Bizu Gelaye

Here we developed and deployed the blended genome exome (BGE) method, a DNA library 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. BGE is cost-effective, empowers most genomic discoveries possible with deep whole-genome sequencing and captures global common single-nucleotide polymorphism diversity. We applied BGE to sequence >53,000 samples from the PUMAS Project (Populations Underrepresented in Mental Illness Associations Studies), including African, African American and Latin American populations. Imputed genotypes showed high concordance with Illumina Global Screening Array calls ( R ² ≥ 95% for minor allele frequency ≥1%; ≥90% for minor allele frequency <1%), with consistent performance across local ancestries in admixed cohorts. For protein-coding copy number variants, deletions and duplications spanning at least three exons had a positive predicted value of ~90% relative to deep whole-genome data. At ~28% of the cost of deep whole-genome sequencing, BGE provides a scalable, reliable platform to expand genomic discovery and equitable access to sequencing in underrepresented populations.

Objective: The objective of this study was to assess the individual and joint association of adverse childhood experiences (ACEs) and migraine with adverse pregnancy outcomes. Purpose: Teenage pregnancy is prevalent, particularly in low‐ and middle‐income countries. Teenage mothers sustain higher risk of adverse birth outcomes compared to their adult counterparts. ACEs and migraine are prevalent among teenage mothers and may contribute to adverse pregnancy outcomes. Methods: Cross‐sectional data were obtained from 819 Peruvian teenage mothers (aged 14 to 18 years) enrolled in the Teen Pregnancy Outcomes, Maternal, and Infant Study from November 2016 to September 2018 in Lima, Peru. Mothers having 4+ ACEs were considered as having high ACEs. Migraine was classified based on ICHD‐3 criteria. Adverse pregnancy outcomes included preterm birth (PTB) and low birth weight (LBW). Results: High ACEs were associated with greater odds of PTB (adjusted odds ratio [aOR] = 2.25, 95% confidence interval [CI]: 1.25, 3.95) and LBW (aOR = 2.64, 95% CI: 1.46, 4.67). Participants with migraine also had higher odds of PTB (aOR = 2.15, 95% CI: 1.20, 3.77). When examined jointly, those with only migraine (aOR = 2.79, 95% CI: 1.41, 5.52) or only high ACEs (aOR = 2.94, 95% CI: 1.48, 5.83) showed increased odds of PTB, whereas the combined exposure to both was weaker (aOR = 2.69, 95% CI: 1.04, 6.95), suggestive of a possible negative interaction, although inferences from this are limited by our relatively small sample size as reflected by the wide 95% CI. Similar patterns were observed for LBW. Conclusions: High ACEs and migraine were each independently associated with increased odds of PTB and LBW, but joint exposure did not increase the odds beyond the individual contributions. The suggestion of a possible negative interaction between high ACEs and migraine warrants further investigation to confirm.

This study aims to prospectively collect harmonized, quantitative, and dimensional psychiatric phenotypes (suicidality, anhedonia, and obsessive‐compulsive symptoms) and information on discrimination, stigma, and unfair treatment in up to 27,500 individuals across diverse ancestries and clinical populations for genetic analysis within the NIMH Ancestral Population Network (APN). Five APN projects are participating in the current study (PUMAS‐Paisa, PUMAS‐NeuroGAP, KOMOGEN‐D, LATINO, and SAX‐II), spanning recruitment over 15 countries across the Americas, Africa, and Asia. Participants are being enrolled via the recruitment protocols specific to each participating project. The harmonized clinical battery includes the Columbia‐Suicide Severity Scale, Snaith‐Hamilton Pleasure Scale, and Florida Obsessive‐Compulsive Inventory‐II to assess suicidality, anhedonia, and obsessive‐compulsive symptoms, respectively. Additionally, we use the Discrimination and Stigma Scale‐Ultra Short to evaluate discrimination and stigma across cultures. This project is a pioneering effort to prospectively assess transdiagnostic phenotypes in large‐scale, diverse ancestral and clinical populations (across different diagnoses) using a harmonized clinical battery, advancing genetic research in mental health in underrepresented populations.

Background: Maternal history of abuse has been associated with their children’s behavior problems, but the role of the timing and chronicity of abuse is less understood. We used a structured life course modeling approach (SLCMA) to examine whether models of accumulation (i.e. cumulative exposure to abuse across periods) or sensitive periods (i.e. developmentally salient timing of abuse) best explained associations with children’s behavior outcomes.Methods: 949 mother-child pairs from the Pregnancy Outcomes, Maternal and Infant Study (PrOMIS), a prospective birth cohort in Peru, were analyzed. Women were recruited during pregnancy and followed up approximately 8 years postpartum. Maternal physical and sexual abuse history during childhood, one year preconception, and during pregnancy was assessed. Maternal report of child behavior problems was obtained using the Child Behavior Check List. Life course hypotheses were tested using SLCMA, and secondary analyses assessed the influence of abuse severity and current stressors.Findings: 65% of mothers reported lifetime experience of abuse, most often physical abuse. Among children, 20% had internalizing and 12% had externalizing behavior problems. The cumulative model of physical abuse and sensitive periods preconception and during pregnancy, most strongly predicted children’s behavior problems (r2 range 0.8% - 1.8%), particularly among girls (externalizing T-score =7.4, 95%CI=1.6, 12.5). Severe maternal physical abuse had the largest association with externalizing behaviors, and current food insecurity was an effect modifier.Interpretation: Maternal physical abuse experienced at critical developmental periods, explained sex-specific problems in child behaviors. Understanding the biological mechanisms behind this transgenerational risk may help design interventions to prevent childhood psychopathology.

Background: Child internalizing and externalizing behavioral problems are highly prevalent psychiatric symptoms worldwide, for which maternal prenatal stress is a known risk factor. However, underlying neuroendocrine mechanisms remain largely unclear. We investigated whether maternal hair cortisol (HCC) and cortisone concentration (HCNC) are associated with offspring's internalizing and externalizing behavior problems in a prospective pre‐birth cohort study from Perú. Methods: N = 271 mother–child dyads were included in this analysis. Recruitment and data collection took place at the Instituto Nacional Materno Perinatal in Lima, Perú. HCC and HCHC were obtained from hair segments representing up to 3 months pre‐pregnancy and first trimester, respectively, and were quantified via liquid chromatography tandem mass spectrometry. The Child Behavior Checklist was used to assess internalizing and externalizing behavioral problems of children (mean age at follow‐up = 6.98 years ( SD = 1.05)). Marginal structural models estimated population average associations between HCC, HCNC, and internalizing and externalizing problems, adjusting for established covariates. Results: At pre‐pregnancy, logHCNC was positively associated with offspring internalizing ( β = 2.21, 95% CI: 0.46; 3.96, p = .013) and externalizing problems ( β = 1.87, 95% CI: 0.34; 3.40, p = .016). At the first trimester, logHCNC was negatively associated with internalizing ( β = −2.51, 95%CI: −4.37; −0.64, p = .008), and externalizing problems ( β = −2.73, 95% CI: −4.18; −1.28, p < .001). Associations were stronger for females and not apparent for logHCC. Conclusions: We found time‐dependent associations between stress‐related prenatal hair glucocorticoid concentration and offspring behavioral problems. Modeling biomarker data time‐dependently may prove critical to identifying the underlying mechanisms of transgenerational stress transmission.

Background: Substance use disorders are increasingly prevalent in sub-Saharan African countries, with evident bidirectional risk for people with severe mental illness (SMI) resulting in more severe and chronic courses. This study examines the association between common substance use, including khat and alcohol, and SMI, comparing affected individuals to age and sex-matched controls in Ethiopia. Method: This study uses data collected as part of the NeuroGAP-Psychosis project, a large multi-country case-control genetics study. This case-control study consisted of 6,500 people with severe mental illness and age and sex-matched 6,500 controls in Ethiopia. Current substance use was defined as any use within the last three months, while current regular use was defined as at least weekly use within the previous three months. Descriptive statistics were used to determine the demographic distribution of participants, and logistic regression was used to estimate the association between substance use and severe mental illness. Results: Most cases were men (65.8%; n = 4,276) with a mean age of 36.9 (SD = 10.3) years, while the controls were 64.7% (n = 4,204) men with a mean age of 36.2 (SD = 10.9) years. Current use of tobacco, alcohol, khat, and cannabis was 15.1%, 17.2%, 20.4% and 1.0% among cases and 6.0%, 41.5%, 12.5%, and 0.8% among controls, respectively. The adjusted odds of regular tobacco and khat use were 4.8 (95% CI: 4.0, 5.9) and 1.6 (95% CI: 1.4, 1.8) times higher in cases than in controls, respectively. However, regular use of alcohol was 0.1 (95% CI: 0.1, 0.2) times lower among cases than among controls. Conclusions: Tobacco and khat use were higher among cases than controls, while alcohol and cannabis use were more prevalent in controls. The high prevalence of khat use is particularly problematic in people with SMI as it adversely affects the course and outcome of mental illness. Tobacco smoking also contributes to physical health morbidity and associated premature mortality. Therefore, evidence-based screening and treatment services are warranted to mitigate the harmful health outcomes of khat use and tobacco consumption among individuals with SMI.

Mental Health Literacy (MHL) is pivotal for understanding and addressing mental disorders, often assessed using the comprehensive Mental Health Literacy Scale (MHLS) across six dimensions and 35 items. However, research on MHL within Arab populations is not just scarce, but alarmingly so, indicating a significant gap in knowledge regarding MHL in this demographic. This study aimed to fill this gap by adapting the MHLS into Arabic and evaluating its psychometric properties among three distinct Arabic-speaking groups: adolescents, students, and the general public. Data were collected using the translated MHLS, the General Health Questionnaire, and sociodemographic measures, employing a cross-sectional design. Validation procedures were conducted, including exploratory factor analysis, reliability testing, and face validity assessment. Construct validity was assessed using Pearson correlation analysis and t-tests. The validation process yielded three modified versions of the MHLS in Arabic: MHLS-Arabic-Adolescents (31 items, 5 factors), MHLS-Arabic-Students (30 items, 6 factors), and MHLS-Arabic-General Public (33 items, 5 factors). These tools demonstrated robust construct validity and high-reliability coefficients and stood as a testament to their adaptability and potential for use in diverse Arabic-speaking populations. This study suggests the nuanced nature of MHL and points to the importance of micro-context-specific validation. Providing three reliable MHLS Arabic versions could facilitate research on MHL among Arabic-speaking populations worldwide, potentially leading to tailored intervention initiatives that aim to enhance mental health outcomes and ensure equitable access to services within Arab communities globally.

Mental health literacy (MHL) plays a key role in promoting mental health outcomes and help-seeking behaviors, making it a critical component of public mental health strategies. While MHL has been widely studied in general populations, little is known about the concept among individuals living in war and conflict zones and refugees displaced from these settings, despite their high burden of mental health challenges. This narrative review aims to collect, synthesize, and summarize the available literature on MHL among individuals residing in ongoing war or armed conflict zones and refugees originating from these regions. Following PRISMA guidelines, we conducted a systematic search of Medline, PsycINFO, CINAHL, and Web of Science for studies published between January 1997 and December 2024. We included studies that examined MHL using an established framework, yielding a final sample of 35 studies. Data were extracted and synthesized thematically using a narrative approach, focusing on five core areas: study characteristics, population characteristics, measures and frameworks, MHL levels and correlates, and discussions of war and conflict contexts. Findings were analyzed separately for populations residing in conflict zones and for refugees or immigrants from those zones. Twenty-six studies focused on populations residing in conflict zones and nine on refugees or immigrants from such areas. Most studies employed quantitative cross-sectional designs and used standard MHL tools. Findings indicated moderate-to-high MHL levels among populations in conflict zones and low-to-moderate levels among refugee groups. Common correlates of higher MHL included younger age, female gender, higher educational attainment, and prior use of mental health services. However, most studies did not integrate war-related experiences into their analytical frameworks. This review highlights a critical gap in the literature: although conflict-affected populations face unique mental health challenges, existing studies often assess MHL using frameworks developed in the global north and non-conflict settings and without incorporating the context of war or displacement. There is an urgent need to reconceptualize MHL frameworks and tools to reflect the lived experiences, needs, and sociopolitical realities of individuals in crisis settings. Context-sensitive approaches are essential for informing relevant interventions and improving mental health outcomes in these vulnerable populations.