Cardiac autonomic dysregulation has been implicated in the comorbidity of major psychiatric disorders and cardiovascular disease, potentially through dysregulation of physiological responses to negative stressful stimuli (here, shortened to stress response). Further, sex differences in these comorbidities are substantial. Here, we tested the hypothesis that mood- and sex-dependent alterations in brain circuitry implicated in the regulation of the stress response are associated with reduced peripheral parasympathetic activity during negative emotional arousal. Fifty subjects (28 females) including healthy controls and individuals with major depression, bipolar psychosis and schizophrenia were evaluated. Functional magnetic resonance imaging and physiology (cardiac pulse) data were acquired during a mild visual stress reactivity challenge. Associations between changes in activity and functional connectivity of the stress response circuitry and variations in cardiovagal activity [normalized high frequency power of heart rate variability (HFn)] were evaluated using GLM analyses, including interactions with depressed mood and sex across disorders. Our results revealed that in women with high depressed mood, lower cardiovagal activity in response to negative affective stimuli was associated with greater activation of hypothalamus and right amygdala and reduced connectivity between hypothalamus and right orbitofrontal cortex, amygdala, and hippocampus. No significant associations were observed in women with low levels of depressed mood or men. Our results revealed mood- and sex-dependent interactions in the central regulation of cardiac autonomic activity in response to negative affective stimuli. These findings provide a potential pathophysiological mechanism for previously observed sex differences in the comorbidity of major depression and cardiovascular disease.

心脏自主神经失调与主要精神疾病和心血管疾病的共病有关，可能是通过对负面压力刺激的生理反应失调（这里简称为压力反应）。此外，这些合并症的性别差异很大。在这里，我们检验了这样一个假设，即与调节压力反应有关的大脑回路的情绪和性别依赖性改变与负性情绪唤起期间外周副交感神经活动减少有关。评估了 50 名受试者（28 名女性），包括健康对照组和患有重度抑郁症、双相情感障碍和精神分裂症的个体。在轻度视觉应激反应挑战期间获得功能性磁共振成像和生理学（心脏脉冲）数据。使用 GLM 分析评估了应激反应电路的活动和功能连接性变化与心血管活动变化 [心率变异性 (HFn) 的标准化高频功率] 之间的关联，包括与抑郁情绪和跨疾病的性行为的相互作用。我们的研究结果表明，在情绪低落的女性中，对负面情感刺激的反应较低的心血管活动与下丘脑和右侧杏仁核的更大激活以及下丘脑与右侧眶额皮质、杏仁核和海马之间的连接性降低有关。在情绪低落的女性或男性中没有观察到显着的相关性。我们的研究结果揭示了情绪和性别依赖的相互作用在心脏自主神经活动的中枢调节中以响应负面情感刺激。这些发现为先前观察到的重度抑郁症和心血管疾病合并症的性别差异提供了潜在的病理生理机制。