Resting-state functional connectivity, cortical GABA, and neuroactive steroids in peripartum and peripartum depressed women: a functional magnetic resonance imaging and spectroscopy study

UMMS Affiliation

Department of Psychiatry, Center for Psychopharmacologic Research and Treatment; Department of Quantitative Health Sciences; Mass Spectrometry Facility; Department of Biochemistry and Molecular Pharmacology; Center for Comparative Neuroimaging

Publication Date


Document Type



Biochemistry | Endocrine System | Female Urogenital Diseases and Pregnancy Complications | Hormones, Hormone Substitutes, and Hormone Antagonists | Nervous System | Neuroscience and Neurobiology | Pharmacology, Toxicology and Environmental Health | Psychiatry | Psychiatry and Psychology | Reproductive and Urinary Physiology | Women's Health


Postpartum depression (PPD) is associated with abnormalities in resting-state functional connectivity (RSFC) but the underlying neurochemistry is unclear. We hypothesized that peripartum GABAergic neuroactive steroids (NAS) are related to cortical GABA concentrations and RSFC in PPD as compared to healthy comparison women (HCW). To test this, we measured RSFC with fMRI and GABA+/Creatine (Cr) concentrations with proton magnetic resonance spectroscopy ((1)H MRS) in the pregenual anterior cingulate (pgACC) and occipital cortices (OCC) and quantified peripartum plasma NAS. We examined between-group differences in RSFC and the relationship between cortical GABA+/Cr concentrations with RSFC. We investigated the relationship between NAS, RSFC and cortical GABA+/Cr concentrations. Within the default mode network (DMN) an area of the dorsomedial prefrontal cortex (DMPFC) had greater connectivity with the rest of the DMN in PPD (peak voxel: MNI coordinates (2, 58, 32), p = 0.002) and was correlated to depression scores (peak HAM-D17 voxel: MNI coordinates (0, 60, 34), p = 0.008). pgACC GABA+/Cr correlated positively with DMPFC RSFC in a region spanning the right anterior/posterior insula and right temporal pole (r = +0.661, p = 0.000). OCC GABA+/Cr correlated positively with regions spanning both amygdalae (right amygdala: r = +0.522, p = 0.000; left amygdala: r = +0.651, p = 0.000) as well as superior parietal areas. Plasma allopregnanolone was higher in PPD (p = 0.03) and positively correlated with intra DMPFC connectivity (r = +0.548, p = 0.000) but not GABA+/Cr. These results provide initial evidence that PPD is associated with altered DMN connectivity; cortical GABA+/Cr concentrations are associated with postpartum RSFC and allopregnanolone is associated with postpartum intra-DMPFC connectivity.


Gonadal hormones, Prefrontal cortex

DOI of Published Version



Neuropsychopharmacology. 2019 Feb;44(3):546-554. doi: 10.1038/s41386-018-0242-2. Epub 2018 Oct 17. Link to article on publisher's site

Journal/Book/Conference Title

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

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