Department of Psychiatry, Harvard Medical School, Boston, MA 02115, USA.
Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA 02478, USA.
Brain. 2020 Dec 1;143(12):3865-3877. doi: 10.1093/brain/awaa314.
Depression is a debilitating disorder that often starts manifesting in early childhood and peaks in onset during adolescence. Neurocognitive impairments have emerged as clinically important characteristics of depression, but it remains controversial which domains specifically index pre-existing vulnerability, state-related or trait-related markers. Here, we disentangled these effects by analysing the Adolescent Brain Cognitive Development dataset (n = 4626). Using information of participants' current and past mental disorders, as well as family mental health history, we identified low-risk healthy (n = 2100), high-risk healthy (n = 2023), remitted depressed (n = 401) and currently depressed children (n = 102). Factor analysis of 11 cognitive variables was performed to elucidate latent structure and canonical correlation analyses conducted to probe regional brain volumes reliably associated with the cognitive factors. Bayesian model comparison of various a priori hypotheses differing in how low-risk healthy, high-risk healthy, remitted depressed and currently depressed children performed in various cognitive domains was performed. Factor analysis revealed three domains: language and reasoning, cognitive flexibility and memory recall. Deficits in language and reasoning ability, as well as in volumes of associated regions such as the middle temporal and superior frontal gyrus, represented state- and trait-related markers of depression but not pre-existing vulnerability. In contrast, there was no compelling evidence of impairments in other domains. These findings-although cross-sectional and specific to 9-10-year-old children-might have important clinical implications, suggesting that cognitive dysfunction may not be useful targets of preventive interventions. Depressed patients, even after remission, might also benefit from less commonly used treatments such as cognitive remediation therapy.
抑郁症是一种使人虚弱的疾病，通常在儿童早期表现出来，并在青少年时期达到发病高峰。神经认知障碍已成为抑郁症的重要临床特征，但哪些特定领域可作为预先存在的易感性、与状态相关或与特质相关的标志物，仍存在争议。在这里，我们通过分析青少年大脑认知发展数据集（n=4626）来厘清这些影响。利用参与者当前和过去的精神障碍以及家族精神健康史的信息，我们确定了低风险健康组（n=2100）、高风险健康组（n=2023）、缓解抑郁组（n=401）和当前抑郁组（n=102）。对 11 个认知变量进行因子分析，以阐明潜在结构，并进行典型相关分析，以可靠地探测与认知因素相关的区域脑容量。对各种先验假设进行贝叶斯模型比较，这些假设在低风险健康、高风险健康、缓解抑郁和当前抑郁儿童在不同认知领域的表现方式上存在差异。因子分析揭示了三个领域：语言和推理、认知灵活性和记忆回忆。语言和推理能力的缺陷，以及与中颞叶和额上回等相关区域的体积减少，代表了抑郁症的状态和特质相关标志物，而不是预先存在的易感性。相比之下，在其他领域没有令人信服的证据表明存在缺陷。这些发现——尽管是横断面的，并且特定于 9-10 岁的儿童——可能具有重要的临床意义，表明认知功能障碍可能不是预防干预的有用目标。即使在缓解后，抑郁患者也可能受益于不太常用的治疗方法，如认知矫正治疗。
