Sex effects on DNA methylation affect discovery in epigenome-wide association study of schizophrenia.

Sex differences in the epidemiology and clinical characteristics of schizophrenia are well-known; however, the molecular mechanisms underlying these differences remain unclear. Further, the potential advantages of sex-stratified meta-analyses of epigenome-wide association studies (EWAS) of schizophrenia have not been investigated. Here, we performed sex-stratified EWAS meta-analyses to investigate whether sex stratification improves discovery, and to identify differentially methylated regions (DMRs) in schizophrenia. Peripheral blood-derived DNA methylation data from 1519 cases of schizophrenia (male n = 989, female n = 530) and 1723 controls (male n = 997, female n = 726) from three publicly available datasets, and the TOP cohort were meta-analyzed to compare sex-specific, sex-stratified, and sex-adjusted EWAS. The predictive power of each model was assessed by polymethylation score (PMS). The number of schizophrenia-associated differentially methylated positions identified was higher for the sex-stratified model than for the sex-adjusted one. We identified 20 schizophrenia-associated DMRs in the sex-stratified analysis. PMS from sex-stratified analysis outperformed that from sex-adjusted analysis in predicting schizophrenia. Notably, PMSs from the sex-stratified and female-only analyses, but not those from sex-adjusted or the male-only analyses, significantly predicted schizophrenia in males. The findings suggest that sex-stratified EWAS meta-analyses improve the identification of schizophrenia-associated epigenetic changes and highlight an interaction between sex and schizophrenia status on DNA methylation. Sex-specific DNA methylation may have potential implications for precision psychiatry and the development of stratified treatments for schizophrenia.

Prenatal social support in low-risk pregnancy shapes placental epigenome.

BACKGROUND: Poor social support during pregnancy has been linked to inflammation and adverse pregnancy and childhood health outcomes. Placental epigenetic alterations may underlie these links but are still unknown in humans. METHODS: In a cohort of low-risk pregnant women (n = 301) from diverse ethnic backgrounds, social support was measured using the ENRICHD Social Support Inventory (ESSI) during the first trimester. Placental samples collected at delivery were analyzed for DNA methylation and gene expression using Illumina 450K Beadchip Array and RNA-seq, respectively. We examined association between maternal prenatal social support and DNA methylation in placenta. Associated cytosine-(phosphate)-guanine sites (CpGs) were further assessed for correlation with nearby gene expression in placenta. RESULTS: The mean age (SD) of the women was 27.7 (5.3) years. The median (interquartile range) of ESSI scores was 24 (22-25). Prenatal social support was significantly associated with methylation level at seven CpGs (PFDR < 0.05). The methylation levels at two of the seven CpGs correlated with placental expression of VGF and ILVBL (PFDR < 0.05), genes known to be involved in neurodevelopment and energy metabolism. The genes annotated with the top 100 CpGs were enriched for pathways related to fetal growth, coagulation system, energy metabolism, and neurodevelopment. Sex-stratified analysis identified additional significant associations at nine CpGs in male-bearing pregnancies and 35 CpGs in female-bearing pregnancies. CONCLUSIONS: The findings suggest that prenatal social support is linked to placental DNA methylation changes in a low-stress setting, including fetal sex-dependent epigenetic changes. Given the relevance of some of these changes in fetal neurodevelopmental outcomes, the findings signal important methylation targets for future research on molecular mechanisms of effect of the broader social environment on pregnancy and fetal outcomes. TRIAL REGISTRATION: NCT00912132 ( ClinicalTrials.gov ).

Genome-wide analyses reveal novel opioid use disorder loci and genetic overlap with schizophrenia, bipolar disorder, and major depression.

Opioid use disorder (OUD) and mental disorders are often comorbid, with increased morbidity and mortality. The causes underlying this relationship are poorly understood. Although these conditions are highly heritable, their shared genetic vulnerabilities remain unaccounted for. We applied the conditional/conjunctional false discovery rate (cond/conjFDR) approach to analyse summary statistics from independent genome wide association studies of OUD, schizophrenia (SCZ), bipolar disorder (BD) and major depression (MD) of European ancestry. Next, we characterized the identified shared loci using biological annotation resources. OUD data were obtained from the Million Veteran Program, Yale-Penn and Study of Addiction: Genetics and Environment (SAGE) (15 756 cases, 99 039 controls). SCZ (53 386 cases, 77 258 controls), BD (41 917 cases, 371 549 controls) and MD (170 756 cases, 329 443 controls) data were provided by the Psychiatric Genomics Consortium. We discovered genetic enrichment for OUD conditional on associations with SCZ, BD, MD and vice versa, indicating polygenic overlap with identification of 14 novel OUD loci at condFDR < 0.05 and 7 unique loci shared between OUD and SCZ (n = 2), BD (n = 2) and MD (n = 7) at conjFDR < 0.05 with concordant effect directions, in line with estimated positive genetic correlations. Two loci were novel for OUD, one for BD and one for MD. Three OUD risk loci were shared with more than one psychiatric disorder, at DRD2 on chromosome 11 (BD and MD), at FURIN on chromosome 15 (SCZ, BD and MD) and at the major histocompatibility complex region (SCZ and MD). Our findings provide new insights into the shared genetic architecture between OUD and SCZ, BD and MD, indicating a complex genetic relationship, suggesting overlapping neurobiological pathways.

Renal function in Ethiopian HIV-positive adults on antiretroviral treatment with and without tenofovir.

BACKGROUND: Limited data are available on the effect of antiretroviral treatment (ART) or Tenofovir disoproxil fumarate (TDF) on renal function in Ethiopians. We aimed to assess factors associated with renal function changes during the first year of ART with special focus on TDF. METHODS: HIV positive persons who were ≥ 18 years of age and eligible for ART initiation were recruited. Creatinine measurement to estimate glomerular filtration rate (eGFR) and spot urine analyses were performed at baseline and after 3, 6 and 12 months of ART. Univariate and multivariate linear regression and univariate logistic regression were used to determine factors associated with eGFR as continuous and categorical variable respectively. A linear mixed model was used to assess 12 month eGFR difference in TDF and non-TDF based regimen. RESULT: Of 340 ART-naïve HIV patients with baseline renal function tests, 82.3% (279/339) were initiated on a TDF based ART regimen. All patients were on non-nucleoside reverse transcriptase inhibitors (NNRTI) based ART regimen. The median (IQR) change in eGFR with 12 months of ART was 0.8 (- 11.1; 10.0) ml/min/1.73m2. About 41 and 26.9% of HIV patients had a drop of greater than 3 and 10 mL/min/1.73 m2 in eGFR at 12 month, respectively. However, none of the HIV patients declined to < 60 ml/min/1.73m2 within 12 months. Moreover, none of the HIV patients had persistent proteinuria or glycosuria. Older HIV patients especially age > 45 years and those with unsuppressed viral load at 6 month of ART had a significantly lower eGFR at 12 months of ART initiation. However, there was no difference in 12 month eGFR between HIV patients initiated on TDF based regimen and non-TDF based regimen. CONCLUSION: Renal function remained stable with no difference between HIV patients treated with TDF or non-TDF NNRTI based ART regimen over 12 months. However, older HIV patients and those with unsuppressed viral load deserve special focus on renal monitoring. Data on long-term safety of TDF (> 1 year) is still warranted in this population.

Taste the Pain: The Role of TRP Channels in Pain and Taste Perception.

Transient receptor potential (TRP) channels are a superfamily of cation transmembrane proteins that are expressed in many tissues and respond to many sensory stimuli. TRP channels play a role in sensory signaling for taste, thermosensation, mechanosensation, and nociception. Activation of TRP channels (e.g., TRPM5) in taste receptors by food/chemicals (e.g., capsaicin) is essential in the acquisition of nutrients, which fuel metabolism, growth, and development. Pain signals from these nociceptors are essential for harm avoidance. Dysfunctional TRP channels have been associated with neuropathic pain, inflammation, and reduced ability to detect taste stimuli. Humans have long recognized the relationship between taste and pain. However, the mechanisms and relationship among these taste-pain sensorial experiences are not fully understood. This article provides a narrative review of literature examining the role of TRP channels on taste and pain perception. Genomic variability in the TRPV1 gene has been associated with alterations in various pain conditions. Moreover, polymorphisms of the TRPV1 gene have been associated with alterations in salty taste sensitivity and salt preference. Studies of genetic variations in TRP genes or modulation of TRP pathways may increase our understanding of the shared biological mediators of pain and taste, leading to therapeutic interventions to treat many diseases.

Body Composition during Early Infancy and Mental Health Outcomes at 5 Years of Age: A Prospective Cohort Study of Ethiopian Children.

OBJECTIVE: To examine the relationship between body composition-specifically fat mass (FM) and fat-free mass (FFM)-in early infancy, and mental health outcomes in early childhood. STUDY DESIGN: In the Infant Anthropometry and Body Composition birth cohort study from Ethiopia, body composition was measured at birth and 1.5, 2.5, 3.5, 4.5, and 6 months of age. Mental health was assessed at 5 years of age using the approved Amharic version of the Strengths and Difficulties Questionnaire (SDQ), a parent report scale covering 4 different domains providing a total difficulties score. The associations of FM or FFM at birth as well as during early infancy, with SDQ score at 5 years of age were examined using multiple linear regression analyses. RESULTS: At 5 years of age, the mean ± SD for SDQ score was 10.4 ± 5.8. FM at birth was positively and FFM negatively associated with SDQ score. For each kg increase in FM at birth, the SDQ score at 5 years was 5.7 points higher (ß = 5.7; 95% CI, 1.4-10.0). In contrast, for each kilogram increase in FFM at birth, the SDQ score was 3.9 points lower (ß = -3.9; 95% CI, -7.0 to -0.8). Neither FM nor FFM accretion rate during early infancy were associated with SDQ score at 5 years of age. CONCLUSIONS: Fetal rather than infant body composition was associated with SDQ score at 5 years of age. Greater FFM accretion during fetal life may have contributed to more optimal neurobehavioral development during early life. However, the potential mechanisms underlying the observed associations need further investigation.

Body composition during early infancy and developmental progression from 1 to 5 years of age: the Infant Anthropometry and Body Composition (iABC) cohort study among Ethiopian children.

Early nutrition and growth have been found to be important early exposures for later development. Studies of crude growth in terms of weight and length/height, however, cannot elucidate how body composition (BC) might mediate associations between nutrition and later development. In this study, we aimed to examine the relation between fat mass (FM) or fat-free mass (FFM) tissues at birth and their accretion during early infancy, and later developmental progression. In a birth cohort from Ethiopia, 455 children who have BC measurement at birth and 416 who have standardised rate of BC growth during infancy were followed up for outcome variable, and were included in the statistical analysis. The study sample was restricted to mothers living in Jimma town who gave birth to a term baby with a birth weight ≥1500 g and no evident congenital anomalies. The relationship between the exposure and outcome variables was examined using linear-mixed regression model. The finding revealed that FFM at birth was positively associated with global developmental progression from 1 to 5 years (ß=1·75; 95 % CI 0·11, 3·39) and from 4 to 5 years (ß=1·34; 95 % CI 0·23, 2·44) in the adjusted model. Furthermore, the rate of postnatal FFM tissue accretion was positively associated with development at 1 year of age (ß=0·50; 95 % CI 0·01, 0·99). Neither fetal nor postnatal FM showed a significant association. In conclusion, fetal, rather than postnatal, FFM tissue accretion was associated with developmental progression. Intervention studies are needed to assess whether nutrition interventions increasing FFM also increase cognitive development.

Challenges of bacterial meningitis case management in low income settings: an experience from Ethiopia.

OBJECTIVE: To investigate the current diagnostic and therapeutic strategies used in the care of patients with suspected bacterial meningitis at teaching hospitals in Ethiopia. METHODS: This was a hospital-based retrospective study conducted at four teaching hospitals in different regions of Ethiopia. Participants were patients aged 14 years and older treated for suspected bacterial meningitis. Presenting complaints, diagnostic strategies used and treatments given were obtained from clinical records. RESULT: A total of 425 patients were included in the study; 52.7% were men and 83.8% were younger than 50 years. Fever, headache, neck stiffness and impaired consciousness were the most common clinical presentations; 55.5% underwent lumbar puncture. Overall, only 96 (22.6%) patients had cerebrospinal fluid abnormalities compatible with bacterial meningitis. A causative bacterium was identified in only 14 cases. Ceftriaxone was used as the empiric treatment of choice, either alone or in combination with other antibiotics; 17.6% of patients were also given vancomycin. Adjunctive dexamethasone was given to 50.4%. CONCLUSION: Most patients treated as bacterial meningitis did not receive a proper diagnostic workup. The choice of antibiotic was not tailored to the specific clinical condition of the patient. Such an approach may result in poor treatment outcomes and lead to antibiotic resistance. Management of patients with suspected bacterial meningitis should be supported by analysis of cerebrospinal fluid, and treatment should be tailored to local evidence and current evidence-based recommendations.

The effect of nutritional supplementation on quality of life in people living with HIV: a randomised controlled trial.

OBJECTIVE: To determine the effects of lipid-based nutrient supplements (LNS) on the quality of life of people living with HIV (PLHIV) during the first 3 months of antiretroviral treatment (ART) and to investigate the effects of timing of supplementation by comparing with supplementation during the subsequent 3 months. METHODS: A randomised controlled trial was conducted in three ART clinics within public health facilities in Jimma, Ethiopia. Participants were PLHIV eligible to start ART with body mass index >17 kg/m(2) and given daily supplements of 200 g of LNS containing whey or soya either during the first 3 months or the subsequent months of ART. The outcome was measured in terms of total quality-of-life scores on the adapted version of the WHOQOL-HIV-BREF assessed at baseline, three and six months. RESULTS: Of the 282 participants, 186 (66.0%) were women. The mean age (SD) was 32.8 (±9.0) years, and the mean (SD) total quality-of-life score was 82.0 (±14.8) at baseline assessment. At 3 months, participants who received LNS showed better quality of life than those who only received ART without LNS (ß = 6.2, 95% CI: 2.9: 9.6). At 6 months, there was no difference in total quality-of-life score between the early and delayed supplementation groups (ß = 3.0, 95% CI: -0.4: 6.4). However, the early supplementation group showed higher scores on the social and spirituality domains than the delayed group. CONCLUSIONS: LNS given during the first three months of ART improves the quality of life of PLHIV.

Change in serum 25-hydroxyvitamin D with antiretroviral treatment initiation and nutritional intervention in HIV-positive adults.

Low vitamin D level in HIV-positive persons has been associated with disease progression. We compared the levels of serum 25-hydroxyvitamin D (25(OH)D) in HIV-positive and HIV-negative persons, and investigated the role of nutritional supplementation and antiretroviral treatment (ART) on serum 25(OH)D levels. A randomised nutritional supplementation trial was conducted at Jimma University Specialized Hospital, Ethiopia. The trial compared 200 g/d of lipid-based nutrient supplement (LNS) with no supplementation during the first 3 months of ART. The supplement provided twice the recommended daily allowance of vitamin D (10 µg/200 g). The level of serum 25(OH)D before nutritional intervention and ART initiation was compared with serum 25(OH)D of HIV-negative individuals. A total of 348 HIV-positive and 100 HIV-negative persons were recruited. The median baseline serum 25(OH)D level was higher in HIV-positive than in HIV-negative persons (42·5 v. 35·3 nmol/l, P<0·001). In all, 282 HIV-positive persons with BMI>17 kg/m2 were randomised to either LNS supplementation (n 189) or no supplementation (n 93) during the first 3 months of ART. The supplemented group had a 4·1 (95 % CI 1·7, 6·4) nmol/l increase in serum 25(OH)D, whereas the non-supplemented group had a 10·8 (95 % CI 7·8, 13·9) nmol/l decrease in serum 25(OH)D level after 3 months of ART. Nutritional supplementation that contained vitamin D prevented a reduction in serum 25(OH)D levels in HIV-positive persons initiating ART. Vitamin D replenishment may be needed to prevent reduction in serum 25(OH)D levels during ART.

Adjunctive dexamethasone therapy in unconfirmed bacterial meningitis in resource limited settings: is it a risk worth taking?

BACKGROUND: Bacterial meningitis is associated with significant morbidity and mortality despite advances in medical care. The main objective of this study was to assess the association of adjunctive dexamethasone treatment with discharge outcome of patients treated as bacterial meningitis in low income setting. METHODS: A retrospective study was conducted at four teaching hospitals across Ethiopia. Patients of age 14 years and older treated as cases of bacterial meningitis between January 1, 2011 and April 30, 2015 were included in this study. Information regarding sociodemographic data, clinical presentations, laboratory data, treatments given and status at hospital discharge were retrieved from patients' medical records using a structured questionnaire. Predefined outcome variables at discharge were analysed using descriptive statistics. Multivariable logistic regression was used to identify factors independently associated with poor outcome. RESULTS: A total of 425 patients treated with the presumptive clinical diagnosis of bacterial meningitis were included in this study (lumbar puncture done in 56 %; only 19 % had CSF findings compatible with bacterial meningitis, and only 3 % had proven etiology). The overall in hospital mortality rate was 20.2 %. Impaired consciousness, aspiration pneumonia, and cranial nerve palsy at admission were independently associated with increased mortality. Adjuvant dexamethasone, which was used in 50.4 % of patients, was associated with increased in-hospital mortality (AOR = 3.38; 95 % CI 1.87-6.12, p < 0.001) and low Glasgow outcome scale (GOS) at discharge (AOR = 4.46 (95 % CI 1.98-10.08). This association between dexamethasone and unfavorable outcome was found to be more pronounced in suspected but unproven cases and in those without CSF alterations compatible with bacterial meningitis. CONCLUSION: Most patients treated for suspected bacterial meningitis did not receive proper diagnostic workup. Adjuvant dexamethasone use in clinically suspected but unproven cases of bacterial meningitis was associated with an increased mortality and poor discharge GOS. These findings show that there are potential deleterious effects in unconfirmed cases in this setting. Physicians practising under such circumstances should thus abide with the current recommendation and defer the use of adjuvant corticosteroid in suspected cases of bacterial meningitis.

Food insecurity, mental health and quality of life among people living with HIV commencing antiretroviral treatment in Ethiopia: a cross-sectional study.

BACKGROUND: Studies from high-income settings show that both food insecurity and common mental disorders (CMDs) are associated with lower quality of life among people living with HIV (PLHIV). However, there is limited research among PLHIV in sub-Saharan Africa. In this study we tested the hypothesis that food insecurity and CMDs would be associated with poorer quality of life of PLHIV in Ethiopia. METHODS: A cross-sectional study was carried out with 348 PLHIV who were initiating antiretroviral therapy recruited from two primary care centers and a tertiary Hospital in southwest Ethiopia. Food insecurity, CMD, and quality of life were measured using instruments adapted and validated in Ethiopia (Household Food Insecurity Access Scale, Kessler-6, and WHOQOL-HIV-BREF-ETH, respectively). Multiple linear regression analysis was used to identify factors associated with quality of life after adjusting for confounders. RESULTS: The prevalence of severe household food insecurity among PLHIV was 38.7 %. After adjusting for confounders, severe food insecurity (ß = -3.24, 95 % CI: -6.19; -0.29) and higher levels of CMD symptoms (ß = -1.72 for each 1 point increase, 95 % CI: -1.94; -1.49) were associated with lower quality of life. Other factors associated with lower quality of life were advanced HIV disease (ß = -3.80, 95 % CI: -6.18; -1.42), and being underweight (BMI = 17.0 - 18.5 kg/m(2)) (ß = -3.45, 95 % CI: -6.18; -0.71). Owning more household assets was associated with higher quality of life (ß = 0.99 for owning one more asset, 95 % CI: 0.09; 1.89). CONCLUSION: Poor mental health and food insecurity are associated with lower quality of life in PLHIV. There is a need for longitudinal studies to elucidate the pathways linking CMD, food insecurity and quality of life.

Khat use in people living with HIV: a facility-based cross-sectional survey from South West Ethiopia.

BACKGROUND: Khat is an evergreen plant with leaves containing the amphetamine-like compounds cathinone and cathine. Many people in the Horn of Africa use khat on a regular basis. Adverse health and social consequences of khat use have been described but little is known about the use of khat in people living with Human Immunodeficiency Virus (PLHIV) in Ethiopia. This study aimed to assess the prevalence of khat use and factors associated with khat use among PLHIV who are in contact with HIV services in a hospital in south-west Ethiopia. METHODS: A cross-sectional study was conducted among 389 PLHIV who attended HIV services at Jimma University Specialized Hospital in September 2012. A structured questionnaire, translated into the local languages, was used to ask about the frequency of khat use and potential risk factors and consequences of khat use in this patient group. Logistic regression analysis was used for bivariate and multivariable analysis. RESULTS: The overall prevalence of current khat use among people living with HIV was 23.0%. The prevalence was 18.3% in females and 33.6% in males. Christians were less likely to use khat when compared to Muslims (adjusted Odds Ratio (aOR) 0.26, 95% CI = 0.13, 0.55). There was a positive association between khat use and mental distress (aOR 1.84, 95% CI = 1.01, 3.36), smoking cigarettes (aOR 21.21, 95% CI = 7.19, 62.51), alcohol use disorders (aOR 2.16, 95% CI = 1.10, 4.21), CD4 count ≤200 cells/mm(3) (aOR 3.46, 95% CI = 1.60, 7.50) and missing at least one dose of antiretroviral medication in the preceding month (ART) (aOR 4.2, 95% CI = 1.80, 5.75). CONCLUSION: In this study there was a high prevalence of khat use among people living with HIV which was associated with poorer adherence to ART. There is a need to adapt and evaluate feasible and acceptable interventions to reduce khat use in people living with HIV.

Household food insecurity and mental distress among pregnant women in Southwestern Ethiopia: a cross sectional study design.

BACKGROUND: There are compelling theoretical and empirical reasons that link household food insecurity to mental distress in the setting where both problems are common. However, little is known about their association during pregnancy in Ethiopia. METHODS: A cross-sectional study was conducted to examine the association of household food insecurity with mental distress during pregnancy. Six hundred and forty-two pregnant women were recruited from 11 health centers and one hospital. Probability proportional to size (PPS) and consecutive sampling techniques were employed to recruit study subjects until the desired sample size was obtained. The Self Reporting Questionnaire (SRQ-20) was used to measure mental distress and a 9-item Household Food Insecurity Access Scale was used to measure food security status. Descriptive and inferential statistics were computed accordingly. Multivariate logistic regression was used to estimate the effect of food insecurity on mental distress. RESULTS: Fifty eight of the respondents (9%) were moderately food insecure and 144 of the respondents (22.4%) had mental distress. Food insecurity was also associated with mental distress. Pregnant women living in food insecure households were 4 times more likely to have mental distress than their counterparts (COR = 3.77, 95% CI: 2.17, 6.55). After controlling for confounders, a multivariate logistic regression model supported a link between food insecurity and mental distress (AOR = 4.15, 95% CI: 1.67, 10.32). CONCLUSION: The study found a significant association between food insecurity and mental distress. However, the mechanism by which food insecurity is associated with mental distress is not clear. Further investigation is therefore needed to understand either how food insecurity during pregnancy leads to mental distress or weather mental distress is a contributing factor in the development of food insecurity.

Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia.

BACKGROUND: The ongoing scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has prompted the interest in surveillance of transmitted and acquired HIV drug resistance. Resistance data on virological failure and mutations in HIV infected populations initiating treatment in sub-Saharan Africa is sparse. METHODS: HIV viral load (VL) and resistance mutations pre-ART and after 6 months were determined in a prospective cohort study of ART-naïve HIV patients initiating first-line therapy in Jimma, Ethiopia. VL measurements were done at baseline and after 3 and 6 months. Genotypic HIV drug resistance (HIVDR) was performed on patients exhibiting virological failure (>1000 copies/mL at 6 months) or slow virological response (>5000 copies/mL at 3 months and <1000 copies/mL at 6 months). RESULTS: Two hundred sixty five patients had VL data available at baseline and at 6 months. Virological failure was observed among 14 (5.3%) participants out of 265 patients. Twelve samples were genotyped and six had HIV drug resistance (HIVDR) mutations at baseline. Among virological failures, 9/11 (81.8%) harbored one or more HIVDR mutations at 6 months. The most frequent mutations were K103N and M184VI. CONCLUSIONS: Our data confirm that the currently recommended first-line ART regimen is efficient in the vast majority of individuals initiating therapy in Jimma, Ethiopia eight years after the introduction of ART. However, the documented occurrence of transmitted resistance and accumulation of acquired HIVDR mutations among failing patients justify increased vigilance by improving the availability and systematic use of VL testing to monitor ART response, and underlines the need for rapid, inexpensive tests to identify the most common drug resistance mutations.

Quality of life in Ethiopia's street youth at a rehabilitation center and the association with trauma.

Quality of life (QOL) tends to be lower among the homeless than the general population, and traumatic events experienced on the streets have a negative impact on QOL. Low-income countries face a high number of street youth, yet little research has been performed so far on QOL, trauma, and posttraumatic stress disorder (PTSD) among this group. This study aimed at examining the QOL of a sample of Ethiopian street youth within a rehabilitation program and at exploring whether the street youth have experienced traumatic events and show posttraumatic stress symptoms. We interviewed 84 street youths with the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) and the Diagnostic Interview for Children and Adolescents (DICA). Mean QOL scores differed significantly between the groups assessed at the beginning and at the end of the program (Cohen's d = 0.48). Eighty-three percent of the Ethiopian street youths had experienced traumatic events, and 25.0% met criteria for PTSD according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders. QOL did not differ between those with and without PTSD symptoms. These findings show the high rate of traumatic events among Ethiopian street youth and the importance for rehabilitation programs that focus on improving QOL. The results of the study may have cultural limitations.

Perceived challenges and opportunities arising from integration of mental health into primary care: a cross-sectional survey of primary health care workers in south-west Ethiopia.

BACKGROUND: The WHO's mental health Gap Action Programme seeks to narrow the treatment gap for mental disorders by advocating integration of mental health into primary health care (PHC). This study aimed to assess the challenges and opportunities of this approach from the perspective of PHC workers in a sub-Saharan African country. METHODS: A facility-based cross-sectional survey of 151 PHC workers was conducted from 1st to 30th November 2011 in Jimma zone, south-west Ethiopia. A structured questionnaire was used to ask about past training and mental health experience, knowledge and attitudes towards mental disorders and provision of mental health care in PHC. Semi-structured interviews were carried out with 12 heads of health facilities for more in-depth understanding. RESULTS: Almost all PHC workers (96.0%) reported that mental health care was important in Ethiopia and the majority (66.9%) expressed interest in actually delivering mental health care. Higher levels of general health training (degree vs. diploma) and pre-service clinical exposure to mental health care were associated with more favourable attitudes. Knowledge about mental disorder diagnoses, symptoms and treatments was low. Almost half (45.0%) of PHC workers reported that supernatural factors were important causes of mental disorders. Health system and structural issues, such as poor medication supply, lack of rooms, time constraints, absence of specialist supervision and lack of treatment guidelines, were identified as challenges. Almost all PHC workers (96.7%) reported a need for more training, including a clinical attachment, in order to be able to deliver mental health care competently. CONCLUSIONS: Despite acceptability to PHC workers, the feasibility of integrating mental health into PHC in this sub-Saharan African setting is limited by important gaps in PHC worker knowledge and expectations regarding mental health care, coupled with health system constraints. In addition to clinically-based refresher mental health training, expansion of the specialist mental health workforce may be needed to support integration in practice.

Public stigma against family members of people with mental illness: findings from the Gilgel Gibe Field Research Center (GGFRC), Southwest Ethiopia.

BACKGROUND: Public stigma against family members of people with mental illness is a negative attitude by the public which blame family members for the mental illness of their relatives. Family stigma can result in self social restrictions, delay in treatment seeking and poor quality of life. This study aimed at investigating the degree and correlates of family stigma. METHODS: A quantitative cross-sectional house to house survey was conducted among 845 randomly selected urban and rural community members in the Gilgel Gibe Field Research Center, Southwest Ethiopia. An interviewer administered and pre-tested questionnaire adapted from other studies was used to measure the degree of family stigma and to determine its correlates. Data entry was done by using EPI-DATA and the analysis was performed using STATA software. Unadjusted and adjusted linear regression analysis was done to identify the correlates of family stigma. RESULTS: Among the total 845 respondents, 81.18% were female. On a range of 1 to 5 score, the mean family stigma score was 2.16 (± 0.49). In a multivariate analysis, rural residents had significantly higher stigma scores (std. ß = 0.43, P < 0.001) than urban residents. As the number of perceived signs (std. ß = -0.07, P < 0.05), perceived supernatural (std. ß = -0.12, P < 0.01) and psychosocial and biological (std. ß = -0.11, P < 0.01) explanations of mental illness increased, the stigma scores decreased significantly. High supernatural explanation of mental illness was significantly correlated with lower stigma among individuals with lower level of exposure to people with mental illness (PWMI). On the other hand, high exposure to PWMI was significantly associated with lower stigma among respondents who had high education. Stigma scores increased with increasing income among respondents who had lower educational status. CONCLUSIONS: Our findings revealed moderate level of family stigma. Place of residence, perceived signs and explanations of mental illness were independent correlates of public stigma against family members of people with mental illness. Therefore, mental health communication programs to inform explanations and signs of mental illness need to be implemented.

A developing world perspective on homicide and personality disorder.

High rates of psychotic disorder among special populations of homicide offenders, females, youth and the mentally disordered, have received much investigation. Personality disorder, especially antisocial personality disorder, augments the relative risk ratio of violence, especially in combination with substance use disorder. Few studies of these correlates of violence and especially homicide have been reported in low- and medium-income countries (LMIC). Using the structured clinical interview for DSM diagnosis (SCID), personality disorders were identified in a cross sectional study involving 546 homicide offenders in Jimma prison, Ethiopia. Predictors of personality disorder were determined using multivariate analysis of various demographic and clinical variables, for example, age, psychiatric history and substance use. Out of the 316 offenders who completed the SCID, only 16% fulfilled DSM IV criteria for personality disorder. The rationale for killing, self-defence, anger and revenge (52% of offenders), planning involved in offending (50%) and reasonably high level of relationship functioning (57% married) were different from most data from the high-income countries. Diagnostically relevant cultural factors in LMIC, not in play in high-income countries, may explain the differences in personality disorders similar to other mental disorders and the underlying mediators of homicide.

Placental accelerated aging in antenatal depression.

BACKGROUND: Antenatal maternal depression is associated with poor pregnancy outcomes and long-term effects on the offspring. Previous studies have identified links between antenatal depression and placental DNA methylation and between placental epigenetic aging and poor pregnancy outcomes, such as preterm labor and preeclampsia. The relationship between antenatal depression and poor pregnancy outcomes may be partly mediated via placental aging. OBJECTIVE: This study aimed to investigate whether antenatal depressive symptoms are associated with placental epigenetic age acceleration, an epigenetic aging clock measure derived from the difference between methylation age and gestational age at delivery. STUDY DESIGN: The study included 301 women who provided placenta samples at delivery as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies - Singletons that recruited participants from diverse race and ethnic groups at 12 US clinical sites (2009-2013). Women underwent depression screening using the Edinburgh Postnatal Depression Scale up to 6 times across the 3 trimesters of pregnancy. Depressive symptoms status was determined for each pregnancy trimester using an Edinburgh Postnatal Depression Scale score, in which a score of ≥10 was defined as having depressive symptoms and a score of <10 was defined as not having depressive symptoms. Placental DNA methylation was profiled from placenta samples. Placental epigenetic age was estimated using a methylation-based age estimator (placental "epigenetic clock") that has previously been found to have high placental gestational age prediction accuracy for uncomplicated term pregnancies. Placental age acceleration was defined to be the residual upon regressing the estimated epigenetic age on gestational age at delivery. Associations between an Edinburgh Postnatal Depression Scale score of ≥10 and an Edinburgh Postnatal Depression Scale score of <10 in the first, second, and third trimesters of pregnancy (ie, depressive symptoms vs none in each trimester) and placental age acceleration were tested using multivariable linear regression adjusting for maternal age, parity, race and ethnicity, and employment. RESULTS: There were 31 (10.3%), 48 (16%), and 49 (16.4%) women with depressive symptoms (ie, Edinburgh Postnatal Depression Scale score of ≥10) in the first, second, and third trimesters of pregnancy, respectively. Of these women, 21 (7.2%) had sustained first- and second-trimester depressive symptoms, 19 (7%) had sustained second- and third-trimester depressive symptoms, and 12 (4.8%) had sustained depressive symptoms throughout pregnancy. Women with depressive symptoms in the second trimester of pregnancy had 0.41 weeks higher placental age acceleration than women without depressive symptoms during the second trimester of pregnancy (ß=0.21 weeks [95% confidence interval, -0.17 to 0.58; P=.28] during the first trimester of pregnancy; ß=0.41 weeks [95% confidence interval, 0.10-0.71; P=.009] during the second trimester of pregnancy; ß=0.17 weeks [95% confidence interval, -0.14 to 0.47; P=.29] during the third trimester of pregnancy). Sustained first- and second-trimester depressive symptoms were associated with 0.72 weeks higher placental age acceleration (95% confidence interval, 0.29-1.15; P=.001) than no depressive symptom in the 2 trimesters. The association between second-trimester depressive symptoms and higher placental epigenetic age acceleration strengthened in the analysis of pregnancies with male fetuses (ß=0.53 weeks; 95% confidence interval, 0.06-1.08; P=.03) but was not significant in pregnancies with female fetuses. CONCLUSION: Antenatal depressive symptoms during the second trimester of pregnancy were associated with an average of 0.41 weeks of increased placental age acceleration. Accelerated placental aging may play an important role in the underlying mechanism linking antenatal depression to pregnancy complications related to placental dysfunction.