Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA, USA.
Departments of Neuroscience, Psychology, and Psychiatry, Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
Neuropsychopharmacology. 2018 Oct;43(11):2212-2220. doi: 10.1038/s41386-018-0083-z. Epub 2018 May 4.
Bipolar disorder (BD) is highly heritable. Thus, studies in first-degree relatives of individuals with BD could lead to the discovery of objective risk markers of BD. Abnormalities in white matter structure reported in at-risk individuals could play an important role in the pathophysiology of BD. Due to the lack of studies with other at-risk offspring, however, it remains unclear whether such abnormalities reflect BD-specific or generic risk markers for future psychopathology. Using a tract-profile approach, we examined 18 major white matter tracts in 38 offspring of BD parents, 36 offspring of comparison parents with non-BD psychopathology (depression, attention-deficit/hyperactivity disorder), and 41 offspring of healthy parents. Both at-risk groups showed significantly lower fractional anisotropy (FA) in left-sided tracts (cingulum, inferior longitudinal fasciculus, forceps minor), and significantly greater FA in right-sided tracts (uncinate fasciculus and inferior longitudinal fasciculus), relative to offspring of healthy parents (P < 0.05). These abnormalities were present in both healthy and affected youth in at-risk groups. Only offspring (particularly healthy offspring) of BD parents showed lower FA in the right superior longitudinal fasciculus relative to healthy offspring of healthy parents (P < 0.05). We show, for the first time, important similarities, and some differences, in white matter structure between offspring of BD and offspring of non-BD parents. Findings suggest that lower left-sided and higher right-sided FA in tracts important for emotional regulation may represent markers of risk for general, rather than BD-specific, psychopathology. Lower FA in the right superior longitudinal fasciculus may protect against development of BD in offspring of BD parents.
双相障碍 (BD) 具有高度遗传性。因此，对 BD 患者一级亲属的研究可能会发现 BD 的客观风险标志物。在风险个体中报告的白质结构异常可能在 BD 的病理生理学中发挥重要作用。然而，由于缺乏对其他风险后代的研究，尚不清楚这些异常是否反映了 BD 特异性或未来精神病理学的通用风险标志物。使用束状轮廓方法，我们检查了 38 名 BD 父母的后代、36 名有非 BD 精神病理学（抑郁症、注意力缺陷/多动障碍）的对照父母的后代和 41 名健康父母的后代的 18 条主要白质束。两个风险组的左侧束（扣带束、下纵束、小内囊束）的分数各向异性 (FA) 明显较低，右侧束（钩束和下纵束）的 FA 明显较高，与健康父母的后代相比（P < 0.05）。这些异常在风险组中的健康和患病青少年中均存在。只有 BD 父母的后代（特别是健康的后代）的右侧上纵束的 FA 明显低于健康父母的健康后代（P < 0.05）。我们首次显示，BD 父母的后代和非 BD 父母的后代之间的白质结构存在重要的相似性和一些差异。研究结果表明，对情绪调节很重要的左侧束的 FA 较低和右侧束的 FA 较高可能代表一般精神病理学而不是 BD 特异性精神病理学的风险标志物。右侧上纵束的 FA 较低可能会保护 BD 父母的后代免受 BD 的发展。
