Active ghrelin and the postpartum

Postpartum depression (PPD) occurs in 10%–15% of women. The appetite hormone ghrelin, which fluctuates during pregnancy, is associated with depression in nonpregnant samples. Here, we examine the association between PPD and active ghrelin from pregnancy to postpartum. We additionally examine whether ghrelin changes from pregnancy to postpartum and differs between breastfeeding and non-breastfeeding women

Late pregnancy thyroid-binding globulin predicts perinatal depression

Previously we found that late pregnancy total and free thyroxine (TT4, FT4) concentrations were negatively related to greater pre and/or postpartum depressive symptoms. In a much larger cohort, the current study examined whether these thyroid indices measured earlier in the third trimester (31-33 weeks) predict subsequent perinatal depression and anxiety ratings as well as syndromal depression. Thyroid-binding globulin (TBG) concentrations increase markedly during pregnancy and may be an index of sensitivity to elevated estrogen levels. TBG was examined in this study because prior findings suggest that postpartum depression is related to sensitivity to mood destabilization by elevated sex hormone concentrations during pregnancy. Our cohort was 199 euthyroid women recruited from a public health obstetrics clinic (63.8% Hispanic, 21.6% Black). After screening and blood draws for hormone measures at pregnancy weeks 31-33, subjects were evaluated during home visits at pregnancy weeks 35-36 as well as postpartum weeks 6 and 12. Evaluations included psychiatric interviews for current and life-time DSM-IV psychiatric history (M.I.N.I.-Plus), subject self-ratings and interviewer ratings for depression and anxiety (Edinburgh Postnatal Depression Scale, Montgomery-Ǻsberg Depression Rating Scale; Spielberger State-Trait Anxiety Inventory, Hamilton Anxiety Inventory), as well as a standardized interview to obtain life-time trauma history. Numerous covariates were included in all regression analyses. Trauma and major depression history were robustly significant predictors of depression and anxiety ratings over the study period when these variables were analyzed individually or in a combined model including FT4 or TBG (p<.001). When analyzed alone, FT4 levels were a less strong but still significant predictor of all depression and anxiety ratings (p<.05) while TBG levels was a significant or nearly significant predictor of most ratings. FT4, TBG and trauma history, but not major depression history, were significant individual predictors of syndromal depression during the study period (p<.05) in single predictor models. In models combining each with trauma and major depression history, FT4 and TBG generally were not significantly predictive of depression or anxiety ratings, and FT4 was also not a significant predictor of syndromal depression: however, in the combined model TBG was a particularly strong predictor of perinatal syndromal depression (p=.005) and trauma history was also significant (p=.016). Further study of the interactions among TBG, FT4, sex hormones, trauma history and perinatal depression may provide insights into the pathophysiological basis of individual variance in vulnerability to mood destabilization by the hormone conditions of pregnancy

The influence of early life sexual abuse on oxytocin concentrations and premenstrual symptomatology in women with a menstrually related mood disorder

Oxytocin (OT), associated with affiliation and social bonding, social salience, and stress/pain regulation, may play a role in the pathophysiology of stress-related disorders, including menstrually-related mood disorders (MRMD's). Adverse impacts of early life sexual abuse (ESA) on adult attachment, affective regulation, and pain sensitivity suggest ESA-related OT dysregulation in MRMD pathophysiology. We investigated the influence of ESA on plasma OT, and the relationship of OT to the clinical phenomenology of MRMD's. Compared to MRMD women without ESA (n=40), those with ESA (n=20) displayed significantly greater OT [5.39 pg/mL (SD, 2.4) vs. 4.36 pg/mL (SD, 1.1); t (58) = −2.26, p =.03]. In women with ESA, OT was significantly, inversely correlated with premenstrual psychological and somatic symptoms (r's = −.45 to −.64, p's < .05). The relationship between OT and premenstrual symptomatology was uniformly low and non-significant in women without ESA. In women with ESA, OT may positively modulate MRMD symptomatology

Associations between Self-Rated Health and Perinatal Depressive and Anxiety Symptoms among Latina Women

Purpose: The objective of this study was to determine whether decreases in or consistently low preconception to pregnancy self-rated health (SRH) were associated with perinatal depressive and anxiety symptoms among Latinas. Methods: This is a secondary data analysis of 153 perinatal Latinas. Three groups were created to capture SRH from preconception to pregnancy: a decline in ratings, consistently low, and good+ (i.e., good, very good, or excellent). SRH was measured using two questions about their perceived physical health before and during pregnancy. Depressive symptoms and anxiety symptoms were assessed in the third trimester and six weeks postpartum using the Edinburgh Postnatal Depression Scale and State-Trait Anxiety Inventory, respectively. Life stressors were assessed in pregnancy using a modified version of the Life Experiences Survey. Linear regressions tested the associations. Results: Women with consistently low (i.e., fair or poor) SRH reported significantly more prenatal depressive symptoms than women who reported consistently good+ SRH. Women who reported a decline in SRH to fair or poor reported more prenatal anxiety symptoms but decreased postpartum anxiety symptoms than women who reported consistently good+ ratings. Life stressors were positively associated with prenatal depressive and anxiety symptoms. Conclusions: Healthcare practitioners should assess changes in SRH ratings to identify risks for prenatal depressive and anxiety symptoms among Latinas, who have elevated rates of depressive and anxiety symptoms compared to non-Hispanic White women. Policymakers should provide healthcare providers with mental health resources to support at-risk during the prenatal period

Maternal Neuroendocrine Serum Levels in Exclusively Breastfeeding Mothers

Background: Low milk supply is a common cause of early weaning, and supply issues are associated with dysregulation of thyroid function and prolactin. However, hormone levels compatible with successful breastfeeding are not well defined, limiting interpretation of clinical lab results. In this study we sought to quantify ranges for thyroid-stimulating hormone (TSH), free thyroxine (T4), total T4, and prolactin in a cohort of exclusively breastfeeding women

Failed Lactation and Perinatal Depression: Common Problems with Shared Neuroendocrine Mechanisms?

In the early postpartum period, mother and infant navigate a critical neuroendocrine transition from pregnancy to lactation. Two major clinical problems that occur during this transition are failed lactation and perinatal mood disorders. These disorders often overlap in clinical settings. Failed lactation is common. Although all major medical organizations recommend 6 months of exclusive breastfeeding, only 13% of women in the United States achieve this recommendation. Perinatal mood disorders affect 10% of mothers, with substantial morbidity for mother and child. We hypothesize that shared neuroendocrine mechanisms contribute to both failed lactation and perinatal mood disorders. In this hypothesis article, we discuss data from both animal models and clinical studies that suggest neuroendocrine mechanisms that may underlie these two disorders. Research to elucidate the role of these underlying mechanisms may identify treatment strategies both to relieve perinatal depression and to enable women to achieve their infant feeding goals

Peripherally administered non-peptide oxytocin antagonist, L368,899®, accumulates in limbic brain areas: A new pharmacological tool for the study of social motivation in non-human primates

Central administration of oxytocin (OT) antagonists inhibits maternal and sexual behavior in non-primates, providing the strongest experimental evidence that endogenous OT facilitates these behaviors. While there have been a few reports that ICV administration of OT increases social behaviors in monkeys, no studies to date have assessed the effects of OT antagonists. Therefore, we studied in rhesus monkeys whether L368,899®, a non-peptide antagonist produced by Merck that selectively blocks the human uterine OT receptor, penetrates the CNS after peripheral administration and alters female maternal and sexual behavior. In two studies in four male monkeys, L368,899 was injected iv (1 mg/kg) after which (1) CSF samples were collected at intervals over 4 h and (2) brains were collected at 60 min. Assay of samples confirmed that iv-administered L368,899 entered CSF and accumulated in the hypothalamus, septum, orbitofrontal cortex, amygdala and hippocampus, but not other areas. An adult female monkey was tested for interest in either an infant or sexual behavior, receiving a different iv treatment prior to each test (1 or 3 mg/kg of L368,899 or saline) OT antagonist treatment reduced or eliminated interest in the infant and sexual behavior. These results, although preliminary, are the first to directly implicate endogenous OT in activation of primate maternal interest and sexual behavior. While it remains to be empirically demonstrated that peripherally administered L368,899 blocks central OT receptors, our behavioral findings suggest that this non-peptide antagonist may facilitate testing OT involvement in a variety of social and other behaviors in primates

Repeated long separations from pups produce depression-like behavior in rat mothers

Long (LMS) versus brief (BMS) daily separations of rat pups from their mothers have contrasting effects on their adult stress responses and maternal behavior by respectively decreasing and increasing licking received from their mothers. We hypothesized that LMS decreases pup licking in mothers by inducing learned helplessness, creating a depression-like state. We subjected postpartum rats to LMS (3 h), BMS (15 min) or no separation (NMS) on postpartum days 2–14. After weaning, mothers were given a forced swim test (FST). LMS mothers exhibited more immobility and fewer escape attempts than BMS or NMS mothers. These results suggest that LMS induces a depression-like state, which may account for the reductions in maternal behavior seen in LMS mothers. Immobility in the FST is recognized as an animal model of depression. Therefore, LMS may be a model of maternal depression

Persistent alterations in biological profiles in women with abuse histories: Influence of premenstrual dysphoric disorder.

To examine dysregulation in biological measures associated with histories of abuse in women and whether women with premenstrual dysphoric disorder (PMDD) differ in their dysregulation

Reversal of social deficits by subchronic oxytocin in two autism mouse models

Social deficits are a hallmark feature of autism spectrum disorder (ASD) and related developmental syndromes. Although there is no standard treatment for social dysfunction, clinical studies have identified oxytocin as a potential therapeutic with prosocial efficacy. We have previously reported that peripheral oxytocin treatment can increase sociability and ameliorate repetitive stereotypy in adolescent mice from the C58/J model of ASD-like behavior. In the present study, we determined that prosocial oxytocin effects were not limited to the adolescent period, since C58/J mice, tested in adulthood, demonstrated significant social preference up to 2 weeks following subchronic oxytocin treatment. Oxytocin was also evaluated in adult mice with underexpression of the N-methyl-D-aspartate receptor NR1 subunit (encoded by Grin1), a genetic model of autism- and schizophrenia- like behavior. Subchronic oxytocin had striking prosocial efficacy in male Grin1 knockdown mice; in contrast, chronic regimens with clozapine (66 mg/kg/day) or risperidone (2 mg/kg/day) failed to reverse deficits in sociability. Neither the subchronic oxytocin regimen, nor chronic treatment with clozapine or risperidone, reversed impaired prepulse inhibition in the Grin1 knockdown mice. Overall, these studies demonstrate oxytocin can enhance sociability in mouse models with divergent genotypes and behavioral profiles, adding to the evidence that this neurohormone could have therapeutic prosocial efficacy across a spectrum of developmental disorders