Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany.
Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany.
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):67-76. doi: 10.1016/j.pnpbp.2017.06.010. Epub 2017 Jun 15.
Major depressive disorder (MDD) patients show impairments of cognitive functioning such as working memory (WM), and furthermore alterations during WM-fMRI tasks especially in frontal and parietal brain regions. The calculation of a polygenic risk score (PRS) can be used to describe the genetic influence on MDD, hence imaging genetic studies aspire to combine both genetics and neuroimaging data to identify the influence of genetic factors on brain functioning. We aimed to detect the effect of MDD-PRS on brain activation during a WM task measured with fMRI and expect healthy individuals with a higher PRS to be more resembling to MDD patients.
In total, n=137 (80 men, 57 women, aged 34.5, SD=10.4years) healthy subjects performed a WM n-back task [0-back (baseline), 2-back and 3-back condition] in a 3T-MRI-tomograph. The sample was genotyped using the Infinium PsychArray BeadChip and a polygenic risk score was calculated for MDD using PGC MDD GWAS results.
A lower MDD risk score was associated with increased activation in the bilateral middle occipital gyri (MOG), the bilateral middle frontal gyri (MFG) and the right precentral gyrus (PCG) during the 2-back vs. baseline condition. Moreover, a lower PRS was associated with increased brain activation during the 3-back vs. baseline condition in the bilateral cerebellum, the right MFG and the left inferior parietal lobule. A higher polygenic risk score was associated with hyperactivation in brain regions comprising the right MFG and the right supplementary motor area during the 3-back vs. 2-back condition.
The results suggest that part of the WM-related brain activation patterns might be explained by genetic variants captured by the MDD-PRS. Furthermore we were able to detect MDD-associated activation patterns in healthy individuals depending on the MDD-PRS and the task complexity. Additional gene loci could contribute to these task-dependent brain activation patterns.
重度抑郁症（MDD）患者表现出认知功能障碍，例如工作记忆（WM），并且在 WM-fMRI 任务期间尤其在前额叶和顶叶脑区发生改变。多基因风险评分（PRS）的计算可用于描述 MDD 的遗传影响，因此影像学遗传研究旨在将遗传学和神经影像学数据相结合，以确定遗传因素对大脑功能的影响。我们旨在检测 MDD-PRS 对 fMRI 测量的 WM 任务期间大脑激活的影响，并期望具有更高 PRS 的健康个体更类似于 MDD 患者。
共有 137 名（80 名男性，57 名女性，年龄 34.5，SD=10.4 岁）健康受试者在 3T-MRI 体层摄影仪中执行 WM n-back 任务[0-back（基线），2-back 和 3-back 条件]。使用 Infinium PsychArray BeadChip 对样本进行基因分型，并使用 PGC MDD GWAS 结果计算 MDD 的多基因风险评分。
较低的 MDD 风险评分与 2-back 与基线条件相比，双侧中枕回（MOG）、双侧额中回（MFG）和右侧中央前回（PCG）的激活增加有关。此外，较低的 PRS 与双侧小脑、右侧 MFG 和左侧顶下小叶在 3-back 与基线条件下的大脑激活增加有关。较高的多基因风险评分与 3-back 与 2-back 条件下右侧 MFG 和右侧辅助运动区的过度激活有关。
结果表明，部分 WM 相关的大脑激活模式可能可以用 MDD-PRS 捕获的遗传变异来解释。此外，我们能够根据 MDD-PRS 和任务复杂性检测健康个体中的 MDD 相关激活模式。其他基因座可能有助于这些依赖于任务的大脑激活模式。
