Non-linear associations between HPA axis activity during infancy and mental health difficulties during early childhood among children in rural Pakistan.

Hypothalamic pituitary adrenal (HPA) axis activity may be a mechanism linking early adversity to child mental health difficulties. However, there is a dearth of longitudinal evidence for the association between HPA axis activity and mental health among children in low-resource contexts. The goal of this study is to examine linear and curvilinear associations between HPA axis activity during infancy and mental health difficulties in early childhood among children in rural Pakistan. Participants included 104 children (46% male) from the Bachpan study, a longitudinal cohort embedded within a maternal depression trial in Pakistan. We examined the associations between hair-derived cortisol and dehydroepiandosterone (DHEA) at 12 months old and mental health difficulties, measured with the Strengths and Difficulties Questionnaire (SDQ), at 36 months old. There was a significant quadratic association between hair cortisol and SDQ scores, with results showing a U-shaped relationship (i.e., having relatively high or low cortisol predicted increased mental health difficulties). DHEA showed a quadratic association with SDQ scores with an inverted U-shaped relationship (i.e., high and low DHEA was associated with decreased mental health difficulties). Results provide evidence of longitudinal and curvilinear effects of cortisol and DHEA during infancy on mental health difficulties in early childhood.

The impact of COVID-related economic shocks on household mental health in Pakistan.

We combine data collected just prior to the unfolding of COVID-19 with follow-up data from July 2020 to document the adverse economic effects of the pandemic and resulting impact on parental and child mental well-being in peri-urban Pakistan. 22% of the households in our sample are affected by job loss, with monthly income down 38% on average. Our difference-in-difference results show that job loss is associated with a 0.88 standard deviation (SD) increase in adult mental distress scores (K10), a 0.43 SD reduction in a Hope index of children's aspirations, agency and future pathways, and a 0.39 SD increase in children's depression symptoms. In addition, we observe higher levels of parental stress and anger reported by children, as well as an increase in reported prevalence of domestic violence. Overall, we document that the pandemic has disproportionately and negatively affected the economic and mental well-being of the most vulnerable households in our sample.

Stressful life events, intimate partner violence, and perceived stress in the postpartum period: longitudinal findings in rural Pakistan.

PURPOSE: While the association between intimate partner violence (IPV) and stress is well documented, the directionality of this relationship is unclear. We use an adjusted longitudinal study design to better understand if stressful life events in the home precipitate or exacerbate intimate partner violence (IPV) and if experiences of IPV, in turn, increase levels of perceived stress. METHODS: Longitudinal data were collected among married women in rural Pakistan at 12 and 24 months postpartum (N = 815). Adjusted Poisson and linear regression models were used to examine stressful life events, past year IPV and severity (number and frequency of violent acts), and perceived stress (Cohen Perceived Stress Scale). RESULTS: At 12 months postpartum, the prevalence of past year physical, psychological, and sexual IPV was 8.5%, 25.7%, and 25.1%, respectively, with 42.6% experiencing any IPV. After adjustment, stressful life events were associated with a subsequent increased likelihood of all IPV types and increased severity of all but physical IPV. Any past year IPV (versus none) and greater IPV severity were associated with 3.43 (95% CI 2.33-4.52) and 2.57 (95% CI 1.87-3.27) point subsequent increases in perceived stress. Physical, psychological, and sexual IPV and their respective severities were all independently associated with increased perceived stress. CONCLUSIONS: Among postpartum women in Pakistan, stressful life events increase the likelihood of IPV and, in turn, experiences of IPV increase stress levels. Support to families undergoing stressful circumstances may be critical to reducing women's IPV exposure and resulting elevated stress.

Trajectories of Early Childhood Skill Development and Maternal Mental Health.

We investigate the impacts of a perinatal psychosocial intervention on trajectories of maternal mental health and child skills, from birth to age 3. We find improved maternal mental health and functioning (0.17 to 0.29 SD), modest but imprecisely estimated improvements in parenting (0.07 to 0.11 SD), and transitory improvements in child socioemotional development (0.06 to 0.39 SD). The intervention had negligible influence on physical health and cognition. Estimates of a skill production function reveal the intervention attenuated the negative association between maternal depression and child outcomes, and narrowed outcome gaps between mothers who were and were not depressed in pregnancy.

Men. Male-biased sex ratios and masculinity norms: evidence from Australia's colonial past.

We document the historical roots and contemporary consequences of masculinity norms-beliefs about the proper conduct of men. We exploit a natural experiment in which convict transportation in the 18th and 19th centuries created a variegated spatial pattern of sex ratios across Australia. We show that in areas with heavily male-biased convict populations, relatively more men volunteered for World War I about a century later. Even at present these areas remain characterized by more violence, higher rates of male suicide and other forms of preventable male mortality, and more male-stereotypical occupational segregation. Moreover, in these historically male-biased areas, more Australians recently voted against same-sex marriage and boys-but not girls-are more likely to be bullied in school. We interpret these results as manifestations of masculinity norms that emerged due to intense local male-male competition. Once established, masculinity norms persisted over time through family socialization as well as peer socialization in schools. Supplementary Information: The online version contains supplementary material available at 10.1007/s10887-023-09223-x.

Adverse childhood experiences and implications of perceived stress, anxiety and cortisol among women in Pakistan: a cross-sectional study.

OBJECTIVES: Adverse childhood experiences (ACEs) are linked to poor maternal mental health. The goal of this study is to examine the associations between ACEs and multiple manifestations of stress (including perceived stress, anxiety and cortisol) among mothers in rural Pakistan. DESIGN: This study used a cross-sectional design. Mothers were originally recruited during their third trimester of pregnancy and followed until 36 months post partum. Cortisol was collected at 12 months post partum, and self-report data were collected at 36 months post partum. SETTING: All participants reside in rural villages in Rawalpindi, Pakistan. The measures were administered at home visits by field interviewers. PARTICIPANTS: Data were collected from 889 mothers. All mothers in the sample provided data on ACEs and perceived stress, 623 provided data on anxiety and 90 provided hair cortisol. PRIMARY AND SECONDARY OUTCOMES MEASURES: ACEs were captured retrospectively using an adapted version of the ACE International Questionnaire, and represented as a continuous variable and subdomains (neglect, home violence, family psychological distress, community violence). Primary outcomes included perceived stress measured with the Cohen Perceived Stress Scale (PSS) and anxiety measured with the Generalised Anxiety Disorder-7 scale (GAD-7). Hair-derived cortisol was included as a secondary outcome. Generalised linear models with cluster-robust SEs were used to estimate associations between ACEs and the outcome variables. RESULTS: All models featured positive associations between ACE items and PSS. The continuous total ACE score (B=0.4; 95% CI 0.0 to 0.8) was associated with higher anxiety symptoms on the GAD-7. Home violence (B=6.7; 95% CI 2.7 to 10.8) and community violence (B=7.5; 95% CI 1.4 to 13.6) were associated with increased hair cortisol production. CONCLUSIONS: All four ACE domains were associated with elevated levels of perceived stress, anxiety and cortisol, with varying precision and strength of estimates, indicating that the type of ACE has a differential impact. This study informed our understanding of the differential impact of specific ACEs on perceived stress, anxiety and hypothalamic pituitary adrenal-axis functioning, providing implications for future clinical intervention and research development.

Effects of a maternal psychosocial intervention on hair derived biomarkers of HPA axis function in mothers and children in rural Pakistan.

Objective: Disruptions in the hypothalamic-pituitary-adrenal (HPA) axis are thought to be key neuroendocrine mechanisms involved in psychopathology and may have intergenerational impacts. Hair-derived HPA hormones offer a measure of long-term HPA axis activity that may be useful in assessing maternal and infant health. Building on a community-based randomized control trial of a perinatal depression intervention in Pakistan, we examine intervention effects on HPA axis activity in a subsample of mothers and infants. Methods: HPA axis activity was assessed using hair-derived cortisol, cortisone, and dehydroepiandosterone (DHEA). Hair samples were collected from mother-child dyads at one year postpartum from prenatally depressed women randomized to a cognitive-behavioral intervention (n = 35 dyads) or to enhanced usual care (n = 37 dyads), and from a comparison sample of women who screened negative for depression in pregnancy (n = 35 dyads). Results: The intervention group had 38 percent (p=0.01) lower maternal cortisol levels and 45 percent (p < 0.01) lower maternal cortisone compared to the EUC group. Maternal DHEA levels were higher among women in the intervention group compared to the EUC group by 29 percent (p = 0.02). Intergenerational intervention effects show higher DHEA levels in infants by 43% (p = 0.03). Infant cortisol and cortisone did not differ across groups. Conclusions: Results suggest that the perinatal depression intervention has effects on HPA axis activity in both mothers and children, providing evidence that treating maternal depression may impact physiological stress system functioning intergenerationally. In addition, utilizing hair-derived biomarkers of HPA-axis activity is a potentially useful clinical indicator of intervention impacts on the neuroendocrine system.

Dihydropyranone formation by ipso C-H activation in a glucal 3-carbamate-derived rhodium acyl nitrenoid.

By using (N-tosyloxy)-3-O-carbamoyl-D-glucal 10, which removes the need for a hypervalent iodine(III) oxidant, we provide evidence for rhodium nitrenoid-mediated ipso C-H activation as the origin of a C3-oxidized dihydropyranone product 3. This system may be especially susceptible to such a pathway because of the ease of forming a cation upon hydride transfer to the rhodium-complexed acyl nitrene.

Treatment as insurance: HIV antiretroviral therapy offers financial risk protection in Malawi.

Many countries have expanded insurance programmes in an effort to achieve universal health coverage (UHC). We assess a complementary path toward financial risk protection: increased access to technologies that improve health and reduce the risk of large health expenditures. Malawi has provided free HIV treatment since 2004 with significant US Government support. We investigate the impact of treatment access on medical spending, capacity to pay and catastrophic health expenditures at the population level, exploiting the phased rollout of HIV treatment in a difference-in-differences design. We find that increased access to HIV treatment generated a 10% decline in medical spending for urban households, a 7% increase in capacity to pay for rural households and a 3-percentage point decrease in the likelihood of catastrophic health expenditure among urban households. These risk protection benefits are comparable to that found from broad-based insurance coverage in other contexts. Our findings show that targeted treatment programmes that provide free care for high burden causes of death can provide substantial financial risk protection against catastrophic health expenditure, while moving developing nations toward UHC.

The contribution of grandmother involvement to child growth and development: an observational study in rural Pakistan.

INTRODUCTION: Early childhood interventions primarily focus on the mother-child relationship, but grandmothers are often critical in childcare in low-resource settings. Prior research is mixed on how grandmother involvement influences child outcomes and there is a paucity of research on grandmother caregiving in low-income and middle-income countries. We examined the role of grandmother involvement on child growth and development in the first 2 years of life cross sectionally and longitudinally in rural Pakistan. METHODS: We used data from the Bachpan Cohort, a longitudinal birth cohort in rural Pakistan. Maternally reported grandmother involvement in daily instrumental and non-instrumental caregiving was collected at 3 and 12 months. A summed score was created and categorised into non-involved, low and high. Outcomes included 12-month and 24-month child growth, 12-month Bayley Scales of Infant and Toddler Development and 24-month Ages and Stages Questionnaire-Socioemotional. We used multivariable generalised linear models to estimate mean differences (MD) at 12 months (n=727) and 24 months (n=712). Inverse probability weighting was used to account for missingness and sampling. RESULTS: In our sample, 68% of children lived with a grandmother, and most grandmothers were involved in caregiving. Greater 3-month grandmother involvement was positively associated with 12-month weight z-scores; however, greater involvement was associated with lower 24-month weight z-scores. High 12-month grandmother involvement was associated with improved 12-month cognitive (MD=0.38, 95% CI -0.01 to 0.76), fine motor skills (MD=0.45, 95% CI 0.08 to 0.83) and 24-month socioemotional development (MD=-17.83, 95% CI -31.47 to -4.19). No meaningful associations were found for length z-scores or language development. CONCLUSION: In rural Pakistan, grandmothers provide caregiving that influences early child development. Our findings highlight the complex relationship between grandmother involvement and child weight, and suggest that grandmothers may positively promote early child cognitive, fine motor and socioemotional development. Understanding how grandmother involvement affects child outcomes in early life is necessary to inform caregiving interventions.

Association of maternal depression and home adversities with infant hypothalamic-pituitary-adrenal (HPA) axis biomarkers in rural Pakistan.

BACKGROUND: Each year, almost 35% of children are exposed to maternal depression and more grow up in persistent poverty, increasing the risk for stress-related disease and other socio-developmental deficits later in life. These impacts are likely related to chronic stress via the hypothalamic-pituitary-adrenal (HPA) axis. However, there is little evidence relating early windows of child HPA axis activity to multiple exposures. METHODS: We investigated chronic measures of hair-derived HPA axis hormones (cortisol and dehydroepiandrosterone (DHEA)) in 104 one-year old infants from rural Pakistan and longitudinal measures of maternal depression, intimate partner violence (IPV), socio-economic status (SES), and the home environment. RESULTS: Estimates from adjusted linear mixed effects models did not reveal consistent significant associations between infant cortisol and maternal depression or home adversities. By contrast, infants exposed to maternal depression during pregnancy had lower DHEA levels (ß= -0.18 95% confidence interval [CI]: -0.34, -0.02) as did those whose mothers experienced multiple types of IPV (ß=-4.14 95% CI: -7.42, -0.79) within one year postpartum. Higher SES had a significant positive association with infant DHEA levels (ß= 0.77 95% CI: 0.08, 1.47). Depression severity and chronicity at one year postpartum had near significant associations with infant DHEA. Measures of home environment had no observable impacts on infant HPA axis activity. LIMITATIONS: Limitations include the modest sample size and aggregation of hair samples for analysis. CONCLUSION: Results point to possible early HPA axis dysregulation driven by changes in DHEA activity, but not cortisol at one year of age. Findings contribute to growing research examining intergenerational transmissions of maternal depression, IPV, and household environment on infant stress-response systems.

Effectiveness of a peer-delivered, psychosocial intervention on maternal depression and child development at 3 years postnatal: a cluster randomised trial in Pakistan.

BACKGROUND: Maternal depression has a recurring course that can influence offspring outcomes. Evidence on how to treat maternal depression to improve longer-term maternal outcomes and reduce intergenerational transmission of psychopathology is scarce, particularly for task-shifted, low-intensity, and scalable psychosocial interventions. We evaluated the effects of a peer-delivered, psychosocial intervention on maternal depression and child development at 3 years postnatal. METHODS: 40 village clusters in Pakistan were randomly allocated using a computerised randomisation sequence to receive a group-based, psychosocial intervention and enhanced usual care for 36 months, or enhanced usual care alone. Pregnant women (≥18 years) were screened for moderate or severe symptoms of depression (patient health questionnaire-9 [PHQ-9] score ≥10) and were recruited into the trial (570 participants), and a cohort without depression (PHQ-9 score <10) was also enrolled (584 participants). Including the non-depressed dyads enabled us to determine how much of the excess risk due to maternal depression exposure the intervention could mitigate. Research teams responsible for identifying, obtaining consent, and recruiting trial participants were blind to the allocation status throughout the duration of the study, and principal investigators, site coordinators, statisticians, and members of the trial steering committee were also blinded to the allocation status until the analysis of 6-month data for the intervention. Primary outcomes were maternal depression symptoms and remission (PHQ-9 score <10) and child socioemotional skills (strengths and difficulties questionnaire [SDQ-TD]) at 36-months postnatal. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02658994. FINDINGS: From Oct 15, 2014 to Feb 25, 2016 46 village clusters were assessed for eligibility, of which 40 (including 1910 mothers were enrolled. After exclusions, 288 women were randomly assigned to the enhanced usual care group and 284 to the intervention group, and 1159 women were included in a group without prenatal depression. At 36-months postnatal, complete data were available from 889 mother-child dyads: 206 (72·5%) in the intervention group, 216 (75·3%) in the enhanced usual care group, and 467 (80·0%) women who did not have prenatal-depression. We did not observe significant outcome differences between the intervention group and the enhanced usual care group for the primary outcomes. The standardised mean difference of PHQ-9 total score was -0·13 (95% CI -0·33 to 0·07), relative risk of patient health questionnaire-9 remission was 1·00 (95% CI 0·88 to 1·14), and the SDQ-TD treatment estimate was -0·10 (95% CI -1·39 to 1·19). INTERPRETATION: Reduced symptom severity and high remission rates were seen across both the intervention and enhanced usual care groups, possibly masking any effects of the intervention. A multi-year, psychosocial intervention can be task-shifted via peers but might be susceptible to reductions in fidelity and dosage over time (which were not among the outcomes of this trial). Early intervention efforts might need to rely on multiple models (eg, collaborative care), be of greater intensity, and potentially targeted at mothers who are at high risk for depression to reduce the intergenerational transmission of psychopathology from mothers to children. FUNDING: National Institutes of Health.

Psychosocial determinants of sustained maternal functional impairment: Longitudinal findings from a pregnancy-birth cohort study in rural Pakistan.

Function is an important marker of health throughout the life course, however, in low-and-middle-income-countries, little is known about the burden of functional impairment as women transition from pregnancy to the first year post-partum. Leveraging longitudinal data from 960 women participating in the Share Child Cohort in Pakistan, this study sought to (1) characterize functional trajectories over time among women in their perinatal period and (2) assess predictors of chronic poor functioning following childbirth. We used a group-based trajectory modeling approach to examine maternal patterns of function from the third trimester of pregnancy through 12 months post-partum. Three trajectory groups were found: persistently well-functioning (51% of women), poor functioning with recovery (39% of women), and chronically poor functioning (10% of women). When compared to mothers in the highest functioning group, psychosocial characteristics (e.g., depression, stress, and serious life events) were significantly associated with sustained poor functioning one-year following child-birth. Mothers living in nuclear households were more likely to experience chronic poor functioning. Higher education independently predicted maternal function recovery, even when controlling for psychosocial characteristics. Education, above and beyond socio-economic assets, appears to play an important protective role in maternal functional trajectories following childbirth. Public health implications related to maternal function and perinatal mental health are discussed.

The indirect impact of antiretroviral therapy: Mortality risk, mental health, and HIV-negative labor supply.

To reduce the burden of the HIV/AIDS epidemic, international donors recently began providing free antiretroviral therapy (ART) in parts of Sub-Saharan Africa. ART dramatically prolongs life and reduces infectiousness for people with HIV. This paper shows that ART availability increases work time for HIV-negative people without caretaker obligations, who do not directly benefit from the medicine. A difference-in-difference design compares people living near and far from ART, before and after treatment becomes available. Next we explore the possible reasons for this pattern. Although we cannot pinpoint the mechanism, we find that ART availability substantially reduces subjective mortality risk and improves mental health. These results show an undocumented economic consequence of the HIV/AIDS epidemic and an important externality of medical innovation. They also provide the first evidence of a link between the disease environment and mental health.