Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

Maternal neuroplasticity and mental health during the transition to motherhood

Nature Mental Health volume 3, pages 396–401 (2025)Cite this article

Subjects

Abstract

The first 6 weeks postpartum are characterized by major changes in the bodies of cisgender women and an increased vulnerability to psychiatric disorders such as postpartum depression (PPD). This Perspective addresses the debate over the onset of PPD in the first 6 weeks postpartum and its probable relationship to physiological adaptation processes. Fluctuations in hormone levels during pregnancy and childbirth trigger simultaneous changes in brain structure and function, which are particularly dynamic in the first 6 weeks postpartum. At the same time, rapid hormone withdrawal coincides with mood disorders such as ‘baby blues’ or PPD. Understanding the covariance between the temporal trajectories of hormonal adaptations, time-dependent neuroplasticity and the onset of mood disorders may shed valuable light on the highly sensitive time frame of the first 6 weeks postpartum, which, in addition to being a critical period of transition, may prove to be crucial for the onset of PPD.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Postpartum disorders and hormonal trajectories throughout the postpartum period divided into acute, subacute and delayed phases.

Similar content being viewed by others

References

  1. Blackman, A. et al. Severe maternal morbidity and mental health hospitalizations or emergency department visits. JAMA Netw. Open 7, e247983 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Trost, S. L. et al. Preventing pregnancy-related mental health deaths: insights from 14 US maternal mortality review committees, 2008–17. Health Aff. 40, 1551–1559 (2021).

    Article  Google Scholar 

  3. Xiao, M. et al. Trajectories of perinatal suicidal ideation from early pregnancy to six weeks postpartum and their influencing factors: a prospective longitudinal study. Psychiatry Res. 328, 115467 (2023).

    Article  PubMed  Google Scholar 

  4. Trautmann-Villalba, P. & Hornstein, C. Tötung des eigenen kindes in der postpartalzeit. Nervenarzt 78, 1290–1295 (2007).

    Article  PubMed  Google Scholar 

  5. Bai, Y. et al. Prevalence of postpartum depression based on diagnostic interviews: a systematic review and meta-analysis. Depress. Anxiety 2023, 8403222 (2023).

  6. Stein, A. et al. Effects of perinatal mental disorders on the fetus and child. Lancet 384, 1800–1819 (2014).

    Article  PubMed  Google Scholar 

  7. Diagnostic and Statistical Manual of Mental Disorders 5th edn (American Psychiatric Association, 2013); https://doi.org/10.1176/appi.books.9780890425596.744053

  8. International Classification of Diseases Eleventh Revision (ICD-11) (World Health Organization, 2022).

  9. Radoš, S. N. et al. Diagnosis of peripartum depression disorder: a state-of-the-art approach from the COST Action Riseup-PPD. Compr. Psychiatry 130, 152456 (2024).

    Article  PubMed  Google Scholar 

  10. Munk-Olsen, T. et al. Postpartum and non-postpartum depression: a population-based matched case-control study comparing polygenic risk scores for severe mental disorders. Transl. Psychiatry 13, 346 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Sharma, V. & Mazmanian, D. The DSM-5 peripartum specifier: prospects and pitfalls. Arch. Womens Ment. Health 17, 171–173 (2014).

    Article  PubMed  Google Scholar 

  12. Lindsay, J. R. & Nieman, L. K. The hypothalamic–pituitary–adrenal axis in pregnancy: challenges in disease detection and treatment. Endocr. Rev. 26, 775–799 (2005).

    Article  PubMed  Google Scholar 

  13. Galea, L. A. M. & Frokjaer, V. G. Perinatal depression: embracing variability toward better treatment and outcomes. Neuron 102, 13–16 (2019).

    Article  PubMed  Google Scholar 

  14. Kepley, J. M., Bates, K. & Mohiuddin, S. S. Physiology, Maternal Changes (StatPearls, 2023).

  15. Bloch, M., Daly, R. C. & Rubinow, D. R. Endocrine factors in the etiology of postpartum depression. Compr. Psychiatry 44, 234–246 (2003).

    Article  PubMed  Google Scholar 

  16. Kennerley, H. & Gath, D. Maternity blues. I. Detection and measurement by questionnaire. Br. J. Psychiatry 155, 356–362 (1989).

    Article  PubMed  Google Scholar 

  17. Chechko, N., Losse, E., Frodl, T. & Nehls, S. Baby blues, premenstrual syndrome and postpartum affective disorders: intersection of risk factors and reciprocal influences. BJPsych Open 10, e3 (2024).

    Article  Google Scholar 

  18. Rezaie-Keikhaie, K. et al. Systematic review and meta-analysis of the prevalence of the maternity blues in the postpartum period. J. Obstet. Gynecol. Neonatal Nurs. 49, 127–136 (2020).

    Article  PubMed  Google Scholar 

  19. Reck, C., Stehle, E., Reinig, K. & Mundt, C. Maternity blues as a predictor of DSM-IV depression and anxiety disorders in the first three months postpartum. J. Affect. Disord. 113, 77–87 (2009).

    Article  PubMed  Google Scholar 

  20. Luciano, M. et al. The transition from maternity blues to full-blown perinatal depression: results from a longitudinal study. Front. Psychiatry 12, 703180 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Glangeaud-Freudenthal, N. M. C., Crost, M. & Kaminski, M. Severe post-delivery blues: associated factors. Arch. Womens Ment. Health 2, 37–44 (1999).

    Article  Google Scholar 

  22. Gotlib, I. H. et al. Subgenual anterior cingulate activation to valenced emotional stimuli in major depression. Neuroreport 16, 1731–1734 (2005).

    Article  PubMed  Google Scholar 

  23. Chechko, N., Stickel, S. & Votinov, M. Neural responses to monetary incentives in postpartum women affected by baby blues. Psychoneuroendocrinology 148, 105991 (2023).

    Article  PubMed  Google Scholar 

  24. Henshaw, C., Foreman, D. & Cox, J. Postnatal blues: a risk factor for postnatal depression. J. Psychosom. Obstet. Gynecol. 25, 267–272 (2004).

    Article  Google Scholar 

  25. Bloch, M., Rotenberg, N., Koren, D. & Klein, E. Risk factors for early postpartum depressive symptoms. Gen. Hosp. Psychiatry 28, 3–8 (2006).

    Article  PubMed  Google Scholar 

  26. Turkmen, S., Backstrom, T., Wahlstrom, G., Andreen, L. & Johansson, I. M. Tolerance to allopregnanolone with focus on the GABA-A receptor. Br. J. Pharmacol. 162, 311–327 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Sundström-Poromaa, I., Comasco, E., Sumner, R. & Luders, E. Progesterone—friend or foe? Front. Neuroendocrinol. 59, 100856 (2020).

  28. Deligiannidis, K. M. et al. Effect of zuranolone vs placebo in postpartum depression: a randomized control trial. JAMA Psychiatry 78, 951–959 (2021).

    Article  PubMed  Google Scholar 

  29. Meltzer-Brody, S. & Kanes, S. J. Allopregnanolone in postpartum depression: role in pathophysiology and treatment. Neurobiol. Stress 12, 100212 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Hantsoo, L. & Epperson, C. N. Allopregnanolone in premenstrual dysphoric disorder (PMDD): evidence for dysregulated sensitivity to GABA-A receptor modulating neuroactive steroids across the menstrual cycle. Neurobiol. Stress 12, 100213 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Perry, A., Gordon-Smith, K., Jones, L. & Jones, I. Phenomenology, epidemiology and aetiology of postpartum psychosis: a review. Brain Sci. 11, 47 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Hedges, V. L. et al. Estrogen withdrawal increases postpartum anxiety via oxytocin plasticity in the paraventricular hypothalamus and dorsal raphe nucleus. Biol. Psychiatry 89, 929–938 (2021).

    Article  PubMed  Google Scholar 

  33. Osborne, L. M., Betz, J. F., Yenokyan, G., Standeven, L. R. & Payne, J. L. The role of allopregnanolone in pregnancy in predicting postpartum anxiety symptoms. Front. Psychol. 10, 438990 (2019).

    Article  Google Scholar 

  34. Nehls, S., Losse, E., Enzensberger, C., Frodl, T. & Chechko, N. Time-sensitive changes in the maternal brain and their influence on mother–child attachment. Transl. Psychiatry 14, 84 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Lotter, L. D., Nehls, S., Losse, E., Dukart, J. & Chechko, N. Temporal dissociation between local and global functional adaptations of the maternal brain to childbirth: a longitudinal assessment. Neuropsychopharmacology https://doi.org/10.1038/s41386-024-01880-9 (2024).

  36. Sacher, J., Chechko, N., Dannlowski, U., Walter, M. & Derntl, B. The peripartum human brain: current understanding and future perspectives. Front. Neuroendocrinol. 59, 100859 (2020).

    Article  PubMed  Google Scholar 

  37. Oatridge, A. et al. Change in brain size during and after pregnancy: study in healthy women and women with preeclampsia. Am. J. Neuroradiol. 23, 19–26 (2002).

    PubMed  PubMed Central  Google Scholar 

  38. Hoekzema, E. et al. Pregnancy leads to long-lasting changes in human brain structure. Nat. Neurosci. 20, 287–296 (2017).

    Article  PubMed  Google Scholar 

  39. Hoekzema, E. et al. Mapping the effects of pregnancy on resting state brain activity, white matter microstructure, neural metabolite concentrations and grey matter architecture. Nat. Commun. 13, 6931 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Paternina-Die, M. et al. Women’s neuroplasticity during gestation, childbirth and postpartum. Nat. Neurosci. 27, 319–327 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Chechko, N. et al. The expectant brain—pregnancy leads to changes in brain morphology in the early postpartum period. Cereb. Cortex https://doi.org/10.1093/cercor/bhab463 (2021).

  42. Rocchetti, M. et al. Neurofunctional maps of the ‘maternal brain’ and the effects of oxytocin: a multimodal voxel‐based meta‐analysis. Psychiatry Clin. Neurosci. 68, 733–751 (2014).

    Article  PubMed  Google Scholar 

  43. Kim, P., Strathearn, L. & Swain, J. E. The maternal brain and its plasticity in humans. Horm. Behav. 77, 113–123 (2016).

    Article  PubMed  Google Scholar 

  44. Barba-Müller, E., Craddock, S., Carmona, S. & Hoekzema, E. Brain plasticity in pregnancy and the postpartum period: links to maternal caregiving and mental health. Arch. Womens Ment. Health 22, 289–299 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Ben Shalom, D. The amygdala–insula–medial prefrontal cortex–lateral prefrontal cortex pathway and its disorders. Front. Neuroanat. 16, 1028546 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Chattarji, S., Tomar, A., Suvrathan, A., Ghosh, S. & Rahman, M. M. Neighborhood matters: divergent patterns of stress-induced plasticity across the brain. Nat. Neurosci. 18, 1364–1375 (2015).

    Article  PubMed  Google Scholar 

  47. Barth, C., Villringer, A. & Sacher, J. Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods. Front. Neurosci. 9, 37 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Green, A. D. & Galea, L. A. M. Adult hippocampal cell proliferation is suppressed with estrogen withdrawal after a hormone-simulated pregnancy. Horm. Behav. 54, 203–211 (2008).

    Article  PubMed  Google Scholar 

  49. Kinsley, C. H. et al. Motherhood and the hormones of pregnancy modify concentrations of hippocampal neuronal dendritic spines. Horm. Behav. 49, 131–142 (2006).

    Article  PubMed  Google Scholar 

  50. Pawluski, J. L. & Galea, L. A. M. Reproductive experience alters hippocampal neurogenesis during the postpartum period in the dam. Neuroscience 149, 53–67 (2007).

    Article  PubMed  Google Scholar 

  51. Servin-Barthet, C. et al. The transition to motherhood: linking hormones, brain and behaviour. Nat. Rev. Neurosci. 24, 605–619 (2023).

    Article  PubMed  Google Scholar 

  52. Carmona, S. et al. Pregnancy and adolescence entail similar neuroanatomical adaptations: a comparative analysis of cerebral morphometric changes. Hum. Brain Mapp. 40, 2143–2152 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Martínez-García, M., Paternina-Die, M., Desco, M., Vilarroya, O. & Carmona, S. Characterizing the brain structural adaptations across the motherhood transition. Front. Glob. Womens Health 2, 742775 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Etkin, A., Egner, T. & Kalisch, R. Emotional processing in anterior cingulate and medial prefrontal cortex. Trends Cogn. Sci. 15, 85–93 (2011).

    Article  PubMed  Google Scholar 

  55. Price, J. L. & Drevets, W. C. Neural circuits underlying the pathophysiology of mood disorders. Trends Cogn. Sci. 16, 61–71 (2012).

    Article  PubMed  Google Scholar 

  56. Hahn, L. et al. Early identification of postpartum depression using demographic, clinical, and digital phenotyping. Transl. Psychiatry 11, 121 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  57. Gidén, K., Vinnerljung, L., Iliadis, S. I., Fransson, E. & Skalkidou, A. Feeling better?—Identification, interventions, and remission among women with early postpartum depressive symptoms in Sweden: a nested cohort study. Eur. Psychiatry 67, e14 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  58. Bäckström, T. et al. Allopregnanolone and mood disorders. Prog. Neurobiol. 113, 88–94 (2014).

    Article  PubMed  Google Scholar 

  59. Bixo, M., Andersson, A., Winblad, B., Purdy, R. H. & Bäckström, T. Progesterone, 5α-pregnane-3,20-dione and 3α-hydroxy-5α-pregnane-20-one in specific regions of the human female brain in different endocrine states. Brain Res. 764, 173–178 (1997).

    Article  PubMed  Google Scholar 

  60. Bethea, C. L., Reddy, A. P., Tokuyama, Y., Henderson, J. A. & Lima, F. B. Protective actions of ovarian hormones in the serotonin system of macaques. Front. Neuroendocrinol. 30, 212–238 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Li, Y., Raaby, K. F., Sánchez, C. & Gulinello, M. Serotonergic receptor mechanisms underlying antidepressant-like action in the progesterone withdrawal model of hormonally induced depression in rats. Behav. Brain Res. 256, 520–528 (2013).

    Article  PubMed  Google Scholar 

  62. Kim, H. J., You, M. J., Sung, S., Rim, C. & Kwon, M. S. Possible involvement of microglial P2RY12 and peripheral IL-10 in postpartum depression. Front. Cell. Neurosci. 17, 1162966 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Tan, X. et al. Inhibition of autophagy in microglia alters depressive-like behavior via BDNF pathway in postpartum depression. Front. Psychiatry 9, 411696 (2018).

    Article  Google Scholar 

  64. Zhai, D. S. et al. TOM40 mediates the effect of TSPO on postpartum depression partially through regulating calcium homeostasis in microglia. J. Affect. Disord. 348, 283–296 (2024).

    Article  PubMed  Google Scholar 

  65. Stickel, S. et al. Neural correlates of depression in women across the reproductive lifespan—an fMRI review. J. Affect. Disord. 246, 556–570 (2019).

    Article  PubMed  Google Scholar 

  66. Deecher, D., Andree, T. H., Sloan, D. & Schechter, L. E. From menarche to menopause: exploring the underlying biology of depression in women experiencing hormonal changes. Psychoneuroendocrinology https://doi.org/10.1016/j.psyneuen.2007.10.006 (2008).

  67. Steiner, M., Dunn, E. & Born, L. Hormones and mood: from menarche to menopause and beyond. J. Affect. Disord. 74, 67–83 (2003).

    Article  PubMed  Google Scholar 

  68. Li, Y. et al. Abnormalities of cortical structures in patients with postpartum depression: a surface-based morphometry study. Behav. Brain Res. 410, 113340 (2021).

    Article  PubMed  Google Scholar 

  69. Chen, C. et al. Aberrant structural and functional alterations in postpartum depression: a combined voxel-based morphometry and resting-state functional connectivity study. Front. Neurosci. 17, 1138561 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  70. Sacher, J. et al. Mapping the depressed brain: a meta-analysis of structural and functional alterations in major depressive disorder. J. Affect. Disord. 140, 142–148 (2012).

    Article  PubMed  Google Scholar 

  71. Kim, P. et al. The plasticity of human maternal brain: longitudinal changes in brain anatomy during the early postpartum period. Behav. Neurosci. 124, 695–700 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Lisofsky, N., Gallinat, J., Lindenberger, U. & Kühn, S. Postpartal neural plasticity of the maternal brain: early renormalization of pregnancy-related decreases? Neurosignals 27, 12–24 (2019).

    Article  PubMed  Google Scholar 

  73. Zhang, K., Wang, M., Zhang, J., Du, X. & Chen, Z. Brain structural plasticity associated with maternal caregiving in mothers: a voxel-and surface-based morphometry study. Neurodegener. Dis. 19, 192–203 (2020).

    Article  Google Scholar 

  74. Martínez-García, M. et al. Do pregnancy-induced brain changes reverse? The brain of a mother six years after parturition. Brain Sci. 11, 168 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Morawetz, C., Bode, S., Derntl, B. & Heekeren, H. R. The effect of strategies, goals and stimulus material on the neural mechanisms of emotion regulation: a meta-analysis of fMRI studies. Neurosci. Biobehav. Rev. 72, 111–128 (2017).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This research is supported by the Deutsche Forschungsgemeinschaft (DFG; grant numbers 410314797 and 512021469).

Author information

Author notes

  1. Natalia Chechko & Susanne Nehls

    Present address: Institute of Neuroscience and Medicine, JARA–Institute Brain Structure Function Relationship (INM-10), Research Center Jülich, Jülich, Germany

  2. These authors contributed equally: Natalia Chechko, Susanne Nehls.

Authors and Affiliations

  1. Institute of Neuroscience and Medicine, Brain and Behavior (INM-7), Research Center Jülich, Jülich, Germany

    Natalia Chechko

  2. Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen University, Aachen, Germany

    Natalia Chechko & Susanne Nehls

Authors
  1. Natalia Chechko
    View author publications

    Search author on:PubMed Google Scholar

  2. Susanne Nehls
    View author publications

    Search author on:PubMed Google Scholar

Contributions

N.C. and S.N. contributed equally to the conceptualization, drafting, writing, and critical revision of this perspective. Both authors approved the final version of the manuscript for submission.

Corresponding authors

Correspondence to Natalia Chechko or Susanne Nehls.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Mental Health thanks Alexander Dufford and the other, anonymous reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chechko, N., Nehls, S. Maternal neuroplasticity and mental health during the transition to motherhood. Nat. Mental Health 3, 396–401 (2025). https://doi.org/10.1038/s44220-025-00399-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s44220-025-00399-2

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing