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African populations are the most diverse in the world yet are sorely underrepresented in medical genetics research. Here, we examine the structure of African populations using genetic and comprehensive multi-generational ethnolinguistic data from the Neuropsychiatric Genetics of African Populations-Psychosis study (NeuroGAP-Psychosis) consisting of 900 individuals from Ethiopia, Kenya, South Africa, and Uganda. We find that self-reported language classifications meaningfully tag underlying genetic variation that would be missed with consideration of geography alone, highlighting the importance of culture in shaping genetic diversity. Leveraging our uniquely rich multi-generational ethnolinguistic metadata, we track language transmission through the pedigree, observing the disappearance of several languages in our cohort as well as notable shifts in frequency over three generations. We find suggestive evidence for the rate of language transmission in matrilineal groups having been higher than that for patrilineal ones. We highlight both the diversity of variation within Africa as well as how within-Africa variation can be informative for broader variant interpretation; many variants that are rare elsewhere are common in parts of Africa. The work presented here improves the understanding of the spectrum of genetic variation in African populations and highlights the enormous and complex genetic and ethnolinguistic diversity across Africa.
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Variação Genética , Genética Populacional , África Austral , População Negra/genética , Estruturas Genéticas , Variação Genética/genética , HumanosRESUMO
Genetic studies in underrepresented populations identify disproportionate numbers of novel associations. However, most genetic studies use genotyping arrays and sequenced reference panels that best capture variation most common in European ancestry populations. To compare data generation strategies best suited for underrepresented populations, we sequenced the whole genomes of 91 individuals to high coverage as part of the Neuropsychiatric Genetics of African Population-Psychosis (NeuroGAP-Psychosis) study with participants from Ethiopia, Kenya, South Africa, and Uganda. We used a downsampling approach to evaluate the quality of two cost-effective data generation strategies, GWAS arrays versus low-coverage sequencing, by calculating the concordance of imputed variants from these technologies with those from deep whole-genome sequencing data. We show that low-coverage sequencing at a depth of ≥4× captures variants of all frequencies more accurately than all commonly used GWAS arrays investigated and at a comparable cost. Lower depths of sequencing (0.5-1×) performed comparably to commonly used low-density GWAS arrays. Low-coverage sequencing is also sensitive to novel variation; 4× sequencing detects 45% of singletons and 95% of common variants identified in high-coverage African whole genomes. Low-coverage sequencing approaches surmount the problems induced by the ascertainment of common genotyping arrays, effectively identify novel variation particularly in underrepresented populations, and present opportunities to enhance variant discovery at a cost similar to traditional approaches.
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Análise Mutacional de DNA/economia , Análise Mutacional de DNA/normas , Variação Genética/genética , Genética Populacional/economia , África , Análise Mutacional de DNA/métodos , Genética Populacional/métodos , Genoma Humano/genética , Estudo de Associação Genômica Ampla , Equidade em Saúde , Humanos , Microbiota , Sequenciamento Completo do Genoma/economia , Sequenciamento Completo do Genoma/normasRESUMO
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.
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COVID-19 , Depressão , Transtornos Psicóticos , Humanos , COVID-19/psicologia , COVID-19/epidemiologia , Etiópia/epidemiologia , Masculino , Adulto , Feminino , Estudos de Casos e Controles , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/psicologia , Doença Crônica/epidemiologia , Doença Crônica/psicologia , Depressão/psicologia , Depressão/epidemiologia , Pessoa de Meia-Idade , Ansiedade/psicologia , Ansiedade/epidemiologia , Saúde Mental , Estresse Psicológico/psicologia , Estresse Psicológico/epidemiologia , SARS-CoV-2 , Angústia PsicológicaRESUMO
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.
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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.
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Transtornos Psicóticos , Humanos , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/psicologia , Transtornos Psicóticos/diagnóstico , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , África Oriental/epidemiologia , Trauma Psicológico/epidemiologia , Trauma Psicológico/psicologia , Alucinações/epidemiologia , Alucinações/psicologia , Alucinações/diagnósticoRESUMO
BACKGROUND: The Mini International Neuropsychiatric Inventory 7.0.2 (MINI-7) is a widely used tool and known to have sound psychometric properties; but very little is known about its use in low and middle-income countries (LMICs). This study aimed to examine the psychometric properties of the MINI-7 psychosis items in a sample of 8609 participants across four countries in Sub-Saharan Africa. METHODS: We examined the latent factor structure and the item difficulty of the MINI-7 psychosis items in the full sample and across four countries. RESULTS: Multiple group confirmatory factor analyses (CFAs) revealed an adequate fitting unidimensional model for the full sample; however, single group CFAs at the country level revealed that the underlying latent structure of psychosis was not invariant. Specifically, although the unidimensional structure was an adequate model fit for Ethiopia, Kenya, and South Africa, it was a poor fit for Uganda. Instead, a 2-factor latent structure of the MINI-7 psychosis items provided the optimal fit for Uganda. Examination of item difficulties revealed that MINI-7 item K7, measuring visual hallucinations, had the lowest difficulty across the four countries. In contrast, the items with the highest difficulty were different across the four countries, suggesting that MINI-7 items that are the most predictive of being high on the latent factor of psychosis are different for each country. CONCLUSIONS: The present study is the first to provide evidence that the factor structure and item functioning of the MINI-7 psychosis vary across different settings and populations in Africa.
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Transtornos Psicóticos , Humanos , Psicometria , Transtornos Psicóticos/diagnóstico , Escalas de Graduação Psiquiátrica , África do Sul , Uganda , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Accumulating evidence indicates that schizophrenia is accompanied by significant activation of the immune system; however, there is limited data from low and middle-income countries (LMIC). Inflammatory markers may be more relevant in LMIC settings where infectious conditions are more prevalent and may thus play some role in the causation and maintenance of schizophrenia. The aim of this study was to assess the level of inflammatory markers high sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6) in patients with schizophrenia. MATERIALS AND METHODS: The study population consisted of a total of 132 study participants; 82 participants with schizophrenia and 50 controls. hsCRP and IL-6 were measured using Cobas Integra 400 Plus and Cobas e 411 analysers respectively. RESULTS: The levels of hsCRP and IL-6 were significantly increased among participants with schizophrenia compared to controls: hsCRP mean value 2.87 ± 5.6 vs 0.67 ± 0.6 mg/L; IL-6 mean value 6.63 ± 5.6 vs 3.37 ± 4.0 pg/ml. Controlling for potential confounders (age, sex and body mass index), having a diagnosis of schizophrenia remained significantly associated with increased hsCRP and IL-6. CONCLUSION: The results confirm that inflammatory processes may have a role in the pathophysiology of schizophrenia regardless of setting. Despite failure of some interventions with anti-inflammatory properties, interventions to reduce inflammation are still worth pursuing.
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Proteína C-Reativa , Esquizofrenia , Biomarcadores , Proteína C-Reativa/análise , Etiópia , Humanos , Inflamação , Interleucina-6RESUMO
BACKGROUND: Globally, the prevalence of metabolic syndrome (MetS) is higher among patients with schizophrenia than the general population, and this leads to higher morbidity and mortality in this population. The aim of this study was to investigate the MetS prevalence among patients with schizophrenia in Ethiopia. METHODS: We conducted a cross-sectional analysis of baseline data of 200 patients with schizophrenia recruited from Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia. Lipid profile and blood glucose levels were measured using Roche Cobas 6000 clinical chemistry analyzer. The prevalence of MetS was assessed based on National Cholesterol Education Program Adult Treatment Panel III criteria. Patients' demographic information, clinical and laboratory data, lifestyle habits, particularly smoking and Khat chewing, were evaluated vis-à-vis MetS. RESULTS: The overall prevalence of MetS in patients with schizophrenia was 21.5% (17.1% male, 29.6% female) where Low HDL-cholesterol value was the most common metabolic disorders components in both males and females subgroups. In the multivariate analysis, the positive and negative symptoms score (PANSS, AOR = 1.03, 95% CI 1.001-1.054) was associated factors with MetS. CONCLUSION: In Ethiopia, patients with schizophrenia were found to have higher prevalence of MetS than the general population. Physicians/health care providers should routinely screen patients with schizophrenia for MetS and initiate timely management of those who develop the syndrome to reduce the health cost from caring for NCDs, improve the patients' quality of life, and prevent premature mortality.
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Síndrome Metabólica , Esquizofrenia , Adulto , Estudos Transversais , Etiópia/epidemiologia , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Prevalência , Qualidade de Vida , Fatores de Risco , Esquizofrenia/epidemiologiaRESUMO
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.
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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.
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INTRODUCTION: Neurotropic pathogens such as Toxoplasma gondii (T. gondii) which result in chronic infections in the brain are associated with mental illnesses. In view of this, a growing body of literature has revealed the possible interaction of schizophrenia and T. gondii infection. METHOD: A case-control study was conducted from February 2018 to January 2019 among 47 Schizophrenia patients and 47 age and sex-matched controls. Data was collected using a structured questionnaire. Serum was used for serological analysis of anti-T. gondii IgG and IgM antibodies through chemiluminescent immunoassay. Proportions and mean with standard deviations (SD) were used as descriptive measures and variables with p-values <0.05 were considered as statistically significant and independently associated with schizophrenia. RESULT: The mean ages of schizophrenia patients and controls were 29.64 ± 5.8 yrs and 30.98 ± 7.3 yrs, respectively. We found that 81.9% (77/94) of the study subjects had a positive anti-T. gondii IgG antibody. While the difference is statistically insignificant, schizophrenic patients have a marginally higher seroprevalence of toxoplasmosis than controls (87.2% vs 80.9%; p = 0.398). Schizophrenia cases who live in homes with soil floors have a significantly higher T. gondii infection as compared to those who live in homes with cement/ceramic floors (90.9% vs 33.3%; p = 0.004). Furthermore, there was a significantly lower T. gondii infection among schizophrenic cases who were taking antipsychotic medication for more than three yrs (79.3% vs 100.0%, p = 0.039). On the other hand, among all study subjects who have T. gondii infection, subjects who are addicted to khat and alcohol were about seven times more likely to develop schizophrenia (71.4% vs 47.7%, OR = 7.13, p = 0.024). CONCLUSION: Our data is not sufficient to show a significant positive correlation between T. gondii infection and schizophrenia. For study subjects with T. gondii infection, addiction to khat and alcohol is one of the risk factors for schizophrenia.
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Esquizofrenia , Toxoplasma , Toxoplasmose , Adulto , Anticorpos Antiprotozoários , Estudos de Casos e Controles , Catha , Humanos , Imunoglobulina G , Imunoglobulina M , Fatores de Risco , Esquizofrenia/complicações , Esquizofrenia/epidemiologia , Estudos Soroepidemiológicos , Inquéritos e Questionários , Toxoplasmose/complicações , Toxoplasmose/epidemiologia , Adulto JovemRESUMO
Background: Traumatic events. e.g., road traffic accidents, violent conflicts, natural and human-made disasters, are common in sub-Saharan Africa. However, validated trauma screening tools to assess trauma at the individual level are lacking in many sub-Saharan African countries, such as Ethiopia, which limits accurate diagnosis and effective care provision. Objective: We sought to measure trauma exposure among cases and controls and evaluate the psychometric properties of the Life Event Checklist for DSM-5 (LEC-5) among Ethiopian adults. Method: This study included 4,183 participants (2,255 cases with a clinical diagnosis of psychosis and 1,928 controls without a history of psychosis) from the Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis) study. We conducted exploratory factor analysis (EFA) to group the items into factors/subscales, and confirmatory factor analysis (CFA) to investigate the best model fit in Ethiopia. Result: 48.7% of participants reported exposure to at least one traumatic event. Physical assault (19.6%), sudden violent death (12.0%), and sudden accidental death (10.9%) were the three most common traumatic experiences. Cases were twice as likely to report experiences of traumatic events compared to controls (p<0.001). EFA revealed a four-factor/subscale model. CFA results indicated a theoretically-driven seven-factor model to be the preferred model by the goodness of fit (comparative fit index of 0.965 and Tucker-Lewis index of 0.951) and accuracy (root mean square error of approximation of 0.019). Conclusion: Exposure to traumatic events was common in Ethiopia, even more so for individuals with a diagnosis of psychotic disorders. The LEC-5 demonstrated good construct validity for measuring traumatic events among Ethiopian adults. Future studies that examine criterion validity and test-retest reliability of the LEC-5 in Ethiopia are warranted.
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BACKGROUND: Many common mental disorders are underdiagnosed and undertreated in low-resource countries. The ten-item Kessler Psychological Distress Scale (K10) is a brief screening tool widely used to assess psychological distress. We evaluated the K10's performance in an Ethiopian population by assessing internal consistency and construct validity through factor structure. METHODS: K10 survey responses and sociodemographic data were collected from 1928 adults, including patients and caregivers from a general medical setting, who served as controls of a large epidemiological study. RESULTS: The K10 had good internal consistency, with a Cronbach's alpha of 0.83. Results from exploratory factor analyses showed that the K10 had a two-factor solution that accounted for approximately 66% of the variance. Confirmatory factor analyses demonstrated that a unidimensional model with correlated errors, informed by a theoretical model, was the best fitting model for the setting (comparative fit index of 0.90 and root mean square error of approximation of 0.10). LIMITATIONS: We did not assess the K10's test-retest reliability or its criterion validity (i.e., agreement with a reference measure). CONCLUSIONS: Based on internal consistency and construct validity, the K10 can effectively assess psychological distress among Ethiopian adults for population-based research and potentially clinical screening, consistent with previous findings in this setting. Further studies are needed to test its criterion validity against a reference measure of psychological distress.
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Estresse Psicológico , Adulto , Etiópia/epidemiologia , Análise Fatorial , Humanos , Psicometria/métodos , Reprodutibilidade dos Testes , Estresse Psicológico/diagnóstico , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: In high income countries, cancer is one of the leading causes of death, with co-morbid depression contributing to the risk of increased mortality. However, both cancer and depression are neglected conditions in low income countries. The current study assessed the magnitude of depression and the association of pain complaints with depression among patients with cancer in a low income country. METHOD: In this cross-sectional study participants were 390 patients with established diagnosis of cancer, who were recruited consecutively when visiting a tertiary treatment centre in Addis Ababa, Ethiopia. The occurrence of depression was determined using the nine items Patient Health Questionnaire (PHQ-9). Major depressive disorder was confirmed: (1) when five or more of the PHQ-9 symptoms were endorsed as occurring for at least 'more than seven days', with the exception of suicidal ideation item which counted as a positive rating if it had occurred even once in the previous fifteen days. (2) one of the symptoms has to be either depressed mood or loss of interest. Pain complaint was measured by Numeral Rating Scale (NRS) and severity of pain was assessed using Verbal Rating Scale (VRS). RESULTS: The prevalence of major depressive disorder was 16.4% (95%CI: 13.1%, 20.4%), and subthreshold depression was 17.4% (95%CI: 14.0%, 21.5%). Pain complaints occurred in 69.0% (95%CI: 64.3%, 73.4%) of the participants. The odds of having a major depressive symptom was over four times higher among participants who had pain. LIMITATIONS: The study was cross sectional and liable to recall bias. Recruitment was carried out in a tertiary referral hospital, which might lead to the selection of more economically well-off and educated participants limiting generalizability of the study. Moreover, we did not control for cancer types, which may be related to pain and the experience of depression. Some of the somatic symptoms in PHQ9 may also be related to the cancer itself. CONCLUSIONS: This study highlights the clinical significance of both depression and pain complaints in patients with cancer in a low income country. Exploration of the impact of depressive disorders on quality of life and outcome of cancer is an important area for further research in low income countries.