Rabl U, Bartova L, Sezen P, Keller J, Schatzberg A, Pezawas L
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria.
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.
J Affect Disord. 2025 May 15;377:14-22. doi: 10.1016/j.jad.2025.02.014. Epub 2025 Feb 13.
Psychotic major depression (PMD) differs from non-psychotic MD (NPMD) in psychopathology and is linked to changes in brain volumetry and hypothalamic-pituitary-adrenal (HPA) axis function that can be reflected by its principal output - the glucocorticoid cortisol. NPMD patients exhibit smaller hippocampi than healthy controls (HC), purportedly representing exposure to chronic stress. However, the relationship between the individual clinical phenotype, hippocampal volume and diurnal cortisol signaling remains unclear.
Since understanding the interplay among symptoms, neuroimaging and HPA function is crucial for discerning biological differences between PMD and NPMD, this study explored the link between clinical phenotype, hippocampal structural MRI and circadian plasma cortisol levels in 32 HC, 27 NPMD and 26 PMD patients.
PMD patients showed significantly elevated evening (6 p.m. - 1 a.m.) cortisol levels compared to NPMD and HC, while NPMD and HC did not differ. No group differences in hippocampal volume were observed, but a significant interaction effect emerged between overnight (1 a.m. - 9 a.m.) cortisol levels, hippocampal volume, and clinical phenotype. NPMD patients displayed a negative correlation between overnight cortisol levels and hippocampal volume, which was specific to the ascending cortisol curve (2 a.m. - 5 a.m.) and absent in PMD and HC. The hippocampus-cortisol interaction was associated with depressive symptom severity in NPMD but not PMD, where cortisol alone predicted greater severity.
These findings imply a time-dependent relationship between hippocampal volume and overnight cortisol in NPMD, which is absent in PMD and HC. In contrast, PMD patients exhibited increased evening cortisol levels. In an exploratory analysis, these effects were also related to symptom severity at similar timepoints. While correlational, these results point to distinct neurobiological mechanisms underlying NPMD and PMD, which are potentially related to the heterogeneous clinical manifestations.
精神病性重度抑郁症（PMD）在精神病理学方面与非精神病性重度抑郁症（NPMD）不同，并且与脑容量测定及下丘脑 - 垂体 - 肾上腺（HPA）轴功能的变化有关，这些变化可通过其主要产物——糖皮质激素皮质醇反映出来。NPMD患者的海马体积小于健康对照（HC），据称这代表了长期暴露于慢性应激。然而，个体临床表型、海马体积与昼夜皮质醇信号之间的关系仍不清楚。
由于了解症状、神经影像学和HPA功能之间的相互作用对于辨别PMD和NPMD之间的生物学差异至关重要，本研究探讨了32名HC、27名NPMD患者和26名PMD患者的临床表型、海马结构MRI与昼夜血浆皮质醇水平之间的联系。
与NPMD和HC相比，PMD患者的夜间（下午6点至凌晨1点）皮质醇水平显著升高，而NPMD和HC之间无差异。未观察到海马体积的组间差异，但夜间（凌晨1点至上午9点）皮质醇水平、海马体积和临床表型之间出现了显著的交互作用。NPMD患者的夜间皮质醇水平与海马体积呈负相关，这在皮质醇上升曲线（凌晨2点至5点）时具有特异性，在PMD和HC中不存在。海马 - 皮质醇相互作用与NPMD患者的抑郁症状严重程度相关，但与PMD患者无关，在PMD中仅皮质醇可预测更严重的症状。
这些发现表明，NPMD患者的海马体积与夜间皮质醇之间存在时间依赖性关系，而PMD和HC中不存在这种关系。相比之下，PMD患者的夜间皮质醇水平升高。在探索性分析中，这些效应也与相似时间点的症状严重程度相关。虽然这些结果是相关性的，但它们指出了NPMD和PMD潜在的不同神经生物学机制，这可能与异质性临床表现有关。
