讨这些候选基因与精神分裂症和双相情感障碍的形态学内表型之间的关系。
共有 383 名受试者（128 名精神疾病患者、194 名未受影响的亲属和 61 名健康对照者）参与了莫兹利家族精神病学研究，这些受试者接受了结构磁共振成像和基因分型。使用线性回归模型，在调整了临床分组、年龄、性别以及同一家庭成员之间的相关性后，检验了候选基因对脑形态的影响。
COMT 基因型与侧脑室以及左侧或右侧海马体体积之间没有明显的相关性。BDNF、5-HTTLPR、NRG1 和 DTNBP1 基因型也不会影响这些脑区的体积。
异常的海马体和侧脑室体积是精神分裂症和双相情感障碍中最常见的内表型之一；但是，如果 COMT、BDNF、5-HTT、NRG1 和 DTNBP1 等基因对这些关键脑区有影响的话，这种影响也非常微小。
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