Igata R, Katsuki A, Kakeda S, Watanabe K, Igata N, Hori H, Konishi Y, Atake K, Kawasaki Y, Korogi Y, Yoshimura R
Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan.
Department of Radiology, University of Occupational and Environmental Health, Kitakyushu, Japan.
Transl Psychiatry. 2017 May 30;7(5):e1140. doi: 10.1038/tp.2017.100.
Major depressive disorder (MDD) has been linked to differences in the volume of certain areas of the brain and to variants in the piccolo presynaptic cytomatrix protein (PCLO), but the relationship between PCLO and brain morphology has not been studied. A single-nucleotide polymorphism (SNP) in PCLO, rs2522833, is thought to affect protein stability and the activity of the hypothalamic-pituitary-adrenal axis. We investigated the relationship between cortical volume and this SNP in first-episode, drug-naive patients with MDD or healthy control subjects. Seventy-eight participants, including 30 patients with MDD and 48 healthy control subjects, were recruited via interview. PCLO rs2522833 genotyping and plasma cortisol assays were performed, and gray matter volume was estimated using structural magnetic resonance images. Among the individuals carrying the C-allele of PCLO rs2522833, the volume of the left temporal pole was significantly smaller in those with MDD than in healthy controls (family-wise error-corrected, P=0.003). No differences were detected in other brain regions. In addition, the C-carriers showed a larger volume reduction in the left temporal pole than those in the individuals with A/A genotype (P=0.0099). Plasma cortisol levels were significantly higher in MDD-affected C-carriers than in the healthy control C-carriers (12.76±6.10 vs 9.31±3.60 nm, P=0.045). We conclude that PCLO SNP rs2522833 is associated with a gray matter volume reduction in the left temporal pole in drug-naive, first-episode patients with MDD carrying the C-allele.
重度抑郁症（MDD）与大脑某些区域的体积差异以及微小突触前细胞基质蛋白（PCLO）的变异有关，但PCLO与脑形态之间的关系尚未得到研究。PCLO中的一个单核苷酸多态性（SNP），即rs2522833，被认为会影响蛋白质稳定性和下丘脑-垂体-肾上腺轴的活性。我们调查了首发、未服用过药物的MDD患者或健康对照者中皮质体积与该SNP之间的关系。通过访谈招募了78名参与者，包括30名MDD患者和48名健康对照者。进行了PCLO rs2522833基因分型和血浆皮质醇检测，并使用结构磁共振图像估计灰质体积。在携带PCLO rs2522833 C等位基因的个体中，MDD患者左颞极的体积明显小于健康对照者（家族性错误校正，P=0.003）。在其他脑区未检测到差异。此外，C等位基因携带者左颞极的体积减少幅度大于A/A基因型个体（P=0.0099）。受MDD影响的C等位基因携带者的血浆皮质醇水平明显高于健康对照C等位基因携带者（12.76±6.10对9.31±3.60 nmol/L，P=0.045）。我们得出结论，PCLO SNP rs2522833与携带C等位基因的未服用过药物的首发MDD患者左颞极灰质体积减少有关。
