Carmel Miri, Zarchi Omer, Michaelovsky Elena, Frisch Amos, Patya Miriam, Green Tamar, Gothelf Doron, Weizman Abraham
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Felsenstein Medical Research Center, Petah Tikva, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; The Child Psychiatry Unit, Edmond and Lily Safra Children's Hospital, Sheba MedicalCenter, Tel Hashomer, Ramat Gan, Israel; Rabin Medical Center, 49100 Petah Tikva, Israel.
J Psychiatr Res. 2014 Sep;56:28-35. doi: 10.1016/j.jpsychires.2014.04.019. Epub 2014 May 9.
The 22q11.2 deletion syndrome (22q11.2DS) carries the highest genetic risk factor for the development of schizophrenia. We investigated the association of genetic variants in two schizophrenia candidate genes with executive function (EF) and IQ in 22q11.2DS individuals. Ninety two individuals with 22q11.2 deletion were studied for the genetic association between COMT and PRODH variants and EF and IQ. Subjects were divided into children (under 12 years old), adolescents (between 12 and 18 years old) and adults (older than 18 years), and genotyped for the COMT Val158Met (rs4680) and PRODH Arg185Trp (rs4819756) polymorphisms. The participants underwent psychiatric evaluation and EF assessment. Our main finding is a significant influence of the COMT Val158Met polymorphism on both IQ and EF performance. Specifically, 22q11.2DS subjects with Met allele displayed higher IQ scores in all age groups compared to Val carriers, reaching significance in both adolescents and adults. The Met allele carriers performed better than Val carriers in EF tasks, being statistically significant in the adult group. PRODH Arg185Trp variant did not affect IQ or EF in our 22q11.2DS cohort. In conclusion, functional COMT variant, but not PRODH, affects IQ and EF in 22q11.2DS subjects during neurodevelopment with a maximal effect at adulthood. Future studies should monitor the cognitive performance of the same individuals from childhood to old age.
22q11.2缺失综合征（22q11.2DS）是精神分裂症发生的最高遗传风险因素。我们研究了两个精神分裂症候选基因中的遗传变异与22q11.2DS个体执行功能（EF）和智商（IQ）之间的关联。对92名患有22q11.2缺失的个体进行了COMT和PRODH变异与EF和IQ之间的遗传关联研究。受试者被分为儿童（12岁以下）、青少年（12至18岁）和成人（18岁以上），并对COMT Val158Met（rs4680）和PRODH Arg185Trp（rs4819756）多态性进行基因分型。参与者接受了精神评估和EF评估。我们的主要发现是COMT Val158Met多态性对IQ和EF表现均有显著影响。具体而言，与携带Val等位基因的22q11.2DS受试者相比，携带Met等位基因的受试者在所有年龄组的IQ得分均更高，在青少年和成人组中均达到显著水平。在EF任务中，携带Met等位基因的受试者表现优于携带Val等位基因的受试者，在成人组中具有统计学意义。在我们的22q11.2DS队列中，PRODH Arg185Trp变异并未影响IQ或EF。总之，功能性COMT变异而非PRODH变异在神经发育过程中影响22q11.2DS受试者的IQ和EF，在成年期影响最大。未来的研究应监测同一批个体从童年到老年的认知表现。
