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.

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.

Psychosis screening questionnaire: Exploring its factor structure among South African adults.

Background: Early detection of psychosis improves treatment outcomes, but there is limited research evaluating the validity of psychosis screening instruments, particularly in low-resourced countries. Aim: This study aims to assess the construct validity and psychometric properties of the psychosis screening questionnaire (PSQ) in South Africa. Setting: This study was conducted at several health centres in the Western and Eastern Cape provinces in South Africa. Methods: The sample consisted of 2591 South African adults participating as controls in a multi-country case-control study of psychiatric genetics. Using confirmatory factor analysis and item response theory, we evaluated the psychometric properties of the PSQ. Results: Approximately 11% of the participants endorsed at least one psychotic experience on the PSQ, and almost half of them (49%) occurred within the last 12 months. A unidimensional model demonstrated good fit (root mean square error of approximation [RMSEA] = 0.023, comparative fit index [CFI] = 0.977 and Tucker-Lewis Index [TLI] = 0.954). The mania item had the weakest association with a single latent factor (standardised factor loading = 0.14). Model fit improved after removing the mania item (RMSEA = 0.025, CFI = 0.991 and TLI = 0.972). With item response theory analysis, the PSQ provided more information at higher latent trait levels. Conclusion: Consistent with prior literature, the PSQ demonstrated a unidimensional factor structure among South Africans. In our study, the PSQ in screening for psychosis performed better without the mania item, but future criterion validity studies are warranted. Contribution: This study highlights that PSQ can be used to screen for early psychosis.

Psychometric properties of the mini international neuropsychiatric interview (MINI) psychosis module: a Sub-Saharan Africa cross country comparison.

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.

Genetic structure correlates with ethnolinguistic diversity in eastern and southern Africa.

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.

Factor structure and item response of psychosis symptoms among Kenyan adults.

BACKGROUND: The aim of this study was to evaluate the construct validity of the psychosis module of the Mini International Neuropsychiatric Interview version 7.0.2 (MINI-7). METHOD: We utilized data collected from 2738 participants with a primary psychotic or bipolar disorder. Participants were drawn from two Kenyan sites of a large multi-center neuropsychiatric genetic study. The factor structure of the MINI-7 psychosis items were explored using confirmatory factor analyses (CFA) and Item Response Theory approach, for the full sample and by gender. RESULTS: The CFA revealed that a 1-factor model provided adequate fit for the MINI-7 psychosis items for the full sample (x2 = 397.92, df = 35, p < .0001; RMSEA = 0.06; CFI = 0.92; TLI = 0.90) as well as for the female (x2 = 185.16.92, df = 35, p < .0001; RMSEA = 0.06; CFI = 0.93; TLI = 0.91) and male groups (x2 = 242.09, df = 35, p < .0001; RMSEA = 0.06; CFI = 0.92; TLI = 0.89). Item thresholds for the full sample, and female and male groups were highest for 'odd beliefs' (-1.42, -1.33, and -1.51 respectively) and lowest for 'visual hallucinations' (-0.03, -0.04, and -0.01 respectively). LIMITATIONS: Our study used a hospital-based population, which may have excluded patients with milder psychotic symptoms. Findings may therefore not be generalizable to the community setting. CONCLUSIONS: Our findings indicate good construct validity of the MINI-7 psychosis module, and provides support for use of the tool in diagnosing psychotic disorders in clinical settings in Kenya.

Construct validity and factor structure of the Kessler-10 in South Africa.

BACKGROUND: The Kessler Psychological Distress Scale (K-10) is a short screening tool developed to identify, with good sensitivity, non-specific psychological distress in the general population. Sensitivity and specificity of the K-10 have been examined in various clinical populations in South Africa; however, other psychometric properties, such as construct validity and factor structure, have not been evaluated. We present evidence of the prevalence and severity of psychological distress in an outpatient setting in South Africa and evaluate the internal reliability, construct validity, and factor structure of the K-10 in this population. METHODS: We explored prevalence estimates of psychological distress using previously established cutoffs and assessed the reliability (consistency) of the K-10 by calculating Cronbach's alpha, item-total correlations and omega total and hierarchical coefficients. Construct validity and factor structure of the K-10 were examined through split-sample exploratory factor analysis (EFA) followed by confirmatory factor analysis (CFA), comparing several theoretical models and the EFA. RESULTS: Overall, there was low prevalence of psychological distress in our sample of 2591 adults, the majority of whom were between the ages of 18-44 (77.7%). The K-10 showed good construct validity and reliability, with a Cronbach's alpha of 0.84 and omega total of 0.88. EFA yielded a four-factor solution with likely measurement artifacts. CFA showed that the four-factor model from EFA displayed the best comparative fit indices, but was likely overfitted. The unidimensional model with correlated errors was deemed the best fitting model based on fit indices, prior theory, and previous studies. CONCLUSION: The K-10 displays adequate psychometric properties, good internal reliability, and good fit with a unidimensional-factor structure with correlated errors. Further work is required to determine appropriate cutoff values in different populations and clinical subgroups within South Africa to aid in determining the K-10's clinical utility.

Construct validity and factor structure of the K-10 among Ugandan adults.

BACKGROUND: Psychological distress is often used as a proxy measure for the mental health of a population. The Kessler Psychological Distress Scale (K-10) is a widely used brief screening tool for psychological distress, yet few studies have evaluated its utility in sub-Saharan Africa. We evaluated its construct validity and factor structure in Uganda. METHODS: We used data from an ongoing case-control study. Participants in the present study were patients seeking general medical outpatient services and caretakers of mentally ill persons. Demographic data were collected using a structured questionnaire, and psychological distress was assessed using the K-10. K-10 construct validity and factorial structure were assessed through exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). RESULTS: A total of 2104 participants were included in this analysis, these were controls from a general medical setting. The mean K-10 score was 2.34 with an internal consistency of 0.86. EFA resulted in a two-factor solution that accounted for 78.37% of the variance. CFA revealed that a unidimensional model of psychological distress with correlated errors between some of K-10 items was superior, with a comparative fit index of 0.95, Tucker-Lewis index of 0.93, and a root mean square error of approximation of 0.08. LIMITATIONS: The study was limited to evaluating internal consistency and construct validity. Future studies are warranted to examine criterion validity and establish cut-offs for psychological distress. CONCLUSIONS: The K-10 had good psychometric properties in this population and may be useful for measuring broad psychological distress in general medical settings.

Cross-country variations in the reporting of psychotic symptoms among sub-Saharan African adults: A psychometric evaluation of the Psychosis Screening Questionnaire.

BACKGROUND: Self-reporting of psychotic symptoms varies significantly between cultures and ethnic groups. Yet, limited validated screening instruments are available to capture such differences in the African continent. METHODOLOGY: Among 9,059 individuals participating as controls in a multi-country case-control study of the genetic causes of psychosis, we evaluated the psychometric properties of the Psychosis Screening Questionnaire (PSQ). We applied multi-group confirmatory factor analysis and item response theory to assess item parameters. RESULTS: The overall positive endorsement of at least one item assessing psychotic symptoms on the PSQ was 9.7%, with variability among countries (Uganda 13.7%, South Africa 11%, Kenya 10.2%, and Ethiopia 2.8%). A unidimensional model demonstrated good fit for the PSQ (root mean square error of approximation = 0.009; comparative fit index = 0.997; and Tucker-Lewis Index = 0.995). Hypomania had the weakest association with single latent factor (standardized factor loading 0.62). Sequential multi-group confirmatory factor analysis demonstrated that PSQ items were measured in equivalent ways across the four countries. PSQ items gave more information at higher levels of psychosis, with hypomania giving the least discriminating information. LIMITATIONS: Participants were recruited from general medical facilities, so findings may not be generalizable to the general population. CONCLUSION: The PSQ demonstrated a unidimensional factor structure in these samples. Items were measured equivalently across all study settings, suggesting that differences in prevalence of psychotic symptoms between countries were less likely to represent measurement artifact. The PSQ is more reliable in screening for psychosis in individuals with higher degrees of psychotic experiences-hypomania excluded-and might decrease the false-positive rate from mild nonspecific psychotic experiences.

Traumatic experiences assessed with the life events checklist for Kenyan adults.

BACKGROUND: Life Events Checklist (LEC-5) has been widely used to assess for exposure to potentially traumatic life events (PTEs), but its psychometric properties have not been evaluated in Kenya. The objectives of this study were to determine the frequency and types of PTEs within this setting and to examine the construct validity of LEC-5 in Kenya. METHODS: The LEC-5 was administered to 5316 participants in the ongoing multisite case-control study of Neuropsychiatric Genetics of African Populations-Psychosis. We used exploratory factor analysis to assess LEC-5 structure, and conducted confirmatory factor analyses to compare these results with two other models: a six-factor model based on the only prior EFA of the LEC and a theoretical seven-factor model. RESULTS: The majority (63.4% overall and 64.4% of cases and 62.4% of controls) of participants had experienced at least one PTE in their lifetime. Results of the exploratory factor analyses for LEC-5 yielded a seven-factor solution with eigenvalues greater than one, accounting for 55.3% of the common variance. Based on confirmatory factor analyses, all three models had good fit for our sample, but the theoretical seven-factor model had the best fit. LIMITATIONS: The study did not assess if the participants perceived experiences as traumatic, we did not carry out test retest reliability or and we did not consider cultural variations in perception of trauma. CONCLUSION: This study provides evidence of a high prevalence of traumatic life events and for the construct validity of LEC-5 in assessing PTE exposures in a Kenyan setting.

Measuring psychological distress using the K10 in Kenya.

BACKGROUND: The Kessler psychological distress scale (K10) is a brief screening tool that assesses psychological distress in both clinical and epidemiological settings. Despite wide applicability of the K10 globally, there are no data on psychometric properties of the K10 in Kenya. This study investigated the reliability, factor structure, and construct validity of the K10 as a measure of psychological distress among adults in Kenya. METHODS: A total of 2556 adults attending 11 outpatient clinics in the western and coastal regions of Kenya without a history or clinical diagnosis of psychotic disorders were included. Data were collected on demographic characteristics of the participants and the K10. Internal consistency was evaluated using Cronbach's alpha. Construct validity and factor structures of the K10 were evaluated using both exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) approaches. RESULTS: The mean K10 score was 3.4 and Cronbach's alpha was 0.85, indicating good internal consistency (reliability). EFA resulted in a two-factor solution that accounted for 67.6% of variance. CFA results indicated that a unidimensional model with correlated errors best fit the data. LIMITATIONS: The K10 was only administered to a control group of our study population, which had low levels of psychological distress. CONCLUSION: The K10 has good construct validity and reliability for use as a broad measure of psychological distress in Kenyan adults and may be useful in general medical setting to assess anxiety and depressive disorders.

Psychometric properties and factor structure of the Kessler-10 among Ethiopian adults.

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.

Low-coverage sequencing cost-effectively detects known and novel variation in underrepresented populations.

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.

Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis): a case-control study protocol and GWAS in Ethiopia, Kenya, South Africa and Uganda.

INTRODUCTION: Schizophrenia and bipolar disorder account for a large proportion of the global burden of disease. Despite their enormous impact, little is known about their pathophysiology. Given the high heritability of schizophrenia and bipolar disorder, unbiased genetic studies offer the opportunity to gain insight into their neurobiology. However, advances in understanding the genetic architecture of schizophrenia and bipolar disorder have been based almost exclusively on subjects of Northern European ancestry. The Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis) project aims to expand our understanding of the causes of schizophrenia and bipolar disorder through large-scale sample collection and analyses in understudied African populations. METHODS AND ANALYSIS: NeuroGAP-Psychosis is a case-control study of 34 000 participants recruited across multiple sites within Ethiopia, Kenya, South Africa and Uganda. Participants will include individuals who are at least 18 years old with a clinical diagnosis of schizophrenia or bipolar disorder ('psychosis') or those with no history of psychosis. Research assistants will collect phenotype data and saliva for DNA extraction. Data on mental disorders, history of physical health problems, substance use and history of past traumatic events will be collected from all participants.DNA extraction will take place in-country, with genotyping performed at the Broad Institute. The primary analyses will include identifying major groups of participants with similar ancestry using the computation-efficient programme single nucleotide polymorphisms (SNP) weights. This will be followed by a GWAS within and across ancestry groups. ETHICS AND DISSEMINATION: All participants will be assessed for capacity to consent using the University of California, San Diego Brief Assessment of Capacity to Consent. Those demonstrating capacity to consent will be required to provide informed consent. Ethical clearances to conduct this study have been obtained from all participating sites. Findings from this study will be disseminated in publications and shared with controlled access public databases, such as the database of Genotypes and Phenotypes, dbGaP.