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ABSTRACT The notion of uncommandability has been central to how we perceive our emotional lives, and particularly romantic love. According to this notion, while we can control how we treat people, we have little control over how we feel about them. The argument from uncommandability is often evoked as a way of sidestepping moral obligations regarding our romantic emotions. One challenge to uncommandability is the potential to manipulate our emotions through psychopharmaceuticals. Much of the debate on so‐called ‘love drugs’ has concerned the permissibility and worth of these interventions. By comparison, there has been less exploration of their implications for moral obligation and responsibility. How might the emergence of these interventions change what can be emotionally demanded of us? We ultimately suggest that it is necessary to view the complex morality of our emotional lives through different evaluative paradigms: one concerning moral duty and obligation, where we have no claim to each other's romantic love irrespective of its commandability, and the other concerning the appropriateness of our reactive attitudes, where we are at times justified in feeling morally injured by another person on account of their failure to love us, regardless of whether they had control in the matter. [ABSTRACT FROM AUTHOR]

Objectives: We describe the harmonized MRI acquisition and quality assessment of an ongoing global OCD study, with the aim to translate representative, well‐powered neuroimaging findings in neuropsychiatric research to worldwide populations. Methods: We report on T1‐weighted structural MRI, resting‐state functional MRI, and multi‐shell diffusion‐weighted imaging of 140 healthy participants (28 per site), two traveling controls, and regular phantom scans. Results: Human image quality measures (IQMs) and outcome measures showed smaller within‐site variation than between‐site variation. Outcome measures were less variable than IQMs, especially for the traveling controls. Phantom IQMs were stable regarding geometry, SNR, and mean diffusivity, while fMRI fluctuation was more variable between sites. Conclusions: Variation in IQMs persists, even for an a priori harmonized data acquisition protocol, but after pre‐processing they have less of an impact on the outcome measures. Continuous monitoring IQMs per site is valuable to detect potential artifacts and outliers. The inclusion of both cases and healthy participants at each site remains mandatory. [ABSTRACT FROM AUTHOR]

Background: Neuroimaging studies have emphasized the impact of prenatal alcohol exposure (PAE) on brain development, traditionally in heavily exposed participants. However, less is known about how naturally occurring community patterns of PAE (including light to moderate exposure) affect brain development, particularly in consideration of commonly occurring concurrent impacts of prenatal tobacco exposure (PTE). Methods: Three hundred thirty‐two children (ages 8 to 12) living in South Africa's Cape Flats townships underwent structural magnetic resonance imaging. During pregnancy, their mothers reported alcohol and tobacco use, which was used to evaluate PAE and PTE effects on their children's brain structure. Analyses involved the main effects of PAE and PTE (and their interaction) and the effects of PAE and PTE quantity on cortical thickness, surface area, and volume. Results: After false‐discovery rate (FDR) correction, PAE was associated with thinner left parahippocampal cortices, while PTE was associated with smaller cortical surface area in the bilateral pericalcarine, left lateral orbitofrontal, right posterior cingulate, right rostral anterior cingulate, left caudal middle frontal, and right caudal anterior cingulate gyri. There were no PAE × PTE interactions nor any associations of PAE and PTE exposure on volumetrics that survived FDR correction. Conclusion: PAE was associated with reduction in the structure of the medial temporal lobe, a brain region critical for learning and memory. PTE had stronger and broader associations, including with regions associated with executive function, reward processing, and emotional regulation, potentially reflecting continued postnatal exposure to tobacco (i.e., second‐hand smoke exposure). These differential effects are discussed with respect to reduced PAE quantity in our exposed group versus prior studies within this geographical location, the deep poverty in which participants live, and the consequences of apartheid and racially and economically driven payment practices that contributed to heavy drinking in the region. Longer‐term follow‐up is needed to determine potential environmental and other moderators of the brain findings here and assess the extent to which they endure over time. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to contribute to the paucity of literature on disability in youth with OCD, particularly in low‐ and middle‐income countries (LMICs). Methods: In South Africa (a LMIC), data was collected from 26 children and adolescents with OCD (12 girls, 14 boys; age range 6–18 years), and their parents, on an outpatient basis. Clinical measures aimed at assessing functional impairment due to OCD were administered. Results: Key findings were 1) that children with OCD reported being most significantly affected by their OC symptomatology within the school domain whereas parents placed emphasis on the impairment within the social domain; 2) scores on the Child Obsessive–Compulsive Impact Scale – Revised and the Children's Global Assessment Scale, were consistent, and 3) clinician‐rated symptom severity was positively associated with parental reports on children's impairment due to OCD. Findings show similarities with data from similar studies in a high‐income country (HIC) context. Conclusions: Children with OCD and their parents do not necessarily agree on the ways in which OCD impacts their lives. A comprehensive view of functional impairment in children with OCD, that is, from the viewpoints of the patient, parents, and clinicians, is critical when treatment is planned. Such information may assist with selection of relevant treatment targets, and ultimately improve the quality of life of all affected. [ABSTRACT FROM AUTHOR]

Background: There is a growing literature that demonstrates the effects of prenatal alcohol exposure (PAE) on brain development in school‐aged children. Less is known, however, on how PAE impacts the brain early in life. We investigated the effects of PAE and child sex on subcortical gray matter volume, cortical surface area (CSA), cortical volume (CV), and cortical thickness (CT) in children aged 2 to 3 years. Methods: The sample was recruited as a nested cross‐sectional substudy of the Drakenstein Child Health Study. Images from T1‐weighted magnetic resonance imaging were acquired on 47 alcohol‐exposed and 124 control children (i.e., with no or minimal alcohol exposure), aged 2 to 3 years, some of whom were scanned as neonates. Brain images were processed through automated processing pipelines using FreeSurfer version 6.0. Subcortical and a priori selected cortical regions of interest were compared. Results: Subcortical volume analyses revealed a PAE by child sex interaction for bilateral putamen volumes (Left: p = 0.02; Right: p = 0.01). There was no PAE by child sex interaction effect on CSA, CV, and CT. Analyses revealed an impact of PAE on CSA (p = 0.04) and CV (p = 0.04), but not CT in this age group. Of note, the inferior parietal gyrus CSA was significantly smaller in children with PAE compared to control children. Conclusions: Findings from this subgroup scanned at age 2 to 3 years build on previously described subcortical volume differences in neonates from this cohort. Findings suggest that PAE persistently affects gray matter development through the critical early years of life. The detectable influence of PAE on brain structure at this early age further highlights the importance of brain imaging studies on the impact of PAE on the young developing brain. [ABSTRACT FROM AUTHOR]

Intimate partner violence (IPV) has been linked to poor fetal and infant growth. However, factors underlying this relationship are not well understood, particularly in the postnatal time period. In a South African cohort, we investigated (1) associations between IPV in pregnancy and growth at birth as well as postnatal IPV and child growth at 12 months and (2) whether maternal depression, tobacco or alcohol use or infant hospitalizations mediated IPV‐growth relationships. Mothers were enrolled in pregnancy. Maternal IPV was measured during pregnancy and 10 weeks postpartum; depression, alcohol and tobacco use were measured during pregnancy and at 6 months postpartum. Child weight and length were measured at birth and 12 months and converted to z‐scores for analysis. Linear regression and structural equation models investigated interrelationships between IPV and potential mediators of IPV‐growth relationships. At birth, among 1,111 mother–infant pairs, maternal emotional and physical IPV were associated with reduced weight‐for‐age z‐scores (WFAZ). Only physical IPV was associated with length‐for‐age z‐scores (LFAZ) at birth. Antenatal maternal alcohol and tobacco use mediated IPV‐growth relationships at birth. Postnatally, among 783 mother–infant pairs, emotional and physical IPV were associated with reduced WFAZ at 12 months. Only emotional IPV was associated with LFAZ at 12 months. Maternal tobacco use was a mediator postnatally. Findings highlight the role of physical and emotional IPV as risk factors for compromised fetal and infant growth. Findings underscore the importance of programmes to address interrelated risk factors for compromised infant growth, specifically IPV and substance use, which are prevalent in high‐risk settings. [ABSTRACT FROM AUTHOR]

Introduction: There is a growing population of children who are HIV‐exposed and uninfected (HEU) with the successful expansion of antiretroviral therapy (ART) use in pregnancy. Children who are HEU are at risk of delayed neurodevelopment; however, there is limited research on early brain growth and maturation. We aimed to investigate the effects of in utero exposure to HIV/ART on brain structure of infants who are HEU compared to HIV‐unexposed (HU). Methods: Magnetic resonance imaging using a T2‐weighted sequence was undertaken in a subgroup of infants aged 2–6 weeks enrolled in the Drakenstein Child Health Study birth cohort, South Africa, between 2012 and 2015. Mother–child pairs received antenatal and postnatal HIV testing and ART per local guidelines. We compared subcortical and total grey matter volumes between HEU and HU groups using multivariable linear regression adjusting for infant age, sex, intracranial volume and socio‐economic variables. We further assessed associations between brain volumes with maternal CD4 cell count and ART exposure. Results: One hundred forty‐six infants (40 HEU; 106 HU) with high‐resolution images were included in this analysis (mean age 3 weeks; 50.7% male). All infants who were HEU were exposed to ART (88% maternal triple ART). Infants who were HEU had smaller caudate volumes bilaterally (5.4% reduction, p < 0.05) compared to HU infants. There were no group differences in other subcortical volumes (all p > 0.2). Total grey matter volume was also reduced in infants who were HEU (2.1% reduction, p < 0.05). Exploratory analyses showed that low maternal CD4 cell count (<350 cells/mm3) was associated with decreased infant grey matter volumes. There was no relationship between timing of ART exposure and grey matter volumes. Conclusions: Lower caudate and total grey matter volumes were found in infants who were HEU compared to HU in the first weeks of life, and maternal immunosuppression was associated with reduced volumes. These findings suggest that antenatal HIV exposure may impact early structural brain development and improved antenatal HIV management may have the potential to optimize neurodevelopmental outcomes of children who are HEU. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with brain alterations particularly involving fronto‐cerebellar and meso‐cortico‐limbic circuitry. However, such abnormalities have additionally been reported in other psychiatric conditions, and until recently there has been few large‐scale investigations to compare such findings. The current study uses the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) consortium method of standardising structural brain measures to quantify case–control differences and to compare brain‐correlates of substance use disorders with those published in relation to other psychiatric disorders. Using the ENIGMA protocols, we report effect sizes derived from a meta‐analysis of alcohol (seven studies, N = 798, 54% are cases) and cannabis (seven studies, N = 447, 45% are cases) dependent cases and age‐ and sex‐matched controls. We conduct linear analyses using harmonised methods to process and parcellate brain data identical to those reported in the literature for ENIGMA case–control studies of major depression disorder (MDD), schizophrenia (SCZ) and bipolar disorder so that effect sizes are optimally comparable across disorders. R elationships between substance use disorder diagnosis and subcortical grey matter volumes and cortical thickness were assessed with intracranial volume, age and sex as co‐variates. After correcting for multiple comparisons, AUD case–control meta‐analysis of subcortical regions indicated significant differences in the thalamus, hippocampus, amygdala and accumbens, with effect sizes (0.23) generally equivalent to, or larger than |0.23| those previously reported for other psychiatric disorders (except for the pallidum and putamen). On measures of cortical thickness, AUD was associated with significant differences bilaterally in the fusiform gyrus, inferior temporal gyrus, temporal pole, superior frontal gyrus, and rostral and caudal anterior cingulate gyri. Meta‐analysis of CUD case–control studies indicated reliable reductions in amygdala, accumbens and hippocampus volumes, with the former effect size comparable to, and the latter effect size around half of that reported for alcohol and SCZ. CUD was associated with lower cortical thickness in the frontal regions, particularly the medial orbitofrontal region, but this effect was not significant after correcting for multiple testing. This study allowed for an unbiased cross‐disorder comparison of brain correlates of substance use disorders and showed alcohol‐related brain anomalies equivalent in effect size to that found in SCZ in several subcortical and cortical regions and significantly greater alterations than those found in MDD in several subcortical and cortical regions. Although modest, CUD results overlapped with findings reported for AUD and other psychiatric conditions, but appear to be most robustly related to reduce thickness of the medial orbitofrontal cortex. [ABSTRACT FROM AUTHOR]

Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA‐Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders. [ABSTRACT FROM AUTHOR]

Introduction: The risk factors for a first episode of psychosis in low and middle‐income countries (LMICs) are not well described. The study compared the association of different risk factors in patients with first‐episode psychosis patients and healthy controls from an LMIC context. Methods: A comparative, descriptive, cross‐sectional study was performed in antipsychotic naïve first‐episode psychosis patients and healthy controls at the National referral hospital in Uganda. Standardized tools were used to assess sociodemographic (e.g., age, sex, socioeconomic status) and clinical (e.g., childhood trauma, quality of life) variables. First episode psychosis participants were compared to healthy controls in terms of sociodemographic and clinical variables, and logistic regression was used to determine predictors of FEP. Results: Our final sample included 198 antipsychotic naïve first‐episode psychosis participants and 82 controls. Most participants were female (68.5%) with a mean age of 29.4 years. After adjusting for age and sex, FEP patients when compared to controls were less likely to be female [AOR 0.18 (95%CI 0.03–0.85; p =.031)], more likely to have experienced emotional abuse [AOR 1.30 (95%CI 1.02–1.65; p =.032)] and more likely to have a poor quality of life [AOR 0.93 (95%CI 0.89–0.97; p =.002)]. Discussion: The risk factors for a first episode of psychosis in this low and middle‐income population were like those described in high‐income countries. Further studies on interventions to prevent the transition to psychotic disorders in this sub‐groups of patients are recommended. Also, the use of specialized early intervention services in improving the quality of life needs to be evaluated. [ABSTRACT FROM AUTHOR]

Limited studies have investigated Tat sequence variation from clinical samples (e.g., blood) of PLWH.7,8 Further, it is not clear to what extent Tat protein sequence variation may influence immune markers in PLWH. Preclinical studies have shown that monocyte cultures treated with Tat C31S resulted in lower levels of several inflammatory markers4,5 and were defective for monocyte chemotactic activity5 compared to Tat C30C31. HIV-associated neurocognitive disorder (HAND) is a common feature of the effects of HIV-1 infection in the central nervous system (CNS).1 The neuropathogenesis of HAND is multifactorial and the prevalence is influenced by several factors including the HIV-1 subtype.2 Subtype-specific differences in amino acids sequences are present in the HIV-1 viral proteins including the transcription of transactivation (Tat) protein. [Extracted from the article]

Background and aims: Following the recognition of 'internet gaming disorder' (IGD) as a condition requiring further study by the DSM‐5, 'gaming disorder' (GD) was officially included as a diagnostic entity by the World Health Organization (WHO) in the 11th revision of the International Classification of Diseases (ICD‐11). However, the proposed diagnostic criteria for gaming disorder remain the subject of debate, and there has been no systematic attempt to integrate the views of different groups of experts. To achieve a more systematic agreement on this new disorder, this study employed the Delphi expert consensus method to obtain expert agreement on the diagnostic validity, clinical utility and prognostic value of the DSM‐5 criteria and ICD‐11 clinical guidelines for GD. Methods: A total of 29 international experts with clinical and/or research experience in GD completed three iterative rounds of a Delphi survey. Experts rated proposed criteria in progressive rounds until a pre‐determined level of agreement was achieved. Results: For DSM‐5 IGD criteria, there was an agreement both that a subset had high diagnostic validity, clinical utility and prognostic value and that some (e.g. tolerance, deception) had low diagnostic validity, clinical utility and prognostic value. Crucially, some DSM‐5 criteria (e.g. escapism/mood regulation, tolerance) were regarded as incapable of distinguishing between problematic and non‐problematic gaming. In contrast, ICD‐11 diagnostic guidelines for GD (except for the criterion relating to diminished non‐gaming interests) were judged as presenting high diagnostic validity, clinical utility and prognostic value. Conclusions: This Delphi survey provides a foundation for identifying the most diagnostically valid and clinically useful criteria for GD. There was expert agreement that some DSM‐5 criteria were not clinically relevant and may pathologize non‐problematic patterns of gaming, whereas ICD‐11 diagnostic guidelines are likely to diagnose GD adequately and avoid pathologizing. [ABSTRACT FROM AUTHOR]

Maternal responses to infant facial expressions were examined in two socioeconomically diverse samples of South African mothers (Study I, N = 111; and Study II, N = 214; age: 17–44 years) using pupil and gaze tracking. Study I showed increased pupil response to infant distress expressions in groups recruited from private as compared to public maternity clinics, possibly reflecting underlying differences in socioeconomic status (SES) across the groups. Study II, sampling uniformly low‐SES neighborhoods, found increased pupil dilation and faster orientation to expressions of infant distress, but only in the highest income group. These results are consistent with maternal physiological and attentional sensitivity to infant distress cues but challenge the universality of this sensitivity across socioeconomic diversity. [ABSTRACT FROM AUTHOR]

Psychiatric genetic research investigates the genetic basis of psychiatric disorders with the aim of more effectively understanding, treating, or, ultimately, preventing such disorders. Given the challenges of recruiting research participants into such studies, the potential for long-term benefits of such research, and seemingly minimal risk, a strong claim could be made that all non-acute psychiatric inpatients, including forensic and involuntary patients, should be included in such research, provided they have capacity to consent. There are tensions, however, regarding the ethics of recruiting psychiatric inpatients into such studies. In this paper our intention is to elucidate the source of these tensions from the perspective of research ethics committee interests and decision-making. We begin by defining inpatient status and outline some of the assumptions surrounding the structures of inpatient care. We then introduce contemporary conceptions of vulnerability, including Florencia Luna's account of vulnerability which we use as a framework for our analysis. While psychiatric inpatients could be subject to consent-related vulnerabilities, we suggest that a particular kind of exploitation-related vulnerability comes to the fore in the context of our case study. Moreover, a subset of these ethical concerns takes on particular weight in the context of genetic research in low- and middle-income countries. At the same time, the automatic exclusion of inpatients from research elicits justice-related vulnerabilities. [ABSTRACT FROM AUTHOR]

Brain imaging studies in children with prenatal methamphetamine exposure (PME) suggest structural and functional alterations of striatal, frontal, parietal, and limbic regions. However, no longitudinal studies have investigated changes in structural connectivity during the first 2 years of formal schooling. The aim of this study was to explore the effects of PME on structural connectivity of brain networks in children over the critical first 2 years of formal schooling when foundational learning takes place. Networks are expected to gradually increase in global connectedness while segregating into defined systems. Graph theoretical analysis was used to investigate changes in structural connectivity at age 6 and 8 years in children with and without PME. While healthy control children showed increased connectivity in frontal and limbic hubs over time, children with PME showed increased connectivity in the superior parietal cortex and striatum in their global network. Furthermore, compared to control children, those with PME were characterized by less change in segregation of structural networks over time. These findings are consistent with previous work on regions implicated in children with PME, but they additionally demonstrate alterations in structural connectivity between regions that underlie primary cognitive, behavioral, and emotional development. Understanding patterns of network development during critical periods in at‐risk children may inform strategies for supporting this group of children in these developmental tasks important for lifelong brain health and development. [ABSTRACT FROM AUTHOR]

Introduction and Aims: As South Africa, especially the Western Cape Province, faces an epidemic of methamphetamine use disorder, therapeutic approaches suited to the South African context are needed. This secondary analysis assessed retention and methamphetamine abstinence outcomes in response to an 8-week pilot contingency management (CM) intervention trial of neural correlates of methamphetamine abstinence, exploring sociodemographic and clinical differences between responders and non-responders.Design and Methods: Research participants provided thrice-weekly monitored urine samples, which were analysed by qualitative radioimmunoassay. The primary outcome for this analysis was therapeutic response, defined as abstinence from methamphetamine (≥23 of 24 possible methamphetamine-negative urine samples).Results: Data from 30 adults living in Cape Town, South Africa (34 ± 6.1 years of age, mean age ± SD, 21 men) were included. Sixty-three percent (12 men) were responders. In bivariate comparisons, baseline measurements showed fewer responders reported monthly household income ≥25 000+ South African Rand (ZAR; ~USD $1880; vs. ZAR < 25 000) than non-responders (15.8% vs. 63.6%; P = 0.007). Furthermore, responders had higher median years of education (12 vs. 10; Kruskal-Wallis χ2 = 4.25, DF = 1, P = 0.039) and lower median body mass index than non-responders (19 vs. 24; Kruskal-Wallis χ2 = 6.84, P = 0.008).Discussion and Conclusions: Therapeutic response in this study were comparable to those obtained with CM for methamphetamine use disorder in North America and Europe. Our findings suggest that CM may be a useful component of treatment strategies to boost retention and continuous abstinence from methamphetamine in Cape Town, South Africa. Larger efficacy studies are needed in this setting. [ABSTRACT FROM AUTHOR]

Fundamental human studies which address associations between glutamate and iron metabolism are needed. Basic research reports associations between glutamate and iron metabolism. Human studies report sex differences in iron metabolism and glutamate concentrations, which suggest that these relationships may differ by sex. We hypothesised associations would be apparent between in vivo glutamate and peripheral markers of iron metabolism, and these associations would differ by sex. To test this, we recruited 40 healthy adults (20 men, 20 women) and measured (a) standard clinical biomarker concentrations for iron metabolism and (b) an in vivo proxy for glutamate concentration, glutamate with glutamine in relation to total creatine containing metabolites using proton magnetic resonance spectroscopy studies with a two‐dimensional chemical shift imaging slice, with voxels located in bilateral dorsolateral prefrontal cortices, anterior cingulate cortices and frontal white matter. Only the female group reported significant associations between peripheral markers of iron metabolism and Glx:tCr concentration: (a) right dorsolateral prefrontal cortex Glx:tCr associated positively with serum transferrin (r =.60, p =.006) and negatively with transferrin saturation (r = −.62, p =.004) and (b) right frontal white matter Glx:tCr associated negatively with iron concentration (r = −.59, p =.008) and transferrin saturation (r = −.65, p =.002). Our results support associations between iron metabolism and our proxy for in vivo glutamate concentration (Glx:tCr). These associations were limited to women, suggesting a stronger regulatory control between iron and glutamate metabolism. These associations support additional fundamental research into the molecular mechanisms of this regulatory control. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to characterise international trends in the use of psychotropic medication, psychological therapies, and novel therapies used to treat obsessive–compulsive disorder (OCD). Methods: Researchers in the field of OCD were invited to contribute summary statistics on the characteristics of their samples. Consistency of summary statistics across countries was evaluated. Results: The study surveyed 19 expert centres from 15 countries (Argentina, Australia, Brazil, China, Germany, Greece, India, Italy, Japan, Mexico, Portugal, South Africa, Spain, the United Kingdom, and the United States) providing a total sample of 7,340 participants. Fluoxetine (n = 972; 13.2%) and fluvoxamine (n = 913; 12.4%) were the most commonly used selective serotonin reuptake inhibitor medications. Risperidone (n = 428; 7.3%) and aripiprazole (n = 415; 7.1%) were the most commonly used antipsychotic agents. Neurostimulation techniques such as transcranial magnetic stimulation, deep brain stimulation, gamma knife surgery, and psychosurgery were used in less than 1% of the sample. There was significant variation in the use and accessibility of exposure and response prevention for OCD. Conclusions: The variation between countries in treatments used for OCD needs further evaluation. Exposure and response prevention is not used as frequently as guidelines suggest and appears difficult to access in most countries. Updated treatment guidelines are recommended. [ABSTRACT FROM AUTHOR]

Background: Cohort studies have noted associations between hazardous alcohol use during pregnancy and infant growth outcomes, but many have not controlled for potential psychosocial confounders. To assess the unique contribution of hazardous alcohol use, we examined its effect on infant growth outcomes while controlling for maternal psychosocial stressors and hazardous tobacco and drug use in a cohort of 986 pregnant South African women enrolled into the Drakenstein Child Health Study between 2012 and 2015. Methods: Data on psychosocial stressors and maternal risk behaviors were collected between 28 and 32 weeks of gestation. Participants were categorized as hazardous alcohol users if they obtained moderate or high scores (>10) on the Alcohol, Smoking and Substance Involvement Screening Test at this assessment or retrospectively reported drinking at least 2 drinks weekly during any trimester of pregnancy. Infant growth outcomes were recorded at delivery. Multivariable regression models examined correlates of hazardous alcohol use and associations between hazardous alcohol use and birth outcomes. Results: Overall, 13% of mothers reported hazardous alcohol use. Recent exposure to intimate partner violence (adjusted odds ratio (aOR) = 2.08; 95% confidence interval (CI): 1.37, 3.18) and hazardous tobacco use (aOR = 5.03; 95% CI: 2.97, 8.52) were significant correlates of hazardous alcohol use. After controlling for potential psychosocial confounders, hazardous alcohol use remained associated with lower infant weight‐for‐age (B = −0.35, 95% CI: −0.56, −0.14), height‐for‐age (B = −0.46, 95% CI: −0.76, −0.17), and head‐circumference‐for‐age z‐scores (B = −0.43, 95% CI: −0.69, −0.17). Conclusions: Interventions to reduce hazardous alcohol use among pregnant women in South Africa are needed to prevent alcohol‐related infant growth restrictions. As these growth deficits may lead to neurodevelopmental consequences, it is critical to identify alcohol‐related growth restrictions at birth and link exposed infants to early interventions for neurodevelopment. [ABSTRACT FROM AUTHOR]

Chronic methamphetamine use is associated with executive functioning deficits that suggest dysfunctional cognitive control networks (CCNs) in the brain. Likewise, abnormal connectivity between intrinsic CCNs and default mode networks (DMNs) has also been associated with poor cognitive function in clinical populations. Accordingly, we tested the extent to which methamphetamine use predicts abnormal connectivity between these networks, and whether, as predicted, these abnormalities are compounded in patients with a history of methamphetamine-associated psychosis (MAP). Resting-state fMRI data were acquired from 46 methamphetamine-dependent patients [19 with MAP, 27 without (MD)], as well as 26 healthy controls (CTRL). Multivariate network modelling and whole-brain voxel-wise connectivity analyses were conducted to identify group differences in intrinsic connectivity across four cognitive control and three DMN networks identified using an independent components analysis approach (meta-ICA). The relationship of network connectivity and psychotic symptom severity, as well as antipsychotic treatment and methamphetamine use variables, was also investigated. Robust evidence of hyper-connectivity was observed between the right frontoparietal and anterior DMN networks in MAP patients, and 'normalized' with increased duration of treatment with antipsychotics. Attenuation of anticorrelated anterior DMN-dorsal attention network activity was also restricted to this group. Elevated coupling detected in MD participants between anterior and posterior DMN networks became less apparent with increasing duration of abstinence from methamphetamine. In summary, we observed both alterations of RSN connectivity between DMN networks with chronic methamphetamine exposure, as well as DMN-CCN coupling abnormalities consistent with possible MAP-specific frontoparietal deficits in the biasing of task-appropriate network activity. [ABSTRACT FROM AUTHOR]

Adjustment disorder (AjD) is a frequent but under-researched diagnosis due in part to a lack of specific symptom criteria and adequate tools of measurement. The ICD-11 for the first time proposes a positive symptom catalogue to define AjD. This study presents a validation of the Adjustment Disorder - New Module (ADNM), the first symptom severity measure for AjD according to the ICD-11 concept. Validity and sensitivity to change were investigated in a sample of 190 individuals with a DSM-IV diagnosis of AjD. The ADNM scales demonstrated convergent and discriminant validity for anxiety symptoms (Hamilton Anxiety Scale; psychic anxiety r = 0.18-0.31), functional impairment (Sheehan Disability Scale; r = 0.18-0.47), and depression (Montgomery-Asberg Depression Scale; r = 0.13-0.30). At baseline 78% of the individuals with a DSM-IV diagnosis of AjD were also classified so by the ADNM. Repeated-measures ANOVA indicated significant ADNM-symptom decrease during treatment, replicating the patterns of the Hamilton Anxiety Scale, Sheehan Disability Scale, and Clinical Global Impression Scale. This article presents the first use of the ADNM as a measure for ICD-11 AjD in a randomized-controlled intervention study of AjD. It provides support for the construct validity and sensitivity to symptom change of this scale during pharmacological treatment. [ABSTRACT FROM AUTHOR]

Many psychiatric disorders are characterized by altered social cognition. The importance of social cognition has previously been recognized by the National Institute of Mental Health Research Domain Criteria project, in which it features as a core domain. Social task-based functional magnetic resonance imaging (fMRI) currently offers the most direct insight into how the brain processes social information; however, resting-state fMRI may be just as important in understanding the biology and network nature of social processing. Resting-state fMRI allows researchers to investigate the functional relationships between brain regions in a neutral state: so-called resting functional connectivity (RFC). There is evidence that RFC is predictive of how the brain processes information during social tasks. This is important because it shifts the focus from possibly context-dependent aberrations to context-independent aberrations in functional network architecture. Rather than being analysed in isolation, the study of resting-state brain networks shows promise in linking results of task-based fMRI results, structural connectivity, molecular imaging findings, and performance measures of social cognition-which may prove crucial in furthering our understanding of the social brain. [ABSTRACT FROM AUTHOR]

The Social Problem Solving Inventory-Revised Short-Form (SPSI-R:SF) has been used in several countries to identify problem-solving deficits among clinical and general populations in order to guide cognitive-behavioural interventions. Yet, very few studies have evaluated its psychometric properties. Three language versions of the questionnaire were administered to a general population sample comprising 1000 participants (771 English-, 178 Afrikaans- and 101 Xhosa-speakers). Of these participants, 210 were randomly selected to establish test-retest reliability (70 in each language). Principal component analysis was performed to examine the applicability of the factor structure of the original questionnaire to the South African data. Supplementary psychometric analyses were performed, including internal consistency and test-retest reliability. Collectively, results provide initial evidence of the reliability and validity of the SPSI-R:SF for the assessment of problem solving deficits in South Africa. Further studies that explore how the Afrikaans language version of the SPSI-R:SF can be improved and that establish the predictive validity of scores on the SPSI-R:SF are needed. [ABSTRACT FROM AUTHOR]

Introduction and Aim: Given the high prevalence and detrimental consequences of alcohol or other drug (AOD) use in low- and middle-income countries, a screening tool for early detection in health care, including emergency care, is critical. We set out to validate the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) for the South African context.Design and Methods: We interviewed emergency centre patients (n = 200) in Cape Town for this cross-sectional study conducted from January to March 2013 utilising a questionnaire battery, including the ASSIST and Mini International Neuropsychiatric Interview. Internal consistency (Cronbach's alpha) and screening properties of the ASSIST (receiver operating characteristic analysis) were examined utilising the Mini International Neuropsychiatric Interview AOD use modules as the gold standard.Results: Cronbach's alpha for alcohol and illicit drugs ranged from 0.81 to 0.95 indicating good internal consistency. ASSIST cut-off scores show a good sensitivity and specificity for discrimination particularly when distinguishing between substance use and abuse, rather than dependence. For alcohol, the area under the curve was 0.94 for distinguishing between use and abuse, and this dropped to 0.68 for distinguishing between abuse and dependence, while the statistic remained high for both use/abuse and abuse/dependence for illicit drugs: 0.95 and 0.96.Discussion and Conclusion: AOD abuse was associated with cut-off scores below the World Health Organization recommended levels, in keeping with various international studies suggesting that individuals with lower scores be offered interventions. The ASSIST was found to be useful for South African health care and holds promise for cost-effective task-shifting approaches in lower resourced settings. [van der Westhuizen C, Wyatt G, Williams JK, Stein DJ, Sorsdahl K. Validation of  the  Alcohol, Smoking and Substance Involvement Screening Test in a low- and middle-income country cross-sectional emergency centre study. Drug Alcohol Rev 2016;35:702-709]. [ABSTRACT FROM AUTHOR]

Introduction The utility of blood for genome-wide gene expression profiling and biomarker discovery has received much attention in patients diagnosed with major neuropsychiatric disorders. While numerous studies have been conducted, statistical rigor and clarity in terms of blood-based biomarker discovery, validation, and testing are needed. Methods We conducted a systematic review of the literature to investigate methodological approaches and to assess the value of blood transcriptome profiling in research on mental disorders. We were particularly interested in statistical considerations related to machine learning, gene network analyses, and convergence across different disorders. Results A total of 108 peripheral blood transcriptome studies across 15 disorders were surveyed: 25 studies used a variety of machine learning techniques to assess putative clinical viability of the candidate biomarkers; 11 leveraged a higher-order systems-level perspective to identify gene module-based biomarkers; and nine performed analyses across two or more neuropsychiatric phenotypes. Notably, ~50% of the surveyed studies included fewer than 50 samples (cases and controls), while ~75% included less than 100. Conclusions Detailed consideration of statistical analysis in the early stages of experimental planning is critical to ensure blood-based biomarker discovery and validation. Statistical guidelines are presented to enhance implementation and reproducibility of machine learning and gene network analyses across independent studies. Future studies capitalizing on larger sample sizes and emerging next-generation technologies set the stage for moving the field forwards. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Methamphetamine (MA) use may lead to white matter injury and to a range of behavioral problems and psychiatric disorders, including psychosis. The present study sought to assess white matter microstructural impairment as well as impulsive behavior in MA dependence and MA-associated psychosis (MAP). Methods: Thirty patients with a history of MAP, 39 participants with MA dependence and 40 healthy controls underwent diffusion tensor imaging (DTI). Participants also completed the UPPS-P impulsive behavior questionnaire. We applied tract-based spatial statistics (TBSS) to investigate group differences in mean diffusivity (MD), fractional anisotropy (FA), axial ( λ|) and radial diffusivity ( λ⊥), and their association with impulsivity scores and psychotic symptoms. Results: The MAP group displayed widespread higher MD, λ| and λ⊥ levels compared to both controls and the MA group, and lower FA in extensive white matter areas relative to controls. MD levels correlated positively with negative psychotic symptoms in MAP. No significant DTI group differences were found between the MA group and controls. Both clinical groups showed high levels of impulsivity, and this dysfunction was associated with DTI measures in frontal white matter tracts. Conclusions: MAP patients show distinct patterns of impaired white matter integrity of global nature relative to controls and the MA group. Future work to investigate the precise nature and timing of alterations in MAP is needed. The results are further suggestive of frontal white matter pathology playing a role in impulsivity in MA dependence and MAP. Hum Brain Mapp 37:2055-2067, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Electroconvulsive therapy (ECT) is known to be one of the most effective treatments for managing depression and other severe mental illnesses. Nevertheless, the exact mechanisms underlying response to ECT remain uncertain. This mini-review presents clinical findings regarding the role of genetic factors in the aetiology of the ECT response. Studies on the role of variation in the catechol- O-methyltransferase ( COMT) gene; other dopamine-, serotonin-, and G-protein-related genes; brain-derived neurotrophic factor (BDNF); apolipoprotein E (APOE); angiotensin I-converting enzyme (ACE) and vascular endothelial growth factor (VEGF) genes in mediating response to ECT are summarized. The existing data support the notion that some genetic factors-particularly the functional COMT val158met polymorphism-may play a role in the magnitude of clinical response to ECT, and thus could serve as potential biomarkers for future personalized treatment approaches. However, much of the work to date is preliminary, and large-scale confirmatory studies are still needed. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background Children exposed to alcohol in utero demonstrate reduced white matter microstructural integrity. While early evidence suggests altered functional brain connectivity in the lateralization of motor networks in school-age children with prenatal alcohol exposure ( PAE), the specific effects of alcohol exposure on the establishment of intrinsic connectivity in early infancy have not been explored. Methods Sixty subjects received functional imaging at 2 to 4 weeks of age for 6 to 8 minutes during quiet natural sleep. Thirteen alcohol-exposed ( PAE) and 14 age-matched control ( CTRL) participants with usable data were included in a multivariate model of connectivity between sensorimotor intrinsic functional connectivity networks. Seed-based analyses of group differences in interhemispheric connectivity of intrinsic motor networks were also conducted. The Dubowitz neurological assessment was performed at the imaging visit. Results Alcohol exposure was associated with significant increases in connectivity between somatosensory, motor networks, brainstem/thalamic, and striatal intrinsic networks. Reductions in interhemispheric connectivity of motor and somatosensory networks did not reach significance. Conclusions Although results are preliminary, findings suggest PAE may disrupt the temporal coherence in blood oxygenation utilization in intrinsic networks underlying motor performance in newborn infants. Studies that employ longitudinal designs to investigate the effects of in utero alcohol exposure on the evolving resting-state networks will be key in establishing the distribution and timing of connectivity disturbances already described in older children. [ABSTRACT FROM AUTHOR]

Background: Maternal antenatal depression may be particularly prevalent in low- and middle-income countries, but there is a paucity of data on its effect on birth outcomes in such settings. We investigated risk factors for antenatal depression and the associations between depression and infant birth outcomes in the Drakenstein Child Health Study (DCHS), a birth cohort study in the Western Cape, South Africa.Methods: The prevalence of depression in pregnant women enrolled in the DCHS from primary care antenatal clinics was measured using the Beck Depression Inventory (BDI-II). Predictors of antenatal depression were investigated using logistic regression, and the associations between depression and infant birth outcomes were examined in linear regression models.Results: Among 726 pregnant women (median age: 26 years), 156 (21%) had BDI-II scores suggesting depression. Independent predictors of depression included single marital status, low socioeconomic status (SES), recent stressful life events, unplanned pregnancy, childhood trauma, and past-year intimate partner violence. No association was observed between antenatal depression and preterm birth. Strong associations were observed between antenatal depression and decreased infant weight-for-age (WAZ) and head circumference-for-age (HCAZ) z-scores at birth. In multivariable analysis, the association between depression and decreased HCAZ remained significant, when adjusted for clinic, SES, and recent stressful life events.Conclusions: Antenatal depression and associated risk factors are highly prevalent in this setting and are associated with adverse fetal growth. Maternal mental health may be an important predictor of infant growth in utero. [ABSTRACT FROM AUTHOR]

Although a great deal of information about the neurobiology of panic disorder is now available, there is a need for an updated etiological model integrating recent findings on the neurobiology of the arousal system and its relationship with higher cortical functions in panic disorder. The current mini-review presents psychophysiological, molecular biological/genetic and functional neuroimaging evidence for dysfunction in major arousal systems of the brain. Such dysfunction may influence the development of panic disorder by precipitating autonomic bodily symptoms and at the same time increasing vigilance to these sensations by modulating cortical attentional networks. A multilevel model of arousal, attention and anxiety-including the norepinephrine, orexin, neuropeptide S and caffeine-related adenosine systems-may be useful in integrating a range of data available on the pathogenesis of panic disorder. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective Anxiety disorders are treatable conditions, but many affected individuals neither seek professional help nor adhere to recommended pharmacological treatments. Increasing the health literacy of people with (or at risk of) anxiety disorders may encourage treatment-seeking and adherence to recommended interventions. Aims of this study were to review the literature relating to health literacy in the treatment of anxiety disorders, focusing on results on public opinion on psychotropic medications and its effectiveness in improving access to psychiatric health care and the actual use of medications. Methods A computerized literature search of the published literature on mental health literacy was undertaken, focusing on the question of whether increased mental health literacy led to increased treatment-seeking and pharmacotherapy adherence in individuals with anxiety disorders. Results Twelve relevant articles were identified. All reported that improving mental health literacy leads to raised awareness, and in 10 out of 12 studies, increased help-seeking. However, there is currently no unequivocal evidence to show that increasing health literacy leads to increased use of medication in any psychiatric disorder, including anxiety disorders. Two studies show that knowledge of presumed biological mechanisms can predict use of psychotropic medication, including antidepressants, in psychiatric disorders, however, not specifically in anxiety disorders. Conclusion There have been few investigations of health literacy focused on psychotropic medications. Given the prevalence, burden and sub-optimal recognition, and treatment of anxiety disorders, further work is needed to determine whether increased mental health literacy is associated with treatment-seeking and medication adherence in patients with these disorders. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Introduction: Pain is one of the most commonly reported symptoms in people living with HIV/AIDS (PLWHA). However, wide ranges of pain prevalence have been reported, making it difficult to determine the relative impact of pain in PLWHA. A systematic review of the literature was conducted to establish the prevalence and characteristics of pain and to explore pain management in PLWHA. Methods: Studies that included cross‐sectional data were included in the search, which was conducted in April 2012. Databases searched using a time limit of March 1982 to March 2012 included PubMed, Scopus, Africa‐wide: NIPAD, CINAHL, PsychARTICLES, PSYCINFO, PSYCHIATRYONLINE, ScienceDirect and Web of Science. Search terms selected were “pain” and “HIV” or “acquired immune deficiency syndrome.” Two reviewers independently screened all citation abstracts for inclusion. Methodological quality was evaluated using a standardized 11‐item critical appraisal tool. Results: After full text review, 61 studies fulfilled the inclusion criteria. Prevalence of pain ranged from a point prevalence of 54% (95%CI 51.14–56.09) to 83% (95%CI 76–88) using a three‐month recall period. The reported pain was of moderate‐to‐severe intensity, and pain was reported in one to two and a half different anatomical sites. Moderate levels of pain interference with function were reported. All nine studies reporting on the adequacy of pain management recorded marked under‐treatment of pain. Discussion: The studies reviewed reported that pain commonly presents at multiple pain sites with a range of severity suggesting that there are several differing pathological processes contributing to pain at one time. The interplay of variables associated with pain suggests that the biopsychosocial model of pain is an appropriate paradigm from which to view pain in PLWHA and from which to approach the problem, explore causes and establish effective treatment. Conclusions: The results highlight that pain is common in PLWHA at all stages of the disease. The prevalence rates for pain in PLWHA do not appear to have diminished over the 30 years spanning the studies reviewed. The body of work available in the literature thus far, while emphasizing the problem of pain, has not had an impact on its management. [ABSTRACT FROM AUTHOR]