Douglas Mental Health University Institute, Montréal, Québec, Canada.
Department of Radiology, University of California San Diego, La Jolla, CA, United States.
J Psychiatr Res. 2022 Jul;151:411-418. doi: 10.1016/j.jpsychires.2022.05.006. Epub 2022 May 12.
Hippocampal circuitry and related cortical connections are altered in first episode psychosis (FEP) and are associated with verbal memory deficits, as well as positive and negative symptoms. There are robust sex differences in the clinical presentation of psychosis, including poorer verbal memory in male patients. Consideration of sex differences in hippocampal-cortical circuitry and their associations with different behavioral dimensions may be useful for understanding the underlying pathophysiology of verbal memory deficits and related symptomatology in psychosis. Here, we use a data-driven approach to simultaneously capture the complex links between sex, verbal memory, symptoms, and cortical-hippocampal brain metrics in FEP. Structural magnetic resonance imaging and behavioral data were acquired from 100 FEP patients (75 males, 25 females) and 87 controls (55 males, 32 females). Multivariate brain-behavior associations were examined in FEP using partial least squares to map sociodemographic, verbal memory, and clinical data onto brain morphometry. The analysis identified two sex-dependent patterns of verbal memory, symptoms, and brain structure. In male patients, verbal memory deficits and core psychotic symptoms were associated with both increased and decreased frontal and temporal cortical thickness and reductions in CA2/3 hippocampal subfield and fornix volumes. In female patients, fewer negative/depressive symptoms were associated with a more attenuated cortical thickness pattern and more diffuse reductions in hippocampal white matter regions. Taken together, the results contribute towards better understanding the underlying pathophysiology of psychosis by highlighting the unique contribution of specific hippocampal subfields and surrounding white matter and their connections with broader cortical networks in a sex-dependent manner.
海马体回路及其相关皮质连接在首发精神病（FEP）中发生改变，与言语记忆缺陷以及阳性和阴性症状有关。精神病的临床表现存在明显的性别差异，包括男性患者的言语记忆较差。考虑到海马体-皮质回路的性别差异及其与不同行为维度的关联，可能有助于理解精神病患者言语记忆缺陷和相关症状的潜在病理生理学。在这里，我们使用一种数据驱动的方法来同时捕捉 FEP 中性别、言语记忆、症状和皮质-海马体脑指标之间的复杂联系。从 100 名 FEP 患者（75 名男性，25 名女性）和 87 名对照者（55 名男性，32 名女性）中获取了结构磁共振成像和行为数据。使用偏最小二乘法（PLS）在 FEP 中检查了大脑形态与行为之间的多变量关联，将社会人口统计学、言语记忆和临床数据映射到大脑形态学上。分析确定了两种依赖于性别的言语记忆、症状和大脑结构模式。在男性患者中，言语记忆缺陷和核心精神病症状与额叶和颞叶皮质厚度的增加和减少以及 CA2/3 海马亚区和穹窿体积的减少有关。在女性患者中，较少的阴性/抑郁症状与皮质厚度模式减弱以及海马白质区域更广泛的弥散性减少有关。总的来说，这些结果通过强调特定海马亚区及其周围白质以及它们与更广泛的皮质网络之间以性别依赖的方式的连接在精神病病理生理学中的独特贡献，有助于更好地理解精神病的潜在病理生理学。
