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.

中文翻译：

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高危青少年双相情感障碍与一般精神病理学风险的弥散成像标记。

双相情感障碍（BD）具有高度遗传性。因此，对 BD 患者的一级亲属进行研究可能会发现 BD 的客观风险标记。高危个体的白质结构异常可能在双相情感障碍的病理生理学中发挥重要作用。然而，由于缺乏对其他高危后代的研究，目前尚不清楚这种异常是否反映了 BD 特定或未来精神病理学的一般风险标记。使用束轮廓方法，我们检查了 38 个 BD 父母的后代、36 个患有非 BD 精神病理学（抑郁症、注意力缺陷/多动障碍）的对照父母的后代以及 41 个健康父母的后代的 18 个主要白质束。相对于后代，两个高危群体的左侧束（扣带带、下纵束、小镊子）的各向异性分数（FA）均显着降低，而右侧束（钩束和下纵束）的各向异性分数显着较高健康父母的比例（P < 0.05）。这些异常现象存在于高危人群中的健康青少年和受影响青少年中。与健康父母的健康后代相比，只有 BD 父母的后代（特别是健康后代）右上纵束 FA 较低（P < 0.05）。我们首次展示了 BD 后代和非 BD 父母的后代之间白质结构的重要相似之处和一些差异。研究结果表明，对于情绪调节很重要的神经束中左侧较低的 FA 和右侧较高的 FA 可能代表一般而非 BD 特异性精神病理学的风险标志。右上纵束中较低的 FA 可能可以防止 BD 父母的后代发生 BD。