Experiences of adversity in childhood and adolescence and cortisol in late adolescence.

Early life adversity influences the diurnal cortisol rhythm, yet the relative influence of different characteristics of adversity remains unknown. In this study, we examine how developmental timing (childhood vs. adolescence), severity (major vs. minor), and domain of early life adversity relate to diurnal cortisol rhythms in late adolescence. We assessed adversity retrospectively in early adulthood in a subsample of 236 participants from a longitudinal study of a diverse community sample of suburban adolescents oversampled for high neuroticism. We used multilevel modeling to assess associations between our adversity measures and the diurnal cortisol rhythm (waking and bedtime cortisol, awakening response, slope, and average cortisol). Major childhood adversities were associated with flatter daily slope, and minor adolescent adversities were associated with greater average daily cortisol. Examining domains of childhood adversities, major neglect and sexual abuse were associated with flatter slope and lower waking cortisol, with sexual abuse also associated with higher cortisol awakening response. Major physical abuse was associated with higher waking cortisol. Among adolescent adversities domains, minor neglect, emotional abuse, and witnessing violence were associated with greater average cortisol. These results suggest severity, developmental timing, and domain of adversity influence the association of early life adversity with stress response system functioning.

Maternal stress and mental health before pregnancy and offspring diurnal cortisol in early childhood.

The current study investigates whether prepregnancy maternal posttraumatic stress disorder (PTSD) symptoms, depressive symptoms, and stress predict children's cortisol diurnal slopes and cortisol awakening responses (CARs) adjusting for relevant variables. Mothers were enrolled after delivering a baby and followed through their subsequent pregnancy with 5 years of longitudinal data on their subsequent child. This prospective design allowed assessment of PTSD symptoms, depressive symptoms, and perceived stress prior to pregnancy. Children provided three saliva samples per day on three consecutive days at two timepoints in early childhood (M age = 3.7 years, SD = 0.38; M age = 5.04 years, SD = 0.43). Mothers' PTSD symptoms prior to pregnancy were significantly associated with flatter child diurnal cortisol slopes at 4 and 5 years, but not with child CAR. Findings at the age of 4 years, but not 5 years, remained statistically significant after adjustment for maternal socioeconomic status, race/ethnicity, child age, and other covariates. In contrast, maternal prepregnancy depressive symptoms and perceived stress did not significantly predict cortisol slopes or CAR. Results suggest that maternal prepregnancy PTSD symptoms may contribute to variation in early childhood physiology. This study extends earlier work demonstrating risk of adverse outcomes among children whose mothers experienced trauma but associations cannot be disentangled from effects of prenatal mental health of mothers on children's early childhood.

Early and current life adversity: Past and present influences on maternal diurnal cortisol rhythms during pregnancy.

Stress during pregnancy affects maternal health and well-being, as well as the health and well-being of the next generation, in part through the hypothalamic-pituitary-adrenal (HPA) axis. Although most studies have focused solely on proximal experiences (i.e., during the pregnancy) as sources of prenatal stress, there has been a recent surge in studies that examine maternal early life adversity as a source of stress system dysregulation during pregnancy. The current study of 178 pregnant women examined the association of economic and life stress experienced during two time periods (i.e., childhood and pregnancy) with maternal HPA axis activity during the third trimester of pregnancy. Findings indicated that a current annual income of less than $15,000 and greater childhood disadvantage were associated with a flatter diurnal cortisol slope. Childhood maltreatment, particularly sexual abuse, was associated with a higher cortisol awakening response (CAR), even when controlling for recent adversity. We found some evidence that past adversity moderates the relationship between current adversity and diurnal cortisol, specifically for economic adversity and waking cortisol. Overall, our findings indicate that early life stressors play an important and underappreciated role in shaping stress biology during pregnancy.

Dissection of subclonal evolution by temporal mutation profiling in chronic lymphocytic leukemia patients treated with ibrutinib.

The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib is inducing durable responses in chronic lymphocytic leukemia (CLL) patients with refractory/relapsed disease or with TP53 defect, with BTK and phospholipase C gamma 2 (PLCG2) mutations representing the predominant mechanisms conferring secondary ibrutinib resistance. To understand the landscape of genomic changes and the dynamics of subclonal architecture associated with ibrutinib treatment, an ultra-deep next-generation sequencing analysis of 30 recurrently mutated genes was performed on sequential samples of 20 patients, collected before and during single-agent ibrutinib treatment. Mutations in the SF3B1, MGAand BIRC3 genes were enriched during ibrutinib treatment, while aberrations in the BTK, PLCG2, RIPK1, NFKBIE and XPO1 genes were exclusively detected in posttreatment samples. Besides the canonical mutations, four novel BTK mutations and three previously unreported PLCG2 variants were identified. BTK and PLCG2 mutations were backtracked in five patients using digital droplet PCR and were detectable on average 10.5 months before clinical relapse. With a median follow-up time of 36.5 months, 7/9 patients harboring BTK mutations showed disease progression based on clinical and/or laboratory features. In conclusion, subclonal heterogeneity, dynamic clonal selection and various patterns of clonal variegation were identified with novel resistance-associated BTK mutations in individual patients treated with ibrutinib.

Emotional Pathways to the Biological Embodiment of Racial Discrimination Experiences.

OBJECTIVE: Racial discrimination experiences are common among youth with an ethnic minority background, and such experiences affect health. Stress-sensitive systems like the hypothalamic-pituitary-adrenal (HPA) axis have been proposed as one mechanism. HPA-axis activity, measured through daily patterns of salivary cortisol, is altered among individuals who experience discrimination. We know little about the day-to-day processes by which discrimination experiences become embodied in stress biology. The HPA axis is responsive to negative social-evaluative (NSE) emotion. The present study investigated whether NSE emotions are a pathway by which discrimination dysregulates HPA-axis functioning as measured by cortisol levels. METHODS: Perceived discrimination, diurnal cortisol, and changes in NSE emotion were assessed in a sample of 102 young adults. Emotions and cortisol were measured across the day for seven consecutive days in naturalistic settings. Multilevel modeling and regression analyses were used to examine average and day-to-day associations between discrimination, NSE emotion, and cortisol. Mediation and specificity analyses were conducted. RESULTS: Discrimination was associated with NSE emotion (ß = 0.34, p = .001). Day-to-day changes (ß = 0.10, p = .002) and average levels (ß = 0.03, p = .013) of NSE emotion were associated with dysregulated cortisol. NSE emotion mediated the association between discrimination and diurnal cortisol slopes (ß = 0.10 [95% confidence interval = 0.01-0.21]). Findings were robust for covariates including stressful life events, more pronounced for NSE emotion compared with negative affect at the day level, similar for NSE emotion and general negative affect at the person level, and specific to cortisol slopes. CONCLUSIONS: Findings suggest that daily NSE and average negative emotions are important pathways by which racial discrimination gets under the skin, or is embodied, in stress biology.

Early life stress and HPA axis function independently predict adult depressive symptoms in metropolitan Cebu, Philippines.

OBJECTIVES: Alterations in adult hypothalamic-pituitary-adrenal (HPA) axis activity have increasingly been linked with early life stress and adult depression, but a limited number of studies have used longitudinal data to explore HPA axis dysregulation as an underlying mechanism driving the long-term depressive impacts of early stressors. Here we address potential long-term impacts of early life, family-based stress on depressive symptoms among young adults in a longitudinal birth cohort study begun in 1983 in the Philippines. MATERIALS AND METHODS: We relate a composite measure of family-based stressors experienced between birth and adolescence to circadian dynamics in adult salivary cortisol and depressive risk measured at 21-22 years of age. Multiple regression analyses were conducted to examine the relationship between early life stress levels and risk of adult depressive symptoms, as well as the role of adult diurnal cortisol activity in this relationship. RESULTS: Greater levels of early life familial stress predicted more severe depressive symptomatology at age 21-22 in a dose-response fashion (p < .0001) independent of adult diurnal cortisol patterns. Flatter diurnal cortisol slopes are directly associated with higher adult depressive symptoms, an effect mostly driven by evening cortisol levels (p = .004). When considering the cumulative effects of early life stress measures, however, exposure to more of these stressors during development is associated with even higher depressive symptoms. DISCUSSION: The long-term depressive effects of early life familial stress extend to this large sample of Cebuano young adults, and early life stress and HPA axis function may shape adult depressive symptoms through independent pathways in this sample. Our findings provide further evidence that HPA axis activity is shaped by early life conditions and is associated with depressive symptoms.

Racial discrimination and ethnic racial identity in adolescence as modulators of HPA axis activity.

We review evidence of racial discrimination as a critical and understudied form of adversity that has the potential to impact stress biology, particularly hypothalamic-pituitary-adrenal (HPA) axis activity. We highlight ethnic racial identity (ERI) as a positive regulatory influence on HPA axis activity, as indexed by levels of salivary cortisol. In past research by our group, Black individuals with high adolescent discrimination had low adult cortisol levels (hypocortisolism). Here, we present new analyses showing that ERI, measured prospectively from ages 12 through 32 in 112 Black and white individuals, is related to better-regulated cortisol levels in adulthood, particularly for Black participants. We also describe ongoing research that explores whether the promotion of ERI during adolescence can reduce ethnic-racial disparities in stress biology and in emotional health and academic outcomes.

Cortisol awakening response and additive serotonergic genetic risk interactively predict depression in two samples: The 2019 Donald F. Klein Early Career Investigator Award Paper.

BACKGROUND: The serotonin system and hypothalamic pituitary-adrenal (HPA)-axis are each implicated in the pathway to depression; human and animal research support these systems' cross-talk. Our work implicates a 5-variant additive serotoninergic multilocus genetic profile score (MGPS) and separately the cortisol awakening response (CAR) in the prospective prediction of depression; other work has shown that the serotonin transporter polymorphism 5HTTLPR predicts CAR and interacts with the CAR to predict depression. METHODS: We tested the hypothesis that a 6-variant MGPS (original plus 5HTTLPR) would interact with CAR to predict prospective depressive episode onsets in 201 emerging adults using four annual follow-up interviews. We also tested whether MGPS predicted CAR. We attempted replication of significant findings in a sample of 77 early adolescents predicting depression symptoms. RESULTS: In sample 1, MGPS did not significantly predict CAR. MGPS interacted with CAR to predict depressive episodes; CAR slopes for depression steepened as MGPS increased, for risk or protection. No single variant accounted for results, though CAR's interactions with 5HTTLPR and the original MGPS were both significant. In sample 2, the 6-variant MGPS significantly interacted with CAR to predict depression symptoms. CONCLUSIONS: Higher serotonergic MGPS appears to sensitize individuals to CAR level-for better and worse-in predicting depression.

Early Term Delivery and Breastfeeding Outcomes.

OBJECTIVE: Higher rates of adverse outcomes have been reported for early term (37 0 to 38 6 weeks) versus full term (≥ 39 0 weeks) infants, but differences in breastfeeding outcomes have not been systematically evaluated. This study examined breastfeeding initiation and exclusivity in early and full term infants in a large US based sample. METHODS: This secondary analysis included 743 geographically- and racially-diverse women from the Measurement of Maternal Stress Study cohort, and 295 women from a quality assessment at a hospital-based clinic in Evanston, IL. Only subjects delivering ≥ 37 weeks were included. Initiation of breastfeeding (IBF) and exclusive breastfeeding (EBF) were assessed via electronic medical record review after discharge. Associations of IBF and EBF with early and full term delivery were assessed via univariate and multivariate logistic regression. RESULTS: Among 872 women eligible for inclusion, 85.7% IBF and 44.0% EBF. Early term delivery was not associated with any difference in frequency of IBF (p = 0.43), but was associated with significantly lower odds of EBF (unadjusted OR 0.61, 95% CI 0.466, 0.803, p < 0.001). This association remained significant (adjusted OR 0.694, 95% CI 0.515, 0.935, p = 0.016) after adjusting for maternal diabetes, hypertensive disorders of pregnancy, cesarean delivery, maternal age, race/ethnicity, parity, Medicaid status, NICU admission, current smoking, and delivery hospital. CONCLUSIONS FOR PRACTICE: Despite comparable breastfeeding initiation frequencies, early term infants were significantly less likely to be exclusively breastfed compared to full term infants. These data suggest that women with early term infants may benefit from counseling regarding the potential for breastfeeding difficulties as well as additional breastfeeding support after delivery.

Cardiovascular and Metabolic Risk in Women in the First Year Postpartum: Allostatic Load as a Function of Race, Ethnicity, and Poverty Status.

OBJECTIVE: Allostatic load (AL) represents multisystem physiological "wear-and-tear" reflecting emerging chronic disease risk. We assessed AL during the first year postpartum in a diverse community sample with known health disparities. STUDY DESIGN: The Eunice Kennedy Shriver National Institute for Child Health and Human Development Community Child Health Network enrolled 2,448 predominantly low-income African-American, Latina, and White women immediately after delivery of liveborn infants at ≥20 weeks' gestation, following them over time with interviews, clinical measures, and biomarkers. AL at 6 and 12 months postpartum was measured by body mass index, waist:hip ratio, blood pressure, pulse, hemoglobin A1c, high-sensitive C-reactive protein, total cholesterol and high-density lipoprotein, and diurnal cortisol slope. RESULTS: Adverse AL health-risk profiles were significantly more prevalent among African-American women compared with non-Hispanic Whites, with Latinas intermediate. Breastfeeding was protective, particularly for White women. Complications of pregnancy were associated with higher AL, and disparities persisted or worsened through the first year postpartum. CONCLUSION: Adverse AL profiles occurred in a substantial proportion of postpartum women, and disparities did not improve from birth to 1 year. Breastfeeding was protective for the mother.

A preliminary investigation of attachment style and inflammation in African-American young adults.

Individuals' social experiences are associated with their mental health, physical health, and even mortality. Over the last 30 years, researchers have examined the ways in which these social experiences might be associated with chronic inflammation - a component underlying many of the chronic diseases of aging. Little research, however, has examined the role of adults' attachment style as a specific social component that might be associated with inflammation. In the present study, we utilized data from a sample of 59 African-American adults from the Maryland Adolescent Development in Context Study (MADICS) to examine the links between attachment avoidance and attachment anxiety and C-reactive protein (CRP) and interleukin (IL)-6. After controlling for demographic characteristics, body mass index, and depressive symptoms, attachment avoidance and anxiety were associated with IL-6 but not CRP. This study adds to the growing body of research identifying the wide range of social experiences associated with inflammation and further suggests that attachment relationship experiences may have implications for biological processes relevant to many chronic diseases of aging.

Chondrogenic differentiation potential of adult and fetal equine cell types.

OBJECTIVE: To determine the chondrogenic potential of cells derived from interzone tissue, the normal progenitor of articular cartilage during fetal development, compared to that of adult bone marrow-derived and adipose-derived mesenchymal cell isolates. The objective of this study was to compare the chondrogenic potential of fetal musculoskeletal progenitor cells to adult cell types, which are currently used therapeutically to facilitate joint cartilage repair in equine clinical practice. The hypothesis tested was that cells derived from interzone tissue have a chondrogenic potential that exceeds that of adult bone marrow-derived and adipose-derived mesenchymal cell isolates. STUDY DESIGN: In vitro study. ANIMALS: Six young adult horses (15-17 months of age) and 6 equine fetuses aged 45-46 days of gestation. METHODS: Three-dimensional pellet cultures were established under chondrogenic conditions with fresh, primary cells isolated from adult (articular cartilage, bone marrow, adipose, dermis) and fetal (interzone, skeletal anlagen cartilage, dermis) tissues. Cellular morphology, pellet architecture, and proteoglycan synthesis were assessed in the pellet cultures. Steady state levels of ACAN (aggrecan core protein), COL2A1 (collagen type II), and COL1A1 (collagen type I) messenger RNA (mRNA) were compared among these cell types as pellet cultures and monolayer cultures. RESULTS: Adult articular chondrocytes, fetal interzone cells, and fetal anlage cells generated the largest pellets under these chondrogenic culture conditions. Pellets derived from adult articular chondrocytes and fetal anlage cells had the highest scores on a neocartilage grading scale. Fetal anlage and adult articular chondrocyte pellets had low steady-state levels of COL1A mRNA but high COL2A1 expression. Anlage chondrocyte pellets also had the highest expression of ACAN. CONCLUSION: Adult articular chondrocytes, fetal interzone cells, and fetal anlage chondrocytes exhibited the highest chondrogenic potential. In this study, adult adipose-derived cells exhibited very limited chondrogenesis, and bone marrow-derived cells had limited and variable chondrogenic potential. CLINICAL SIGNIFICANCE: Additional investigation of the high chondrogenic potential of fetal interzone cells and anlage chondrocytes to advance cell-based therapies in diarthrodial joints is warranted.

Negative cognitive style and cortisol recovery accentuate the relationship between life stress and depressive symptoms.

When exposed to stressful life events, a significant number of adolescents will experience depressive symptoms. One model of depression suggests that individuals with a negative cognitive style are most vulnerable to depression following life stress. Alternatively, altered activation of the hypothalamic-pituitary-adrenal axis may explain vulnerability to depression following life stress. Each of these models plausibly explains the emergence of depressive symptoms during adolescence and have been investigated largely independently. The current study recruited a sample of urban adolescents (N = 179) to evaluate whether cortisol response to a laboratory stress induction and negative cognitive style are related and whether they independently interact with exposure to stressful life events to predict symptoms of depression. Negative cognitive style was not associated with cortisol response to the laboratory stressor. Rather, negative cognitive style and cortisol recovery independently interacted with stressful life events to predict current symptoms of depression. Results support a heterogeneous etiology of depression.

Violence and Vigilance: The Acute Effects of Community Violent Crime on Sleep and Cortisol.

The data combine objectively measured sleep and thrice-daily salivary cortisol collected from a 4-day diary study in a large Midwestern city with location data on all violent crimes recorded during the same time period for N = 82 children (Mage  = 14.90, range = 11.27-18.11). The primary empirical strategy uses a within-person design to measure the change in sleep and cortisol from the person's typical pattern on the night/day immediately following a local violent crime. On the night following a violent crime, children have later bedtimes. Children also have disrupted cortisol patterns the following morning. Supplementary analyses using varying distances of the crime to the child's home address confirm more proximate crimes correspond to later bedtimes.

Antenatal depression, psychotropic medication use, and inflammation among pregnant women.

To evaluate the association between psychotropic medication and inflammatory biomarkers in women with antenatal depressive symptoms (ADS). In this cross-sectional secondary analysis of a prospective multicenter observational study, 723 pregnant women underwent a depression screen using the Center for Epidemiologic Studies Depression Scale (CES-D) between 12 and 21 weeks gestation. Self-reported use of medications for depression and/or anxiety was corroborated with the medical record to document exposure to pharmacotherapy. Serum was collected and inflammatory biomarkers (IFNγ, IL13, IL6, IL8, TNFα, CRP) were measured concomitantly. Women were included if they fell into one of three categories: ADS responsive to treatment (CES-D < 16 with medication), ADS not responsive to medication (CES-D ≥ 23 despite medication), and untreated ADS (CES-D ≥ 23 with no medication). Levels of inflammatory biomarkers were compared among groups and multivariable regressions performed. Of the 85 women studied, 16 (19%) had ADS responsive to treatment, 12 (14%) had ADS not responsive to medication, and 57 (67%) had untreated ADS. TNFα concentrations significantly differed (P = 0.016) across the cohorts. Post hoc bivariate analyses demonstrated that women with ADS responsive to treatment had lower serum TNFα than non-responders (p = 0.02) and women with untreated ADS (p = 0.01). There were no differences in IFNγ, IL13, IL6, IL8, or CRP among the groups. Regressions demonstrated that, compared to women with ADS responsive to treatment, non-responders or women with untreated ADS had higher TNFα levels (ß = 0.27, 95% CI 0.02-0.52 and ß = 0.23, 95% CI 0.02-0.44, respectively). Pregnant women on pharmacotherapy who respond to treatment for ADS have lower TNFα compared to women not responsive to medication or women with untreated ADS. These data suggest the possibility that either the therapeutic response in the context of pharmacotherapy is accompanied by modulation of the immune system or that pre-existing higher levels of TNFα may be associated with a poorer response to traditional pharmacotherapy.

Taking on the stress-depression link: Meaning as a resource in adolescence.

We investigated how meaning in life affects the link between stress and depression symptoms in adolescents. Adolescents (N = 177; 58.4% female, mean age = 14.75 years) reported on their meaning in life, exposure to stressors, and depression symptomatology. Higher meaning in life predicted lower depression symptoms. Importantly, meaning in life moderated the relationship between stress exposure and depressive symptoms: stress exposure was associated with higher depression when meaning in life was low, when meaning in life was high, there was no association between stressors and depression. These findings indicate the importance of having a sense of meaning in life adolescence. A positive relationship was found between stress exposure and depression symptomatology levels at a time-point seven months earlier. This lends a longitudinal perspective; meaning in life moderated a relationship that had been present for seven months. Therapeutic implications for protecting at-risk youth are discussed.

[Change in paradigm in the treatment of pediatric acquired bone marrow failure syndromes in Hungary]. / Korszakváltás a gyermekkori szerzett csontvelo-elégtelenséggel járó kórképek kezelésében Magyarországon.

INTRODUCTION: Acquired bone marrow failures are rare but fatal diseases in childhood. Since 2013, Hungary has been participating as a full member in the work of the European Working Group on uniform diagnostics and therapy in patients with acquired bone marrow failure syndromes. Hypocellular refractory cytopenia of childhood has been emphasized as a frequent entity, transplanted by reduced intensity conditioning with excellent outcomes. AIM: To analyse and compare the results of treatment before and after our joining. METHOD: A total of 55 patients have been treated in the 8 centres of the Hungarian Pediatric Oncology Network during 5 years between 2013 and 2017 (severe aplastic anemia: 9, myelodysplastic syndrome: 41, juvenile myelomonocytic leukemia: 5 patients). Allogeneic hematopoietic stem cell transplantation was performed in severe aplastic anemia in 7 cases, while antithymocyte globulin was administered in one case and one patient died before diagnosis. In patients with myelodysplastic syndromes, watch and wait strategy was applied in 4, while transplantation in 37 cases. Reduced intensity conditioning was used in 54 percent of these cases. Transplantation was the treatment of choice in all 5 patients with juvenile myelomonocytic leukemia. RESULTS: In the whole patient cohort, the time from diagnosis to treatment was median 92 (3-393) days, while in severe aplastic anemia median 28 (3-327) days only. Grade II-IV acute graft versus host disease occurred in 22.6%, grade III-IV in 6.8% and chronic in 11.2%. All the patients treated with severe aplastic anemia are alive and in complete remission (100%). The overall estimated survival rate is 85.1% in myelodysplastic syndrome, while 75% in juvenile myelomonocytic leukemia. The median follow-up was 30.4 (1.1-62.5) months. There was a remarkable increase in overall survival comparing the data before (1992-2012) and after (2013) joining the international group, 70% vs. 100% (p = 0.133) in severe aplastic anemia and 31.3% vs. 85.1% (p = 0.000026) in myelodysplastic syndrome. CONCLUSION: Due to a change in the paradigm of the conditioning regimen in hypocellular refractory cytopenia of childhood, the overall survival rate has significantly increased. Orv Hetil. 2018; 159(42): 1710-1719.

Mothers' childhood hardship forecasts adverse pregnancy outcomes: Role of inflammatory, lifestyle, and psychosocial pathways.

Research suggests the health consequences of economic hardship can be transmitted across generations. Some of these disparities are thought to be passed to offspring during gestation. But this hypothesis has not been tested in contemporary American samples, and the mechanisms of transmission have not been characterized. Accordingly, this study had two goals: first, to determine if women exposed to economic hardship during childhood showed higher rates of adverse birth outcomes; and second, to evaluate the contribution of inflammation, psychosocial, lifestyle, and obstetric characteristics to this phenomenon. This prospective study enrolled 744 women with singleton pregnancies (59.1% White; 16.3% Black; 18.7% Latina; 5.9% Other). Childhood economic hardship was measured by self-report. Birth outcomes included length of gestation and incidence of preterm birth; birth weight percentile and small for gestational age; length of hospital stay and admission to Special Care Nursery. Analyses revealed that mothers' childhood economic hardship was independently associated with multiple adverse birth outcomes, even following adjustment for demographics, maternal education, and obstetrical confounders. Women raised in economically disadvantaged conditions had shorter gestation length and higher preterm delivery rates. Their babies had lower birth weights, were more likely to be small for gestational age, stayed in the hospital longer, and had more Special Care Nursery admissions. Mediation analyses suggested these associations arose through multiple pathways, and highlighted roles for inflammation, education, adiposity, and obstetric complications. Collectively, these findings suggest that childhood economic hardship predisposes women to adverse birth outcomes, and highlights likely behavioral and biological mechanisms.

High paternal testosterone may protect against postpartum depressive symptoms in fathers, but confer risk to mothers and children.

Following the birth of an infant, decreases in testosterone and increases in depressive symptoms have been observed in fathers. Paternal testosterone may reflect fathers' investment in pair-bonding and paternal caregiving and, as such, may be associated with maternal and familial well-being. This study tests associations between paternal testosterone, paternal and maternal postpartum depressive symptoms, and subsequent family functioning. Within 149 couples, fathers provided testosterone samples when infants were approximately nine months old and both parents reported on postpartum depressive symptoms at two, nine, and 15months postpartum. Fathers with lower aggregate testosterone reported more depressive symptoms at two and nine months postpartum. Mothers whose partners had higher evening testosterone reported more depressive symptoms at nine and 15months postpartum. Maternal relationship satisfaction mediated this effect, such that mothers with higher testosterone partners reported more relationship dissatisfaction, which in turn predicted more maternal depressive symptoms. Higher paternal testosterone and paternal depressive symptoms at nine months postpartum each independently predicted greater fathering stress at 15months postpartum. Higher paternal testosterone also predicted more mother-reported intimate partner aggression at 15months postpartum. In addition to linear relationships between testosterone and depression, curvilinear relationships emerged such that fathers with both low and high testosterone at nine months postpartum reported more subsequent (15-month) depressive symptoms and fathering stress. In conclusion, whereas higher paternal testosterone may protect against paternal depression, it contributed to maternal distress and suboptimal family outcomes in our sample. Interventions that supplement or alter men's testosterone may have unintended consequences for family well-being.