Functional connectomics of affective and psychotic pathology
Functional connectomics of affective and psychotic pathology
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DOI：
10.1073/pnas.1820780116
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发表时间：
2019-04-30
影响因子：
11.1
通讯作者：
Holmes, Avram J.
中科院分区：
文献类型：
--
作者：
Baker, Justin T.;Dillon, Daniel G.;Holmes, Avram J.
越来越多的证据表明，名义上有不同精神疾病诊断的患者群体并没有被尖锐或不连续的神经生物学边界分开。在健康人群中，行为的个体差异反映在大脑功能连接(功能连接体)集体集合的可变性上。这些数据表明，在精神病患者中观察到的跨诊断症状谱可能映射到网络功能的可检测模式。为了检验神经生物学变异可能成为临床表现的基础的方式，我们获得了超过1,000人的fMRI数据，其中包括210名被诊断为原发性精神病或情感性精神病(伴精神病和精神分裂症或分裂情感性障碍)的人，192名表现为无精神病的原发性情感性障碍(单相抑郁，无精神病的双相情感障碍)，以及通过大规模的脑成像和遗传学研究招募的608名人口统计学匹配的健康对照参与者。在这里，我们检查了精神诊断中功能连接的变异，发现了疾病连接“指纹”的显著证据，这些“指纹”通常在不同形式的病理中被破坏，并似乎随着疾病严重程度的变化而变化。情感性和精神病性疾病的存在与额顶网络连接的分级中断有关(包括背外侧前额叶、背内侧前额叶、外侧顶叶和后颞叶皮质)。相反，网络连接的其他特性，包括默认的网络完整性，在患有精神病的患者中优先受到干扰，而没有精神病症状的患者则不受影响。这项工作使我们能够确定严重精神疾病的功能连接的关键生物学和临床特征。
Converging evidence indicates that groups of patients with nominally distinct psychiatric diagnoses are not separated by sharp or discontinuous neurobiological boundaries. In healthy populations, individual differences in behavior are reflected in variability across the collective set of functional brain connections (functional connectome). These data suggest that the spectra of transdiagnostic symptom profiles observed in psychiatric patients may map onto detectable patterns of network function. To examine the manner through which neurobiological variation might underlie clinical presentation, we obtained fMRI data from over 1,000 individuals, including 210 diagnosed with a primary psychotic disorder or affective psychosis (bipolar disorder with psychosis and schizophrenia or schizoaffective disorder), 192 presenting with a primary affective disorder without psychosis (unipolar depression, bipolar disorder without psychosis), and 608 demographically matched healthy comparison participants recruited through a large-scale study of brain imaging and genetics. Here, we examine variation in functional connectomes across psychiatric diagnoses, finding striking evidence for disease connectomic "fingerprints" that are commonly disrupted across distinct forms of pathology and appear to scale as a function of illness severity. The presence of affective and psychotic illnesses was associated with graded disruptions in frontoparietal network connectivity (encompassing aspects of dorsolateral prefrontal, dorsomedial prefrontal, lateral parietal, and posterior temporal cortices). Conversely, other properties of network connectivity, including default network integrity, were preferentially disrupted in patients with psychotic illness, but not patients without psychotic symptoms. This work allows us to establish key biological and clinical features of the functional connectomes of severe mental disease.