Department of Psychiatry and Psychology, School for Mental Health and Neuroscience, European Graduate School of Neuroscience (EURON), South Limburg Mental Health Research and Teaching Network (SEARCH), Maastricht University Medical Centre, P,O, Box 616 (DRT 12), Maastricht, MD, 6200, The Netherlands.
BMC Psychiatry. 2013 Feb 19;13:63. doi: 10.1186/1471-244X-13-63.
There is a negative association between the use of antipsychotics and cognitive functioning in bipolar patients, which may be mediated by altered dopamine signaling in selected brain areas, and moderation thereof by genetic sequence variation such as COMT Val108/158Met. The interaction between antipsychotic drug use and the COMT Val108/158Met genotype on two-year cognitive functioning in bipolar patients was examined.
Interaction between the COMT Val108/158Met and antipsychotics on a composite cognitive measure was examined in 51 bipolar patients who were assessed 12 times at two-monthly intervals over a period of two years (379 observations).
There was a significant negative effect of the interaction between antipsychotic medications and Val allele load on the composite cognitive measure in bipolar patients (p < 0.001).
The negative effects of antipsychotics on cognitive functioning in bipolar disorder may be moderated by the COMT Val 108/158 Met genotype, with a negative effect of Val allele load. If replicated, the results may be indicative of pharmacogenetic interactions in bipolar disorder.
在双相情感障碍患者中,抗精神病药物的使用与认知功能呈负相关,这可能与特定脑区多巴胺信号的改变有关,而 COMT Val108/158Met 等遗传序列变异可能会对此产生调节作用。本研究旨在探讨双相情感障碍患者中抗精神病药物使用与 COMT Val108/158Met 基因型之间的相互作用对两年认知功能的影响。
本研究纳入了 51 例双相情感障碍患者,在两年的时间内,每隔两个月评估一次,共进行了 12 次评估(共 379 次观察),采用复合认知测量来评估 COMT Val108/158Met 与抗精神病药物之间的相互作用对认知功能的影响。
在双相情感障碍患者中,抗精神病药物与 Val 等位基因负荷之间的相互作用对复合认知测量有显著的负性影响(p<0.001)。
COMT Val108/158Met 基因型可能会调节抗精神病药物对双相情感障碍认知功能的负面影响,Val 等位基因负荷与认知功能呈负相关。如果这些结果得到复制,可能表明在双相情感障碍中存在药物遗传学相互作用。