Clock genes beyond the clock: CLOCK genotype biases neural correlates of moral valence decision in depressed patients
Clock genes beyond the clock: CLOCK genotype biases neural correlates of moral valence decision in depressed patients
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DOI：
10.1111/j.1601-183x.2007.00312.x
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发表时间：
2008-02-01
影响因子：
2.5
通讯作者：
Smeraldi, E.
中科院分区：
文献类型：
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作者：
Benedetti, F.;Radaelli, D.;Smeraldi, E.
哺乳动物生物钟系统中的基因多态影响个体的节律。Clock基因3‘侧翼区(3111T/C；rs1801260)的单核苷酸多态(SNP)影响健康人的昼夜偏好，并导致双相情感障碍患者的睡眠相延迟和失眠。生物钟的基因在许多大脑结构中表达，而不是在“主钟”视交叉上核团中表达。这些区域，如扣带皮质，参与了许多人类行为的控制。时钟基因可能会使信息处理和决策等“非时钟”功能产生偏差。30例严重抑郁发作的住院患者接受了血氧水平依赖(BOLD)功能磁共振成像(FMRI)。认知激活范式基于进行/不进行任务。介绍了具有道德意味的词语。对每个患者进行CLOCK基因分型。在功能磁共振研究的前一天，我们通过活动测量测量了活动水平。时钟3111T/C SNP与第二天的活动水平、神经心理表现和BOLD功能磁共振相关(基因型和刺激的道德效价的交互作用)相关。我们的结果支持这样的假设，即在正常和精神病理条件下，个体时钟基因可能会影响与人类行为相关的几个变量。
Gene polymorphisms in the mammalian biological clock system influence individual rhythms. A single nucleotide polymorphism (SNP) in the 3' flanking region of CLOCK (3111 T/C; rs1801260) influenced diurnal preference in healthy humans and caused sleep phase delay and insomnia in patients affected by bipolar disorder. Genes of the biological clock are expressed in many brain structures other than in the 'master clock' suprachiasmatic nuclei. These areas, such as cingulate cortex, are involved in the control of many human behaviors. Clock genes could then bias 'nonclock' functions such as information processing and decision making. Thirty inpatients affected by a major depressive episode underwent blood oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI). The cognitive activation paradigm was based on a go/no-go task. Morally connoted words were presented. Genotyping of CLOCK was performed for each patients. We measured activity levels through actimetry during the day before the fMRI study. CLOCK 3111 T/C SNP was associated with activity levels in the second part of the day, neuropsychological performance and BOLD fMRI correlates (interaction of genotype and moral valence of the stimuli). Our results support the hypothesis that individual clock genotype may influence several variables linked with human behaviors in normal and psychopathological conditions.