Haploinsufficiency of the E3 Ubiquitin Ligase C-Terminus of Heat Shock Cognate 70 Interacting Protein (CHIP) Produces Specific Behavioral Impairments

The multifunctional E3 ubiquitin ligase CHIP is an essential interacting partner of HSP70, which together promote the proteasomal degradation of client proteins. Acute CHIP overexpression provides neuroprotection against neurotoxic mitochondrial stress, glucocorticoids, and accumulation of toxic amyloid fragments, as well as genetic mutations in other E3 ligases, which have been shown to result in familial Parkinson's disease. These studies have created a great deal of interest in understanding CHIP activity, expression and modulation. While CHIP knockout mice have the potential to provide essential insights into the molecular control of cell fate and survival, the animals have been difficult to characterize in vivo due to severe phenotypic and behavioral dysfunction, which have thus far been poorly characterized. Therefore, in the present study we conducted a battery of neurobehavioral and physiological assays of adult CHIP heterozygotic (HET) mutant mice to provide a better understanding of the functional consequence of CHIP deficiency. We found that CHIP HET mice had normal body and brain weight, body temperature, muscle tone and breathing patterns, but do have a significant elevation in baseline heart rate. Meanwhile basic behavioral screens of sensory, motor, emotional and cognitive functions were normative. We observed no alterations in performance in the elevated plus maze, light-dark preference and tail suspension assays, or two simple cognitive tasks: novel object recognition and spontaneous alternation in a Y maze. Significant deficits were found, however, when CHIP HET mice performed wire hang, inverted screen, wire maneuver, and open field tasks. Taken together, our data indicate a clear subset of behaviors that are altered at baseline in CHIP deficient animals, which will further guide whole animal studies of the effects of CHIP dysregulation on cardiac function, brain circuitry and function, and responsiveness to environmental and cellular stress

Water Insecurity and Gendered Risk for Depression in Rural Uganda: A Hotspot Analysis

Background: Water insecurity is linked to depression in low- and middle-income countries (LMICs), though it remains unclear how geospatial clustering of water insecurity in rural regions is associated with risk for depression. Methods: We conducted a population-based survey of a rural parish in southwestern Uganda (N = 1603) to evaluate the joint geospatial clustering of water insecurity and risk for depression among men and women living in rural Uganda. Results: Geospatial clustering of self-reported water insecurity and depressive symptoms was found to be present among both men and women. Depression hotspots were more often observed near water insecurity hotspots among women, relative to men. Multivariable regression revealed that residing in a water insecurity hotspot significantly increased risk for depressive symptoms among women, but not among men. Conclusions: Residing in a water insecurity hotspot is associated with greater risk for probable depression among women, but not among men, pointing to the need for focused depression screening among women residing in water insecure households. Keywords: Water insecurity, Depression, Geospatial, Gender, Sub-Saharan Afric

Household Water Insecurity, Missed Schooling, and the Mediating role of Caregiver Depression in Rural Uganda

Background: School attendance rates in sub-Saharan Africa are among the lowest worldwide, placing children at heightened risk for poor educational and economic outcomes. One understudied risk factor for missed schooling is household water insecurity, which is linked to depression among women and may increase children’s water-fetching burden at the expense of educational activities, particularly among children of depressed caregivers. In this study conducted in rural Uganda, we assessed the association between household water insecurity and child school participation and the mediating pathways behind these associations. Method: We conducted a population-based, cross-sectional study of female household heads (N = 257) and their children ages 5–17 (N = 551) in the rural regions surrounding the town of Mbarara, in southwestern Uganda. We used multivariable linear regressions to estimate the association between water insecurity and missed schooling. We then assessed the extent to which the association was mediated by caregiver depression. Results: Among children, water insecurity had a statistically significant association with the number of missed school days (a standard deviation increase in water insecurity resulted in 0.30 more missed school days in the last week). The estimated association was partially mediated by caregiver depression. When stratified by sex, this mediating pathway remained significant for boys, but not among girls. Conclusions: Water insecurity is a risk factor for missed schooling among children in rural Uganda. Caregiver depression partially mediated this relationship. Also addressing caregiver mental health in water insecure families may more fully address the needs of sub-Saharan African families and promote educational participation among youth

Measuring personal beliefs and perceived norms about intimate partner violence: Population-based survey experiment in rural Uganda

Background: Demographic and Health Surveys (DHS) conducted throughout sub-Saharan Africa indicate there is widespread acceptance of intimate partner violence, contributing to an adverse health risk environment for women. While qualitative studies suggest important limitations in the accuracy of the DHS methods used to elicit attitudes toward intimate partner violence, to date there has been little experimental evidence from sub-Saharan Africa that can be brought to bear on this issue. Methods and findings We embedded a randomized survey experiment in a population-based survey of 1,334 adult men and women living in Nyakabare Parish, Mbarara, Uganda. The primary outcomes were participants’ personal beliefs about the acceptability of intimate partner violence and perceived norms about intimate partner violence in the community. To elicit participants’ personal beliefs and perceived norms, we asked about the acceptability of intimate partner violence in five different vignettes. Study participants were randomly assigned to one of three survey instruments, each of which contained varying levels of detail about the extent to which the wife depicted in the vignette intentionally or unintentionally violated gendered standards of behavior. For the questions about personal beliefs, the mean (standard deviation) number of items where intimate partner violence was endorsed as acceptable was 1.26 (1.58) among participants assigned to the DHS-style survey variant (which contained little contextual detail about the wife’s intentions), 2.74 (1.81) among participants assigned to the survey variant depicting the wife as intentionally violating gendered standards of behavior, and 0.77 (1.19) among participants assigned to the survey variant depicting the wife as unintentionally violating these standards. In a partial proportional odds regression model adjusting for sex and village of residence, with participants assigned to the DHS-style survey variant as the referent group, participants assigned the survey variant that depicted the wife as intentionally violating gendered standards of behavior were more likely to condone intimate partner violence in a greater number of vignettes (adjusted odds ratios [AORs] ranged from 3.87 to 5.74, with all p < 0.001), while participants assigned the survey variant that depicted the wife as unintentionally violating these standards were less likely to condone intimate partner violence (AORs ranged from 0.29 to 0.70, with p-values ranging from <0.001 to 0.07). The analysis of perceived norms displayed similar patterns, but the effects were slightly smaller in magnitude: participants assigned to the “intentional” survey variant were more likely to perceive intimate partner violence as normative (AORs ranged from 2.05 to 3.51, with all p < 0.001), while participants assigned to the “unintentional” survey variant were less likely to perceive intimate partner violence as normative (AORs ranged from 0.49 to 0.65, with p-values ranging from <0.001 to 0.14). The primary limitations of this study are that our assessments of personal beliefs and perceived norms could have been measured with error and that our findings may not generalize beyond rural Uganda. Conclusions: Contextual information about the circumstances under which women in hypothetical vignettes were perceived to violate gendered standards of behavior had a significant influence on the extent to which study participants endorsed the acceptability of intimate partner violence. Researchers aiming to assess personal beliefs or perceived norms about intimate partner violence should attempt to eliminate, as much as possible, ambiguities in vignettes and questions administered to study participants. Trial registration ClinicalTrials.gov NCT02202824

Water insecurity and gendered risk for depression in rural Uganda: a hotspot analysis

Abstract Background Water insecurity is linked to depression in low- and middle-income countries (LMICs), though it remains unclear how geospatial clustering of water insecurity in rural regions is associated with risk for depression. Methods We conducted a population-based survey of a rural parish in southwestern Uganda (N = 1603) to evaluate the joint geospatial clustering of water insecurity and risk for depression among men and women living in rural Uganda. Results Geospatial clustering of self-reported water insecurity and depressive symptoms was found to be present among both men and women. Depression hotspots were more often observed near water insecurity hotspots among women, relative to men. Multivariable regression revealed that residing in a water insecurity hotspot significantly increased risk for depressive symptoms among women, but not among men. Conclusions Residing in a water insecurity hotspot is associated with greater risk for probable depression among women, but not among men, pointing to the need for focused depression screening among women residing in water insecure households

When You Have No Water, It Means You Have No Peace : A Mixed-methods, Whole-population Study of Water Insecurity and Depression in Rural Uganda

Background Lack of access to clean water has well known implications for communicable disease risks, but the broader construct of water insecurity is little studied, and its mental health impacts are even less well understood. Methods and findings We conducted a mixed-methods, whole-population study in rural Uganda to estimate the association between water insecurity and depression symptom severity, and to identify the mechanisms underlying the observed association. The whole-population sample included 1776 adults (response rate, 91.5%). Depression symptom severity was measured using a modified 15-item Hopkins Symptom Checklist for Depression. Water insecurity was measured with a locally validated 8-item Household Water Insecurity Access Scale. We fitted multivariable linear and Poisson regression models to the data to estimate the association between water insecurity and depression symptom severity, adjusting for age, marital status, self-reported overall health, household asset wealth, and educational attainment. These models showed that water insecurity was associated with depression symptom severity (b = 0.009; 95% confidence interval [CI], 0.004–0.15) and that the estimated association was larger among men (b = 0.012; 95% CI, 0.008–0.015) than among women (b = 0.008; 95% CI, 0.004–0.012. We conducted qualitative interviews with a sub-group of 30 participants, focusing on women given their traditional role in household water procurement in the Ugandan context. Qualitative analysis, following an inductive approach, showed that water insecurity led to “choice-less-ness” and undesirable social outcomes, which in turn led to emotional distress. These pathways were amplified by gender-unequal norms. Conclusions Among men and women in rural Uganda, the association between water insecurity and depression symptom severity is statistically significant, substantive in magnitude, and robust to potential confounding. Data from the qualitative interviews provide key narratives that reveal the mechanisms through which women\u27s lived experiences with water insecurity may lead to emotional distress

Perceived norms about the acceptability of intimate partner violence, adjusted estimates by survey condition, using partial proportional odds regression (<i>n =</i> 1,334).

<p>Perceived norms about the acceptability of intimate partner violence, adjusted estimates by survey condition, using partial proportional odds regression (<i>n =</i> 1,334).</p

Characteristics of the sample (<i>n =</i> 1,334).

<p>Characteristics of the sample (<i>n =</i> 1,334).</p

Personal beliefs about the acceptability of intimate partner violence, unadjusted estimates by survey condition (<i>n =</i> 1,334).

<p>Personal beliefs about the acceptability of intimate partner violence, unadjusted estimates by survey condition (<i>n =</i> 1,334).</p

Perceived norms about the acceptability of intimate partner violence, unadjusted estimates by survey condition (<i>n =</i> 1,334).

<p>Perceived norms about the acceptability of intimate partner violence, unadjusted estimates by survey condition (<i>n =</i> 1,334).</p