Psychological Distress Among Ethnically Diverse Participants From Eastern and Southern Africa.

Importance: Psychological distress is characterized by anxiety and depressive symptoms. Although prior research has investigated the occurrence and factors associated with psychological distress in low- and middle-income countries, including those in Africa, these studies' findings are not very generalizable and have focused on different kinds of population groups. Objective: To investigate the prevalence and characteristics (sociodemographic, psychosocial, and clinical) associated with psychological distress among African participants. Design, setting, and participants: This case-control study analyzed data of participants in the Neuropsychiatric Genetics in African Populations-Psychosis (NeuroGAP-Psychosis) study, which recruited from general outpatient clinics in Eastern (Uganda, Kenya, and Ethiopia) and Southern (South Africa) Africa. Individuals who participated in the control group of NeuroGAP-Psychosis from 2018 to 2023 were analyzed as part of this study. Data were analyzed from May 2023 to January 2024. Main outcomes and measures: The prevalence of psychological distress was determined using the Kessler Psychological Distress Scale (K10), which measures distress on a scale of 10 to 50, with higher scores indicating more distress. Participants from the NeuroGAP-Psychosis study were categorized into cases as mild (score of 20-24), moderate (score of 25-29), and severe (score of 30-50), and participants with scores less than 20 were considered controls. Factors that were associated with psychological distress were examined using binomial logistic regression. Results: From the data on 21 308 participants, the mean (SD) age was 36.5 (11.8) years, and 12 096 participants (56.8%) were male. The majority of the participants were married or cohabiting (10 279 participants [48.2%]), most had attained secondary education as their highest form of learning (9133 participants [42.9%]), and most lived with their families (17 231 participants [80.9%]). The prevalence of mild, moderate, and severe psychological distress was 4.2% (869 participants), 1.5% (308 participants), and 0.8% (170 participants), respectively. There were 19 961 participants (93.7%) who served as controls. Binomial logistic regression analyses indicated that the independent associations of psychological distress were experience of traumatic events, substance use (alcohol, tobacco, or cannabis), the physical comorbidity of arthritis, chronic neck or back pain, and frequent or severe headaches. Conclusions and relevance: In this case-control study among ethnically diverse African participants, psychological distress was associated with traumatic stress, substance use, and physical symptoms. These findings were observed to be consistent with previous research that emphasizes the importance of traumatic events as a factor associated with risk for psychopathology and notes the frequent co-occurrence of conditions such as physical symptoms, depression, and anxiety.

A blended genome and exome sequencing method captures genetic variation in an unbiased, high-quality, and cost-effective manner.

We deployed the Blended Genome Exome (BGE), a DNA library blending approach that generates low pass whole genome (1-4× mean depth) and deep whole exome (30-40× mean depth) data in a single sequencing run. This technology is cost-effective, empowers most genomic discoveries possible with deep whole genome sequencing, and provides an unbiased method to capture the diversity of common SNP variation across the globe. To evaluate this new technology at scale, we applied BGE to sequence >53,000 samples from the Populations Underrepresented in Mental Illness Associations Studies (PUMAS) Project, which included participants across African, African American, and Latin American populations. We evaluated the accuracy of BGE imputed genotypes against raw genotype calls from the Illumina Global Screening Array. All PUMAS cohorts had R 2 concordance ≥95% among SNPs with MAF≥1%, and never fell below ≥90% R 2 for SNPs with MAF<1%. Furthermore, concordance rates among local ancestries within two recently admixed cohorts were consistent among SNPs with MAF≥1%, with only minor deviations in SNPs with MAF<1%. We also benchmarked the discovery capacity of BGE to access protein-coding copy number variants (CNVs) against deep whole genome data, finding that deletions and duplications spanning at least 3 exons had a positive predicted value of ~90%. Our results demonstrate BGE scalability and efficacy in capturing SNPs, indels, and CNVs in the human genome at 28% of the cost of deep whole-genome sequencing. BGE is poised to enhance access to genomic testing and empower genomic discoveries, particularly in underrepresented populations.

An Item Response Theory Analysis of the Psychosis Screening Questionnaire in Ethiopia.

AIM: Few psychosis screening instruments have been tested for use in Africa, yet appropriate tools can increase the detection of self-reported psychotic symptoms, improve the detection of psychosis and impact its prognosis. METHOD: The construct validity and factor structure of Psychosis Screening Questionnaire (PSQ) were tested with confirmatory factor analysis (CFA) and item response theory (IRT) in a sample of 1928 Ethiopian adults without any history of psychosis. We tested a unidimensional model with and without an item on mania. For IRT, unidimensional latent structure one-parameter logistic (1PL) and two-parameter (2PL) logistic models were tested and compared for relative fit using a likelihood-ratio test. RESULT AND DISCUSSION: The prevalence of lifetime positive screens was 2.8% in an Ethiopian sample of adults from a general medical setting. A unidimensional model demonstrated good fit for the PSQ, (CFI = 0.993, TLI = 0.986 and RMSEA = 0.025). For IRT, a 2PL model was the best fitting one. IRT tests of item difficulty and discrimination parameters showed that paranoia had the highest discrimination α = 4.59 $$ \left(\alpha =4.59\right) $$ and lowest difficulty ( ß = 2.53 $$ \beta =2.53 $$ ), likely to be endorsed at low levels of psychotic features. Thought insertion had the highest item difficulty ( ß = 2.98 $$ \beta =2.98 $$ ). Overall, the measure captures the psychosis construct at higher levels of the latent trait and may be suited for detecting moderate to severe levels of psychosis. CONCLUSION: The PSQ is found to have good construct validity in screening for psychosis among Ethiopian adults. Future studies may focus on the diagnostic validity of the PSQ comparing it with a structured clinical interview.

'I want to be a different kind of father': a qualitative analysis of adolescent fatherhood in Perú.

Adolescent parents and their offspring experience worse health outcomes throughout the life course. While over 90% of adolescent births occur in low- and middle-income countries, data from many such countries are lacking, particularly from fathers. This qualitative study conducted in Lima, Peru characterises the experience of adolescent fathers and identifies potential intervention targets. Interviews with young fathers and the mothers of their children were coded and analysed using thematic analysis and a grounded theory approach. Factors impacting their experience included family support, changes in their relationship with their partner, gender dynamics, and financial pressure. The study identified family and couple conflict, gendered expectations, and the father's personal development as potential intervention targets. Further research is needed to develop interventions that effectively engage adolescent fathers in low- and middle-income countries such as Peru, and support their transition to fatherhood.

Evaluation of the psychometric properties of the UBACC questionnaire in a multi-country psychiatric study in Africa.

BACKGROUND: The University of California, San Diego Brief Assessment of Capacity to Consent (UBACC) is a tool to assess the capacity of participants to consent in psychiatric research. However, little is known about the psychometric properties in low and middle-income countries. This study aimed to examine the psychometric properties of the UBACC. METHODS: We examined the reliability, latent factor structure, and item response of the first attempt of the UBACC items in a sample of 32,208 adults (16,467 individuals with psychosis and 15,741 controls) in Ethiopia, Kenya, South Africa, and Uganda; exploring these properties in the full sample and stratified by country, diagnostic status, sex, and ethnolinguistic language groups. RESULTS: Exploratory factor analysis (EFA) suggested a two-factor model for the overall sample. However, a three-factor model was more appropriate when examining the latent structure across country, language, and sex. Confirmatory factor analyses (CFA) revealed an adequately fitting three-factor model for the full sample and across country, sex, and language. A two-factor model, however, was more appropriate for English and Amharic languages. Across all groups, the internal consistency of the UBACC was low, indicating below-threshold reliability (Cronbach's α (95 % CI = 0.58 (0.57-0.59). Using a multidimensional item-response theory framework for the full sample revealed that UBACC item 8, measuring understanding of the benefits of study participation, was the most discriminating item. Many of the other items had below-threshold discriminating characteristics. CONCLUSION: EFA and CFA converged towards a two and three-dimensional structure for the UBACC, in line with the developers of the original scale. The differences in properties between populations and language groups, low internal consistency, and below-threshold item functioning suggest that investigations into the cultural and linguistic nuances are still warranted. Understanding the utility of consent tools, such as the UBACC, in underrepresented populations will be a part of the larger process which ensures that research participants are adequately protected.

Prevalence and correlates of common mental disorders among participants of the Uganda Genome Resource: Opportunities for psychiatric genetics research.

Genetics research has potential to alleviate the burden of mental disorders in low- and middle-income-countries through identification of new mechanistic pathways which can lead to efficacious drugs or new drug targets. However, there is currently limited genetics data from Africa. The Uganda Genome Resource provides opportunity for psychiatric genetics research among underrepresented people from Africa. We aimed at determining the prevalence and correlates of major depressive disorder (MDD), suicidality, post-traumatic stress disorder (PTSD), alcohol abuse, generalised anxiety disorder (GAD) and probable attention-deficit hyperactivity disorder (ADHD) among participants of the Uganda Genome Resource. Standardised tools assessed for each mental disorder. Prevalence of each disorder was calculated with 95% confidence intervals. Multivariate logistic regression models evaluated the association between each mental disorder and associated demographic and clinical factors. Among 985 participants, prevalence of the disorders were: current MDD 19.3%, life-time MDD 23.3%, suicidality 10.6%, PTSD 3.1%, alcohol abuse 5.7%, GAD 12.9% and probable ADHD 9.2%. This is the first study to determine the prevalence of probable ADHD among adult Ugandans from a general population. We found significant association between sex and alcohol abuse (adjusted odds ratio [AOR] = 0.26 [0.14,0.45], p < 0.001) and GAD (AOR = 1.78 [1.09,2.49], p = 0.019) respectively. We also found significant association between body mass index and suicidality (AOR = 0.85 [0.73,0.99], p = 0.041), alcohol abuse (AOR = 0.86 [0.78,0.94], p = 0.003) and GAD (AOR = 0.93 [0.87,0.98], p = 0.008) respectively. We also found a significant association between high blood pressure and life-time MDD (AOR = 2.87 [1.08,7.66], p = 0.035) and probable ADHD (AOR = 1.99 [1.00,3.97], p = 0.050) respectively. We also found a statistically significant association between tobacco smoking and alcohol abuse (AOR = 3.2 [1.56,6.67], p = 0.002). We also found ever been married to be a risk factor for probable ADHD (AOR = 2.12 [0.88,5.14], p = 0.049). The Uganda Genome Resource presents opportunity for psychiatric genetics research among underrepresented people from Africa.

Relationships between trauma types and psychotic symptoms: A network analysis of patients with psychotic disorders in a large, multi-country study in East Africa.

BACKGROUND: The link between trauma exposure and psychotic disorders is well-established. Further, specific types of trauma may be associated with specific psychotic symptoms. Network analysis is an approach that can advance our understanding of the associations across trauma types and psychotic symptoms. METHODS: We conducted a network analysis with data from 16,628 adult participants (mean age [standard deviation] = 36.3 years [11.5]; 55.8% males) with psychotic disorders in East Africa recruited between 2018 and 2023. We used the Life Events Checklist and the Mini International Neuropsychiatric Interview to determine whether specific trauma types experienced over the life course and specific psychotic symptoms were connected. We used an Ising model to estimate the network connections and bridge centrality statistics to identify nodes that may influence trauma types and psychotic symptoms. RESULTS: The trauma type "exposure to a war zone" had the highest bridge strength, betweenness, and closeness. The psychotic symptom "odd or unusual beliefs" had the second highest bridge strength. Exposure to a war zone was directly connected to visual hallucinations, odd or unusual beliefs, passivity phenomena, and disorganized speech. Odd or unusual beliefs were directly connected to transportation accidents, physical assault, war, and witnessing sudden accidental death. CONCLUSION: Specific trauma types and psychotic symptoms may interact bidirectionally. Screening for psychotic symptoms in patients with war-related trauma and evaluating lifetime trauma in patients with odd or unusual beliefs in clinical care may be considered points of intervention to limit stimulating additional psychotic symptoms and trauma exposure. This work reaffirms the importance of trauma-informed care for patients with psychotic disorders.

The cumulative impact of trauma, chronic illness, and COVID-19 stress on mental health in a case-control study of adults with psychotic disorders in Ethiopia.

BACKGROUND: The COVID-19 pandemic has profoundly impacted the economic, psychological, and social well-being of people in Ethiopia. Pandemic-related fears can exacerbate anxiety and depression symptoms among those with pre-existing physical and mental health conditions as well as those with prior exposure to traumatic events. METHODS: We used data from the Ethiopia NeuroGAP-Psychosis study (898 cases and 941 controls with and without a diagnosis of psychosis respectively, 66% male, mean age = 37 years). Data was collected between November 2021 and June 2022 during the COVID-19 pandemic from four hospitals in Ethiopia (three in Addis Ababa and one in Jimma city). Structural equation modeling analysis was conducted to examine the associations between trauma exposure, physical health conditions (like arthristis, neurological disorders, diabetes), COVID-19 stress, and psychological distress (depression and anxiety symptoms). We assessed direct and indirect effects for mediation, and conducted multigroup analysis to examine moderation by case control status. RESULTS: We found evidence that the impact of greater trauma exposure and physical health conditions on higher psychological distress was mediated through higher COVID-19 stress. Sociodemographic characteristics (older age and being maried) were associated with higher psychological distress, with these associations mediated through greater trauma, physical health conditions, and COVID-19 stress. Case-control status also moderated the associations between these variables, with the mediation effects being stronger in cases and weaker in controls. Further, cases reported greater trauma and psychological distress, while controls reported more physical health conditions and COVID-19 stress. IMPLICATIONS: Our findings uniquely assess the interaction of health and emergency related factors in understudied settings like Ethiopia. They underscore the importance of including daily hardships and environmental stressors, along with prior trauma exposure, as risk factors for the assessment of mental health symptoms. This study has key implications for mental health screening and intervention research in response to complex emergency contexts like Ethiopia with a history of armed conflict in addition to the COVID-19 pandemic. Our findings can aid the development of targeted services that address the mental health of at-risk groups with pre-existing mental and physical health conditions.

Characterization of hair cortisol concentration pre-conception and during pregnancy.

BACKGROUND: The hypothalamic pituitary adrenal (HPA) axis is a system involved in stress and pregnancy regulation, and hair cortisol concentration (HCC) is a promising biomarker of its activity. Assessing factors that influence HCC in the prenatal period is critical to understand whether and how HPA axis (dys-)regulation influences maternal health and child development, particularly in high-risk populations from low- and middle-income countries (LMICs). AIMS: This study aimed at characterizing preconception and pregnancy HCC with respect to multiple sociodemographic, pregnancy-related, and hair-related factors. METHODS: In a sample of N = 2581 pregnant women in Perú, participants from two cohort studies provided a 6 cm scalp hair sample at three prenatal timepoints. Each hair sample was cut into two segments of 3 cm that represent cortisol secretion at four times: preconception, first-, second- and third trimester of pregnancy. Hair cortisol was extracted using liquid chromatography tandem mass spectrometry (LC-MS/MS). Spearman correlations, paired t-tests, and ANOVA were used to assess differences in log-transformed values of HCC (logHCC) across maternal sociodemographic, pregnancy-related, and hair-related factors. Multivariable linear regressions were used to examine independent associations of HCCs with selected correlates. RESULTS: Mean logHCC values showed an increase across the four prenatal periods. Preconception BMI was consistently associated with HCC in all three trimesters, while difficulty accessing basic foods, education, hair dyeing, and infant sex showed time-specific associations with HCCs. In sensitivity analyses, we detected no substantial segment effects in the associations of HCCs with maternal characteristics. CONCLUSION: This study is the largest to characterize HCC in pregnant women from a LMIC. Our findings provide a foundation for the use of HCC as a biomarker of prenatal HPA axis activity for future studies. This foundation may contribute to finding valid biomarkers of stress-response systems to promote maternal and child health.

Cross-cultural equivalence of the Kessler Psychological Distress Scale (K10) across four African countries in a multi-national study of adults.

The Kessler Psychological Distress Scale (K10) has been widely used to screen psychological distress across many countries. However, its performance has not been extensively studied in Africa. The present study sought to evaluate and compare measurement properties of the K10 across four African countries: Ethiopia, Kenya, Uganda, and South Africa. Our hypothesis is that the measure will show equivalence across all. Data are drawn from a neuropsychiatric genetic study among adult participants (N = 9179) from general medical settings in Ethiopia (n = 1928), Kenya (n = 2556), Uganda (n = 2104), and South Africa (n = 2591). A unidimensional model with correlated errors was tested for equivalence across study countries using confirmatory factor analyses and the alignment optimization method. Results displayed 30 % noninvariance (i.e., variation) for both intercepts and factor loadings across all countries. Monte Carlo simulations showed a correlation of 0.998, a good replication of population values, indicating minimal noninvariance, or variation. Items "so nervous," "lack of energy/effortful tasks," and "tired" were consistently equivalent for intercepts and factor loadings, respectively. However, items "depressed" and "so depressed" consistently differed across study countries (R2 = 0) for intercepts and factor loadings for both items. The K10 scale likely functions equivalently across the four countries for most items, except "depressed" and "so depressed." Differences in K10 items were more common in Kenya and Ethiopia, suggesting cultural context may influence the interpretation of some items and the potential need for cultural adaptations in these countries.

The Association Between Pre-Pregnancy and First-Trimester Hair Cortisol and Preterm Birth: A Causal Inference Model.

Background Adverse life events and chronic psychological distress before and during pregnancy have frequently been associated with preterm birth (PTB) but the biological underpinnings remain unclear. We investigated the association between corticosteroid levels in pre-pregnancy and first-trimester hair and the risk of PTB. Methods We followed 1,808 pregnant women from a prospective pre-birth cohort study in Lima, Perú. Hair samples were taken at the end of the first pregnancy trimester. The two most proximal 3cm segments to the scalp (representing pre-pregnancy and first-trimester) were analyzed to obtain hair cortisol and cortisone concentrations (HCC and HCNC). PTB was defined as birth < 37 completed gestational weeks. We constructed four generalized propensity scores for pre-pregnancy and first-trimester HCC and HCNC to create corresponding inverse probability weights before fitting marginal structural models for estimating the effect of HCC and HCNC on PTB risk. Results Pre-pregnancy Log HCC was not independently associated with PTB risk (RR = 0.97; 95%CI: 0.79, 1.19). In contrast, one SD increase from the mean first-trimester Log HCC was independently associated with a 37% (95%CI: 1.11, 1.69) increased risk of PTB. Although imprecise, pre-pregnancy Log HCNC was negatively associated with PTB risk (RR = 0.84; 95%CI: 0.58, 1.20), whereas the association between first-trimester Log HCNC and PTB risk was positive (RR = 1.20; 95%CI: 0.87, 1.65). Conclusions Our findings show that chronic corticosteroid levels in early pregnancy are causally linked to PTB risk in pregnant Peruvian women. This finding contributes to understanding the biological underpinnings of PTB better to enhance PTB prevention.

Experiences of trauma and psychometric properties of the Life Events Checklist among adults in Uganda.

Exposure to potentially traumatic events (PTE) is common and increases an individual's risk of developing post-traumatic stress disorder (PTSD) and other psychiatric disorders. PTEs can be screened with the Life Events Checklist for DSM 5 (LEC-5). However, the psychometric properties of the LEC-5 have never been assessed in Uganda. We aimed to estimate the prevalence of PTEs and evaluate the factor structure of the LEC-5 in a sample of N = 4,479 Ugandan adults between February 2018 -March 2020. We used the phenotyping data from a case-control study (NeuroGAP-Psychosis) in Uganda investigating the genetic and environmental risk factors for psychosis spectrum disorders with 4,479 participants (2,375 cases and 2,104 controls). Prevalence for PTEs was determined for all participants and by case-control status. The factor structure of the LEC-5 was assessed using an exploratory factor analysis (EFA) and a confirmatory factor analysis (CFA). The overall prevalence of exposure to one or more types of PTEs was 60.5%. Cases reported more frequency of exposure to PTEs than controls (64.2% vs 55.4%; p<0.001). The most frequently endorsed traumatic event was physical assault (22.8%), while exposure to toxic substances was the least endorsed (1.7%). There were several differences among the types of events experienced between cases and controls, including cases reporting more experiences of physical (28.6% vs. 16.2%, p<0.001) and sexual assault (11.5% vs. 5.0%, p<0.001) than controls. The EFA yielded a six-factor model that explained 49.8% of the total variance. The CFA showed that a theoretical seven-factor model based on the South African Stress and Health survey was a better fitting model (CFI = 0.935; TLI = 0.908; RMSEA = 0.026) than the EFA. This study revealed a high prevalence of PTEs among cases and controls, and the LEC-5 was found to have good psychometric properties among Ugandan adults.

The association between maternal prenatal hair cortisol concentration and preterm birth: A systematic review and meta-analysis.

BACKGROUND: The risk of preterm birth (PTB) increases when experiencing stress during pregnancy. Chronic stress has been associated with a dysregulation of the hypothalamic-pituitary-adrenal axis, for which hair cortisol concentration (HCC) is a promising biomarker. However, previous studies on the association between HCC and PTB yielded inconsistent results. This systematic review and meta-analysis synthesized previous studies on the association between maternal HCC before and during pregnancy and spontaneous PTB. METHODS: Data was extracted from N = 11 studies with k = 19 effect sizes retrieved from PubMed, Embase, Web of Science, CINAHL and citation searching by hand in June 2023 and updated in October 2023. Standardized mean differences were calculated, and a random-effects three-level meta-analysis was conducted. Effect heterogeneity was assessed using Q and I2. RESULTS: HCC during pregnancy was higher among PTB than term groups, but effects were not statistically significant (z = 0.11, 95% CI: - 0.28, 0.51, p = .54) and total heterogeneity was high (Q16 = 60.01, p < .001, I2Total = 92.30%). After leaving out two possible outlier studies in sensitivity analyses, HCC was lower among preterm compared to term delivering groups, although not statistically significant (z = - 0.06, 95% CI: - 0.20, 0.08, p = .39) but with a substantially reduced total heterogeneity (Q12 = 16.45, p = .17, I2Total = 42.15%). No moderators affected the estimates significantly, but an effect of trimester and gestational age at delivery is likely. CONCLUSION: There is currently no evidence of prenatal HCC differences between PTB and term groups as effects were small, imprecise, and not significant. Low statistical power and methodological weaknesses of the small-scale studies challenge possible biological inferences from the small effects, but further research on HCC during pregnancy is highly encouraged.

A qualitative analysis of adolescent motherhood within the broader family context in Peru.

Objective: The purpose of this study was to characterize the impact of adolescent pregnancy on families and describe the needs of adolescent mothers and their infants in order to assess the need for intervention and identify potential intervention targets. Background: Adolescent mothers and their offspring face an increased risk of mental health problems. Adolescent mothers and their families also face significant resource constraints; 95% live in low- and middle-income countries (LMICs). Cost-effective interventions are needed to improve outcomes for this vulnerable group. Method: This qualitative study conducted in Lima, Peru, consisted of four clinician focus groups and 18 in-depth interviews with adolescent mothers and their family members. Data were coded thematically, and direct content analysis was employed. Results: The study identified the following issues facing adolescent parents: the transition to parenthood, the need for family support, difficulty accessing support, the difficulty for family members of providing support, and ideas about responsibility and adolescent autonomy. Conclusion: Overall, these findings demonstrate the need for interventions that engage families and address barriers to accessing support, including relationship conflict and differing beliefs about responsibility and autonomy. Implications: Interventions are needed for adolescent mothers in LMICs that mobilize family support. Clinicians who care for these patients need to be aware of the family context and the resources available where they practice.

Determinants of intentions to seek formal mental health help among Palestinian adolescents in Israel.

BACKGROUND: Mental health challenges are widespread among adolescents undergoing significant physical, emotional, social, and academic changes. However, rates of formal help-seeking remain low, particularly among those from ethnic minorities. AIMS: This study investigated the determinants of intentions to seek formal mental health help among Palestinian adolescents in Israel, focusing on mental health literacy (MHL) and trust in formal sources of information. METHODS: A total of 178 adolescents (Mage = 16.24 ± 1.24 years, 61.8% female) completed measures assessing intention for formal help-seeking, psychological distress, MHL, trust in formal sources of information, sociodemographic, and clinical characteristics. RESULTS: Findings revealed low levels of intention to seek formal help and psychological distress, alongside average or above-average levels on all MHL dimensions and trust in formal sources for information. Our analysis identified socioeconomic status (ß = .17, p < .05), psychological distress (ß = .18, p < .05), trust in formal sources of information (ß = .28, p < .001), and two MHL dimensions: knowledge of where to seek information (ß = .25, p < .01) and attitudes that promote recognition or appropriate help-seeking behavior (ß = .16, p < .05) - as the main determinants of intention for formal help-seeking. CONCLUSIONS: This study underscores the critical role of trust in formal sources of information and MHL in seeking formal help among adolescents from ethnic minorities. Interventions aiming to improve access to mental health-related information, address and enhance attitudes, and foster trust in formal professionals and institutions may contribute to an increased tendency for formal mental health help-seeking among this population and others.

Mediation of the association between depression and coronary heart disease by metabolic syndrome components.

BACKGROUND: Depression is associated with incident coronary heart disease (CHD) via a pathway that may be causal, but the mechanisms underlying this association are unclear. We assessed the extent to which metabolic syndrome (MetS) and its components (i.e., elevated waist circumference, low high-density lipoprotein [HDL] cholesterol, elevated triglycerides, elevated blood pressure, and elevated fasting plasma glucose) may mediate this association. METHODS: Data were Framingham Heart Study Research Materials obtained from the National Heart, Lung, and Blood Institute (NHLBI) Biologic Specimen and Data Repository Information Coordinating Center. We used Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) representing the total effect (aHRTE) of probable depression, measured via the Centers for Epidemiological Studies - Depression scale, on incident CHD over approximately 18 years. Using inverse odds ratio weighting, we decomposed this estimate into natural direct effects (aHRNDE) and natural indirect effects (aHRNIE) through potential mediators (measured approximately three years after depression). RESULTS: Probable depression was associated with incident CHD (aHRTE=1.45, 95% confidence interval [CI]: 0.93, 2.25), and elevated waist circumference partially mediated this association (aHRNDE=1.34, 95% CI: 0.76-2.32; aHRNIE=1.08, 95% CI: 0.63-1.91). We did not find evidence of additional mediation by additional MetS components. CONCLUSIONS: Elevated waist circumference appears to play a role in the association between depression and CHD.

Factor structure of psychosis screening questionnaire in Ugandan adults.

BACKGROUND: Psychotic disorders are common and contribute significantly to morbidity and mortality of people with psychiatric diseases. Therefore, early screening and detection may facilitate early intervention and reduce adverse outcomes. Screening tools that lay persons can administer are particularly beneficial in low resource settings. However, there is limited research evaluating the validity of psychosis screening instruments in Uganda. We aimed to assess the construct validity and psychometric properties of the Psychosis Screening Questionnaire (PSQ) in Uganda in a population with no history of a psychotic disorder. METHODS: The sample consisted of 2101 Ugandan adults participating as controls in a larger multi-country case-control study on psychiatric genetics who were recruited between February 2018 and March 2020. Participants were individuals seeking outpatient general medical care, caretakers of individuals seeking care, and staff or students recruited from five medical facilities that were age 18 years or older and able to provide consent. Individuals were excluded who had acute levels of alcohol or substance use, including being under inpatient hospitalization or acute medical care for one of these conditions. We used confirmatory factor analysis (CFA) and item response theory (IRT) to evaluate the factor structure and item properties of the PSQ. RESULTS: The overall prevalence screening positive for psychotic symptoms was 13.9% 95% CI (12.4,15.4). "Strange experiences" were the most endorsed symptoms 6.6% 95% CI (5.6,7.8). A unidimensional model seemed to be a good model or well-fitting based on fit indices including the root mean square error of approximation (RMSEA of 0.00), comparative fit index (CFI of 1.000), and Tucker-Lewis Index (TLI of 1.000). The most discriminating items along the latent construct of psychosis were items assessing thought disturbance followed by items assessing paranoia, with a parameter (discrimination) value of 2.53 and 2.40, respectively. CONCLUSION: The PSQ works well in Uganda as an initial screening tool for moderate to high-level of psychotic symptoms.

Fourteen-item perceived stress scale assessment using item response theory among pregnant women.

The current study aimed to assess the psychometric properties of the Spanish language version of the 14-item Perceived Stress Scale (PSS-S) in a population of pregnant women who speak Spanish in Peru using item response theory (IRT). Our study consisted of 5,435 pregnant women who participated in the Pregnancy Outcomes Maternal and Infant Study (PrOMIS) cohort in Peru. Exploratory and confirmatory factor analyses were conducted to determine dimensionality of the scale in this population, and item response theory was conducted to determine the applicability of the PSS. The PSS consisted of a 2-factor questionnaire measuring perceived stress and coping capacity accounting for 77% of variability. The IRT analysis showed differences in item difficulty and discrimination. Item difficulty represents the level of the latent construct where 50% of respondents endorse a particular response, and item discrimination determines the rate of change of the probability of endorsing an item for differing ability levels. For the first factor, perceived stress, item 12 was the least difficult and item 2 was the most difficult. For the second factor, coping capacity, item 9 was the least difficult and item 6 was the most difficult. The Spanish version of the 14-item PSS can be a useful assessment tool for perceived stress, but more IRT should be done to delve further into the psychometric properties of the questionnaire to inform clinicians and policy makers more appropriately.

Genetic association study of Preterm birth and Gestational age in a population-based case-control study in Peru: Genetics of PTB and GA in pregnant women in Peru.

Preterm birth (PTB) is an adverse pregnancy outcome affecting ~15 million pregnancies worldwide. Genetic studies have identified several candidate loci for PTB, but results remain inconclusive and limited to European populations. Thus, we conducted a genome-wide association study (GWAS) of PTB and gestational age at delivery (GA) among 2,212 Peruvian women. PTB cases delivered ≥ 20 weeks' but < 37 weeks' gestation, while controls delivered at term (≥ 37 weeks but < 42 weeks). After imputation (TOPMED) and quality control, we assessed the association of ~6 million SNPs with PTB and GA using multivariable regression models adjusted for maternal age and the first two genetic principal components. In silico functional analysis (FUMA-GWAS) was conducted among top signals detected with an arbitrary P < 1.0×10-5 in each GWAS. We sought to replicate genetic associations with PTB and GA identified in Europeans, and we developed a genetic risk score for GA based on European markers. Mean GA was 30 ± 4 weeks in PTB cases (N=933) and 39 ± 1 in the controls (N=1,279). PTB cases were slightly older and had higher C-sections and vaginal bleeding than controls. No association was identified at genome-wide level. Top suggestive (P < 1.0×10-5) signals were seen at rs13151645 (LINC01182) for PTB, and at rs72824565 (CTNNA2) for GA. Top PTB variants were enriched for biological pathways associated with polyketide, progesterone, steroid hormones, and glycosyl metabolism. Top GA variants were enriched in intronic regions and cancer pathways, and these genes were upregulated in the brain and subcutaneous adipose tissue. In combination with non-genetic risk factors, top SNPs explained 14% and 15% of the phenotypic variance of PTB and GA in our sample, but these results need to be interpreted with caution. Variants in WNT4 associated with GA in Europeans were replicated in our study. The genetic risk score based in European markers, was associated with a 2-day longer GA (R2=0.003, P=0.002) per standard deviation increase in the score in our sample. This genetic association study identified various signals suggestively associated with PTB and GA in a non-European population; they were linked to relevant biological pathways related to the metabolism of progesterone, prostanoid, and steroid hormones, and genes associated with GA were significantly upregulated in relevant tissues for the pathophysiology of PTB based on the in-silico functional analysis. None of these top variants overlapped with signals previously identified for PTB or GA in Europeans.