抑郁癥是困擾人類的重大精神疾病之一，早期的雙生子研究和領(lǐng)養(yǎng)研究證實,，抑郁癥是由遺傳因素與外界環(huán)境共同作用的一種疾病,。近年來，隨著研究手段的不斷成熟以及樣本量的逐漸增大,，越來越多的抑郁癥易感基因被報道出來,，然而絕大多數(shù)易感基因在中樞神經(jīng)系統(tǒng)中的作用仍不甚清楚。
SLC6A15基因是首先在歐洲人群中通過全基因組關(guān)聯(lián)分析發(fā)現(xiàn)的一個易感基因,，位于SLC6A15基因區(qū)域的單核苷酸多態(tài)性位點（SNP）rs1545843在幾份來自不同國家和地區(qū)的人群樣本中均與抑郁癥相關(guān),。同時，這個位點也被證實可以影響SLC6A15基因的mRNA表達(dá),，海馬體積的變化以及神經(jīng)元的完整性,。不過，對于這個易感位點的研究僅限于此,，其在中樞神經(jīng)系統(tǒng)中的其它作用仍然不清楚,。
研究表明，絕大多數(shù)精神疾病易感基因均可以影響腦結(jié)構(gòu)的變化,，而這種效應(yīng)無論是在病人中還是健康人群中均存在,。有鑒于此，中國科學(xué)院昆明動物研究所宿兵研究員實驗室（李明博士）通過與復(fù)旦大學(xué)馮建峰教授的實驗室合作,，對來自昆明的包含278個健康個體的人群進(jìn)行了腦部結(jié)構(gòu)的核磁共振掃描（MRI）,，并在全腦范圍內(nèi)分析了rs1545843與腦區(qū)結(jié)構(gòu)變化的關(guān)系,。他們的研究結(jié)果發(fā)現(xiàn)，rs1545843與大腦中部扣帶回體積顯著相關(guān)（下圖）,。
眾所周知,，扣帶回在大腦中主要參與情緒以及認(rèn)知進(jìn)程，而情緒及認(rèn)知能力的改變是抑郁癥患者的一個主要癥狀,，并且有證據(jù)表明扣帶回體積在抑郁癥患者中發(fā)生了明顯病變,。因此，他們的研究結(jié)果進(jìn)一步支持了SLC6A15基因在抑郁癥發(fā)病中的作用,，并且提示了其可能的致病機(jī)制,。
該研究結(jié)果7月1日發(fā)表于國際精神病學(xué)刊物American Journal of Psychiatry。昆明動物所等人群大腦結(jié)構(gòu)差異遺傳基礎(chǔ)研究取得新進(jìn)展
生物谷推薦英文摘要：
The American Journal of Psychiatry Am J Psychiatry 2013;170:805-805. 10.1176/appi.ajp.2013.12111458
SLC6A15 rs1545843 and Depression: Implications From Brain Imaging Data
Ming Li, Ph.D.; Tian Ge, B.Sc.; Jianfeng Feng, Ph.D.; Bing Su, Ph.D.
Major depression is a common neuropsychiatric disorder involving genetic components. A recent genome-wide association study identified a risk single-nucleotide polymorphism (SNP), rs1545843 in SLC6A15 (1), which encodes a sodium-dependent branched-chain amino acid transporter. The risk SNP also revealed associations with alterations in hippocampal volume, neuronal integrity, and SLC6A15 expression (1), but it remains unclear how rs1545843 affects brain development, causing deficits in a specific brain region and eventually leading to susceptibility to major depression.
An informative way of dissecting the functional role of the risk SNP is to test its associations with brain structures using in vivo MRI methods. We recruited 278 unrelated healthy Han Chinese individuals without alcohol dependence, mental disorders, drug abuse, or brain injury. Structural images were acquired using a 3-T Philips MRI scanner, and a voxel-based morphometry method was used to provide voxel-wise assessment of volumetric difference. Detailed information about the sample, MRI acquisition, image preprocessing, and genotyping methods are provided in the data supplement that accompanies the online edition of this letter. The effect of the genotype was examined using a linear regression at each voxel, adjusting for age, gender, and intracranial volume. Voxel-wise p values were corrected over the brain to control family-wise error rate.
We observed brain-wide significant association of rs1545843 with local gray matter volume in the median cingulate gyrus (family-wise error-corrected, voxel-wise p=0.031, cluster-wise p=0.0071, Figure 1). The cingulate cortex is a structurally heterogeneous brain region mainly involved in emotion and cognition processes (2), and deficits in patients with major depression have been frequently reported in this brain region. In addition, smaller regional gray matter volume of the cingulate gyrus has been observed in patients with major depression (3), although this has been more frequently reported in the anterior cingulate gyrus, while the median cingulate gyrus was rarely studied and the biological effects of this region on major depression are still unclear. However, we did not find a significant association in the hippocampus as described by Kohli et al. (1), and the discrepancy is possibly a result of sample difference. Patients with major depression and healthy comparison subjects were both evaluated in the Kohli et al. study, while we assessed only healthy individuals.
