Immune transcriptional profiles in mothers with clinically elevated depression and anxiety symptoms several years post-delivery.

BACKGROUND: Most research on maternal mental health focuses on the perinatal period and does not extend beyond 12 months postpartum. However, emerging evidence suggests that for some women (30%-50%), psychological symptoms may persist beyond the first year postpartum or even emerge later increasing the risk of chronic mood and anxiety symptoms. Despite the high prevalence rates and devastating maternal-child consequences, studies examining maternal depression, anxiety, and post-traumatic stress disorder (PTSD) beyond the first year postpartum are rare and our understanding of the underlying biological mechanisms is incomplete. Inflammatory processes are thought to be involved in the pathophysiology of depression, anxiety, & PTSD outside of the postpartum period. Therefore, the purpose of the current investigation was to examine the relationship between depression, anxiety, and PTSD two to three years post-delivery, and transcriptional control pathways relevant to inflammatory and antiviral processes. METHODS: Women over 18 years of age enrolled in ongoing research studies at Cedars Sinai Medical Center who were 2-3 years postpartum were invited to participate in the current study. Women (N = 33) reported on their levels of depression, anxiety, and PTSD and provided a blood sample approximately 2-3 years post-delivery. Bioinformatic analyses of differential gene expression (DGEs) to infer transcription factor activity were used. Gene expression was assayed by RNA sequencing and TELiS bioinformatics analysis of transcription factor-binding motifs in the promoters of differentially expressed genes. RESULTS: DGE analyses revealed that women with clinically elevated symptoms of depression, anxiety and PTSD (n = 16) showed upregulation of genes activated by transcription control pathways associated with inflammation (NF-Κ B, p = 0.004; JUN, p = 0.02), including ß-adrenergic responsive CREB (p = 0.01) and reduced activation of genes associated with the antiviral response (IRFs, p = 0.02) and the glucocorticoid signaling pathway (GR, p = 0.02) compared to women without clinical symptoms (n = 17). CONCLUSIONS: This is one of the first investigations into the immune signaling pathways involved in depression, anxiety, and PTSD two to three years post-delivery. The results of this study suggest that clinically elevated symptoms of depression, anxiety, and PTSD two to three years post-delivery are associated with a gene expression profile characterized by upregulated expression of pro-inflammatory genes and downregulated expression of antiviral genes. The data also point to two potential stress responsive pathways linking symptoms to increased inflammatory signaling in immune cells: sympathetic nervous system mediated ß-adrenergic signaling and reduced hypothalamic pituitary adrenal axis activity. Together, these findings highlight the need for investigations into maternal mental health beyond the first year postpartum.

Younger Women Living with Chronic Disease: Comparative Challenges, Resiliencies, and Needs in Heart Disease and Breast Cancer.

Background: Younger women with chronic disease (<60 years of age), especially women with stereotypically "men's" heart disease (HD), are understudied. Unique difficulties may occur with HD, which is less commonly associated with women, compared with breast cancer (BC). Similarities may also exist across younger women, as chronic disease is less normative in younger people. Intersections of gender, age, and the specific disease experience require greater attention for improving women's health. This exploratory qualitative study compared younger women's experiences of HD or BC. Methods: Semistructured interviews with 20 women (n = 10 per disease) were analyzed using applied thematic analysis. Results: Amidst building careers, intimate relationships, and families, women felt thwarted by disease-related functional problems. Cognitive-behavioral coping strategies spurred resilience, including integrating the illness experience with self-identity. Barriers arose when medical professionals used representativeness heuristics (e.g., chronic disease occurs in older age). Important experiences in HD included worsened self-image from disability, negative impact of illness invisibility, and persisting isolation from lacking peer availability. Initial medical care reported by women with HD may reflect gender biases (e.g., HD missed in emergency settings and initial diagnostics). New information provided by the younger women includes limited illness-related optimism in women with HD facing age and gender stereotypes, as well as the advantages and disadvantages of peer availability in BC. Conclusions: Greater public awareness of younger women with chronic disease, alongside structural support and connection with similarly challenged peers, is suggested. As advocacy for BC awareness and action has strengthened over past decades, similar efforts are needed for younger women with HD.

Low Prenatal Vitamin D Metabolite Ratio and Subsequent Postpartum Depression Risk.

Background: Depression is a common complication of pregnancy and vitamin D deficiency is one biological risk factor for postpartum depression (PPD). Materials and Methods: We evaluated the ratio of 24,25(OH)2D and 25(OH)D serum concentrations referred to as the Vitamin D Metabolite Ratio (VMR), a new candidate biomarker during pregnancyand its relationship with PPD. Women were enrolled in the first trimester of pregnancy and followed through four timepoints. Results: A total of 89 women had complete depression, biomarker and demographic data and 34% were at risk for PPD (CES-D≥16). Stepwise multiple logistic regression models for PPD risk were carried out with eight predictors. Results showed that only lower VMR, OR = 1.43, 95% CI 1.10-1.86, p = 0.007, and Hispanic/Latina identification, OR = 3.83, 95% CI 1.44-10.92, p = 0.007 were significantly associated with higher PPD risk. Conclusion: Routine prenatal screening for vitamin D metabolites, particularly in Hispanic/Latina women, may identify women at risk for PPD.

Association of Spontaneous Preterm Delivery and Future Maternal Cardiovascular Disease.

Cardiovascular disease (CVD) risk factors are well established. However, little is known about a woman's cardiovascular response to pregnancy, which appears to be an early marker of future maternal CVD risk. Spontaneous preterm delivery (sPTD) has been associated with a ≤3-fold increased risk of maternal CVD death later in life compared with having a term delivery. This review focuses on 3 key areas to critically assess the association of sPTD and future maternal CVD risk: (1) CVD risk factors, (2) inflammatory biomarkers of interest, and (3) specific forms of vascular dysfunction, such as endothelial function and arterial stiffness, and mechanisms by which each may be linked to sPTD. The association of sPTD with subsequent future maternal CVD risk suggests that a woman's abnormal response to pregnancy may serve as her first physiological stress test. These findings suggest that future research is needed to understand why women with sPTD may be at risk for CVD to implement effective interventions earlier in a woman's life.

Depression and vasomotor symptoms in young breast cancer survivors: the mediating role of sleep disturbance.

Depression, sleep disturbance, and vasomotor symptoms are common in breast cancer survivors (BCS), especially in younger women diagnosed before menopause. Risk factors and mechanisms for depression in this population are relatively unexplored. In 163 young BCS, vasomotor symptoms were significantly associated with higher depressive symptoms (ß = 0.26, p = 0.001) and 64 % of the total effect was mediated through sleep disturbance (beta for specific indirect effect = 1.296, 95 % CI 0.591-2.212). Treatments reducing vasomotor symptoms might alleviate sleep disturbance and depression in this population.

Personal history of major depression may put women at risk for premenstrual dysphoric symptomatology.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a chronic condition that significantly affects a woman's well-being on a monthly basis. Although co-occurrence of PMDD and major depressive disorder (MDD) is common, most studies examine whether women with PMDD are at risk for depression and investigations of PMDD in depressed women are scant. Therefore, the present study examined rates of PMDD in young depressed women. METHODS: PMDD was assessed using a structured clinical interview (SCID-PMDD) in a sample of 164 young women with (n=85) and without (n=79) any history of depression. RESULTS: Rates of PMDD were elevated among women with MDD in this sample. This result held true regardless of participants' MDD status (current, lifetime or past history-only symptoms of MDD) and regardless of whether all or most DSM-IV-TR PMDD criteria were met. LIMITATIONS: Sample size in the present study was relatively small, and daily diary data were not available to confirm a PMDD diagnosis. CONCLUSIONS: The current study highlights the need for clinicians to assess for PMDD in young female patients with major depression. Depressed women experiencing the added physical and psychological burden of PMDD may have a more severe disease course, and future studies will need to identify appropriate treatments for this subset of depressed women.

Prefrontal brain asymmetry and pre-menstrual dysphoric disorder symptomatology.

BACKGROUND: Pre-menstrual dysphoric disorder (PMDD), a dysphoric form of pre-menstrual syndrome, is included as a diagnosis for further study in the DSM-IV-TR (APA, 2000). The present study investigated whether a marker of risk for major depressive disorder (MDD), prefrontal brain asymmetry, also characterizes women with PMDD. METHODS: In a sample of 25 college women with PMDD symptomatology and 25 matched controls, resting frontal electroencephalographic (EEG) activity was assessed on four occasions within a two-week span. RESULTS: Across several frontal sites women with PMDD had relatively less left than right prefrontal brain activity, consistent with a diathesis-stress model for menstrual-related dysphoria. CONCLUSIONS: The findings suggest an overlap in the risk profile for MDD and PMDD.