Liu Zhongwan, Lu Weicong, Zou Wenjin, Gao Yanling, Li Xiaoyue, Xu Guiyun, So Kwok-Fai, McIntyre Roger S, Lin Kangguang, Shao Robin
Department of Affective Disorder, The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, People's Republic of China.
Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, People's Republic of China; Department of Radiology, The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2024 Jun 21. doi: 10.1016/j.bpsc.2024.06.005.
Risk for bipolar disorder (BD) is increased among individuals with a family history or subthreshold mood symptoms. However, the brain structural developments associated with these BD risks remain unknown.
This longitudinal cohort study examined the brain gray matter volume (GMV) developmental features of familial and symptomatic risks for BD and their associations with participants' global function levels. We recruited unaffected BD offspring with (n = 26, 14 female, mean ± SD age = 14.9 ± 2.9 years) or without (n = 35, 19 female, age = 15.3 ± 2.7 years) subthreshold manic or depressive symptoms and unaffected non-BD offspring with (n = 49, 30 female, age = 14.5 ± 2.2 years) or without (n = 68, 37 female, age = 15.0 ± 2.3 years) symptoms. The offspring had no mood disorder diagnosis prior to the study. The average follow-up duration was 2.63 ± 1.63 years.
At baseline, we found significant interactive effects of familial risk and subthreshold symptoms that indicated that the symptomatic offspring exhibited markedly large GMV in the brain affective and cognitive circuitries. During follow-up, the combined group of BD offspring (symptomatic and nonsymptomatic) displayed a more accelerated GMV decrease than BD nonoffspring in the hippocampus and anterior cingulate cortex. In contrast, the combined group of symptomatic participants (offspring and nonoffspring) displayed a slower GMV decrease than nonsymptomatic participants in the ventromedial prefrontal cortex. Larger GMV at baseline and accelerated GMV decrease during follow-up prospectively and longitudinally predicted positive global function changes. All results survived multiple testing correction.
These findings indicated that familial and symptomatic risks of BD are associated with distinct brain structural developments and unraveled key brain developmental features of particularly vulnerable high-risk individuals to subsequent functional deterioration.
有家族病史或阈下情绪症状的个体患双相情感障碍（BD）的风险会增加。然而，与这些BD风险相关的脑结构发育情况仍不清楚。
这项纵向队列研究考察了BD家族风险和症状风险的脑灰质体积（GMV）发育特征及其与参与者整体功能水平的关联。我们招募了有阈下躁狂或抑郁症状（n = 26，14名女性，平均±标准差年龄 = 14.9 ± 2.9岁）或无此类症状（n = 35，19名女性，年龄 = 15.3 ± 2.7岁）的未患BD后代，以及有症状（n = 49，30名女性，年龄 = 14.5 ± 2.2岁）或无症状（n = 68，37名女性，年龄 = 15.0 ± 2.3岁）的未患BD的非BD后代。这些后代在研究前未被诊断为情绪障碍。平均随访时长为2.63 ± 1.63年。
在基线时，我们发现家族风险和阈下症状存在显著的交互作用，这表明有症状的后代在脑情感和认知回路中表现出明显更大的GMV。在随访期间，BD后代（有症状和无症状）的组合组在海马体和前扣带回皮质中GMV下降速度比非BD后代更快。相比之下，有症状参与者（后代和非后代）的组合组在腹内侧前额叶皮质中GMV下降速度比无症状参与者更慢。基线时较大的GMV以及随访期间GMV的加速下降可前瞻性和纵向预测整体功能的积极变化。所有结果均经过多重检验校正。
这些发现表明，BD的家族风险和症状风险与不同的脑结构发育相关，并揭示了特别易患后续功能恶化的高危个体的关键脑发育特征。
