Association of childhood maltreatment with internalising and externalising disorders in trauma-exposed adolescents

Introduction: South African adolescents experience high levels of trauma, including various types of childhood maltreatment. Different types of maltreatment often co-occur. Previous research suggests that childhood maltreatment provokes a latent liability to internalising and externalising dimensions of psychopathology. Our objective was to examine the effects of childhood maltreatment on internalising and externalising disorders in trauma-exposed adolescents and to assess the mediating effect of post-traumatic stress disorder (PTSD) on these associations. Methods: A cross-sectional study was conducted with 262 trauma exposed adolescents (aged 12–18 years) in South Africa. Childhood maltreatment and PTSD severity were assessed using the Childhood Trauma Questionnaire and the Child PTSD Checklist, respectively. Psychiatric disorders were diagnosed utilising the Kiddie Schedule for Affective Disorders and Schizophrenia – Present and Lifetime version – and were grouped into internalising and externalising disorders. Hierarchal logistic regression was used to assess the association between childhood maltreatment types and internalising and externalising disorders, controlling for statistically significant socio-demographic characteristics, with PTSD severity added to the final model as a potential mediator. Results: Sexual abuse was significantly associated with internalising disorders (B = 0.07, p = 0.011), although this effect was mediated by PTSD severity (B = 0.05, p = 0.001; not included as an internalising disorder). In contrast, physical abuse (B = 0.09, p = 0.004) and gender (B = 0.70, p = 0.035) were associated with externalising disorders, but the addition of PTSD severity did not significantly alter these associations. Conclusion: The association between sexual abuse and internalising disorders was fully mediated by PTSD symptom severity. Gender and physical abuse severity, but not PTSD severity, was associated with the presence of externalising disorders. Adolescents displaying internalising or externalising psychopathology need to be assessed for exposure to childhood physical and sexual abuse and PTSD comorbidity

A Genome-Wide Association Study and Polygenic Risk Score Analysis of Posttraumatic Stress Disorder and Metabolic Syndrome in a South African Population

Posttraumatic stress disorder (PTSD) is a trauma-related disorder that frequently co-occurs with metabolic syndrome (MetS). MetS is characterized by obesity, dyslipidemia, and insulin resistance. To provide insight into these co-morbidities, we performed a genome-wide association study (GWAS) meta-analysis to identify genetic variants associated with PTSD, and determined if PTSD polygenic risk scores (PRS) could predict PTSD and MetS in a South African mixed-ancestry sample. The GWAS meta-analysis of PTSD participants (n = 260) and controls (n = 343) revealed no SNPs of genome-wide significance. However, several independent loci, as well as five SNPs in the PARK2 gene, were suggestively associated with PTSD (p < 5 × 10–6). PTSD-PRS was associated with PTSD diagnosis (Nagelkerke’s pseudo R2 = 0.0131, p = 0.00786), PTSD symptom severity [as measured by CAPS-5 total score (R2 = 0.00856, p = 0.0367) and PCL-5 score (R2 = 0.00737, p = 0.0353)], and MetS (Nagelkerke’s pseudo R2 = 0.00969, p = 0.0217). These findings suggest an association between PTSD and PARK2, corresponding with results from the largest PTSD-GWAS conducted to date. PRS analysis suggests that genetic variants associated with PTSD are also involved in the development of MetS. Overall, the results contribute to a broader goal of increasing diversity in psychiatric genetics

Sleep quality and neurocognitive functioning in metabolic syndrome

Background: The incidence of metabolic syndrome (MetS), a cluster of metabolic risk factors in a single individual, is increasing worldwide, making it important to study the possible risk and protective factors. Accumulating evidence has suggested sleep deprivation and/or fragmentation is among the key factors involved in the onset and treatment resistance of MetS components. Moreover, bidirectional associations between sleep complaints and MetS have been described. In addition, there is mounting evidence of the effect of MetS on cognitive functioning. Aims: The aim of this study was to assess whether MetS and sleep complaints are associated with clinically determined neurocognitive disturbances in a sample of participants with MetS symptoms, ranging from none to all criteria met. Methods: Participants comprised 153 mixed race individuals from the Western Cape province of South Africa. Sleep (Pittsburgh Sleep Quality Index), neurocognition (Repeatable Battery for the Assessment of Neuropsychological Status) and anthropometric (MetS components) assessments were performed on all participants. A hierarchical regression model, including potentially confounding variables (e.g. IQ), demographic variables (e.g. age and gender) and clinical variables (e.g. [BMI] and cholesterol), was then constructed. Results: The model was significant: adjusted R square = 0.486; F(13, 110) = 9.952, p < 0.0001. The demographic variables accounted for 32.3% of variability. This increased to 48.5% when the clinical variables were added. Sleep and metabolic criteria only added 0.1%. Discussion: Although we did not find sleep and metabolic factors to significantly influence cognition when other factors were accounted for, further investigation into risk and outcome factors, such as these, may assist in the identification of mechanistic links, which may also improve management of patients who are at risk, thereby improving health outcomes

Agreement and Discrepancy on Emotional and Behavioral Problems Between Caregivers and HIV-Infected Children and Adolescents From Uganda.

Background: HIV-infected children and adolescents (CA-HIV) face significant mental health challenges related to a broad range of biological and psychosocial factors. Data are scarce on the agreement and discrepancy between caregivers and CA-HIV regarding emotional and behavioral problems (EBPs) in CA-HIV. Objectives: We determined agreement between self- versus caregiver- reported EBPs and describe factors associated with informant discrepancy among caregiver-youth dyads who participated in the "Mental health among HIV-infected CHildren and Adolescents in KAmpala and Masaka, Uganda" (CHAKA) study. Methods: In a cross-sectional sample, caregiver-reported EBPs were assessed with the Child and Adolescent Symptom Inventory-5 (CASI-5), and self-reported problems were evaluated with the Youth Inventory-4 (YI-4) in 469 adolescents aged 12-17 years and the Child Inventory-4 (CI-4) in 493 children aged 8-11 years. Adolescents were questioned about experiences of HIV stigma. Caregiver psychological distress was assessed with the Self-Reporting Questionnaire (SRQ-20). Linear regression models were applied to identify variables associated with discrepancy scores. Results: Self-reported emotional problems (EPs) were present in 28.8% of adolescents and 36.9% of children, and 14.5% of adolescents self-reported behavioral problems (BPs). There was only a modest correlation (r ≤ 0.29) between caregiver- and CA-HIV-reported EBPs, with caregivers reporting more EPs whereas adolescents reported more BPs. Informant discrepancy between adolescents and caregivers for BPs was associated with adolescent age and caregiver's employment and HIV status. Among adolescents, EP discrepancy scores were associated with adolescent's WHO HIV clinical stage, caregiver level of education, and caregivers caring for other children. Among children, EP discrepancy scores were associated with child and caregiver age, caregiver level of education, and caregiver self-rated health status. HIV stigma and caregiver psychological distress were also associated with discrepancy, such that adolescents who experienced HIV stigma rated their EPs as more severe than their caregivers did and caregivers with increased psychological distress rated EBPs as more severe than CA-HIV self-rated. Conclusions: EBPs are frequently endorsed by CA-HIV, and agreement between informants is modest. Informant discrepancy is related to unique psychosocial and HIV-related factors. Multi-informant reports enhance the evaluation of CA-HIV and informant discrepancies can provide additional insights into the mental health of CA-HIV

Caregiver and youth self-reported emotional and behavioural problems in Ugandan HIV-infected children and adolescents

Introduction: We determined the prevalence of, and factors associated with, self-rated emotional and behavioural problems (EBPs) and assessed the agreement between self-rated and caregiver-rated EBPs in the ‘Mental health among HIV-infected Children and Adolescents (CA-HIV) in Kampala and Masaka, Uganda’ (CHAKA) study. Existing literature demonstrates that CA-HIV face increased mental health challenges related to a broad range of biological and psychosocial factors. There is scarce data on self-reported EBPs in CA-HIV. Methods: In a cross-sectional sample, caregiver-reported EBPs were assessed with the Child and Adolescent Symptom Inventory-5 (CASI-5), and self-reported problems were evaluated with the Youth Inventory-4 (YI-4) in 469 adolescents aged 12–17 years and the Child Inventory-4 (CI-4) in 493 children aged 8–11 years. Logistic regression models were utilised to determine factors related to self-reported EBPs. Results: Self-reported emotional problems (EPs) were present in 28.8% of the adolescents and were associated with caregivers being separated and having a lower level of education. Among adolescents, 14.5% had self-reported behavioural problems (BPs), and these were associated with caregiver unemployment and food insecurity. Self-reported EPs were reported by 36.9% of children and were associated with rural study sites, having missed school and caregivers having a lower level of education. There was only modest agreement (maximum r = 0.29) between caregiver- and CA-HIV-reported EBPS, with caregivers reporting more EPs and adolescents reporting more BPs. Conclusion: Self-reported EBPs are frequently endorsed by CA-HIV, and these problems are related to unique psychosocial factors. Including CA-HIV, self-report measures can assist in identifying problems that caregivers may not be aware of, particularly BPs

The prevalence of mental health problems in sub-saharan adolescents : a systematic review

Background and purpose Most research regarding child and adolescent mental health prevention and promotion in low-and middle-income countries is undertaken in high-income countries. This systematic review set out to synthesise findings from epidemiological studies, published between 2008 and 2020, documenting the prevalence of mental health problems in adolescents from across sub-Saharan Africa. Methods A systematic search of multiple databases (MEDLINE, PsycINFO, Scopus) and Google Scholar was conducted guided by the Joanna Briggs Institute (JBI) Reviewer's manual for systematic reviews of observational epidemiological studies. Studies included reported prevalence outcomes for adolescents aged 10-19 using either clinical interviews or standardized questionnaires to assess psychopathology. Clinical samples were excluded. Results The search yielded 1 549 records of which 316 studies were assessed for eligibility and 51 met the inclusion criteria. We present a qualitative synthesis of 37 of these 51 included articles. The other 14 studies reporting prevalence rates for adolescents living with HIV are published elsewhere. The prevalence of depression, anxiety disorders, emotional and behavioural difficulties, posttraumatic stress and suicidal behaviour in the general adolescent population and selected at-risk groups in 16 sub-Saharan countries (with a total population of 97 616 adolescents) are reported.Hochschule für Angewandte Wissenschaften HamburgPeerReviewe

The effect of the COVID-19 lockdown on mental health care use in South Africa: an interrupted time-series analysis.

AIMS The coronavirus disease 2019 (COVID-19) pandemic and ensuing restrictions have negatively affected the mental health and well-being of the general population, and there is increasing evidence suggesting that lockdowns have led to a disruption of health services. In March 2020, South Africa introduced a lockdown in response to the COVID-19 pandemic, entailing the suspension of all non-essential activities and a complete ban of tobacco and alcohol sales. We studied the effect of the lockdown on mental health care utilisation rates in private-sector care in South Africa. METHODS We conducted an interrupted time-series analysis using insurance claims from 1 January 2017 to 1 June 2020 of beneficiaries 18 years or older from a large private sector medical insurance scheme. We calculated weekly outpatient consultation and hospital admission rates for organic mental disorders, substance use disorders, serious mental disorders, depression, anxiety, other mental disorders, any mental disorder and alcohol withdrawal syndrome. We calculated adjusted odds ratios (OR) for the effect of the lockdown on weekly outpatient consultation and hospital admission rates and the weekly change in rates during the lockdown until 1 June 2020. RESULTS 710 367 persons were followed up for a median of 153 weeks. Hospital admission rates (OR 0.38; 95% confidence interval (CI) 0.33-0.44) and outpatient consultation rates (OR 0.74; 95% CI 0.63-0.87) for any mental disorder decreased substantially after the introduction of the lockdown and did not recover to pre-lockdown levels by 1 June 2020. Health care utilisation rates for alcohol withdrawal syndrome doubled after the introduction of the lockdown, but the statistical uncertainty around the estimates was large (OR 2.24; 95% CI 0.69-7.24). CONCLUSIONS Mental health care utilisation rates for inpatient and outpatient services decreased substantially after the introduction of the lockdown. Hospital admissions and outpatient consultations for alcohol withdrawal syndrome increased after the introduction of the lockdown, but statistical uncertainty precludes strong conclusions about a potential unintended effect of the alcohol sales ban. Governments should integrate strategies for ensuring access and continuity of essential mental health services during lockdowns in pandemic preparedness planning

Development of a mobile application for detection of adolescent mental health problems and feasibility assessment with primary health care workers

INTRODUCTION : There has been a sharp increase in the use of digital health interventions in global health, particularly mobile health applications, in recent years. The extreme shortage of health care providers trained in mental health screening and intervention in low- and middle-income countries raises questions about the applicability of mobile applications to deliver these services due to their accessibility and availability. This exploratory paper describes the development and feasibility assessment of a mobile screening application for the detection of mental disorders among adolescents in Zambia and South Africa. METHODS : Eighty-two health care workers (HCW) working in primary care evaluated the acceptability and practicality of the mobile screening application after receiving brief training. The evaluation included questions from the Mobile Application Rating Scale (MARS) as well as open-ended questions. RESULTS : The acceptability of the screening app was high and study participants were positive about using the app in routine care. Problems with internet connectivity, and time and staff constraints were perceived as the main barriers to regular use. CONCLUSION : HCW in primary care were able and willing to use a mobile screening app for the detection of mental health problems among treatment-seeking adolescents. Implementation in clinical practice needs to be further evaluated.Erasmus + Capacity Building.https://www.tandfonline.com/loi/imhn20hj2023Psychiatr

Region-Specific Expression of Mitochondrial Complex I Genes during Murine Brain Development

Mutations in the nuclear encoded subunits of mitochondrial complex I (NADH:ubiquinone oxidoreductase) may cause circumscribed cerebral lesions ranging from degeneration of the striatal and brainstem gray matter (Leigh syndrome) to leukodystrophy. We hypothesized that such pattern of regional pathology might be due to local differences in the dependence on complex I function. Using in situ hybridization we investigated the relative expression of 33 nuclear encoded complex I subunits in different brain regions of the mouse at E11.5, E17.5, P1, P11, P28 and adult (12 weeks). With respect to timing and relative intensity of complex I gene expression we found a highly variant pattern in different regions during development. High average expression levels were detected in periods of intense neurogenesis. In cerebellar Purkinje and in hippocampal CA1/CA3 pyramidal neurons we found a second even higher peak during the period of synaptogenesis and maturation. The extraordinary dependence of these structures on complex I gene expression during synaptogenesis is in accord with our recent findings that gamma oscillations – known to be associated with higher cognitive functions of the mammalian brain – strongly depend on the complex I activity. However, with the exception of the mesencephalon, we detected only average complex I expression levels in the striatum and basal ganglia, which does not explain the exquisite vulnerability of these structures in mitochondrial disorders

Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Funding Information: This work was supported by the National Institute of Mental Health / U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium ), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience . Statistical analyses were carried out on the LISA/Genetic Cluster Computer ( https://userinfo.surfsara.nl/systems/lisa ) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. Funding Information: MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc., RallyPoint Networks, Inc., Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled “Genotype-guided dosing of opioid agonists,” filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Funding Information: This work was supported by the National Institute of Mental Health/ U.S. Army Medical Research and Development Command (Grant No. R01MH106595 [to CMN, IL, MBS, KJRe, and KCK], National Institutes of Health (Grant No. 5U01MH109539 to the Psychiatric Genomics Consortium), and Brain & Behavior Research Foundation (Young Investigator Grant [to KWC]). Genotyping of samples was provided in part through the Stanley Center for Psychiatric Genetics at the Broad Institute supported by Cohen Veterans Bioscience. Statistical analyses were carried out on the LISA/Genetic Cluster Computer (https://userinfo.surfsara.nl/systems/lisa) hosted by SURFsara. This research has been conducted using the UK Biobank resource (Application No. 41209). This work would have not been possible without the financial support provided by Cohen Veterans Bioscience, the Stanley Center for Psychiatric Genetics at the Broad Institute, and One Mind. This material has been reviewed by the Walter Reed Army Institute of Research. There is no objection to its presentation and/or publication. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting true views of the U.S. Department of the Army or the Department of Defense. We thank the investigators who comprise the PGC-PTSD working group and especially the more than 206,000 research participants worldwide who shared their life experiences and biological samples with PGC-PTSD investigators. We thank Mark Zervas for his critical input. Full acknowledgments are in Supplement 1. MBS has in the past 3 years received consulting income from Actelion, Acadia Pharmaceuticals, Aptinyx, Bionomics, BioXcel Therapeutics, Clexio, EmpowerPharm, GW Pharmaceuticals, Janssen, Jazz Pharmaceuticals, and Roche/Genentech and has stock options in Oxeia Biopharmaceuticals and Epivario. In the past 3 years, NPD has held a part-time paid position at Cohen Veterans Bioscience, has been a consultant for Sunovion Pharmaceuticals, and is on the scientific advisory board for Sentio Solutions for unrelated work. In the past 3 years, KJRe has been a consultant for Datastat, Inc. RallyPoint Networks, Inc. Sage Pharmaceuticals, and Takeda. JLM-K has received funding and a speaking fee from COMPASS Pathways. MU has been a consultant for System Analytic. HRK is a member of the Dicerna scientific advisory board and a member of the American Society of Clinical Psychopharmacology Alcohol Clinical Trials Initiative, which during the past 3 years was supported by Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Dicerna, Ethypharm, Indivior, Lundbeck, Mitsubishi, and Otsuka. HRK and JG are named as inventors on Patent Cooperative Treaty patent application number 15/878,640, entitled ?Genotype-guided dosing of opioid agonists,? filed January 24, 2018. RP and JG are paid for their editorial work on the journal Complex Psychiatry. OAA is a consultant to HealthLytix. All other authors report no biomedical financial interests or potential conflicts of interest. Publisher Copyright: © 2021 Society of Biological PsychiatryBackground: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). Methods: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. Results: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. Conclusions: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.publishersversionpublishe