Abstract
Background
Postpartum depression is a common and disabling condition that differs from major depressive disorder and shows marked variation in symptoms and outcomes. Identifying distinct biological subtypes could improve diagnosis and treatment. The present study aims to uncover neurophysiological subtypes of postpartum depression and explore their underlying neural and molecular features.
Methods
We analyzed structural brain images from a cohort of postpartum women recruited at the West China Second Hospital, Sichuan University, including 76 patients with postpartum depression (age range: 24-39 years) and 62 healthy postpartum women (age range: 23-40 years). An unsupervised clustering approach was applied to gray matter volume patterns to identify neurobiological subtypes. Individualized structural covariance networks were then constructed to compare subtype-specific connectivity. Transcriptomic profiles and neurotransmitter density maps were further integrated to examine molecular mechanisms underlying the structural alterations.
Results
Here we show that postpartum depression can be divided into two neurobiological subtypes. Subtype 1 displays reduced gray matter volume in the dorsal attention network, consistent with cognitive impairments. Subtype 2 shows increased gray matter volume in the default mode network, reflecting emotional dysregulation. Subtype 2 also exhibits weaker structural connectivity between the middle temporal gyrus, parahippocampus, and amygdala. Molecular analysis indicates that Subtype 1 is related to energy metabolism and the neurotransmitter receptor mGluR5, whereas Subtype 2 is associated with synaptic regulation, neuroplasticity, and neurotransmitter receptors such as 5-HT1B, dopamine D2, cholinergic M1 and μ-opioid receptor (MOR).
Conclusions
These findings suggest that postpartum depression comprises two biologically distinct forms with different cognitive and emotional characteristics. Recognizing these subtypes may enhance our understanding of its neuropathology and support the development of personalized therapeutic strategies.
Plain language summary
After childbirth, some women experience a serious form of depression called postpartum depression. This condition affects thinking, emotions, and daily life, but not all women experience it in the same way. In this study, we used brain scans to see if there are different types of postpartum depression based on brain structure. We found two groups: one showing changes in brain areas linked to attention and thinking, and another showing changes in regions involved in emotions. These differences were also reflected in brain chemistry and gene activity. Our findings suggest that postpartum depression is not one single disorder, and understanding its biological types may help doctors offer more personalized care and treatment in the future.
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Acknowledgements
This study was supported by Yunnan Fundamental Research Projects (202501AV070005), National Natural Science Foundation of China (32560206), Yunnan Provincial International Joint R&D Center for Precision Healthcare in Maternal-Fetal Medicine (202503AP140051), Key Research and Development Plan of Yunnan Province (202403AC100002), Sichuan Science and Technology Program (2024TFFK0361), Natural Science Foundation of Chongqing (CSTB2024NSCQ-MSX1116), and Open Research Fund of the State Key Laboratory of Brain–Machine Intelligence, Zhejiang University (BMI2500002).
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J.W., K.C., B.C., and X.D. contributed to the conception and design of the study. J.C., Y.L., W.L., M.C., and Y.W. contributed to the acquisition and analysis of data; P.X., X.T., and T.Z. contributed to material preparation and data collection; J.C., Y.L., B.C., K.C., and J.W. wrote and edited the manuscript. All the authors discussed the paper.
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Communications Medicine thanks Yasmin Harrington, Xiaoyu Tong and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. A peer review file is available.
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Chen, J., Liang, Y., Li, W. et al. Mapping neurophysiological biotypes of postpartum depression and underlying neural and molecular basis. Commun Med (2026). https://doi.org/10.1038/s43856-026-01477-x
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DOI: https://doi.org/10.1038/s43856-026-01477-x
