Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
Transl Psychiatry. 2017 Nov 30;7(11):1264. doi: 10.1038/s41398-017-0012-7.
Mood instability is a core clinical feature of affective and psychotic disorders. In keeping with the Research Domain Criteria approach, it may be a useful construct for identifying biology that cuts across psychiatric categories. We aimed to investigate the biological validity of a simple measure of mood instability and evaluate its genetic relationship with several psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, attention deficit hyperactivity disorder (ADHD), anxiety disorder and post-traumatic stress disorder (PTSD). We conducted a genome-wide association study (GWAS) of mood instability in 53,525 cases and 60,443 controls from UK Biobank, identifying four independently associated loci (on chromosomes 8, 9, 14 and 18), and a common single-nucleotide polymorphism (SNP)-based heritability estimate of ~8%. We found a strong genetic correlation between mood instability and MDD (r = 0.60, SE = 0.07, p = 8.95 × 10) and a small but significant genetic correlation with both schizophrenia (r = 0.11, SE = 0.04, p = 0.01) and anxiety disorders (r = 0.28, SE = 0.14, p = 0.04), although no genetic correlation with BD, ADHD or PTSD was observed. Several genes at the associated loci may have a role in mood instability, including the DCC netrin 1 receptor (DCC) gene, eukaryotic translation initiation factor 2B subunit beta (eIF2B2), placental growth factor (PGF) and protein tyrosine phosphatase, receptor type D (PTPRD). Strengths of this study include the very large sample size, but our measure of mood instability may be limited by the use of a single question. Overall, this work suggests a polygenic basis for mood instability. This simple measure can be obtained in very large samples; our findings suggest that doing so may offer the opportunity to illuminate the fundamental biology of mood regulation.
情绪不稳定是情感和精神病障碍的核心临床特征。根据研究领域标准方法，它可能是一种有用的构建，用于识别跨越精神科类别的生物学。我们旨在研究一种简单的情绪不稳定测量方法的生物学有效性，并评估其与几种精神疾病（包括重度抑郁症（MDD）、双相情感障碍（BD）、精神分裂症、注意缺陷多动障碍（ADHD）、焦虑症和创伤后应激障碍（PTSD））的遗传关系。我们对来自英国生物库的 53525 例病例和 60443 例对照进行了情绪不稳定的全基因组关联研究（GWAS），确定了四个独立相关的基因座（染色体 8、9、14 和 18），以及一个常见的基于单核苷酸多态性（SNP）的约 8%的遗传可遗传性估计值。我们发现情绪不稳定与 MDD 之间存在很强的遗传相关性（r=0.60，SE=0.07，p=8.95×10），与精神分裂症（r=0.11，SE=0.04，p=0.01）和焦虑症（r=0.28，SE=0.14，p=0.04）之间存在很小但有统计学意义的遗传相关性，但与 BD、ADHD 或 PTSD 之间没有观察到遗传相关性。相关基因座上的几个基因可能在情绪不稳定中起作用，包括 DCC 轴突向导因子 1 受体（DCC）基因、真核翻译起始因子 2B 亚基β（eIF2B2）、胎盘生长因子（PGF）和蛋白酪氨酸磷酸酶，受体 D 型（PTPRD）。这项研究的优势包括非常大的样本量，但我们的情绪不稳定测量方法可能受到使用单个问题的限制。总的来说，这项工作表明情绪不稳定具有多基因基础。这种简单的测量方法可以在非常大的样本中获得；我们的研究结果表明，这样做可能有机会阐明情绪调节的基本生物学。
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