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Provide a critical overview of recent global advances in student mental health from a public health perspective, highlighting key challenges and gaps in the literature.Mental disorders and suicidality are common among university students globally. However, there is a significant treatment gap even though evidence-based treatments are available. To overcome barriers to treatment, public health interventions should be conceptualized within a developmental paradigm that takes cognizance of the developmental tasks of young adulthood. Traditional one-on-one treatment approaches will not be a cost-effective or sustainable way to close the treatment gap among students. A range of evidence-based interventions is available to promote students' mental health; however, novel approaches are needed to scale up services and adapt intervention delivery to suit student specific contexts. Digital interventions and peer-to-peer interventions could be a cost-effective way to scale-up and expand the range of services.

We examined oral PrEP interest among adolescents and its association with perceived parental support and PrEP stigma. Cross-sectional data were collected during baseline procedures of the "Our Family Our Future" intervention trial in South Africa. Adolescents (14-16 years) at elevated risk for acquiring HIV and their parents or caregivers were dyadically enrolled from 2018 to 2021. There were 879 complete adolescent-parent dyads. Among adolescents, 27% had heard about PrEP, 67% reported they would want to use PrEP, and 58% thought their parent would want them to use PrEP. Among parents, 33% had heard about PrEP and 85% reported they would want their adolescent to use PrEP. Adolescents who thought their parent would want them to use PrEP were more likely to be interested in PrEP than adolescents who thought their parent would not want them to use PrEP (adjusted prevalence ratio (aPR) = 2.11, 95% CI 1.82, 2.44). Further, adolescents with higher average PrEP stigma scores above the adolescent sample median were less likely to be interested in PrEP than adolescents with lower average PrEP stigma scores (aPR = 0.81, 95% CI 0.72, 0.91). In conclusion, parents were more supportive of their adolescent taking PrEP than adolescents perceived they would be, and perceptions of low parental support and greater PrEP stigma were associated with reduced PrEP interest among adolescents. Interventions should aim to improve adolescent-parent communication around sexual health and effective HIV prevention tools.

We set out to test the hypothesis that greater brain ageing will be observed in people with HIV (PWH) and those who engage in heavy episodic drinking (HED), with their combined effects being especially detrimental in cognitive control brain networks. We correlated measures of "brain age gap" (BAG) and neurocognitive impairment in participants with and without HIV and HED. Sixty-nine participants were recruited from a community health centre in Cape Town: HIV - /HED - (N = 17), HIV + /HED - (N = 14), HIV - /HED + (N = 21), and HIV + /HED + (N = 17). Brain age was modelled using structural MRI features from the whole brain or one of six brain regions. Linear regression models were employed to identify differences in BAG between patient groups and controls. Associations between BAG and clinical data were tested using bivariate statistical methods. Compared to controls, greater global BAG was observed in heavy drinkers, both with (Cohen's d = 1.52) and without (d = 1.61) HIV. Differences in BAG between HED participants and controls were observed for the cingulate and parietal cortex, as well as subcortically. A larger BAG was associated with higher total drinking scores but not nadir CD4 count or current HIV viral load. The association between heavy episodic drinking and BAG, independent of HIV status, points to the importance of screening for alcohol use disorders in primary care. The relatively large contribution of cognitive control brain regions to BAG highlights the utility of assessing the contribution of different brain regions to brain age.

Neuroimaging studies suggest involvement of frontal, striatal, limbic and cerebellar regions in trichotillomania, an obsessive-compulsive related disorder. However, findings regarding the underlying neural circuitry remains limited and inconsistent. Graph theoretical analysis offers a way to identify structural brain networks in trichotillomania. T1-weighted MRI scans were acquired in adult females with trichotillomania (n = 23) and healthy controls (n = 16). Graph theoretical analysis was used to investigate structural networks as derived from cortical thickness and volumetric FreeSurfer output. Hubs, brain regions with highest connectivity in the global network, were identified, and group differences were determined. Regions with highest connectivity on a regional level were also determined. There were no differences in small-worldness or other network measures between groups. Hubs in the global network of trichotillomania patients included temporal, parietal, and occipital regions (at 2SD above mean network connectivity), as well as frontal and striatal regions (at 1SD above mean network connectivity). In contrast, in healthy controls hubs at 2SD represented different frontal, parietal and temporal regions, while at 1SD hubs were widespread. The inferior temporal gyrus, involved in object recognition as part of the ventral visual pathway, had significantly higher connectivity on a global and regional level in trichotillomania. The study included women only and sample size was limited. This study adds to the trichotillomania literature on structural brain network connectivity. Our study findings are consistent with previous studies that have implicated somatosensory, sensorimotor and frontal-striatal circuitry in trichotillomania, and partially overlap with structural connectivity findings in obsessive-compulsive disorder.

Maternal perinatal depression is associated with risk of adverse child developmental outcomes and differences in offspring brain structure. Evidence from low- and middle-income countries is lacking as is an investigation of antenatal, postnatal, and persistent depression in the same sample. In a South African birth cohort, we investigated the effect of antenatal and postpartum maternal depressive symptoms on offspring brain structure at 2–3 years of age. Magnetic resonance imaging was performed, extracting cortical thickness and surface areas in frontal cortex regions of interest and subcortical volumes using FreeSurfer software. Maternal depressive symptoms were measured using the Edinburgh Postpartum Depression Scale and the Beck Depression Inventory II antenatally and at 6–10 weeks, 6 months, 12 months, and 18 months postpartum and analyzed dichotomously and continuously. Linear regressions were used controlling for child age, sex, intracranial volume, maternal education, age, smoking, alcohol use and HIV. 146 children were included with 38 (37%) exposed to depressive symptoms antenatally and 44 (35%) exposed postnatally. Of these, 16 (13%) were exposed to both. Postpartum, but not antenatal, depressive symptoms were associated with smaller amygdala volumes in children (B = −74.73, p = 0.01). Persistent maternal depressive symptoms across pregnancy and postpartum were also independently associated with smaller amygdala volumes (B = −78.61, p = 0.047). Differences in amygdala volumes among children exposed to postnatal as well as persistent maternal depressive symptomatology underscore the importance of identifying women at-risk for depression during the entire perinatal period.

Prenatal exposure to maternal depression increases the risk for onset of emotional and behavioral disorders in children. Here, we investigated the effects of exposure to prenatal depression on white matter microstructural integrity at birth and at 2–3 years, and associated neurodevelopment. Diffusion-weighted images were acquired for children of the Drakenstein Child Health Study at 2–4 weeks postpartum (n = 70, 47% boys) and at 2–3 years of age (n = 60, 58% boys). Tract-Based Spatial Statistics was used to compare diffusion tensor metrics across groups defined by presence (> 19 on Beck’s Depression Inventory and/or > 12 on the Edinburgh Postnatal Depression Scale) or absence (below depression thresholds) of depression, and associations with neurodevelopmental measures at age 2–3 years were determined. We did not detect group differences in white matter integrity at neonatal age in this cohort, but at 2–3 years, children in the exposed group demonstrated higher fractional anisotropy, and lower mean and radial diffusivity in association tracts compared to control children. This was notable in the sagittal stratum (radial diffusivity: p

Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.

PURPOSE: Suicidal ideation and behaviour (SIB) in the perinatal period is prevalent in low- and middle-income countries (LMICs). Past work has been limited by reliance on self-rated scales, and there are few data on SIB severity in such settings. We collected cross-sectional data on SIB using a clinician-administered scale and explored risk factors associated with the presence of SIB and SIB severity. METHODS: Data were collected from the Drakenstein Child Health Study cohort antenatally and at 6 months postpartum. SIB was measured using the Mini International Neuropsychiatric Interview and potential sociodemographic, psychosocial, and psychiatric risk factors were assessed. Multivariable analysis determined cross-sectional risk factors. Multinomial regressions determined predictors of SIB risk categories. RESULTS: Among 748 women the antenatal SIB prevalence was 19.9% and postpartum 22.6%. SIB was associated with younger age (antepartum), PTSD (postpartum), and depression (ante- and postpartum). Depression and PTSD predicted belonging to the high risk SIB group. The medium risk group was more likely to have depression, alcohol use during pregnancy and substance abuse. Depression, PTSD, food insecurity, recent intimate partner violence (IPV), and childhood trauma were associated with the low risk group versus the no risk group. CONCLUSION: Screening is needed for perinatal SIB. Associations of perinatal SIB with younger age and major depression are consistent with previous work. The association with PTSD is novel, and underscores the importance of assessment of trauma exposure and outcomes in this population. Different risk categories of SIB may have different causal pathways and require different interventions.

Introduction The purpose of this study is to investigate the effects of agomelatine on anxious symptoms and functional impairment in a pooled dataset from randomized placebo-controlled trials for generalized anxiety disorder (GAD). Methods Data from three randomized, placebo-controlled trials that evaluated the efficacy of agomelatine 25–50 mg were pooled. The short-term (12 weeks) efficacy of agomelatine was assessed in regards to (1) anxious symptoms using the Hamilton Anxiety Scale (HAM-A), and (2) functional impairment using the Sheehan Disability Scale (SDS). Meta-analysis using a random effect model was used to assess differences between groups. Remission and response rates for the HAM-A and SDS were calculated, and analyses were repeated in participants with more severe anxiety symptoms. Results In total, 669 patients (340 on agomelatine; 329 on placebo) were included in the analyses. Compared to placebo, the agomelatine group had a significant reduction in HAM-A total score at week 12 (between group difference: 6.30 ± 2.51, p = 0.012). Significant effects were also found for symptom response on the HAM-A (67.1% of patients on agomelatine vs. 32.5% on placebo) and symptom remission (38.8% of patients on agomelatine vs. 17.3% on placebo). Compared to placebo, there was a significant difference in favour of the agomelatine group at week 12 on the SDS total score (5.11 ± 1.81, p = 0.005). Significant effects were also found for functional response on the SDS (79.1% of patients on agomelatine vs. 43.2% of placebo) and functional remission (55.2% of patients on agomelatine vs. 25.4% on placebo). All findings for anxious symptoms and functional impairment were confirmed in the subset of more severely anxious patients. Agomelatine was well tolerated by patients. Conclusion This meta-analysis confirms that agomelatine reduces anxiety symptoms and improves the global functioning of GAD patients. Supplementary Information The online version of this article (10.1007/s12325-020-01583-9) contains supplementary material, which is available to authorized users.

Purpose Childhood maltreatment elevates risk for common mental disorders (CMDs) during late adolescence and adulthood. Although CMDs are highly prevalent among university students, few studies have examined the relationship between childhood maltreatment and 12 month CMDs in a low- to middle-income countries. This paper describes the prevalence of maltreatment and the relationship between type, number and patterns of maltreatment exposure and 12 month CMDs among first-year university students in South Africa. Methods Maltreatment and CMD data were collected via well-validated self-report scales (corresponding with DSM-IV diagnoses) in a web-based survey of first-year students from two large urban universities (n = 1290) in South Africa. Various multivariate modelling approaches (additive, restrictive interactive and latent class) were used to examine the relationship between maltreatment and CMDs. Results Overall, 48.4% of participants reported childhood maltreatment, the most common type being emotional abuse (26.7%). Regardless of the modelling approach used, emotional abuse was the only type of maltreatment independently associated with 12-month diagnoses of major depressive disorder (MDD), generalised anxiety disorder (GAD) or drug use disorder (DUD) even after adjusting for types and number of types of maltreatment. Similarly, students in the latent class reflecting histories of emotional abuse (either alone or combined with physical abuse) were more likely to meet criteria for 12-month MDD, GAD or DUD. Conclusion Findings confirm the high prevalence of childhood maltreatment among South African students. As this exposure elevates risk for MDD, GAD and DUD, interventions aimed at preventing and treating CMDs among first-year students should address experiences of childhood maltreatment. Electronic supplementary material The online version of this article (10.1007/s00127-020-01992-9) contains supplementary material, which is available to authorized users.

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = −0.111 to −0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.

Gambling disorder (GD) is classified as a behavioural addiction and has some phenotypic similarities with substance use disorders (SUDs). Childhood adversity and life stressors are associated with increased risk for SUDs in adulthood. However, there is limited research investigating the association between childhood trauma, stressors and behavioural addictions such as GD. In this case-control cross-sectional study, 31 adult patients with GD were compared to 31 matched healthy controls (HCs) in terms of exposure to early adversity using the Childhood Trauma Questionnaire (CTQ-SF). In addition, past 12-month stressful life event exposure was assessed using the Life Event Stress Scale (LESS) and investigated as a possible moderator of the relationship between childhood trauma and GD by means of a two-way analysis of variance (ANOVA). Logistic regression analyses were used to test if childhood trauma (CTQ-SF) and its subtypes were significant predictors of a diagnosis of GD. Severity of childhood trauma in general, and on all five subtypes, was significantly higher in GD patients compared to HCs. Childhood trauma was a significant predictor of a diagnosis of GD, with physical neglect being the single trauma subtype to significantly increase odds of GD in adulthood. Stressful life events moderated the relationship between childhood trauma and GD, i.e. childhood trauma was significantly higher in GD patients compared to HCs when LESS was low. The findings support a link between childhood trauma and GD, with current stress as a moderating variable, and may be useful for future individualized therapeutic strategies.

To determine the prevalence of substance use disorders (SUDs) in patients with schizophrenia in a sample from South Africa and compare the clinical and demographic correlates in those with and without co-occurring SUDs. Patients with schizophrenia were interviewed using the Xhosa version SCID-I for DSM-IV. We used logistic regression to determine the predictors of SUDs. In the total sample of 1420 participants, SUDs occurred in 47.8%, with the most prevalent SUD being cannabis use disorders (39.6%), followed by alcohol (20.5%), methaqualone (6.2%), methamphetamine (4.8%) and other SUDs (cocaine, ecstasy, opioids, 0.6%). Polydrug use occurred in 40%, abuse occurred in 13.5%, and 39.6% had at least one substance dependence diagnosis. Significant predictors of any SUD were younger age (41–55 vs. 21–30: OR = 0.7, 95% CI = 0.5–0.9), male sex (OR = 8.6, 95% CI = 5.1–14.6), inpatient status (OR = 1.7, 95% CI = 1.3–2.1), post-traumatic stress symptoms (OR = 4.6, 95% CI = 1.6–13.3), legal (OR = 3.4, 95% CI = 2.0–5.5) and economic problems (OR = 1.4, 95% CI = 1.0–2.0). Methamphetamine use disorders occurred significantly less often in the Eastern compared to the Western Cape provinces. Inpatient status and higher levels of prior admissions were significantly associated with cannabis and methamphetamine use disorders. Post-traumatic stress symptoms were significantly associated with alcohol use disorders. Anxiety disorders were associated with other SUDs. SUDs occurred in almost half of the sample. It is important for clinicians to identify the presence of SUDs as their presence is associated with characteristics, such as male sex, younger age, inpatient status, more prior hospitalisations, legal and economic problems, PTSD symptoms and anxiety.

The relationship between cognitive performance, macro and microstructural brain anatomy and accelerated aging as measured by a highly accurate epigenetic biomarker of aging known as the epigenetic clock in healthy adolescents has not been studied. Healthy adolescents enrolled in the Cape Town Adolescent Antiretroviral Cohort Study were studied cross sectionally. The Illumina Infinium Methylation EPIC array was used to generate DNA methylation data from the blood samples of 44 adolescents aged 9 to 12 years old. The epigenetic clock software and method was used to estimate two measures, epigenetic age acceleration residual (AAR) and extrinsic epigenetic age acceleration (EEAA). Each participant underwent neurocognitive testing, T1 structural magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI). Correlation tests were run between the two epigenetic aging measures and 10 cognitive functioning domains, to assess for differences in cognitive performance as epigenetic aging increases. In order to investigate the associations of epigenetic age acceleration on brain structure, we developed stepwise multiple regression models in R (version 3.4.3, 2017) including grey and white matter volumes, cortical thickness, and cortical surface area, as well as DTI measures of white matter microstructural integrity. In addition to negatively affecting two cognitive domains, visual memory (p = .026) and visual spatial acuity (p = .02), epigenetic age acceleration was associated with alterations of brain volumes, cortical thickness, cortical surface areas and abnormalities in neuronal microstructure in a range of regions. Stress was a significant predictor (p = .029) of AAR. Understanding the drivers of epigenetic age acceleration in adolescents could lead to valuable insights into the development of neurocognitive impairment in adolescents.

Obsessive–compulsive disorder (OCD) is characterized by executive function impairment and by clinical responsivity to selective serotonin reuptake inhibitors (SSRIs). Executive planning deficits constitute a candidate endophenotype for OCD. It is not known whether this endophenotype is responsive to acute serotonin manipulation. The study aimed to investigate the effects of acute SSRI administration on executive function in patients with OCD, first-degree relatives of patients with OCD, and healthy controls. A randomized double-blind cross-over study assessed the effects of single-dose escitalopram (20 mg) and placebo on executive planning in 24 patients with OCD, 13 clinically unaffected first-degree relatives of patients with OCD, and 28 healthy controls. Performance on a Tower of London task measuring executive planning was assessed 4 h after oral administration of the pharmacological challenge/placebo and compared across and within groups using a mixed model analysis of variance. On the outcome measure of interest, i.e., the mean number of choices to obtain the correct solution, there was a marginally significant effect of group (F(2, 59) = 3.1; p = 0.052), with patients (least square (LS) mean 1.43; standard error [SE] 0.06; 95% confidence interval (CI), 1.31–1.55) and their relatives (LS mean 1.46; SE 0.08; 95% CI, 1.30–1.62) performing worse than matched healthy controls (LS mean 1.26; SE 0.05; 95% CI, 1.15–1.37) on placebo. There was a trend towards a significant group × treatment interaction (F(2, 58) = 2.8, p = 0.069), with post hoc tests showing (i) patients (p = 0.009; LS mean difference 0.23; SE 0.08) and relatives (p = 0.03; LS mean difference 0.22; SE 0.10) were more impaired compared to controls and (ii) escitalopram was associated with improved executive planning in patients with OCD (p = 0.013; LS mean difference 0.1; SE 0.04), but not other groups (both p > 0.1; controls: LS mean difference − 0.03; SE 0.04; relatives: LS mean difference 0.02; SE 0.05). Our findings are consistent with a view that there is impaired executive planning in OCD and that this constitutes a behavioural endophenotype. In patients with OCD, but not in relatives, acute SSRI administration ameliorated this deficit. Further investigation is needed to understand common and differential involvement of neurochemical systems in patients with OCD and their relatives.

Inflammatory markers like C-reactive protein (CRP) have been associated with post-traumatic stress disorder (PTSD) and traumatic experiences, but the underlying mechanisms are unclear. We investigated the relationship among serum CRP, PTSD, and traits related to traumatic events and social support using genetic association data from the Psychiatric Genomics Consortium (23,185 PTSD cases and 151,309 controls), the UK Biobank (UKB; up to 117,900 individuals), and the CHARGE study (Cohorts for Heart and Aging Research in Genomic Epidemiology, 148,164 individual). Linkage disequilibrium score regression, polygenic risk scoring, and two-sample Mendelian randomization (MR) analyses were used to investigate genetic overlap and causal relationships. Genetic correlations of CRP were observed with PTSD (rg = 0.16, p = 0.026) and traits related to traumatic events, and the presence of social support (−0.28

Diversion of antiretroviral therapy (ART) for recreational use is concerning for countries with high HIV prevalence. This paper presents reports of recreational use of ART among adolescents from two HIV prevention studies in South Africa: (1) a cross-sectional survey of N = 200 adolescents and (2) a qualitative study of pre-exposure prophylaxis with N = 57 adolescents and N = 25 clinicians. Among adolescents, 3% used and 14% knew someone who used non-prescribed ART for recreational purposes. Administration included smoking (71%), snorting (15%), injecting (15%), ingesting (15%), and inserting (3%). Participants predicted increased crime as recreational use of ART increased. Future studies should investigate prevalence, composition, and diversion of ART from HIV prevention and treatment.

Dysregulated expression of neuro-immune markers has previously been linked to HIV-associated neurocognitive impairment. We undertook an exploratory approach in a HIV clade-C cohort, investigating the association between eight immune markers and neurocognitive performance in 99 HIV+ and 51 HIV- participants. Markers were selected on preliminary and putative evidence of their link to key neuro-immune functions. Cognitive performance was established using a battery of tests sensitive to HIV-associated neurocognitive impairment, with domain-based scores utilized in analysis. The markers Thymidine phosphorylase (TYMP) and Neutrophil gelatinase-associated lipocalin (NGAL) were significantly higher while Matrix Metalloproteinase (MMP)9 was significantly lower in HIV+ participants. Our results further showed that in the HIV+ group, worse psychomotor processing speed was associated with higher TYMP and NGAL levels and worse motor function was associated with higher NGAL levels. Future studies should explore the underlying mechanisms of these markers in HIV-associated neurocognitive impairment. Graphical Abstract The association of peripheral immune markers with neurocognitive performance in South African HIV-positive patients.

Trichotillomania (TTM) is a disorder characterized by repetitive hair-pulling resulting in hair loss. Key processes affected in TTM comprise affective, cognitive, and motor functions. Emerging evidence suggests that brain matter aberrations in fronto-striatal and fronto-limbic brain networks and the cerebellum may characterize the pathophysiology of TTM. The aim of the present voxel-based morphometry (VBM) study was to evaluate whole brain grey and white matter volume alteration in TTM and its correlation with hair-pulling severity. High-resolution magnetic resonance imaging (3 T) data were acquired from 29 TTM patients and 28 age-matched healthy controls (CTRLs). All TTM participants completed the Massachusetts General Hospital Hair-Pulling Scale (MGH-HPS) to assess illness/pulling severity. Using whole-brain VBM, between-group differences in regional brain volumes were measured. Additionally, within the TTM group, the relationship between MGH-HPS scores, illness duration and brain volumes were examined. All data were corrected for multiple comparisons using family-wise error (FWE) correction at p

The year 2018 was marked by the official recognition of Gaming Disorder (GD) as a mental condition with its inclusion in the proposed eleventh edition of the International Classification of Diseases (ICD-11). Recently, a group of scholars has repeatedly criticized the notion of GD proposed by the World Health Organization (WHO), arguing that its inclusion in ICD-11 would pathologize highly involved but healthy gamers. It is therefore of crucial importance to clarify the characteristics of high involvement versus pathological involvement in video games, the boundaries between these constructs, and the implementation of screening and diagnostic GD tools that distinguish the two. Increasing evidence supports the view that intense video game playing may involve patterns of gaming that are characterized by high involvement but that are non-pathological. Furthermore, some criteria for addictive and related disorders may reflect peripheral features that are not necessarily indicative of pathology, whereas others may reflect core features that are more likely to adequately identify pathological behavior and so have diagnostic validity. Finally, it is key to assess functional impairment associated with gaming, so that a GD diagnosis has clinical utility. Available evidence supports the crucial need to distinguish between high and pathological involvement in video games, in order to avoid overdiagnosis and pathologization of normal behavior. The definition of GD adopted in ICD-11 has clinical utility and diagnostic validity since it explicitly mentions the functional impairment caused by problem gaming and its diagnostic guidelines refer to core addiction features, reflecting pathological involvement.

Rapid maturation of major white matter pathways occurs in the first 2 years of life, indicating a critical neuronal developmental period. The impact of initiating antiretroviral therapy (ART) in children perinatally infected with HIV-1, after the age of 2 years on neurocognitive functioning and white matter development in adolescence has not been studied. Forty-six adolescents who initiated ART during the first 2 years of life ( 2 years) and 79 adolescents who initiated ART after 2 years of age ( 2 years), with perinatally acquired HIV were enrolled in the Cape Town Adolescent Antiretroviral Cohort. Adolescents completed a comprehensive neurocognitive battery testing a number of cognitive domains. Diffusion tensor imaging (DTI) was done to determine fractional anisotropy (FA), mean diffusivity (MD), axial diffusion (AD), and radial diffusion (RD) in a region of interest analysis. Neurocognitive performance was similar between adolescents who initiated ART 2 years or 2 years. There was a trend towards attention (p = .07) and working memory (p = .05) being poorer in the group who initiated ART 2 years. FA was lower in the 2-year group in the superior corona radiata (p = .03), and the external capsule (p = .04). MD was higher in the 2-year group in the cerebral peduncle (p = .02), the superior corona radiata (p = .01), and the superior fronto-occipital fasciculus (p = .03). RD was higher in the 2-year group in the superior corona radiata (p = .02), the cerebral peduncle (p = .01), and the superior fronto-occipital fasciculus (p = .01). However, the higher AD in the 2-year group in the superior corona radiata was not in the expected direction (p = .01). Initiation of ART after the neuronal development period of the second postnatal year is associated with white matter alterations on neuroimaging.

BackgroundObsessive-compulsive disorder (OCD) has a lifetime prevalence of 2–3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results.MethodsWe will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations.DiscussionUsing harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it.

Tobacco-attributable deaths in South Africa have increased since 1990, yet data are scanty from healthcare settings. Internationally, emergency centre (EC) visits are increasingly utilised as opportunities for health risk behaviour screening and intervention, but this is not the case in South Africa. Effective advocacy for these services requires data on the prevalence and correlates of tobacco use among South African EC patients. The study objectives were to investigate tobacco prevalence and associated factors in ECs. Demographics, hospital presentation and substance use data were collected as part of a screening and brief intervention programme for alcohol and drugs in three ECs. We conducted descriptive statistics and utilised logistic regression to examine the associations of demographics, presenting complaint and substance use with moderate–high risk-tobacco use as the dependent variable. Of 12,522 patients screened, 37.0% used tobacco and 35.7% showed moderate–high risk for tobacco-related harms. Factors associated with tobacco-related harms included male gender and moderate–high risk for other substances. Of the patients who met criteria and received an intervention for alcohol or drugs, 65.5% were at moderate–high risk for tobacco-related harms. Given the high prevalence of tobacco use among patients attending ECs, intervening on this platform has the potential to reduce risk for non-communicable disease.

Some lines of evidence have indicated that immune dysregulation could play a role in the pathophysiology of obsessive-compulsive disorder (OCD). However, results have been inconsistent across studies. Thus, a systematic review and meta-analysis of studies measuring immune mediators in participants with OCD compared to healthy controls (HC) was conducted. The PubMed/MEDLINE, PsycINFO, and EMBASE electronic databases were systematically searched from inception through June 21, 2018. Sixteen studies met inclusion criteria comprising data from 1001 participants (538 with OCD and 463 were HCs). Levels of TNF-α, IL-6, IL-1β, IL-4, IL-10, and interferon-γ did not significantly differ between participants with OCD and healthy controls. In addition, the ex vivo production of TNF-α and IL-6 by isolated macrophages did not significantly differ between participants with OCD and HCs. Nevertheless, included studies have varied in methodological quality with the enrollment of samples that differed regarding medication status, the proper matching of OCD participants and HCs, age groups, and the presence of psychiatric comorbidities. In conclusion, an association between immune dysregulation and OCD remains unproven. Future studies should consider enrolling larger and more homogeneous samples with OCD.

Although depression and anxiety disorders are common comorbid conditions in alcohol dependence, few structural brain imaging studies have compared alcohol-dependent subjects with and without such comorbidity. In the current study, brain scans of 35 alcohol-dependent with and 40 individuals without diagnosis of a comorbid ICD-10 depressive or anxiety disorder receiving detoxification inpatient treatment were evaluated. Thickness and volumes of automatically segmented neuroanatomical structures were measured in FreeSurfer. Furthermore, associations of brain structure with biological markers and clinical severity markers of alcohol dependence were assessed. Despite comparable addiction severity, the non-comorbid group had evidence of higher cytotoxic effects of alcohol use on hepatic and haematological markers, and showed significantly smaller volumes of total cerebral, and cerebellar grey matter. Similarly, they showed unexpected smaller hippocampal and nucleus accumbens volumes, and thinner frontal, temporal and occipital cortices. Smaller brain volumes correlated with increased markers of hepatic and haematological dysfunction, and with longer duration of alcohol dependence in the non-comorbid group. Evidence of higher biomarkers of alcohol use may be indicative of more severe alcohol dependence or higher vulnerability to ethanol toxicity in this group. Furthermore, psychopathology-related drug treatment, which occurred in 53% of the comorbid group over the recent years, or tissue inflammation may have a moderate effect on the grade of cerebral atrophy in alcohol-dependent patients. Longitudinal studies are needed to investigate this issue more fully.

Methylphenidate (MPH) and other stimulants have been shown to enhance physical performance. However, stimulant research has almost exclusively been conducted in young, active persons with a normal BMI, and may not generalize to other groups. The purpose of this study was to determine whether the ergogenic response to MPH could be predicted by individual level characteristics. We investigated whether weekly minutes of moderate-to-vigorous physical activity (MVPA), age, and BMI could predict the ergogenic response to MPH. In a double-blind, cross-over design 29 subjects (14M, 15F, 29.7 ± 9.68 years, BMI: 26.1 ± 6.82, MVPA: 568.8 ± 705.6 min) ingested MPH or placebo before performing a handgrip task. Percent change in mean force between placebo and MPH conditions was used to evaluate the extent of the ergogenic response. Mean force was significantly higher in MPH conditions [6.39% increase, T(25) = 3.09, p = 0.005 118.8 ± 37.96 (± SD) vs. 111.8 ± 34.99 Ns] but variable (coefficient of variation:163%). Using linear regression, we observed that min MVPA (T(25) = −2.15, β = −0.400, p = 0.044) and age [T(25) = −3.29, β = −0.598, p = 0.003] but not BMI [T(25) = 1.67, β = 0.320 p = 0.109] significantly predicted percent change in mean force in MPH conditions. We report that lower levels of physical activity and younger age predict an improved ergogenic response to MPH and that this may be explained by differences in dopaminergic function. This study illustrates that the ergogenic response to MPH is partly dependent on individual differences such as habitual levels of physical activity and age.

Improving AIDS Care after Trauma (ImpACT), a coping intervention for HIV-infected women with sexual abuse histories, was evaluated for feasibility and potential efficacy in a public clinic in Cape Town, South Africa. Sixty-four participants were enrolled prior to starting antiretroviral therapy (ART). After completing baseline assessments, participants were randomly assigned to standard of care (SoC: three adherence counseling sessions) or ImpACT (SoC plus four individual and three group sessions). Participants completed assessments at 3 months (after individual sessions) and 6 months post-baseline. In exploratory analysis of primary outcomes, ImpACT participants, compared to SoC, reported greater reductions in avoidance and arousal symptoms of PTSD and greater increases in ART adherence motivation at 3 months. Clinically significant decreases in overall PTSD symptoms were also demonstrated at 3 months. These effects continued as trends at the 6-month assessment, in addition to increases in social/spiritual coping. In analysis of secondary outcomes, high levels of non-adherence to ART and poor care engagement were evident at 6 months, with no differences between study arms. A trauma-focused, culturally-adapted individual intervention delivered by a non-specialist in the HIV care setting is feasible and acceptable. Preliminary findings suggest ImpACT has potential to reduce PTSD symptoms and increase ART adherence motivation, but a more intensive intervention may be needed to improve and maintain care engagement among this population. Trial Registration: ClinicalTrials.gov NCT02223390.

We assessed the sensitivity and specificity of the Self-Reporting Questionnaire (SRQ-20) and the Edinburgh Postnatal Depression Scale (EPDS), against the major depression module of the Mini International Neuropsychiatric Interview (MINI). Data were utilised from antenatal (n = 296) and postnatal participants (n = 366) in the Drakenstein Child Health Study (DCHS), a multidisciplinary birth cohort investigating the determinants of child health. Mothers were interviewed using the SRQ-20, the EPDS and the MINI. Receiver operating characteristic (ROC) curve analysis was performed in order to establish optimal cut-off scores. Current major depressive episode was diagnosed in 5% of antenatal and 4% of postnatal participants. At widely used threshold scores, the sensitivity of the tools ranged from 50 to 67%, although the positive predictive values at these scores were much lower (14–25%). Both tools perform acceptably in identifying mothers at risk for major depression perinatally. In identifying appropriate cut-off scores, optimising specificity and maintaining at least 30% sensitivity seems to be a feasible approach given the resourcing of South African mental health services.

In substance use and psychotic disorders, socially problematic behaviours, such as high aggression may, in part, be explained by deficits in social cognition skills, like the detection of emotions or intentions in others. The aim of this study was to assess the magnitude of social cognition impairment and its association with aggression in individuals with methamphetamine (MA) dependence, methamphetamine-associated psychosis (MAP), and healthy controls (CTRL). A total of 20 MAP participants, 21 MA-dependent participants without psychosis, and 21 CTRL participants performed a facial morphing emotion recognition task (ERT) across four basic emotions (anger, fear, happiness and sadness) and the reading the mind in the eyes task (RMET), and completed the aggression questionnaire. Both MA-dependent groups showed impairment in social cognition in terms of lower RMET scores relative to CTRL participants (MA; p = .047; MAP: p

Obsessive-compulsive disorder (OCD) is a prevalent and debilitating condition, characterized by intrusive thoughts and repetitive behavior. Animal models of OCD arguably have the potential to contribute to our understanding of the condition. Deer mice (Permomyscus maniculatus bairdii) are characterized by stereotypic behavior which is reminiscent of OCD symptomology, and which may serve as a naturalistic animal model of this disorder. Moreover, a range of deer mouse repetitive behaviors may be representative of different compulsive-like phenotypes. This paper will review work on deer mouse behavior, and evaluate the extent to which this serves as a valid and useful model of OCD. We argue that findings over the past decade indicate that the deer mouse model has face, construct and predictive validity.

While there is mounting evidence of abnormal reactivity of several brain regions in social anxiety disorder, and disrupted functional connectivity between these regions at rest, relatively little is known regarding resting regional neural activity in these structures, or how such activity is affected by pharmacotherapy. Using 2-deoxy-2-(F-18)fluoro-D-glucose positron emission tomography, we compared resting regional brain metabolism between SAD and healthy control groups; and in SAD participants before and after moclobemide therapy. Voxel-based analyses were confined to a predefined search volume. A second, exploratory whole-brain analysis was conducted using a more liberal statistical threshold. Fifteen SAD participants and fifteen matched controls were included in the group comparison. A subgroup of SAD participants (n = 11) was included in the therapy effect comparison. No significant clusters were identified in the primary analysis. In the exploratory analysis, the SAD group exhibited increased metabolism in left fusiform gyrus and right temporal pole. After therapy, SAD participants exhibited reductions in regional metabolism in a medial dorsal prefrontal region and increases in right caudate, right insula and left postcentral gyrus. This study adds to the limited existing work on resting regional brain activity in SAD and the effects of therapy. The negative results of our primary analysis suggest that resting regional activity differences in the disorder, and moclobemide effects on regional metabolism, if present, are small. While the outcomes of our secondary analysis should be interpreted with caution, they may contribute to formulating future hypotheses or in pooled analyses.

Purpose of review The management of treatment-resistant posttraumatic stress disorder (TRPTSD) is a complex clinical challenge, and many patients may continue to endure a heavy symptom burden, even despite the best available treatments. We review the recent literature to provide an update on the evidence base and offer guidance to clinicians on available approaches, including a number of novel and emerging options. Recent findings If adequate trials of treatment with first-line antidepressants (SSRIs or venlafaxine) or trauma-focused psychotherapy have failed, dosage increase, switching to an alternative first-line option, or combining medication and psychotherapy are reasonable initial approaches. If these remain insufficient, augmentation strategies should be offered, including addition of second-generation antipsychotics (such as risperidone) or the adrenergic antagonist prazosin (especially if sleep disturbance or nightmares are problematic). Further options include the use of other antidepressants (most notably mirtazapine, duloxetine, and trazodone), and the anticonvulsants topiramate or lamotrigine, though the evidence for these is relatively weak. Having tried all these possibilities, the clinician may wish to suggest complementary approaches such as yoga, mindfulness meditation, or acupuncture for symptom reduction and overall well-being. Emerging alternatives, if available, could also be considered, such as augmentation of exposure therapy with d-cycloserine or MDMA, or the use of device-based brain stimulation (such as transcranial magnetic stimulation), though the evidence for these is still preliminary. Summary Comprehensive assessment of TRPTSD, including a thorough evaluation of associated comorbidity, should inform individualized care, incorporating a process of shared decision-making. Despite the complex clinical challenge of TRPTSD, clinicians should remain hopeful however, that translational neuroscience and clinical trials of emerging approaches will allow progressively better treatment alternatives to be established.

Maternal separation (MS) is a well-established rodent model of depression. Chronic constant light (CCL) treatment during adolescence has been shown to reverse the depression-like behaviour induced by MS. We aimed to further delineate the antidepressant effect of light by investigating the involvement of the dopaminergic, serotonergic and orexinergic systems. MS was used to induce changes in adult male Sprague-Dawley rats, some of whom were also treated with CCL for 3 weeks during adolescence. At P80, rats were decapitated and brain tissue collected for analysis of glutamate- and potassium-stimulated dopamine release in the nucleus accumbens (NAc) using an in vitro superfusion technique. Enzyme-linked immunosorbent assays were employed to measure 5-hydroxytryptamine (5-HT) levels in the hypothalamus and prefrontal cortex (PFC). Western blotting was used to measure orexin receptor 1 (OXR-1) and 2 (OXR-2) in the PFC. MS did not affect 5-HT levels in these rats. However, CCL increased hypothalamic 5-HT and reduced 5-HT levels in the PFC. CCL had opposite effects on OXR levels in the PFC of maternally separated and non-separated rats. MS increased OXR-1 and OXR-2 levels in the PFC, an effect that was normalized by CCL treatment. MS reduced glutamate-stimulated dopamine release in the NAc, an effect that was not reversed by CCL. The present results suggest that CCL treatment affects 5-HT and orexinergic systems in the MS model while not affecting the MS-induced decrease in dopamine release in the NAc. The reversal of changes in the orexinergic system may be of particular relevance to the antidepressant effect of CCL in depression.

Trichotillomania is a prevalent but often hidden psychiatric condition, characterized by repetitive hair pulling. The aim of this study was to confirm or refute structural brain abnormalities in trichotillomania by pooling all available global data. De-identified MRI scans were pooled by contacting authors of previous studies. Cortical thickness and sub-cortical volumes were compared between patients and controls. Patients (n = 76) and controls (n = 41) were well-matched in terms of demographic characteristics. Trichotillomania patients showed excess cortical thickness in a cluster maximal at right inferior frontal gyrus, unrelated to symptom severity. No significant sub-cortical volume differences were detected in the regions of interest. Morphometric changes in the right inferior frontal gyrus appear to play a central role in the pathophysiology of trichotillomania, and to be trait in nature. The findings are distinct from other impulsive-compulsive disorders (OCD, ADHD, gambling disorder), which have typically been associated with reduced, rather than increased, cortical thickness. Future work should examine sub-cortical and cerebellar morphology using analytic approaches designed for this purpose, and should also characterize grey matter densities/volumes.

Contains fulltext : 191289.pdf (Publisher’s version ) (Open Access) Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 x 10(-21)), left fusiform gyrus (d=-0.288; P=8.25 x 10(-21)) and left rostral middle frontal cortex (d=-0.276; P=2.99 x 10(-19)). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

To determine if mavoglurant (modified release) as an augmentation therapy to selective serotonin reuptake inhibitors (SSRIs) could have beneficial effects reducing Yale–Brown Obsessive Compulsive Scale (Y-BOCS) total score in patients with obsessive–compulsive disorder (OCD) resistant to SSRI treatment. This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2 study. Patients remained on their SSRI treatment and mavoglurant or placebo was added on. Non-smoking men and women aged 18–65 years primarily diagnosed with OCD according to Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR) criteria were randomized (1:1) to mavoglurant or placebo groups. After 50 patients were randomized, an interim analysis was conducted to determine whether the study should be continued. The primary outcome measure was absolute change in Y-BOCS from baseline at week 17. Safety was assessed by recording adverse events (AEs) and serious adverse events (SAEs). Interim analysis led to a decision to terminate the study. In total 38 (76.0%) participants completed 17 weeks of treatment and 37 (74.0%) completed the study. There was no significant difference in least squares (LS) mean change from baseline at week 17 in Y-BOCS total score for mavoglurant compared with placebo groups [−6.9 (1.75) vs. −8.0 (1.78), respectively; LS mean difference 1.1; 95% CI −3.9, 6.2; p = 0.671]. The incidence of AEs was higher in the mavoglurant compared with the placebo group (80.8% vs. 70.8%, respectively). This study of mavoglurant in OCD was terminated because of the lack of efficacy at interim analysis. The study did not support the use of an antagonist of mGluR5 receptors for OCD treatment. The study was registered with ClinicalTrials.gov: NCT01813019. This study was sponsored by Novartis Pharma AG, Basel, Switzerland.

Evidence suggests that women who suffer from intimate partner violence (IPV) and posttraumatic stress disorder (PTSD) have structural and functional alterations in specific brain regions. Yet, little is known about how brain connectivity may be altered in individuals with IPV, but without PTSD. Women exposed to IPV (n = 18) and healthy controls (n = 18) underwent structural brain imaging using a Siemens 3T MRI. Global and regional brain network connectivity measures were determined, using graph theory analyses. Structural covariance networks were created using volumetric and cortical thickness data after controlling for intracranial volume, age and alcohol use. Nonparametric permutation tests were used to investigate group differences. Findings revealed altered connectivity on a global and regional level in the IPV group of regions involved in cognitive-emotional control, with principal involvement of the caudal anterior cingulate, the middle temporal gyrus, left amygdala and ventral diencephalon that includes the thalamus. To our knowledge, this is the first evidence showing different brain network connectivity in global and regional networks in women exposed to IPV, and without PTSD. Altered cognitive-emotional control in IPV may underlie adaptive neural mechanisms in environments characterized by potentially dangerous cues.

The concept of ‘addiction’ has long been used with reference to substance use disorders. There has, however, been growing interest in applying the term to other conditions, i.e. behavioural addictions, which are characterized by preoccupation with and decreased control over a range of behaviours other than substance intake that are rewarding but have adverse consequences. The best studied behavioural addiction, gambling disorder, is now included in DSM-5 under the rubric of substance-related and addictive disorders. In contrast, an ICD-11 proposal argues that pathological gambling continues to be classified as an impulse control disorder. Other putative behavioural addictions, such as compulsive sexual behaviour and internet gaming addiction, are equally controversial. Here, we review some of the relevant debates. We argue that while the construct of behavioural addiction may be useful in clinical practice and in research contexts, further work is needed to assess the extent of its diagnostic validity and clinical utility.

Glutamatergic neurotransmission has been shown to be dysregulated in bipolar disorder (BD), alcohol use disorder (AUD) and substance use disorder (SUD). Similarly, disruption in the hypothalamic-pituitary-adrenal (HPA)-axis has also been observed in these conditions. BD is often comorbid with AUD and SUD. The effects of the glutamatergic and HPA systems have not been extensively examined in individuals with BD-AUD and BD-SUD comorbidity. The aim of this investigation was to determine whether variants in the glutamatergic pathway and HPA-axis are associated with BD-AUD and BD-SUD comorbidity. The research cohort consisted of 498 individuals with BD type I from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). A subset of the cohort had comorbid current AUD and current SUD. A total of 1935 SNPs from both the glutamatergic and HPA pathways were selected from the STEP-BD genome-wide dataset. To identify population stratification, IBS clustering was performed using the program Plink 1.07. Single SNP association and gene-based association testing were conducted using logistic regression. A pathway analysis of glutamatergic and HPA genes was performed, after imputation using IMPUTE2. No single SNP was associated with BD-AUD or BD-SUD comorbidity after correction for multiple testing. However, from the gene-based analysis, the gene PRKCI was significantly associated with BD-AUD. The pathway analysis provided overall negative findings, although several genes including GRIN2B showed high percentage of associated SNPs for BD-AUD. Even though the glutamatergic and HPA pathways may not be involved in BD-AUD and BD-SUD comorbidity, PRKCI deserves further investigation in BD-AUD.

Anxiety symptoms can occur in up to 65 % of patients with schizophrenia, and may reach the threshold for diagnosis of various comorbid anxiety disorders, including obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). We review the clinical presentation, diagnosis, neurobiology, and management of anxiety in patients with schizophrenia, with a particular focus on pharmacotherapy. The prevalence of any anxiety disorder (at syndrome level) in schizophrenia is estimated to be up to 38 %, with social anxiety disorder (SAD) being the most prevalent. Severity of positive symptoms may correlate with severity of anxiety symptoms, but anxiety can occur independently of psychotic symptoms. While anxiety may be associated with greater levels of insight, it is also associated with increased depression, suicidality, medical service utilization, and cognitive impairment. Patients with anxiety symptoms are more likely to have other internalizing symptoms as opposed to externalizing symptoms. Diagnosis of anxiety in schizophrenia may be challenging, with positive symptoms obscuring anxiety, lower levels of emotional expressivity and communication impeding diagnosis, and conflation with akathisia. Higher diagnostic yield may be achieved by assessment following the resolution of the acute phase of psychosis as well as by the use of screening questions and disorder-specific self-report instruments. In schizophrenia patients with anxiety, there is evidence of underactive fear circuitry during anxiety-provoking stimuli but increased autonomic responsivity and increased responsiveness to neutral stimuli. Recent findings implicate the serotonin transporter (SERT) genes, brain-derived neurotropic factor (BDNF) genes, and the serotonin 1a (5HT1a) receptor, but are preliminary and in need of replication. There are few randomized controlled trials (RCTs) of psychotherapy for anxiety symptoms or disorders in schizophrenia. For pharmacotherapy, data from a few randomized and open trials have shown that aripiprazole and risperidone may be efficacious for obsessive-compulsive and social anxiety symptoms, and quetiapine and olanzapine for generalized anxiety. Older agents such as trifluoperazine may also reduce comorbid anxiety symptoms. Alternative options include selective serotonin re-uptake inhibitor (SSRI) augmentation of antipsychotics, although evidence is based on a few randomized trials, small open trials, and case series, and caution is needed with regards to cytochrome P450 interactions and QTc interval prolongation. Buspirone and pregabalin augmentation may also be considered. Diagnosis and treatment of anxiety symptoms and disorders in schizophrenia is an important and often neglected aspect of the management of schizophrenia.

Many stress-related psychiatric disorders are more common in women than in men. We aimed to determine how female rats respond to maternal separation (MS; removal of the dam from the litter for 3 h/day from postnatal day (P) 2-14)). A subset of MS females were also exposed to chronic constant light for 3 weeks during adolescence (P42-63) to investigate whether the antidepressant effect of light treatment, previously observed in male rats, could be seen in female rats. Ultrasonic vocalizations (22 kHz) were recorded and the forced swim test was conducted immediately after light exposure (P65-67) and 33 days later (P98-99) to determine depressive-like behaviour. Key proteins in the MAPK signal transduction pathway (MKP-1, phospho-ERK, total ERK) and a synaptosomal marker (synaptophysin) were measured in the ventral hippocampus. We found that MS decreased the duration of 22 kHz vocalizations at P65 which was reversed by subsequent light. Light exposure increased time spent in the inner zone of the open field and the number of 22 kHz calls in response to novelty at P98. MS decreased the time females spent immobile and increased time actively swimming in the forced swim test at P67 but not at P99. MKP-1 and synaptophysin levels remained unchanged while MS decreased phospho-ERK levels in the ventral hippocampus. In contrast to clinical findings, the results suggest that female rats may be resistant to MS-induced depression-like behaviour. The behavioural effects of MS and light treatment in female rats may involve the MAPK/ERK signal transduction pathway.

Common mental disorders are highly prevalent in emergency centre (EC) patients, yet few brief screening tools have been validated for low- and middle-income country (LMIC) ECs. This study explored the psychometric properties of the SRQ-20 screening tool in South African ECs using the Mini Neuropsychiatric Interview (MINI) as the gold standard comparison tool. Patients (n=200) from two ECs in Cape Town, South Africa were interviewed using the SRQ-20 and the MINI. Internal consistency, screening properties and factorial validity were examined. The SRQ-20 was effective in identifying participants with major depression, anxiety disorders or suicidality and displayed good internal consistency. The optimal cutoff scores were 4/5 and 6/7 for men and women respectively. The factor structure differed by gender. The SRQ-20 is a useful tool for EC settings in South Africa and holds promise for task-shifted approaches to decreasing the LMIC burden of mental disorders.

The high burden of witnessing traumatic events has been demonstrated in previous research in South Africa. However, previous work has focused on PTSD rather than a broader range of psychopathological outcomes. This study examined the association between witnessing trauma and multiple outcomes including mood, anxiety, and substance use disorders.Regression models measured the odds of mood, anxiety, and substance use disorders among those who reported witnessing in the South African Stress and Health Study. Discrete-time survival analysis was used to examine whether witnessing was associated with earlier onset of mental disorders.Witnessing trauma was more commonly reported among males and those with low-average education. Posttraumatic stress disorder, mood, and anxiety disorders varied significantly with witnessing status, and witnessing was associated with exposure to a higher number of traumatic events compared to other types of traumatic events. Respondents reporting witnessing trauma had elevated odds of mood and anxiety disorders, but not substance use disorders.Witnessing trauma is common in the South African population and results in increased risk of mood and anxiety disorders. Interventions aimed at reducing the burden of trauma and its outcomes must now increase their focus on bystanders and other observers, rather than just focusing on those directly affected.

A range of factors contributes to white matter damage in vertically infected HIV-positive children. These may include combination antiretroviral treatment (cART) regimen, sociodemographic factors, nutritional-hematological status, HIV-relevant clinical variables, and cognitive functioning. We explored associations between a number of these factors and diffusion tensor imaging (DTI) measures in 50 cART-treated children aged 6 to 15 years. Fractional anisotropy (FA), mean diffusion (MD), radial diffusion (RD), and axial diffusion (AD) were derived from 48 cerebral white matter regions. Significant associations between a number of the clinical variables and white matter integrity were found. Decreased FA, a measure of neuronal damage, was associated with being on second-line cART, low hemoglobin, and younger age. Children with increased MD, a measure of neuronal damage, were younger, had reduced albumin and hemoglobin, and increased viral load. Decreased AD, a measure of axonal damage, was associated with increased viral load and total protein, decreased albumin and hemoglobin, younger age, poorer fronto-striatal cognition, and being on second-line cART. Increased RD, a measure of myelin loss, was associated with younger age, low current CD4 count, low albumin and hemoglobin, and higher viral load and total protein. The current findings underline the possible association of first-line treatment failure with white matter brain dysfunction in pediatric neuroHIV and the importance of examining the effects of HIV disease in the context of treatable clinical variables such as anemia and nutritional status.

Antenatal mental disorders compromise maternal and child health, and women who have experienced childhood trauma may be at increased risk for such disorders. One hypothesis is that early trauma leads to the development and use of maladaptive coping strategies as an adult, which in turn could predict mental health difficulties during stressful transitions such as pregnancy. To test this hypothesis, this study examined the relationship between childhood trauma and mental health (depression, PTSD) in a sample of 84 pregnant women seeking antenatal care in Cape Town, South Africa, and explored whether maladaptive coping mediated this relationship. The majority of women (62 %) met established criteria for antenatal depression and 30 % for antenatal PTSD; in addition, 40 % reported a history of childhood trauma. Childhood trauma, especially childhood sexual abuse and emotional abuse, was significantly associated with depression and PTSD. The relationships between childhood trauma and depression and PTSD were significantly mediated by maladaptive coping, even when adjusted for the woman's age, gestational age, and HIV status. Findings highlight the need for coping-based interventions to prevent and treat antenatal mental disorders among women with childhood trauma, particularly in high-trauma settings such as South Africa.

Pathological gambling is a prevalent and disabling mental illness, which is frequently associated with mood, anxiety, and substance use disorders. However, there is relatively little data on comorbidity in individuals with pathological gambling from low and middle income countries such as South-Africa. The Mini-International Neuropsychiatric Interview was used to assess the frequency of DSM-IV-TR disorders among 100 male and 100 female treatment-seeking individuals with pathological gambling in South-Africa. The Sheehan Disability Scale was used to assess functional impairment. In a South-African sample of individuals with pathological gambling, the most frequent current comorbid psychiatric disorders were major depressive disorder (28 %), anxiety disorders (25.5 %) and substance use disorders (10.5 %). Almost half of the individuals had a lifetime diagnosis of major depressive disorder (46 %). Female pathological gamblers were significantly more likely to be diagnosed with a comorbid major depressive disorder or generalised anxiety disorder than their male counterparts. Data from South-Africa are consistent with previously published data from high income countries. Psychiatric comorbidity is common among individuals with pathological gambling.

South Africa has a high lifetime prevalence of substance use disorders, estimated at 13.3% of the general population. Despite this high prevalence, treatment rates remain relatively low compared to need. A key reason for low treatment rates is the lack of expertise among professionals for the detection and treatment of substance use disorders and the limited size of the addiction care workforce. Workforce development is thus essential for the implementation of a comprehensive strategy to reduce substance-related harm within South Africa. In response to this need, the University of Cape Town has introduced a Postgraduate Diploma in Addictions Care and a Master of Philosophy in Addictions Mental Health. These postgraduate courses have been designed to equip health and social welfare professionals with the necessary skills to provide evidence-based early intervention, treatment and aftercare services for children, adolescents, adults and families affected by substance use disorders. This paper provides an overview of both programmes and reflects on lessons learnt from the inaugural group of students enrolled for the Postgraduate Diploma in Addictions Care and from the cohort of professionals who completed the Master of Philosophy in Addictions Mental Health since its inception.