Abnormalities of cortical structures in patients with postpartum depression: A surface-based morphometry study.

BACKGROUND: Postpartum depression (PPD) is a serious postpartum mental health problem worldwide. However, the cortical structural alterations in patients with PPD remain unclear. This study investigated the cortical structural alterations of PPD patients through multidimensional structural patterns and their potential correlations with clinical severity. METHODS: High-resolution 3D T1 structural images were acquired from 21 drug-naive patients with PPD and 18 healthy postpartum women matched for age, educational level, and body mass index. The severity of PPD was assessed by using the Hamilton Depression Scale (HAMD) and Edinburgh Postnatal Depression Scale (EPDS) scores. Cortical morphological parameters including cortical thickness, surface area, and mean curvature were calculated using the surface-based morphometric (SBM) method. General linear model (GLM) analyses were performed to evaluate the relationship of cortical morphological parameters with clinical scales. RESULTS: In the present study, PPD patients showed a thinner cortical thickness in the right inferior parietal lobule compared with the healthy controls. Increased surface area was observed in the left superior frontal gyrus, caudal middle frontal gyrus, middle temporal gyrus, insula, and right supramarginal cortex in PPD patients. Likewise, PPD patients exhibited a higher mean curvature in the left superior and right inferior parietal lobule. Furthermore, increased cortical surface area in the left insula had a positive correlation with EPDS scores, and higher mean curvature in the left superior parietal lobule was negatively correlated with EPDS scores. LIMITATIONS: First, SBM cannot reflect the changes of subcortical structures that are considered to play a role in the development of PPD. Second, the sample size of this study is small. These positive results should be interpreted with caution. Third, this cross-sectional study does not involve a comparison of structural MRI before and after pregnancy. CONCLUSIONS: The complex cortical structural alterations of patients with PPD mainly involved the prefrontal and parietal regions. The morphometric alterations in these specific regions may provide promising markers for assessing the severity of PPD.

A prospective study to explore the relationship between MTHFR C677T genotype, physiological folate levels, and postpartum psychopathology in at-risk women.

BACKGROUND: The etiology of postpartum psychopathologies are not well understood, but folate metabolism pathways are of potential interest. Demands for folate increase dramatically during pregnancy, low folate level has been associated with psychiatric disorders, and supplementation may improve symptomatology. The MTHFR C677T variant influences folate metabolism and has been implicated in depression during pregnancy. OBJECTIVE: To conduct a prospective longitudinal study to explore the relationship between MTHFR C677T genotype, folate levels, and postpartum psychopathology in at-risk women. HYPOTHESIS: In the first three months postpartum, folate will moderate a relationship between MTHFR genotype and depression, with TT homozygous women having more symptoms than CC homozygous women. METHODS: We recruited 365 pregnant women with a history of mood or psychotic disorder, and at 3 postpartum timepoints, administered the Edinburgh Postnatal Depression Scale (EPDS); Clinician-Administered Rating Scale for Mania (CARS-M) and the Positive and Negative Symptom Scale (PANSS) and drew blood for genotype/folate level analysis. We used robust linear regression to investigate interactions between genotype and folate level on the highest EPDS and CARS-M scores, and logistic regression to explore interactions with PANSS psychosis scores above/below cut-off. RESULTS: There was no significant interaction effect between MTHFR genotype and folate level on highest EPDS (p = 0.36), but there was a significant interaction between genotype, folate level and log(CARS-M) (p = 0.02); post-hoc analyses revealed differences in the effect of folate level between CC/CT, and TT genotypes, with folate level in CC and CT having an inverse relationship with symptoms of mania, while there was no relationship in participants with TT genotype. There was no significant interaction between MTHFR genotype and folate level on the likelihood of meeting positive symptom criteria for psychosis on the PANSS (p = 0.86). DISCUSSION: These data suggest that perhaps there is a relationship between MTHFR C677T, folate level and some symptoms of postpartum psychopathology.

Factors associated with postpartum depression among women in Vientiane Capital, Lao People's Democratic Republic: A cross-sectional study.

Postpartum depression is a worldwide public health concern. The prevalence of postpartum depression is reported to be greater in developing countries than in developed countries. However, to the best of our knowledge, no papers on postpartum depression in the Lao People's Democratic Republic have been published. In order to strengthen maternal and child health, the current situation of postpartum depression should be understood. This study aims to determine the prevalence of postpartum depression and identify factors associated with postpartum depression in Vientiane Capital, Lao People's Democratic Republic. Study participants were 428 women 6-8 weeks postpartum who visited four central hospitals in Vientiane Capital for postnatal care from July to August 2019. Structured questionnaires were used to collect socio-demographic, obstetrical and infant, and psychiatric data about the women and their partners. The Edinburgh Postnatal Depression Scale (EPDS) was used to identify suspected cases of postpartum depression with the cut-off score of 9/10. Multivariable logistic regression was used to examine independent factors that were associated with suspected postpartum depression (EPDS ≥10). The mean age of the 428 women was 28.1 years, and the prevalence of suspected postpartum depression was 31.8%. Multivariable logistic regression using variables that were statistically significant on bivariate analyses indicated that three variables were associated with suspected postpartum depression: unintended pregnancy (AOR = 1.66, 95% CI 1.00-2.73, P = 0.049), low birth satisfaction (AOR = 1.85, 95% CI 1.00-3.43, P = 0.049), and depression during pregnancy (AOR = 3.99, 95% CI 2.35-6.77, P <0.001). In this study, unintended pregnancy, low birth satisfaction, and depression during pregnancy were independent risk factors for postpartum depression. These results suggest that the mental health of pregnant women should be monitored, and that health care services, especially family planning and supportive birth care, should be strengthened to prevent postpartum depression.

A comparative study of domestic decision-making power and social support as predictors of postpartum depressive and physical symptoms between immigrant and native-born women.

BACKGROUND: Women's participation in decision-making in the household is an indicator of women's empowerment. Few studies have compared domestic decision-making power and its effect on postpartum health between immigrant and native-born women. This study aimed to examine the effect of domestic decision-making power and social support during pregnancy on predicting postpartum depressive and physical symptoms among immigrant and native-born mothers in Taiwan. METHODS AND FINDINGS: This prospective study recruited 177 marriage-based immigrant mothers and 230 native-born women who were at least twelve weeks pregnant from hospitals, clinics and health centers. Data were collected in the 2nd or 3rd trimester of pregnancy and at 3 months postpartum from March 2013 to March 2015. Postpartum depression and the severity of postpartum physical symptoms were measured using the Edinburgh Postnatal Depression Scale, and a 17-item, 4-point Likert scale, respectively. Linear regression was used to examine the relationship between "domestic decision-making power and social support during pregnancy" and "depressive and physical symptoms at 3 months postpartum." Women who had lower domestic decision-making power and social support during pregnancy had higher postpartum depressive and physical symptoms. Those women with full-time employment and insufficient family income had higher postpartum depressive symptoms. Though immigrant women scored lower in domestic decision-making power and social support than native-born women, they had lower mean scores in postpartum depressive and physical symptoms. After accounting for the abovementioned factors, immigrant women remained at lower risk for postpartum depressive and physical symptoms than native-born women. There was significant interaction between domestic decision-making power and immigrant status, suggesting that the association between domestic decision-making and postpartum depressive and physical symptoms was smaller for immigrants than for native women. CONCLUSIONS: Domestic decision-making power and social support during pregnancy are protective predictors of postpartum depressive and physical symptoms. However, the effect of domestic decision-making power appeared to be less salient for immigrants, probably due to the "healthy immigrant effect" and/or lower expectations toward domestic decision-making power among immigrants. The finding that immigrant women demonstrated a lower level of domestic decision-making power suggests that empowerment issues need to be addressed among immigrants.

Inhibition of expression of glucocorticoids receptors may contribute to postpartum depression.

Although postpartum depression (PPD) is the leading cause of disability worldwide, its molecular mechanisms are poorly understood. Recent evidence has suggested that impaired glucocorticoid receptor (GR), the signaling of key molecules of the HPA axis, plays a key role in the behavioral and neuroendorcrine alterations of major depression. However, the role of GR in postpartum period, which following with the abrupt withdrawal of placental corticotropin releasing hormone (CRH) and resulting in a re-equilibration of the maternal HPA axis in the days of post-delivery, is still not entirely clear. Previously, a hormone-simulated pregnancy (HSP), and the subsequent 'postpartum' withdrawal in estrogen has been employed to mimic the fluctuations in estradiol associated with pregnancy and postpartum. Using the HSP model, we investigated here the effect of 'postpartum' withdrawal in estrogen as well as depression- and anxiety-like behavior by intra-hippocampal infusion with GR inhibitor-RU486. Following the successful acquisition of PPD model by withdrawal in estrogen, reduced GR expression was observed in hippocampus. Further, HSP-rats suffered intra-hippocampal RU486 infusion presented depression- and anxiety-like behavior as postpartum depression. Together, these results suggest an important, though complex, role for GR in the behavioral regulation of postpartum depression.

Association between vitamin D deficiency and antepartum and postpartum depression: a systematic review and meta-analysis of longitudinal studies.

PURPOSE: The two previous reviews performed on the association of vitamin D deficiency in pregnancy with antepartum and postpartum depression were limited in reporting forms as they were both systematic reviews and the conclusions were also deemed to be inconclusive. Considering the high prevalence of vitamin D deficiency and depression during and after pregnancy as well as their numerous hazards to pregnancy outcomes, it is of great need to synthesize existing evidence in a more accurate statistical method, so that reliable guidance related to vitamin D supplementation during pregnancy could be provided for clinical decision making. METHODS: We performed a systematic review and meta-analysis to investigate the association of vitamin D deficiency with antepartum and postpartum depression. RESULTS: Nine longitudinal studies with 8470 participants were included in the meta-analysis. We found serum 25(OH)D levels < 50 nmol/l was associated with 2.67 times (OR 3.67; 95% CI 1.72-7.85) increased risk of postpartum depression than those 25(OH)D levels ≥ 50 nmol/l, but we did not find a significant association between low vitamin D levels and depressive symptoms during pregnancy with a serum 25(OH)D cut-off level of 30 nmol/l (OR 1.47; 95% CI 0.92-2.36). CONCLUSIONS: The low status of maternal vitamin D could be an adverse factor for postpartum depression, but the available evidence suggested no association between vitamin D deficiency and depressive symptoms during pregnancy. However, this result should be interpreted with caution owning to the small number of studies. Well-designed intervention studies are also needed to further evaluate the benefits of vitamin D supplementation during pregnancy.

High nursing demand reduces depression-like behavior despite increasing glucocorticoid concentrations and reducing hippocampal neurogenesis in late postpartum rats.

Approximately 15% of women who give birth develop postpartum depression (PPD), and the risk is greater in women who do not breastfeed or who cease breastfeeding early. In some women, early cessation or absence of breastfeeding precedes PPD, but the neuroendocrine mechanisms of this relationship are unknown. We tested whether nursing demand would alter behavioral and endocrine endpoints relevant for depression in postpartum rats. Adult female Sprague-Dawley rats underwent thelectomy (thel; removal of teats), sham surgery (sham), or no surgery (control). Litters were rotated between thel and sham rats every 12 h, yielding a higher nursing burden for sham rats. We investigated behavior in the forced swim test (FST), open field test, and sucrose preference test, and serum corticosterone (CORT) concentrations. Because the hippocampus changes structurally in depression and with maternal experience, we investigated cell proliferation using Ki-67 and hippocampal neurogenesis and immature neuron development using doublecortin (DCX) immunohistochemistry. Sham rats spent less time immobile in the FST compared with control and thel rats. Sham rats also had higher CORT concentrations and fewer Ki-67 cells. Thel rats had more DCX-expressing cells and a greater proportion of mature DCX-expressing cells compared with control and sham rats. These data suggest that greater nursing demand reduces stress-related behavioral responses despite increasing CORT concentrations and suppressing hippocampal neurogenesis. This work is an important step in identifying how lactation buffers behavioral responses to stress and reorganizes stress-related neural circuitry and is crucial for identifying mechanisms of postpartum psychiatric illnesses.

Antidepressant-like effects of translocator protein (18 kDa) ligand ZBD-2 in mouse models of postpartum depression.

The 18 kDa translocator protein (TSPO) is primarily localized in the outer mitochondrial membrane of steroid-synthesizing cells in the central and peripheral nervous systems. One of the protein's main functions is transporting substrate cholesterol into the mitochondria in a prerequisite process for steroid synthesis. Clinical trials have indicated that TSPO ligands might be valuable in treating some neuropathies and psychopathies. However, limited information is known about the role of TSPO in postpartum depression (PPD). The TSPO ligand ZBD-2, a derivative of XBD173, was synthesized in our laboratory. Behavioral tests, enzyme linked immunosorbent assay, and Western blot were employed to evaluate ZBD-2's efficacy against PPD and to elucidate the potential underlying molecular mechanism. The TSPO levels significantly decreased in the basolateral amygdala of PPD models. After treatment for 2 weeks, ZBD-2 alleviated depression-like behaviors and enhanced the TSPO level in a PPD animal model. The underlying mechanisms of ZBD-2 were related to regulate the hypothalamic-pituitary-adrenal axis, enhance 5-HT and BDNF secretion, and maintain the excitatory and inhibitory synaptic protein expression to normal levels. Our results directly confirm that ZBD-2 exerts a therapeutic effect on PPD, which provides a new target for anti-PPD drug development.

White matter integrity in medication-free women with peripartum depression: a tract-based spatial statistics study.

Diffusion tensor imaging (DTI) studies in depression show decreased structural connectivity in the left anterior limb of the internal capsule and the genu of the corpus callosum but no such studies exist in peripartum depression (PPD), which affects 1 in 8 women. We analyzed fractional anisotropy (FA) as a measure of white matter integrity of these two tracts using tract-based spatial statistics (TBSS). We then conducted an exploratory whole-brain analysis to identify additional regions implicated in PPD. Seventy-five pregnant, medication-free women were evaluated with the Edinburgh Postnatal Depression Scale (EPDS) and Structured Clinical Interview (SCID) for DSM-IV-TR in pregnancy and in the postpartum. Structural MRI and DTI sequences were acquired in forty-four women within 2-8 weeks postpartum. TBSS data were analyzed between healthy comparison postpartum women (HCW) and women who developed PPD to determine differences in white matter integrity within the left anterior limb of the internal capsule and the genu of the corpus callosum, then analyzed across participants to explore correlation between FA and the EPDS score. An exploratory whole-brain analysis was also conducted to identify other potential regions showing differences in white matter integrity between groups, as well as correlation between EPDS and FA across groups. All results were corrected for multiple comparisons and analyses conducted using FSL, p < 0.05, K > 10. In comparison to HCW, women with PPD had significantly lower FA in left anterior limb of the internal capsule (p = 0.010). FA was negatively correlated with EPDS scores in the left anterior limb of the internal capsule (p = 0.019). In the whole-brain analysis, FA in the right retrolenticular internal capsule (p = 0.03) and two clusters within the body of the corpus callosum (p = 0.044, p = 0.050) were negatively correlated with EPDS; there were no between-group differences in FA. Reduced FA in the left anterior limb of the internal capsule suggests disruption of fronto-subcortical circuits in PPD. A negative correlation between FA within the body of the corpus callosum and EPDS total score could additionally reflect disrupted interhemispheric structural connectivity in women with depressive symptoms.

Understanding Peripartum Depression Through Neuroimaging: a Review of Structural and Functional Connectivity and Molecular Imaging Research.

PURPOSE OF REVIEW: Imaging research has sought to uncover brain structure, function, and metabolism in women with postpartum depression (PPD) as little is known about its underlying pathophysiology. This review discusses the imaging modalities used to date to evaluate postpartum depression and highlights recent findings. RECENT FINDINGS: Altered functional connectivity and activity changes in brain areas implicated in executive functioning and emotion and reward processing have been identified in PPD. Metabolism changes involving monoamine oxidase A, gamma-aminobutyric acid, glutamate, serotonin, and dopamine have additionally been reported. To date, no studies have evaluated gray matter morphometry, voxel-based morphometry, surface area, cortical thickness, or white matter tract integrity in PPD. Recent imaging studies report changes in functional connectivity and metabolism in women with PPD vs. healthy comparison women. Future research is needed to extend these findings as they have important implications for the prevention and treatment of postpartum mood disorders.

Influences of prenatal and postnatal maternal depression on amygdala volume and microstructure in young children.

Maternal depressive symptoms influence neurodevelopment in the offspring. Such effects may appear to be gender-dependent. The present study examined contributions of prenatal and postnatal maternal depressive symptoms to the volume and microstructure of the amygdala in 4.5-year-old boys and girls. Prenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) at 26 weeks of gestation. Postnatal maternal depression was assessed at 3 months using the EPDS and at 1, 2, 3 and 4.5 years using the Beck's Depression Inventory-II. Structural magnetic resonance imaging and diffusion tensor imaging were performed with 4.5-year-old children to extract the volume and fractional anisotropy (FA) values of the amygdala. Our results showed that greater prenatal maternal depressive symptoms were associated with larger right amygdala volume in girls, but not in boys. Increased postnatal maternal depressive symptoms were associated with higher right amygdala FA in the overall sample and girls, but not in boys. These results support the role of variation in right amygdala structure in transmission of maternal depression to the offspring, particularly to girls. The differential effects of prenatal and postnatal maternal depressive symptoms on the volume and FA of the right amygdala suggest the importance of the timing of exposure to maternal depressive symptoms in brain development of girls. This further underscores the need for intervention targeting both prenatal and postnatal maternal depression to girls in preventing adverse child outcomes.

Activation of Sigma-1 Receptor Alleviates Postpartum Estrogen Withdrawal-Induced "Depression" Through Restoring Hippocampal nNOS-NO-CREB Activities in Mice.

Postpartum depression affects approximately 15 % of mothers; however, its pathological mechanisms still remain unclear. Ovariectomized adult mice received the administration of estrogen (E2) and progesterone with a subsequent alone E2, termed hormone-simulated pregnancy (HSP). Affective behaviors as assessed by forced swim and tail suspension tests, hippocampal neuronal nitric oxide synthase (nNOS), nitric oxide (NO), cyclic AMP (cAMP) response element binding protein (CREB) phosphorylation (phosphor-CREB), and neurosteroidogenesis were examined before E2 withdrawal (EW; HSP mice) and on days 2-4 (early-EW mice) and days 8-10 (late-EW mice) after EW. Depressive-like behaviors were observed in early-EW mice but not in late-EW mice. Levels of nNOS, NO, and phosphor-CREB were increased in HSP mice followed by a significant decline in early-EW mice with a subsequent restoration in late-EW mice. The treatment of early-EW mice with NO donor alleviated depressive-like behaviors and decline of phosphor-CREB. The nNOS inhibitor and NO scavenger caused depressive-like behaviors and reduced phosphor-CREB in HSP mice and late-EW mice. Notably, the levels of steroidogenic enzymes StAR and P450scc were elevated in late-EW mice. The sigma-1 receptor (σ1R) agonist could alleviate depressive-like behaviors and decline of nNOS-NO-CREB in early-EW mice. The pharmacological blockade or deficiency of σ1R in late-EW mice caused depressive-like behaviors with decline of nNOS-NO-CREB. The reduction of hippocampal brain-derived neurotrophic factor (BDNF) or N-methyl-D-aspartic acid (NMDA) receptor NR2B phosphorylation in early-EW mice could recover in late-EW mice, which was sensitive to the blockade of σ1R. The NMDA receptor agonist, but not TrkB receptor activator, could correct the decline of nNOS-NO-CREB in early-EW mice. The findings indicate that the activation of σ1R can alleviate postpartum "depression" through increasing nNOS-NO-CREB activities.

Stress induces equivalent remodeling of hippocampal spine synapses in a simulated postpartum environment and in a female rat model of major depression.

Stress and withdrawal of female reproductive hormones are known risk factors of postpartum depression. Although both of these factors are capable of powerfully modulating neuronal plasticity, there is no direct electron microscopic evidence of hippocampal spine synapse remodeling in postpartum depression. To address this issue, hormonal conditions of pregnancy and postpartum period were simulated in ovariectomized adult female Sprague-Dawley rats (n=76). The number of hippocampal spine synapses and the depressive behavior of rats in an active escape task were investigated in untreated control, hormone-withdrawn 'postpartum', simulated proestrus, and hormone-treated 'postpartum' animals. After 'postpartum' withdrawal of gonadal steroids, inescapable stress caused a loss of hippocampal spine synapses, which was related to poor escape performance in hormone-withdrawn 'postpartum' females. These responses were equivalent with the changes observed in untreated controls that is an established animal model of major depression. Maintaining proestrus levels of ovarian hormones during 'postpartum' stress exposure did not affect synaptic and behavioral responses to inescapable stress in simulated proestrus animals. By contrast, maintaining pregnancy levels of estradiol and progesterone during 'postpartum' stress exposure completely prevented the stress-induced loss of hippocampal spine synapses, which was associated with improved escape performance in hormone-treated 'postpartum' females. This protective effect appears to be mediated by a muted stress response as measured by serum corticosterone concentrations. In line with our emerging 'synaptogenic hypothesis' of depression, the loss of hippocampal spine synapses may be a novel perspective both in the pathomechanism and in the clinical management of postpartum affective illness.

Demographic, maternal, and infant health correlates of post-partum depression in Jordan.

This cross-sectional correlational study examined post-partum depression and its relationship with demographic, maternal, and infant health problems in urban Jordanian women. Participants (n = 315) were selected from five maternal child healthcare centers and one major hospital in Amman, Jordan. Patient Health Questionnaire-9 was used to measure post-partum depression within 12 weeks of birth. A number of socio-demographic and health problems were examined for an association with post-partum depression. Results showed that 25% of post-partum women suffered moderate to severe depression and 50% of the sample had mild depression. None of the socio-demographic variables (age, education, employment, income) were significantly related to post-partum depression; however, two obstetric/infant variables (mode of birth and breastfeeding), were significantly associated with post-partum depression. There was a significant association between post-partum depression and 15 health problems of obstetric, gynecologic (i.e. episiotomy pain, infection), and general health conditions (i.e. fatigue, headache). Nurses and midwives need to emphasize post-partum depression screening, follow-up, and proper management of maternal and infant health factors predisposing to post-partum depression rather than merely focusing on women's inherent demographic factors.

Magnetic Resonance Imaging Studies of Postpartum Depression: An Overview.

Postpartum depression is a frequent and disabling condition whose pathophysiology is still unclear. In recent years, the study of the neural correlates of mental disorders has been increasingly approached using magnetic resonance techniques. In this review we synthesize the results from studies on postpartum depression in the context of structural, functional, and spectroscopic magnetic resonance studies of major depression as a whole. Compared to the relative wealth of data available for major depression, magnetic resonance studies of postpartum depression are limited in number and design. A systematic literature search yielded only eleven studies conducted on about one hundred mothers with postpartum depression overall. Brain magnetic resonance findings in postpartum depression appear to replicate those obtained in major depression, with minor deviations that are not sufficient to delineate a distinct neurobiological profile for this condition, due to the small samples used and the lack of direct comparisons with subjects with major depression. However, it seems reasonable to expect that studies conducted in larger populations, and using a larger variety of brain magnetic resonance techniques than has been done so far, might allow for the identification of neuroimaging signatures for postpartum depression.

Gestational stress induces persistent depressive-like behavior and structural modifications within the postpartum nucleus accumbens.

Postpartum depression (PPD) is a common complication following childbirth experienced by one in every five new mothers. Pregnancy stress enhances vulnerability to PPD and has also been shown to increase depressive-like behavior in postpartum rats. Thus, gestational stress may be an important translational risk factor that can be used to investigate the neurobiological mechanisms underlying PPD. Here we examined the effects of gestational stress on depressive-like behavior during the early/mid and late postpartum periods and evaluated whether this was accompanied by altered structural plasticity in the nucleus accumbens (NAc), a brain region that has been linked to PPD. We show that early/mid (postpartum day 8) postpartum female rats exhibited more depressive-like behavior in the forced swim test as compared with late postpartum females (postpartum day 22). However, 2 weeks of restraint stress during pregnancy increased depressive-like behavior regardless of postpartum timepoint. In addition, dendritic length, branching and spine density on medium spiny neurons in the NAc shell were diminished in postpartum rats that experienced gestational stress although stress-induced reductions in spine density were evident only in early/mid postpartum females. In the NAc core, structural plasticity was not affected by gestational stress but late postpartum females exhibited lower spine density and reduced dendritic length. Overall, these data not only demonstrate structural changes in the NAc across the postpartum period, they also show that postpartum depressive-like behavior following exposure to gestational stress is associated with compromised structural plasticity in the NAc and thus may provide insight into the neural changes that could contribute to PPD.

Postpartum corticosterone administration reduces dendritic complexity and increases the density of mushroom spines of hippocampal CA3 arbours in dams.

Postpartum depression (PPD) affects approximately 15% of mothers after giving birth. A complete understanding of depression during the postpartum period has yet to be established, although disruptions in the hypothalamic-pituitary-adrenal axis and stress during the postpartum may be involved. To model these components in rats, we administered high corticosterone (CORT) postpartum, which increases immobility in the forced swim test (FST), and reduces maternal care, body weight and hippocampal cell proliferation in dams. The hippocampus is altered in response to chronic stress, exposure to high glucocorticoids and in major depression in humans. In the present study, we examined whether high CORT reduced dendritic complexity and spines in the CA3 region of the hippocampus. Additionally, housing complexity was manipulated so that dams and litters were housed either with tubes (complex) or without tubes (impoverished) to investigate the consequences of new animal care regulations. Dams received 40 mg/kg/day of CORT or oil starting on day 2 postpartum for 23 days. Maternal behaviours were assessed on postpartum days 2-8 and dams were tested using the FST on days 21 and 22. Dams were killed on day 24 and brains were processed for Golgi impregnation. Pyramidal cells in the CA3 subfield were traced using a camera lucida and analysed for branch points and dendritic complexity, as well as spine density and type on both basal and apical arbours. As previously established, high CORT postpartum reduced maternal care and increased immobility in the FST, which is a measure of depressive-like behaviour. High CORT postpartum reduced the complexity of basal arbours and increased mushroom spines on both apical and basal dendrites. Housing complexity had no effect on spines of CA3 pyramidal cells but modest effects on cell morphology. These data show that chronic high CORT in postpartum females alters hippocampal morphology and may provide insight regarding the neurobiological consequences of high stress or CORT during the postpartum period, as well as be relevant for postpartum stress or depression.

Increased glutamate levels in the medial prefrontal cortex in patients with postpartum depression.

The medial prefrontal cortex (MPFC) is a key brain area in depressive symptomatology; specifically, glutamate (Glu) has been reported to play a significant role in major depression (MD) in this area. MPFC Glu levels are sensitive to ovarian hormone fluctuations and pregnancy and the postpartum period are associated with the most substantial physiological alterations of female hormones. It is therefore logical to measure MPFC Glu levels in women with postpartum depression (PPD). Using in vivo magnetic resonance spectroscopy (MRS) at a field strength of 3 T, we acquired single-voxel spectra from the MPFC of 12 women with PPD and 12 healthy controls (HCs) matched for postpartum scan timing. Water-referenced MPFC Glu levels were measured using a MRS technique that allowed us to be specific for Glu with very little glutamine contamination. The concentrations of other water-quantified brain metabolites such as glycerophosphorylcholine plus phosphorylcholine, N-acetylaspartate (NAA), and creatine plus phosphocreatine were measured in the same MR spectra. MPFC Glu levels were higher in women with PPD (7.21±1.20) compared to matched HCs (6.04±1.21). There were no differences between groups for other brain metabolites measured. These findings suggest an association between Glu dysregulation in the MPFC and PPD. Whether the pathophysiology of PPD differs from the pathophysiology of MD remains to be determined. Further investigations are needed to determine the chronological associations between the occurrence of symptoms of PPD and the onset of changes in MPFC Glu levels.