GABAergic neuroactive steroids and resting-state functional connectivity in postpartum depression: A preliminary study

Deligiannidis, Kristina M.; Sikoglu, Elif; Shaffer, Scott A.; Frederick, Blaise; Svenson, Abby E.; Kopoyan, Andre; Kosma, Chelsea A.; Rothschild, Anthony J.; Moore, Constance M.

doi:10.1016/j.jpsychires.2013.02.010

Cited by 135 publications

(127 citation statements)

References 75 publications

(86 reference statements)

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“…Furthermore, there is a growing literature on the important role of reproductive hormones in modulating neural circuits and biological systems implicated in depression, suggesting that the characteristic hormone instability of the perinatal period could contribute to mood dysregulation in post-partum depression. 14,29 …”

Section: Discussionmentioning

confidence: 99%

Clinical phenotypes of perinatal depression and time of symptom onset: analysis of data from an international consortium

Putnam

Wilcox

Robertson-Blackmore

et al. 2017

The Lancet Psychiatry

234

184

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Summary Background The perinatal period is a time of high risk for onset of depressive disorders and is associated with substantial morbidity and mortality, including maternal suicide. Perinatal depression comprises a heterogeneous group of clinical subtypes, and further refinement is needed to improve treatment outcomes. We sought to empirically identify and describe clinically relevant phenotypic subtypes of perinatal depression, and further characterise subtypes by time of symptom onset within pregnancy and three post-partum periods. Methods Data were assembled from a subset of seven of 19 international sites in the Postpartum Depression: Action Towards Causes and Treatment (PACT) Consortium. In this analysis, the cohort was restricted to women aged 19–40 years with information about onset of depressive symptoms in the perinatal period and complete prospective data for the ten-item Edinburgh postnatal depression scale (EPDS). Principal components and common factor analysis were used to identify symptom dimensions in the EPDS. The National Institute of Mental Health research domain criteria functional constructs of negative valence and arousal were applied to the EPDS dimensions that reflect states of depressed mood, anhedonia, and anxiety. We used k-means clustering to identify subtypes of women sharing symptom patterns. Univariate and bivariate statistics were used to describe the subtypes. Findings Data for 663 women were included in these analyses. We found evidence for three underlying dimensions measured by the EPDS: depressed mood, anxiety, and anhedonia. On the basis of these dimensions, we identified five distinct subtypes of perinatal depression: severe anxious depression, moderate anxious depression, anxious anhedonia, pure anhedonia, and resolved depression. These subtypes have clear differences in symptom quality and time of onset. Anxiety and anhedonia emerged as prominent symptom dimensions with post-partum onset and were notably severe. Interpretation Our findings show that there might be different types and severity of perinatal depression with varying time of onset throughout pregnancy and post partum. These findings support the need for tailored treatments that improve outcomes for women with perinatal depression. Funding Janssen Research & Development.

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Section: Discussionmentioning

confidence: 99%

Clinical phenotypes of perinatal depression and time of symptom onset: analysis of data from an international consortium

Putnam

Wilcox

Robertson-Blackmore

et al. 2017

The Lancet Psychiatry

234

184

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“…Significant research links low levels of allopregnanolone to depressed mood Eser et al, 2006;Le Melledo and Baker, 2004;Padberg et al, 2002;Pinna et al, 2006;Schule et al, 2014;Strohle et al, 1999;Uzunova et al, 2006) and other evidence links mood states or histories thereof with alterations in the ratio of allopregnanolone to its precursors (Girdler et al, 2012;Schiller et al, 2014). In the perinatal period specifically, Deligiannidis et al (2013), in a small sample, found no relationship between pregnancy allopregnanolone and the development of PPD, whereas Hellgren et al (2014) found significantly lower levels of allopregnanolone in depressed pregnant women when compared with healthy controls (Hellgren et al, 2014). In a separate analysis, our group found that low levels of allopregnanolone measured in the second trimester predicted the development of PPD (p = 0.01); this effect was driven by women who were euthymic in the second trimester (Osborne et al, under review).…”

Section: Discussionmentioning

confidence: 99%

Replication of Epigenetic Postpartum Depression Biomarkers and Variation with Hormone Levels

Osborne

Clive

Kimmel

et al. 2015

Neuropsychopharmacol

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DNA methylation variation at HP1BP3 and TTC9B is modified by estrogen exposure in the rodent hippocampus and was previously shown to be prospectively predictive of postpartum depression (PPD) when modeled in antenatal blood. The objective of this study was to replicate the predictive efficacy of the previously established model in women with and without a previous psychiatric diagnosis and to understand the effects of changing hormone levels on PPD biomarker loci. Using a statistical model trained on DNA methylation data from N = 51 high-risk women, we prospectively predicted PPD status in an independent N = 51 women using first trimester antenatal gene expression levels of HP1BP3 and TTC9B, with an area under the receiver operator characteristic curve (AUC) of 0.81 (95% CI: 0.69-0.92, po5 × 10 − 4 ). Modeling DNA methylation of these genes in N = 240 women without a previous psychiatric diagnosis resulted in a cross-sectional prediction of PPD status with an AUC of 0.81 (95% CI: 0.68-0.93, p = 0.01). TTC9B and HP1BP3 DNA methylation at early antenatal time points showed moderate evidence for association to the change in estradiol and allopregnanolone over the course of pregnancy, suggesting that epigenetic variation at these loci may be important for mediating hormonal sensitivity. In addition both loci showed PPD-specific trajectories with age, possibly mediated by age-associated hormonal changes. The data add to the growing body of evidence suggesting that PPD is mediated by differential gene expression and epigenetic sensitivity to pregnancy hormones and that modeling proxies of this sensitivity enable accurate prediction of PPD.

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“…A second study by Deligiannidis et al . (146) of eight PPD and nine healthy mothers studied at 9 weeks postpartum similarly showed attenuated functional connectivity in numerous corticolimbic circuits, including coupling within the DMN of ACC, inferior parietal cortex and precuneus, as well as between DMN nodes and amygdala. A contradictory report by Xiao-juan et al .…”

Section: Default Mode Networkmentioning

confidence: 97%

In Search of Neural Endophenotypes of Postpartum Psychopathology and Disrupted Maternal Caregiving

Moses‐Kolko

Horner

Phillips

et al. 2014

J Neuroendocrinology

123

100

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This is a selective review that provides the context for the study of perinatal affective disorder mechanisms and outlines directions for future research. We integrate existing literature along neural networks of interest for affective disorders and maternal caregiving: (i) the salience/fear network; (ii) the executive network; (iii) the reward/social attachment network; and (iv) the default mode network. Extant salience/fear network research reveals disparate responses and corticolimbic coupling to various stimuli based upon a predominantly depressive versus anxious (post-traumatic stress disorder) clinical phenotype. Executive network and default mode connectivity abnormalities have been described in postpartum depression (PPD), although studies are very limited in these domains. Reward/social attachment studies confirm a robust ventral striatal response to infant stimuli, including cry and happy infant faces, which is diminished in depressed, insecurely attached and substance-using mothers. The adverse parenting experiences received and the attachment insecurity of current mothers are factors that are associated with a diminution in infant stimulus-related neural activity similar to that in PPD, and raise the need for additional studies that integrate mood and attachment concepts in larger study samples. Several studies examining functional connectivity in resting state and emotional activation functional magnetic resonance imaging paradigms have revealed attenuated corticolimbic connectivity, which remains an important outcome that requires dissection with increasing precision to better define neural treatment targets. Methodological progress is expected in the coming years in terms of refining clinical phenotypes of interest and experimental paradigms, as well as enlarging samples to facilitate the examination of multiple constructs. Functional imaging promises to determine neural mechanisms underlying maternal psychopathology and impaired caregiving, such that earlier and more precise detection of abnormalities will be possible. Ultimately, the discovery of such mechanisms will promote the refinement of treatment approaches toward maternal affective disturbance, parenting behaviours and the augmentation of parenting resiliency.

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GABAergic neuroactive steroids and resting-state functional connectivity in postpartum depression: A preliminary study

Cited by 135 publications

References 75 publications

Clinical phenotypes of perinatal depression and time of symptom onset: analysis of data from an international consortium

Clinical phenotypes of perinatal depression and time of symptom onset: analysis of data from an international consortium

Replication of Epigenetic Postpartum Depression Biomarkers and Variation with Hormone Levels

In Search of Neural Endophenotypes of Postpartum Psychopathology and Disrupted Maternal Caregiving

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