Gadow Kenneth D, Smith Ryan M, Pinsonneault Julia K
*Department of Psychiatry, Stony Brook University, Stony Brook, NY †Department of Pharmacology, Center for Pharmacogenomics, The Ohio State University Wexner Medical Center, Columbus, OH.
Cogn Behav Neurol. 2014 Jun;27(2):107-16. doi: 10.1097/WNN.0000000000000028.
Our aim was to characterize the association of 2 functional single nucleotide polymorphisms (rs6311 and rs6314) in the serotonin 2A receptor gene (HTR2A) with severity of depression symptoms in children with autism spectrum disorder. These polymorphisms have been shown to be associated with depression symptom severity and response to selective serotonin reuptake inhibitor drugs in adults with diagnosed depressive disorder.
Parents of 104 children with autism spectrum disorder rated their children's depressive symptoms using a validated scale based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. We compared severity of depression symptoms across the rs6311 and rs6314 genotypes, measured from the children's genomic DNA.
Children homozygous for the G allele of rs6311 had significantly more severe depression symptoms than those with G/A or A/A genotypes (P=0.025). The effect size (partial eta-squared) was small (ηp=0.047) but was somewhat larger when we controlled for severity of generalized anxiety disorder symptoms (P=0.006, ηp=0.072). When we restricted our analyses to white participants, our results were essentially the same as for the entire sample (P=0.004, ηp=0.086). There was no significant association between rs6314 (C/C versus T carriers) and severity of depression.
Our findings suggest that the HTR2A functional rs6311 polymorphism, which other studies have associated with differential HTR2A mRNA expression, may modulate the severity of depression symptoms in children with autism spectrum disorder. These tentative, hypothesis-generating findings need replication with larger, independent samples.
我们的目的是确定血清素2A受体基因（HTR2A）中的两个功能性单核苷酸多态性（rs6311和rs6314）与自闭症谱系障碍儿童抑郁症状严重程度之间的关联。这些多态性已被证明与已确诊抑郁症的成年人的抑郁症状严重程度及对选择性血清素再摄取抑制剂药物的反应有关。
104名自闭症谱系障碍儿童的家长使用基于《精神疾病诊断与统计手册》第4版标准的有效量表对其孩子的抑郁症状进行评分。我们比较了根据孩子基因组DNA测得的rs6311和rs6314基因型的抑郁症状严重程度。
rs6311的G等位基因纯合子儿童的抑郁症状明显比G/A或A/A基因型儿童更严重（P = 0.025）。效应量（偏 eta 平方）较小（ηp = 0.047），但在我们控制广泛性焦虑症症状严重程度时效应量稍大（P = 0.006，ηp = 0.072）。当我们将分析限制在白人参与者中时，结果与整个样本基本相同（P = 0.004，ηp = 0.086）。rs6314（C/C与T携带者）与抑郁严重程度之间无显著关联。
我们的研究结果表明，其他研究已将其与HTR2A mRNA表达差异相关联的HTR2A功能性rs6311多态性可能会调节自闭症谱系障碍儿童的抑郁症状严重程度。这些初步的、产生假设的研究结果需要在更大的独立样本中进行重复验证。
