Preliminary evidence of reduced occipital GABA concentrations in puerperal women: A 1H-MRS study

Department of Psychiatry, Yale University School of Medicine, and Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT 06519, USA.
Psychopharmacology (Impact Factor: 3.88). 07/2006; 186(3):425-33. DOI: 10.1007/s00213-006-0313-7
Source: PubMed


Childbirth is associated with rapid neuroendocrine fluctuations, which are thought to contribute to the phatogenesis of postpartum major depression (PPD).
The aim of this proton magnetic resonance spectroscopy (1H-MRS) study was two-fold; 1) to examine whether puerperium is associated with alterations in occipital cortex gamma-aminobutyric acid (GABA) concentrations and 2) to determine whether such alterations may be more prominent in women with PPD.
Nine women with PPD, 14 postpartum healthy controls, and ten healthy follicular phase females underwent 1H-MRS at 2.1 Tesla to measure occipital cortex GABA concentrations. Postpartum women were scanned within 6 months of delivery and prior to resumption of menstruation. Healthy non-puerperal controls, drawn from a historical sample, were scanned during the early to mid-follicular phase when ovarian hormone levels would be similar to those found in the puerperium. GABA data were analyzed using analysis of covariance, and regression models were used to explore the relationship between cortical GABA concentrations and blood levels of estradiol, progesterone, and neurosteroids.
Cortical GABA and plasma allopregnanolone (ALLO) concentrations were reduced in both groups of postpartum women, regardless of PPD diagnosis, compared to healthy follicular phase women. There was no correlation between cortical GABA concentrations and estradiol, progesterone, ALLO, or pregnenolone (PREG).
This study is the first to describe reductions in occipital cortex GABA levels in the postpartum period, a time of increased vulnerability to mood disturbances in women. The concomitant reduction in peripheral ALLO levels provides further evidence of alterations in the balance between cortical excitation and inhibition during the puerperium. Women with PPD may represent a subgroup of women who fail to adequately adapt to this alteration in the neuroendocrine milieu.

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    • "One limitation of our study is that only males were enrolled in our cohort; in the literature, there is a lack of data on females because of the effects of the menstrual cycle on GABA concentrations (Silveri et al., 2013;Epperson et al., 2006). In our statistical analysis, we found a significant correlation in TIOM 2B-0B , but not in TIOM 1B-0B or TIOM rest . "

    Full-text · Dataset · Jan 2016
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    • "One limitation of our study is that only males were enrolled in our cohort; in the literature, there is a lack of data on females because of the effects of the menstrual cycle on GABA concentrations (Silveri et al., 2013;Epperson et al., 2006). In our statistical analysis, we found a significant correlation in TIOM 2B-0B , but not in TIOM 1B-0B or TIOM rest . "
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    ABSTRACT: Detailed studies on the association between neural oscillations and the neurotransmitters gamma-aminobutyric acid (GABA) and glutamate have been performed in vitro. In addition, recent functional magnetic resonance imaging studies have characterized these neurotransmitters in task-induced deactivation processes during a working memory (WM) task. However, few studies have investigated the relationship between these neurotransmitters and task-induced oscillatory changes in the human brain. Here, using combined magnetoencephalography (MEG) and magnetic resonance spectroscopy (MRS), we investigated the modulation of GABA and glutamate + glutamine (Glx) concentrations related to task-induced oscillations in neural activity during a WM task. We first acquired resting-state MRS and MEG data from 20 healthy male volunteers using the n-back task. Time-frequency analysis was employed to determine the power induced during the encoding and retention phases in perigenual anterior cingulate cortex (pg-ACC), mid-ACC, and occipital cortex (OC). Statistical analysis showed that increased WM load was associated with task-induced oscillatory modulations (TIOMs) of the theta-gamma band relative to the zero-back condition (TIOM0B) in each volume of interest during the encoding phase of the n-back task. The task-induced oscillatory modulations in the two-back condition relative to the zero-back condition (TIOM2B-0B) were negatively correlated with the percent rate change of the correct hit rate for 2B-0B, but positively correlated with GABA/Glx. The positive correlation between TIOM2B-0B and GABA/Glx during the WM task indicates the importance of the inhibition/excitation ratio. In particular, a low inhibition/excitation ratio is essential for the efficient inhibition of irrelevant neural activity, thus producing precise task performance.
    Full-text · Article · Jan 2016 · NeuroImage
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    • "The evidence for altered GABA signaling contributing to depression and anxiety disorders is growing (reviewed; [7]–[10]). There are decreased GABA concentrations in plasma [11], CSF and brain [12]–[14], and fewer GABA neurons in the orbitofrontal cortex of individuals with various forms of depression [15]. There are links for polymorphisms of the GAD 65 gene with anxiety behaviors in children [16] and of the GAD 67 gene with depression in women [17]. "
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    ABSTRACT: Neurons of the paraventricular nucleus of the hypothalamus (PVN) regulate the hypothalamic- pituitary-adrenal (HPA) axis and the autonomic nervous system. Females lacking functional GABAB receptors because of a genetic disruption of the R1 subunit have altered cellular characteristics in and around the PVN at birth. The genetic disruption precluded appropriate assessments of physiology or behavior in adulthood. The current study was conducted to test the long term impact of a temporally restricting pharmacological blockade of the GABAB receptor to a 7-day critical period (E11-E17) during embryonic development. Experiments tested the role of GABAB receptor signaling in fetal development of the PVN and later adult capacities for adult stress related behaviors and physiology. In organotypic slices containing fetal PVN, there was a female specific, 52% increase in cell movement speeds with GABAB receptor antagonist treatment that was consistent with a sex-dependent lateral displacement of cells in vivo following 7 days of fetal exposure to GABAB receptor antagonist. Anxiety-like and depression-like behaviors, open-field activity, and HPA mediated responses to restraint stress were measured in adult offspring of mothers treated with GABAB receptor antagonist. Embryonic exposure to GABAB receptor antagonist resulted in reduced HPA axis activation following restraint stress and reduced depression-like behaviors. There was also increased anxiety-like behavior selectively in females and hyperactivity in males. A sex dependent response to disruptions of GABAB receptor signaling was identified for PVN formation and key aspects of physiology and behavior. These changes correspond to sex specific prevalence in similar human disorders, namely anxiety disorders and hyperactivity.
    Full-text · Article · Aug 2014 · PLoS ONE
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