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

Kristina M. Deligiannidis, Christina L. Fales, Aimee R. Kroll-Desrosiers, Scott A. Shaffer, Vanessa Villamarin, Yanglan Tan, Janet E. Hall, Blaise B. Frederick, Elif M. Sikoglu, Richard Anthony Edward Edden, Anthony J. Rothschild, Constance M. Moore

Research output: Contribution to journalArticle

Abstract

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 (1H 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.

Original languageEnglish (US)
JournalNeuropsychopharmacology
DOIs
StateAccepted/In press - Jan 1 2018

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Peripartum Period
Creatine
gamma-Aminobutyric Acid
Postpartum Depression
Steroids
Prefrontal Cortex
Amygdala
Pregnanolone
Occipital Lobe
Postpartum Period
Neurochemistry
Gyrus Cinguli
Magnetic Resonance Imaging
Depression

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Resting-state functional connectivity, cortical GABA, and neuroactive steroids in peripartum and peripartum depressed women : a functional magnetic resonance imaging and spectroscopy study. / Deligiannidis, Kristina M.; Fales, Christina L.; Kroll-Desrosiers, Aimee R.; Shaffer, Scott A.; Villamarin, Vanessa; Tan, Yanglan; Hall, Janet E.; Frederick, Blaise B.; Sikoglu, Elif M.; Edden, Richard Anthony Edward; Rothschild, Anthony J.; Moore, Constance M.

In: Neuropsychopharmacology, 01.01.2018.

Research output: Contribution to journalArticle

Deligiannidis, Kristina M. ; Fales, Christina L. ; Kroll-Desrosiers, Aimee R. ; Shaffer, Scott A. ; Villamarin, Vanessa ; Tan, Yanglan ; Hall, Janet E. ; Frederick, Blaise B. ; Sikoglu, Elif M. ; Edden, Richard Anthony Edward ; Rothschild, Anthony J. ; Moore, Constance M. / Resting-state functional connectivity, cortical GABA, and neuroactive steroids in peripartum and peripartum depressed women : a functional magnetic resonance imaging and spectroscopy study. In: Neuropsychopharmacology. 2018.
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abstract = "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 (1H 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.",
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T2 - a functional magnetic resonance imaging and spectroscopy study

AU - Deligiannidis, Kristina M.

AU - Fales, Christina L.

AU - Kroll-Desrosiers, Aimee R.

AU - Shaffer, Scott A.

AU - Villamarin, Vanessa

AU - Tan, Yanglan

AU - Hall, Janet E.

AU - Frederick, Blaise B.

AU - Sikoglu, Elif M.

AU - Edden, Richard Anthony Edward

AU - Rothschild, Anthony J.

AU - Moore, Constance M.

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N2 - 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 (1H 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.

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