Publications by authors named "Dan J Stein"

1,028 Publications

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Help-Seeking Intention in Obsessive-Compulsive Disorder: Predictors and Barriers in South Africa.

Front Psychiatry 2021 24;12:733773. Epub 2021 Sep 24.

Department of Global Health, Institute for Life Course Health Research, Stellenbosch University, Stellenbosch, South Africa.

Many individuals with obsessive-compulsive disorder (OCD) delay seeking help, leading to greater illness severity, additional comorbidity, and increased functional impairment. Patterns of help-seeking for OCD have however not yet been described in South Africa, a low-and middle-income country with many health service challenges. Using the health belief model as a conceptual framework, study aims were to identify predictors of and barriers to help-seeking among South Africans with OCD. Fifty adults with OCD completed an online survey to assess (1) socio-demographic characteristics, (2) OCD symptom severity, (3) treatment barriers, (4) perceived treatment benefits, (5) self-efficacy, and (6) help-seeking intention. Multiple linear regression analysis was used to establish predictors of help-seeking intention. Descriptive statistics were used to determine the most endorsed help-seeking barriers. 42.6% of the variance in help-seeking intention was explained by the investigated constructs ( = 0.426, = 4.45 and < 0.01). Perceived treatment benefits were the only significant predictor of help-seeking intention ( = 1.37, = 5.16, and < 0.01). More than a third (36%) of the sample endorsed wanting to handle the problem independently as a significant barrier, followed by treatment concerns (26%), affordability (22%), and shame (20%). An innovative analysis of help-seeking patterns suggested that perceived treatment benefits were the only significant predictor of help-seeking intention among South African adults with OCD. Psychoeducation and mental health literacy programmes may be useful in increasing public appreciation of the benefits of OCD treatment, and in mitigating key help-seeking barriers.
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http://dx.doi.org/10.3389/fpsyt.2021.733773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497739PMC
September 2021

Associations Between Maternal Depression, Antidepressant Use During Pregnancy, and Adverse Pregnancy Outcomes: An Individual Participant Data Meta-analysis.

Obstet Gynecol 2021 Oct;138(4):633-646

Department for Health Evidence, Radboud Institute for Health Sciences, and the Radboud REshape Innovation Center, Radboud University Medical Center, Nijmegen, the Netherlands; the Environmental Research Group, King's College, London, United Kingdom; the Department of Clinical Science, Obstetrics and Gynecology, Umeå University, Umeå, Sweden; the Singapore Institute for Clinical Sciences, Singapore; the Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel; the Department of Child and Adolescent Psychiatry, the Department of Psychology, Education and Child Studies, Erasmus School of Social and Behavioral Sciences, and the Department of Pediatrics, Erasmus University Rotterdam, Rotterdam, the Netherlands; the Department of Pharmacy (Centre IMAGe), Centre Hospitalier Universitaire Sainte-Justine and Faculté de Pharmacie, Université de Montréal, Montréal, Québec, Canada; the Division of Reproductive and Perinatal Health, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; the Department of Health Science, Medical Faculty, Lund University, Lund, Sweden; the Vincent van Gogh Institute for Psychiatry, Venlo, the Netherlands; the Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan; the Department of Obstetrics & Gynecology, NorthShore University HealthSystem, and the University of Chicago Pritzker School of Medicine, Chicago, Illinois; the School of Public Health and the Irish Centre for Fetal and Neonatal Translational Research (INFANT), University College Cork, Cork, Ireland; the London School of Hygiene and Tropical Medicine, London, United Kingdom; the Elisabeth TweeSteden Hospital (ETZ), Tilburg, the Netherlands; the Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland; the Bradford Teaching Hospitals NHS Foundation Trust, Bradford, United Kingdom; Wayne State University, Detroit, Michigan; the Department of Public Health Science, Karolinska Institutet, Stockholm, Sweden; the PharmacoEpidemiology & Drug Safety Research Group, School of Pharmacy, University of Oslo, and the Department of Child Health and Development, Norwegian Institute of Public Health, Oslo, Norway; the Department of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire; the University of York, York, United Kingdom; the Faculty of Health, School of Nursing, York University, Toronto, Ontario, Canada; the Department of Psychiatry, University of Necmettin Erbakan, Meram Faculty of Medicine, Konya, Turkey; the School of Nursing and Midwifery, Aga Khan University, Karachi, Pakistan; the Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota; the Department of Psychiatry and Mental Health, University of Cape Town, and the South African Medical Research Council, Unit on Risk and Resilience in Mental Disorders, Cape Town, South Africa; the Charles Perrens Hospital and the Bordeaux Population Health Center, INSERM 1219, Bordeaux University, Bordeaux, France; the Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; the "Alexandra" General Hospital of Athens, Athens, Greece; the Department of Public and Occupational Health, Amsterdam Public Health Research Institute, Academic Medical Center - University of Amsterdam, Amsterdam, the Netherlands; the STIS and Clinical Pharmacology Service, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; the Department of Medical Psychology, Radboud Institute for Health Sciences, and the Department of Psychiatry, Radboud University Medical Center, Nijmegen, the Netherlands.

Objective: To evaluate the associations of depressive symptoms and antidepressant use during pregnancy with the risks of preterm birth, low birth weight, small for gestational age (SGA), and low Apgar scores.

Data Sources: MEDLINE, EMBASE, ClinicalTrials.gov, and PsycINFO up to June 2016.

Methods Of Study Selection: Data were sought from studies examining associations of depression, depressive symptoms, or use of antidepressants during pregnancy with gestational age, birth weight, SGA, or Apgar scores. Authors shared the raw data of their studies for incorporation into this individual participant data meta-analysis.

Tabulation, Integration, And Results: We performed one-stage random-effects meta-analyses to estimate odds ratios (ORs) with 95% CIs. The 215 eligible articles resulted in 402,375 women derived from 27 study databases. Increased risks were observed for preterm birth among women with a clinical diagnosis of depression during pregnancy irrespective of antidepressant use (OR 1.6, 95% CI 1.2-2.1) and among women with depression who did not use antidepressants (OR 2.2, 95% CI 1.7-3.0), as well as for low Apgar scores in the former (OR 1.5, 95% CI 1.3-1.7), but not the latter group. Selective serotonin reuptake inhibitor (SSRI) use was associated with preterm birth among women who used antidepressants with or without restriction to women with depressive symptoms or a diagnosis of depression (OR 1.6, 95% CI 1.0-2.5 and OR 1.9, 95% CI 1.2-2.8, respectively), as well as with low Apgar scores among women in the latter group (OR 1.7, 95% CI 1.1-2.8).

Conclusion: Depressive symptoms or a clinical diagnosis of depression during pregnancy are associated with preterm birth and low Apgar scores, even without exposure to antidepressants. However, SSRIs may be independently associated with preterm birth and low Apgar scores.

Systematic Review Registration: PROSPERO, CRD42016035711.
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http://dx.doi.org/10.1097/AOG.0000000000004538DOI Listing
October 2021

Disentangling sex differences in the shared genetic architecture of posttraumatic stress disorder, traumatic experiences, and social support with body size and composition.

Neurobiol Stress 2021 Nov 17;15:100400. Epub 2021 Sep 17.

Department of Psychiatry, Yale School of Medicine and VA CT Healthcare Center, West Haven, CT, 06516, USA.

There is a well-known association of traumatic experiences and posttraumatic stress disorder (PTSD) with body size and composition, including consistent differences between sexes. However, the biology underlying these associations is unclear. To understand the genetic underpinnings of this complex relationship, we investigated genome-wide datasets informative of African and European ancestries from the Psychiatric Genomic Consortium, the UK Biobank, the GIANT Consortium, and the Million Veteran Program. We used genome-wide association statistics to estimate sex-specific genetic correlations ( ) of traumatic experiences, social support, and PTSD with multiple anthropometric traits. After multiple testing corrections (false discovery rate, FDR q < 0.05), we observed 58 significant relationships in females (e.g., childhood physical abuse and body mass index, BMI  = 0.245, p = 3.88 × 10) and 21 significant relationships in males (e.g., been involved in combat or exposed to warzone and leg fat percentage;  = 0.405, p = 4.42 × 10). We performed causal inference analyses of these genetic overlaps using Mendelian randomization and latent causal variable approaches. Multiple female-specific putative causal relationships were observed linking body composition/size with PTSD (e.g., leg fat percentage→PTSD; beta = 0.319, p = 3.13 × 10), traumatic experiences (e.g., childhood physical abuse→waist circumference; beta = 0.055, p = 5.07 × 10), and childhood neglect (e.g., "someone to take you to doctor when needed as a child"→BMI; beta = -0.594, p = 1.09 × 10). In males, we observed putative causal effects linking anthropometric-trait genetic liabilities to traumatic experiences (e.g., BMI→childhood physical abuse; beta = 0.028, p = 8.19 × 10). Some of these findings were replicated in individuals of African descent although the limited sample size available did not permit us to conduct a sex-stratified analysis in this ancestry group. In conclusion, our findings provide insights regarding sex-specific causal networks linking anthropometric traits to PTSD, traumatic experiences, and social support
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http://dx.doi.org/10.1016/j.ynstr.2021.100400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477211PMC
November 2021

Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group.

Transl Psychiatry 2021 10 1;11(1):502. Epub 2021 Oct 1.

Center Of Excellence On Mood Disorders, Louis A. Faillace, MD, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA.

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5-90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology.
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http://dx.doi.org/10.1038/s41398-021-01622-1DOI Listing
October 2021

Pharmacotherapy for trichotillomania.

Cochrane Database Syst Rev 2021 09 28;9:CD007662. Epub 2021 Sep 28.

Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.

Background: Trichotillomania (TTM; hair-pulling disorder) is a prevalent and disabling disorder characterised by recurrent hair-pulling. Here we update a previous Cochrane Review on the effects of medication for TTM.

Objectives: To assess the effects of medication for trichotillomania (TTM) in adults, children and adolescents compared with placebo or other medication.

Search Methods: We searched CENTRAL, MEDLINE, Embase, PsycINFO, eleven other bibliographic databases, trial registries and grey literature sources (to 26 November 2020). We checked reference lists and contacted subject experts.

Selection Criteria: We selected randomised controlled trials of medication versus placebo or other medication for TTM in adults, children and adolescents.

Data Collection And Analysis: We used standard methodological procedures expected by Cochrane.

Main Results: Twelve studies were included. We identified 10 studies in adults (286 participants) with a mean sample size of 29 participants per trial; one study in children and adolescents (39 participants); and, one study in adults and adolescents (22 participants: 18 adults and 4 adolescents). All studies were single-centre, outpatient trials. Eleven studies compared medication and placebo (334 participants); one study compared two medications (13 participants). Studies were 5 to 13 weeks duration. We undertook meta-analysis only for opioid antagonists as other comparisons contained a single study, or reported insufficient data. Antioxidants versus placebo in adults There was little to no difference in treatment response between antioxidant (35.7%) and placebo groups (28.6%) after six weeks, based on a single trial of silymarin (risk ratio (RR) 2.25, 95% confidence interval (CI) 0.84 to 5.99; 36 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (18 participants; low-certainty evidence). Antioxidants versus placebo in adolescents There was little to no difference in treatment response between antioxidant (50%) and placebo groups (25%) after six weeks, based on a single trial of silymarin (RR 2.00, 95% CI 0.28 to 14.20; 8 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (8 participants; low-certainty evidence). Antipsychotics versus placebo in adults There may be greater treatment response in the antipsychotic group (85%) compared to the placebo group (17%) after 12 weeks, based on a single trial of olanzapine (RR 5.08, 95% CI 1.4 to 18.37; 25 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (25 participants; low-certainty evidence). Cell signal transducers versus placebo in adults There was little to no difference in treatment response between cell signal transducer (42.1%) and placebo groups (31.6%) after 10 weeks, based on a single trial of inositol (RR 1.33, 95% CI 0.57 to 3.11; 38 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (38 participants; low-certainty evidence). Glutamate modulators versus placebo in adults There is probably greater treatment response in the glutamate modulator group (56%) compared to the placebo group (16%) after 12 weeks, based on a single trial of N-acetylcysteine (RR 3.5, 95% CI 1.34 to 9.17; 50 participants; moderate-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (50 participants; low-certainty evidence). Glutamate modulators versus placebo in children and adolescents There was little to no difference in treatment response between the glutamate modulator (25%) and placebo groups (21.1%) in children and adolescents, based on a single trial of N-acetylcysteine (RR 1.19, 95% CI 0.37 to 3.77; 39 participants; low-certainty evidence). There was little to no difference in dropouts due to adverse events between glutamate modulator (5%) and placebo (0%) groups, based on a single trial (RR 2.86, 95% CI 0.12 to 66.11; 39 participants; low-certainty evidence). Opioid antagonists versus placebo in adults There may be little to no difference in treatment response between opioid antagonist (37.5%) and placebo groups (25%) after six to eight weeks, based on two studies of naltrexone, but the evidence is very uncertain (RR 2.14, 95% CI 0.25 to 18.17; 2 studies, 68 participants; very low-certainty evidence). No data were available regarding dropouts due to adverse events. Selective serotonin reuptake inhibitors (SSRIs) versus placebo in adults There were no data available for treatment response to SSRIs. There was little to no difference in dropouts due to adverse events in the SSRI group (5.1%) compared to the placebo group (0%) after 6 to 12 weeks, based on two trials of fluoxetine (RR 3.00, 95% CI 0.33 to 27.62; 2 studies, 78 participants; low-certainty evidence). Tricyclic antidepressants (TCAs) with predominantly serotonin reuptake inhibitor (SRI) actions versus placebo in adults There may be greater treatment response in the TCAs with predominantly SRI actions group (40%) compared to the placebo group (0%) after nine weeks, but the evidence is very uncertain, based on a single trial of clomipramine (RR 5.73, 95% CI 0.36 to 90.83; 16 participants; very low-certainty evidence). There may be increased dropouts due to adverse events in the TCAs with predominantly SRI actions group (30%) compared to the placebo group (0%), but the evidence is very uncertain (RR 4.45, 95% CI 0.27 to 73.81; 16 participants; very low-certainty evidence). TCAs with predominantly SRI actions versus other TCAs in adults There may be greater treatment response in the TCAs with predominantly SRI actions group compared to the other TCAs group after five weeks, based on a single trial comparing clomipramine to desipramine (mean difference (MD) -4.00, 95% CI -6.13 to -1.87; 26 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (26 participants; low-certainty evidence).

Authors' Conclusions: There was insufficient evidence from meta-analysis to confirm or refute the efficacy of any agent or class of medication for the treatment of TTM in adults, children or adolescents. Preliminary evidence suggests there may be beneficial treatment effects for N-acetylcysteine, clomipramine and olanzapine in adults based on four trials, albeit with relatively small sample sizes.
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http://dx.doi.org/10.1002/14651858.CD007662.pub3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478440PMC
September 2021

Alcohol use is associated with mental health problems and brain structural alterations in adolescents with perinatally acquired HIV infection on ART.

Alcohol 2021 Sep 15. Epub 2021 Sep 15.

Department of Psychiatry and Mental Health, University of Cape Town, South Africa. Electronic address:

Alcohol use, presents unique challenges for HIV-1 treatment in adolescents with perinatally acquired infection. The effects of alcohol on host-virus interaction in the brain and the immune system remains understudied in this population. Adolescents with perinatally acquired HIV infection (PHIV) well established on ART, from the Cape Town Adolescent Antiretroviral Cohort who self-reported alcohol use (PHIV+alcohol) (n=26) were compared to age matched 26 PHIV (PHIV-alcohol) and 26 healthy controls (HC) who reported no use of alcohol. Participants completed clinical investigations including highly-sensitive CRP (hs-CRP), a comprehensive neurocognitive test battery and mental health measures. In addition, we investigated the relationship between alcohol use in PHIV and diffusion tensor imaging (DTI) and structural brain magnetic resonance imaging (MRI) to determine fractional anisotropy (FA), mean diffusivity (MD), grey and white matter volumes and cortical thickness. PHIV (mean age 12,5 years; mean age of ART initiation 3.15 years) reported an occasional weekend drinking pattern of alcohol use. hs-CRP was significantly different between groups, with PHIV+alcohol higher than PHIV-alcohol and HC. General intelligence, attention, working memory, processing speed and executive function were more impaired in the PHIV+alcohol than PHIV alone, with HC having the highest scores. In addition, self-concept was significantly lower in PHIV+alcohol. The Child Behavior Checklist (CBCL) Externalizing behaviour, internalising behaviour and CBCL Total problems were significantly higher in PHIV+alcohol. FA of the superior corona radiata, superior fronto-occipital fasciculus and corpus callosum was significantly lower in PHIV+alcohol compared to PHIV-alcohol and MD of the corona radiata was significantly increased in PHIV+alcohol. The cortical thickness of the lateral orbitofrontal, middle frontal and precentral gyri were significantly lower in PHIV+ alcohol compared to PHIV-alcohol and HC. In conclusion PHIV associated impairments in systemic inflammation, cognitive function, mental health and changes in brain structure may be exacerbated by alcohol use, even if only occasional use. However, the study is cross-sectional, which is not able to distinguish between cause and effect.
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http://dx.doi.org/10.1016/j.alcohol.2021.09.006DOI Listing
September 2021

Evaluating Community Engagement Strategies to Manage Stigma in Two African Genomics Studies Involving People Living with Schizophrenia or Rheumatic Heart Disease.

Glob Health Epidemiol Genom 2021 26;2021:9926495. Epub 2021 Jun 26.

Department of Medicine, University of Cape Town, Cape Town, South Africa.

In global health research and genomics research specifically, community engagement has gained prominence in enhancing ethical conduct, particularly in managing the risk of stigmatization, but there is minimal scientific evidence on how to do this effectively. This article reports on community engagement evaluation strategies in two African genomics studies: the Stigma in African Genomics Research study and the Genomics of Schizophrenia in South African Xhosa People (SAX) study. Within the Stigma in African Genomics Research study, a self-report rating scale and open-ended questions were used to track participant responses to an experiential theatre workshop. The workshop focused on participant experiences of living with schizophrenia or rheumatic heart disease (RHD). While the schizophrenia group reported more alienation and less stigma resistance than the RHD group, both groups demonstrated increased stigma resistance over time, after participating in the workshops. Hearing from others living with and managing the same illness normalised participants' own experiences and encouraged them. Within the SAX study, a short rating scale and qualitative feedback methods were used to evaluate a Mental Health Literacy Day targeting mental health stigma. Information talks about (i) the symptoms of schizophrenia and treatment options and (ii) the illness experiences of a patient in recovery were rated as the most helpful on the day. Audience members reported that these talks challenged negative perceptions about severe mental illness. Three important learnings emerged from these evaluations: firstly, integration of evaluation strategies at the research study planning phase is likely to promote more effective community engagement. Secondly, a combination of quantitative and qualitative methods that draw on simple descriptive statistics and thematic analysis can provide nuanced perspectives about the value of community engagement. Thirdly, such evidence is necessary in establishing and promoting the science of community engagement in genomics research and health research more broadly.
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http://dx.doi.org/10.1155/2021/9926495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415068PMC
June 2021

Implications of the COVID-19 pandemic for people with bipolar disorders: A scoping review.

J Affect Disord 2021 Sep 4;295:740-751. Epub 2021 Sep 4.

IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, Australia. Electronic address:

Introduction: The COVID-19 (coronavirus disease 2019)-related pandemic represents a global source of societal and health burden. Yet, the impact of the pandemic on people with severe mental illness, including bipolar disorder (BD), remains unclear, warranting scoping review on the matter.

Methods: The MEDLINE and EMBASE databases were systematically searched from inception up to April 24, 2021, adopting broad inclusion criteria to assess a variety of clinical and public health themes related to people with a primary diagnosis of BD during the COVID-19 pandemics. The present work complying with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) registered in the Open Science Framework (OSF) repository (https://osf.io/7evpx/).

Results: Fourteen papers informed the present scoping review. Four major themes were identified: (i) impact of COVID-19-related stressors on BD; (ii) impact of COVID-19 on mental health service utilization among people with BD; (iii) impact of BD on the risk of acquiring SARS-CoV-2 infection; (iv) engagement in preventative behaviors among people with BD. Additional themes warranting further research were nonetheless detected.

Limitations: Further original studies are needed.

Conclusion: The present study confirmed the high-vulnerability hypothesis concerning people with BD versus the general population, reinforcing the need for further research related to the COVID-19 pandemic. Additional information is warranted to compare the impact of the pandemic period among BD people against pre-pandemic records, the general population, and other severe mental illnesses, namely people with schizophrenia or major depressive disorder, to inform the public health and the delivery of patient-tailored interventions.
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http://dx.doi.org/10.1016/j.jad.2021.08.091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416293PMC
September 2021

The clinical characterization of the adult patient with an anxiety or related disorder aimed at personalization of management.

World Psychiatry 2021 Oct;20(3):336-356

Department of Psychiatry, University of Campania "L. Vanvitelli", Naples, Italy.

The clinical construct of "anxiety neurosis" was broad and poorly defined, so that the delineation of specific anxiety disorders in the DSM-III was an important advance. However, anxiety and related disorders are not only frequently comorbid, but each is also quite heterogeneous; thus diagnostic manuals provide only a first step towards formulating a management plan, and the development of additional decision support tools for the treatment of anxiety conditions is needed. This paper aims to describe systematically important domains that are relevant to the personalization of management of anxiety and related disorders in adults. For each domain, we summarize the available research evidence and review the relevant assessment instruments, paying special attention to their suitability for use in routine clinical practice. We emphasize areas where the available evidence allows the clinician to personalize the management of anxiety conditions, and we point out key unmet needs. Overall, the evidence suggests that we are becoming able to move from simply recommending that anxiety and related disorders be treated with selective serotonin reuptake inhibitors, cognitive-behavioral therapy, or their combination, to a more complex approach which emphasizes that the clinician has a broadening array of management modalities available, and that the treatment of anxiety and related disorders can already be personalized in a number of important respects.
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http://dx.doi.org/10.1002/wps.20919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429350PMC
October 2021

A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium.

Hum Brain Mapp 2021 Sep 8. Epub 2021 Sep 8.

Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS) [Georgia State University, Georgia Institute of Technology], Emory University, Atlanta, Georgia, USA.

Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.
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http://dx.doi.org/10.1002/hbm.25625DOI Listing
September 2021

Preliminary data on increased reactivity towards children in distress after testosterone administration in women: A matter of protection?

Biol Psychol 2021 Aug 30;165:108176. Epub 2021 Aug 30.

Department of Experimental Psychology, Utrecht University, Heidelberglaan 1, 3584 CS, Utrecht, the Netherlands.

Emotional reactivity to others' distress is a vital prerequisite for a caring response. Testosterone, in contrast, is mostly associated with protection of personal dominance and decreased responsiveness to others' needs. However, experimental work also indicates that rising testosterone levels in response to infant distress can potentially facilitate protection. We assessed the impact of testosterone administration on participants' emotional reactivity to infants in distress, measuring their facial responses on the corrugator supercilii forehead muscle ('frowning') and the zygomaticus major ('smiling') as an index of emotional responses towards children. Moreover, we probed whether the effect of testosterone is moderated by participants' self-reported nurturance and protective tendencies. Our preliminary results showed that testosterone not only increased emotional reactivity to empathy eliciting images of children, but that this increase was strongest in participants with strong protective tendencies. Our administration study is the first to link testosterone to infant protection.
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http://dx.doi.org/10.1016/j.biopsycho.2021.108176DOI Listing
August 2021

Preliminary data on increased reactivity towards children in distress after testosterone administration in women: A matter of protection?

Biol Psychol 2021 Aug 30;165:108176. Epub 2021 Aug 30.

Department of Experimental Psychology, Utrecht University, Heidelberglaan 1, 3584 CS, Utrecht, the Netherlands.

Emotional reactivity to others' distress is a vital prerequisite for a caring response. Testosterone, in contrast, is mostly associated with protection of personal dominance and decreased responsiveness to others' needs. However, experimental work also indicates that rising testosterone levels in response to infant distress can potentially facilitate protection. We assessed the impact of testosterone administration on participants' emotional reactivity to infants in distress, measuring their facial responses on the corrugator supercilii forehead muscle ('frowning') and the zygomaticus major ('smiling') as an index of emotional responses towards children. Moreover, we probed whether the effect of testosterone is moderated by participants' self-reported nurturance and protective tendencies. Our preliminary results showed that testosterone not only increased emotional reactivity to empathy eliciting images of children, but that this increase was strongest in participants with strong protective tendencies. Our administration study is the first to link testosterone to infant protection.
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http://dx.doi.org/10.1016/j.biopsycho.2021.108176DOI Listing
August 2021

Preliminary data on increased reactivity towards children in distress after testosterone administration in women: A matter of protection?

Biol Psychol 2021 Aug 30;165:108176. Epub 2021 Aug 30.

Department of Experimental Psychology, Utrecht University, Heidelberglaan 1, 3584 CS, Utrecht, the Netherlands.

Emotional reactivity to others' distress is a vital prerequisite for a caring response. Testosterone, in contrast, is mostly associated with protection of personal dominance and decreased responsiveness to others' needs. However, experimental work also indicates that rising testosterone levels in response to infant distress can potentially facilitate protection. We assessed the impact of testosterone administration on participants' emotional reactivity to infants in distress, measuring their facial responses on the corrugator supercilii forehead muscle ('frowning') and the zygomaticus major ('smiling') as an index of emotional responses towards children. Moreover, we probed whether the effect of testosterone is moderated by participants' self-reported nurturance and protective tendencies. Our preliminary results showed that testosterone not only increased emotional reactivity to empathy eliciting images of children, but that this increase was strongest in participants with strong protective tendencies. Our administration study is the first to link testosterone to infant protection.
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http://dx.doi.org/10.1016/j.biopsycho.2021.108176DOI Listing
August 2021

Executive Function and Contingency Management in Methamphetamine Use Disorder.

J Alcohol Drug Depend 2021 12;9(5). Epub 2021 May 12.

Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Los Angeles, California, United States of America.

Objectives: Contingency management is a promising intervention for Methamphetamine Use Disorder (MUD).Impaired executive function may decrease adherence to such treatment, but there are few data on whether impairment in executive function predicts treatment outcomes. We therefore evaluated whether baseline performance on tests of executive function predicted treatment response in a trial of contingency management for MUD.

Methods: Thirty participants with MUD and 23 healthy controls performed the Connors Continuous Performance Task (CPT) and the Trail Making Task. MUD participants then entered an 8-week contingency management trial. Participants were categorized as responders (n=17; no methamphetamine-positive urine tests) or non-responders (n=13; >1 positive test). The Kruskal-Wallis test was used to compare scores in participants with MUD and healthy controls, and in responders versus non-responders.

Results: Participants withMUD performed worse than controls on the CPT (d-prime) (p=0.012); non-responders performed worse than responders (p = 0.034). Performance of MUD participants did not differ significantly from controls on the Trail Making Task B (time to completion), but variation was high with non-responders performing worse than responders (p=0.013).

Conclusion: These findings suggest that tests of executive function at baseline may be useful in predicting treatment response in MUD. Future work in larger samples may ultimately allow a more personalized treatment approach to methamphetamine use disorder.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378238PMC
May 2021

Evidence-Based Pharmacotherapy of Generalised Anxiety Disorder: Focus on Agomelatine.

Authors:
Dan J Stein

Adv Ther 2021 09 21;38(Suppl 2):52-60. Epub 2021 Aug 21.

SAMRC Unit On Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, Groote Schuur Hospital, University of Cape Town, Anzio Road, Cape Town, 7925, South Africa.

Recent network meta-analyses support the use of pharmacotherapy in patients with generalised anxiety disorder (GAD). Compared with placebo, drug treatment can improve symptoms and quality of life, and is more effective in preventing relapse. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are generally considered the first-line agents of choice in GAD, but in some patients, an alternative evidence-based treatment with a different mechanism of action may also be considered (e.g. those with severe GAD, inadequate response, adverse effects and/or contraindications). One example is agomelatine, a melatonin receptor agonist and serotonin 2C (5-HT) receptor antagonist, which has been shown to have efficacy that is greater than placebo in patients with GAD, and to have a tolerability profile that compares favourably with that of escitalopram. Both agomelatine and escitalopram are efficacious in treating patients with GAD, including those with severe symptoms. Video Abstract.
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http://dx.doi.org/10.1007/s12325-021-01860-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437845PMC
September 2021

Generalised Anxiety Disorder and Depression: Contemporary Treatment Approaches.

Adv Ther 2021 09 21;38(Suppl 2):45-51. Epub 2021 Aug 21.

SA MRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

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http://dx.doi.org/10.1007/s12325-021-01859-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437834PMC
September 2021

The neurobiology of obsessive-compulsive personality disorder: a systematic review.

CNS Spectr 2021 Aug 11:1-12. Epub 2021 Aug 11.

South African Medical Research Council (MRC) Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

Background: A number of recent investigations have focused on the neurobiology of obsessive-compulsive personality disorder (OCPD). However, there have been few reviews of this literature with no detailed model proposed. We therefore undertook a systematic review of these investigations, aiming to map the available evidence and investigate whether it is possible to formulate a detailed model of the neurobiology of OCPD.

Methods: OCPD can be considered from both categorical and dimensional perspectives. An electronic search was therefore conducted using terms that would address not only OCPD as a category, but also related constructs, such as perfectionism, that would capture research on neuropsychology, neuroimaging, neurochemistry, and neurogenetics.

Results: A total of 1059 articles were retrieved, with 87 ultimately selected for abstract screening, resulting in a final selection of 49 articles focusing on neurobiological investigations relevant to OCPD. Impaired executive function and cognitive inflexibility are common neuropsychological traits in this condition, and suggest that obsessive-compulsive disorder (OCD) and OCPD may lie on a continuum. However, neuroimaging studies in OCPD indicate the involvement of specific neurocircuitry, including the precuneus and amygdala, and so suggest that OCD and OCPD may have important differences. Although OCPD has a heritable component, we found no well-powered genetic studies of OCPD.

Conclusion: Although knowledge in this area has advanced, there are insufficient data on which to base a comprehensive model of the neurobiology of OCPD. Given the clinical importance of OCPD, further work to understand the mechanisms that underpin this condition is warranted.
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http://dx.doi.org/10.1017/S1092852921000754DOI Listing
August 2021

Perceived helpfulness of treatment for generalized anxiety disorder: a World Mental Health Surveys report.

BMC Psychiatry 2021 08 9;21(1):392. Epub 2021 Aug 9.

Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.

Background: Treatment guidelines for generalized anxiety disorder (GAD) are based on a relatively small number of randomized controlled trials and do not consider patient-centered perceptions of treatment helpfulness. We investigated the prevalence and predictors of patient-reported treatment helpfulness for DSM-5 GAD and its two main treatment pathways: encounter-level treatment helpfulness and persistence in help-seeking after prior unhelpful treatment.

Methods: Data came from community epidemiologic surveys in 23 countries in the WHO World Mental Health surveys. DSM-5 GAD was assessed with the fully structured WHO Composite International Diagnostic Interview Version 3.0. Respondents with a history of GAD were asked whether they ever received treatment and, if so, whether they ever considered this treatment helpful. Number of professionals seen before obtaining helpful treatment was also assessed. Parallel survival models estimated probability and predictors of a given treatment being perceived as helpful and of persisting in help-seeking after prior unhelpful treatment.

Results: The overall prevalence rate of GAD was 4.5%, with lower prevalence in low/middle-income countries (2.8%) than high-income countries (5.3%); 34.6% of respondents with lifetime GAD reported ever obtaining treatment for their GAD, with lower proportions in low/middle-income countries (19.2%) than high-income countries (38.4%); 3) 70% of those who received treatment perceived the treatment to be helpful, with prevalence comparable in low/middle-income countries and high-income countries. Survival analysis suggested that virtually all patients would have obtained helpful treatment if they had persisted in help-seeking with up to 10 professionals. However, we estimated that only 29.7% of patients would have persisted that long. Obtaining helpful treatment at the person-level was associated with treatment type, comorbid panic/agoraphobia, and childhood adversities, but most of these predictors were important because they predicted persistence rather than encounter-level treatment helpfulness.

Conclusions: The majority of individuals with GAD do not receive treatment. Most of those who receive treatment regard it as helpful, but receiving helpful treatment typically requires persistence in help-seeking. Future research should focus on ensuring that helpfulness is included as part of the evaluation. Clinicians need to emphasize the importance of persistence to patients beginning treatment.
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http://dx.doi.org/10.1186/s12888-021-03363-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351147PMC
August 2021

Artificial intelligence for classification of temporal lobe epilepsy with ROI-level MRI data: A worldwide ENIGMA-Epilepsy study.

Neuroimage Clin 2021 24;31:102765. Epub 2021 Jul 24.

Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany; Institute for Diagnostic and Interventional Radiology, Pediatric and Neuroradiology, University Medical Centre Rostock, Rostock, Germany.

Artificial intelligence has recently gained popularity across different medical fields to aid in the detection of diseases based on pathology samples or medical imaging findings. Brain magnetic resonance imaging (MRI) is a key assessment tool for patients with temporal lobe epilepsy (TLE). The role of machine learning and artificial intelligence to increase detection of brain abnormalities in TLE remains inconclusive. We used support vector machine (SV) and deep learning (DL) models based on region of interest (ROI-based) structural (n = 336) and diffusion (n = 863) brain MRI data from patients with TLE with ("lesional") and without ("non-lesional") radiographic features suggestive of underlying hippocampal sclerosis from the multinational (multi-center) ENIGMA-Epilepsy consortium. Our data showed that models to identify TLE performed better or similar (68-75%) compared to models to lateralize the side of TLE (56-73%, except structural-based) based on diffusion data with the opposite pattern seen for structural data (67-75% to diagnose vs. 83% to lateralize). In other aspects, structural and diffusion-based models showed similar classification accuracies. Our classification models for patients with hippocampal sclerosis were more accurate (68-76%) than models that stratified non-lesional patients (53-62%). Overall, SV and DL models performed similarly with several instances in which SV mildly outperformed DL. We discuss the relative performance of these models with ROI-level data and the implications for future applications of machine learning and artificial intelligence in epilepsy care.
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http://dx.doi.org/10.1016/j.nicl.2021.102765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346685PMC
September 2021

HIV-Related Stigma and Psychological Adjustment Among Perinatally HIV-Infected Youth in Cape Town, South Africa.

AIDS Behav 2021 Jul 27. Epub 2021 Jul 27.

Department of Psychiatry and Mental Health in the Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

The effect of chronic HIV-infection on psychological adjustment, including the impact of HIV-related stigma in perinatally HIV-infected (PHIV+) youth across Africa is largely unknown. This study examined psychological adjustment and HIV-related stigma using the Strengths and Difficulties Questionnaire (SDQ) and a 10-item stigma questionnaire in a cohort of PHIV+ youth in Cape Town, South Africa. The relationships between SDQ scores, elevated viral load, and suboptimal antiretroviral therapy (ART) adherence were also explored. Among 473 PHIV+ youth (aged 9-14 years, on ART > 6 months at enrollment), higher perceived HIV-related stigma was associated with higher scores across all adolescent and caregiver-reported SDQ difficulty subscales. Higher socioeconomic status (SES) was associated with lower scores on adolescent self- and caregiver-reported hyperactivity subscales. Higher adolescent-reported prosocial scores were associated with lower odds of self-reported suboptimal ART adherence, and higher caregiver-reported conduct scores were associated with higher odds of elevated viral load. No associations were observed between perceived HIV-related stigma and treatment outcomes. These findings highlight the potentially detrimental impact of perceived stigma on psychological adjustment in PHIV+ youth. The use of psychosocial metrics and interventions aimed at reducing illness related stigma in PHIV+ youth is also considered.
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http://dx.doi.org/10.1007/s10461-021-03398-3DOI Listing
July 2021

Hair-Pulling Does Not Necessarily Serve an Emotion Regulation Function in Adults With Trichotillomania.

Front Psychol 2021 5;12:675468. Epub 2021 Jul 5.

South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

Trichotillomania (TTM) has been associated with childhood trauma and perceived stress. While it has been hypothesized that hair-pulling regulate negative emotions, the relationship between childhood trauma, perceived stress, emotion regulation, and hair-pulling has not been well-studied. Fifty-six adults with TTM and 31 healthy controls completed the Childhood Trauma Questionnaire (CTQ), Perceived Stress Scale (PSS), and Difficulties in Emotion Regulation Scale (DERS). Hair-pulling severity was measured with the Massachusetts General Hospital-Hair Pulling Scale. CTQ, PSS, and DERS total scores were compared across groups using ANCOVA and the correlation between hair-pulling severity and emotion dysregulation was determined. Regression analyses were used to estimate the association of CTQ and PSS totals with DERS, and to determine whether associations between predictors and dependent variable (DERS) differed across groups. TTM patients reported higher rates of childhood trauma ( <= 0.01), perceived stress ( = 0.03), and emotion dysregulation ( <= 0.01). There was no association between emotion dysregulation and pulling severity ( = -0.02, = 0.89). Perceived stress was associated with emotion dysregulation in both groups ( < 0.01), and no association between childhood trauma and emotion dysregulation in either group. Perceived stress was the only significant predictor of emotion dysregulation in both groups ( = 28.29, < 0.01). The association between perceived stress and emotion dysregulation is not specific to TTM, and there is no association between emotion dysregulation and hair-pulling severity, suggesting that key factors other than emotion dysregulation contribute to hair-pulling. Alternative explanatory models are needed.
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http://dx.doi.org/10.3389/fpsyg.2021.675468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287019PMC
July 2021

Cerebrospinal fluid immune markers and HIV-associated neurocognitive impairments: A systematic review.

J Neuroimmunol 2021 Sep 30;358:577649. Epub 2021 Jun 30.

Department of Psychiatry and Mental Health, Brain Behaviour Unit, University of Cape Town, Cape Town, South Africa; Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

HIV-1 is responsible for the development of a spectrum of cognitive impairments known as HIV-associated neurocognitive disorder (HAND). In the era of antiretroviral therapy (ART), HAND remains prevalent in people living with HIV (PLWH), despite low or undetectable viral loads. Persistent neuroinflammation likely plays an important role in the contributing biological mechanisms. Multiple cerebrospinal fluid (CSF) immune markers have been studied but it is unclear which markers most consistently correlate with neurocognitive impairment. We therefore conducted a systematic review of studies of the association of CSF immune markers with neurocognitive performance in ART-experienced PLWH. We aimed to synthesize the published data to determine consistent findings and to indicate the most noteworthy CSF markers of HAND. Twenty-nine studies were included, with 20 cross-sectional studies and 9 longitudinal studies. From the group of markers most often assayed, specific monocyte activation (higher levels of Neopterin, sCD163, sCD14) and neuroinflammatory markers (higher levels of IFN-γ, IL-1α, IL-7, IL-8, sTNFR-II and lower levels of IL-6) showed a consistent direction in association with HIV-associated neurocognitive impairment. Furthermore, significant differences exist in CSF immune markers between HIV-positive people with and without neurocognitive impairment, regardless of viral load and nadir/current CD4 count. These markers may be useful in furthering our understanding of the neuropathology, diagnosis and prognosis of HAND. Studies using prospective designs (i.e. pre- and post-interventions), "multi-modal" methods (e.g. imaging, inflammation and neurocognitive evaluations) and utilizing a combination of the markers most commonly associated with HAND may help delineate the mechanisms of HAND.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577649DOI Listing
September 2021

Investigating pupillometry to detect emotional regulation difficulties in post-traumatic stress disorder.

World J Biol Psychiatry 2021 Jul 19:1-9. Epub 2021 Jul 19.

Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.

Objective: Individuals with posttraumatic stress disorder (PTSD) have been found to exhibit emotional regulation difficulties. However, the specific neural mechanisms that underlie these difficulties remain understudied. This study aimed to use pupillometry as an index function of parasympathetic nervous system activation, to investigate the mechanisms underlying emotional regulation difficulties in individuals with PTSD.

Method: A total of 87 trauma-exposed mothers (34 with PTSD and 53 non-PTSD controls) completed an eye tracking assessment in which pupillary dilation in response to emotionally valenced stimuli was measured. The participants also completed two self-report measures of emotional regulation, namely the Difficulties in Emotional Regulation Scale and the Emotional Regulations Questionnaire. Linear mixed-effect modelling was used to assess potential group differences.

Results: The PTSD group exhibited increased pupillary dilation to positively valenced stimuli compared to the non-PTSD group. However, no significant associations between the self-report measures and pupillary response to emotionally valenced stimuli were found.

Conclusion: Increased pupillary dilation in PTSD may reflect impaired parasympathetic nervous system processes. The lack of association of these measures with self-reported emotion regulation may suggest reporting biases. Larger studies with more generalised populations are required to consolidate these preliminary findings.
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http://dx.doi.org/10.1080/15622975.2021.1935316DOI Listing
July 2021

Adaptation and validation of a computerized neurocognitive battery in the Xhosa of South Africa.

Neuropsychology 2021 Sep 5;35(6):581-594. Epub 2021 Jul 5.

Department of Epidemiology, Mailman School of Public Health, Columbia University.

Objective: Large-scale studies have revolutionized biomedical research, and neurocognitive tests can help elucidate the biological basis of neuropsychiatric diseases. However, studies have predominantly been conducted in Western settings. We describe the development and validation of a computerized battery (PennCNB) with the Xhosa population of South Africa.

Method: Individuals with schizophrenia (n = 525) and a normative comparison group (n = 744) were balanced on age, sex, education, and region. Participants provided blood samples, were assessed psychiatrically, and were administered a PennCNB translation to isiXhosa, including measures of executive functions, episodic memory, complex cognition, social cognition, and sensorimotor speed. Feasibility was examined with test completion rates and input from administrators, and psychometric structural validity and associations with clinical and demographic characteristics were examined.

Results: Tests were well tolerated by participants, as >87% had one (or fewer) test missing. Results suggested a similar factor structure to prior PennCNB studies in Western contexts, and expected age and sex effects were apparent. Furthermore, a similar profile of schizophrenia was observed, with neurocognitive deficits most pronounced for executive functions, especially attention, as well as memory, social cognition, and motor speed relative to complex cognition and sensorimotor speed.

Conclusions: Results support the feasibility of implementing a culturally adapted computerized neurocognitive battery in sub-Saharan African settings and provide evidence supporting the concurrent validity of the translated instrument. Thus, the PennCNB is implementable on a large scale in non-Western contexts, shows expected factor structure, and can detect cognitive deficits associated with neuropsychiatric disorders. Obtaining valid measures of cognition by nonspecialized proctors is especially suitable in resource-limited settings, where traditional testing is prohibitive. Future work should establish normative standards, test-retest reliability, and sensitivity to treatment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/neu0000742DOI Listing
September 2021

The association between mental health and metabolic outcomes in youth living with perinatally acquired HIV in the Cape Town Adolescent Antiretroviral Cohort.

AIDS Care 2021 Jul 8:1-8. Epub 2021 Jul 8.

SA MRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.

Youth living with perinatally acquired HIV (YLPHIV) have been found to have a range of mental disorders. Some adult HIV studies have linked mental health to adverse metabolic outcomes due to dysregulation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, but this association has not previously been explored in YLPHIV.We investigated the association of mental health measures with metabolic outcomes in YLPHIV and HIV-uninfected youth (HIV-U) and linear regression was used to assess the adjusted associations.Overall, 203 YLPHIV (median age = 10.7years; 52% female; mean duration on ART 8 years, 12% CD4 count <500 cells/µL, 18% viral load >50 copies/mL) and 44 HIV-U (median age = 10.3 years; 55% female) were enrolled. YLPHIV had higher median total cholesterol (4.2 vs 3.9 mmol/L, = 0.049) and triglyceride (0.9 vs 0.7 mmol/L, < 0.001) compared to HIV-U. We found higher percentage of poor functional competence (40% vs 25%, = 0.02) and self-concept (23% vs 9%, = 0.03) and higher depression (6% vs 2%, < 0.01), anger (6% vs 2%, = 0.04) and disruptive behaviour (4% vs 0%, < 0.01) in YLPHIV as compared to HIV-U. Among YLPHIV, higher scores of anger were associated with higher total cholesterol and higher low-density lipoprotein (ß = 0.010, = 0.041 and ß = 0.012, = 0.048 respectively) and disruptive behaviour with higher low-density lipoprotein (ß = 0.010, = 0.043) after adjusting for age, sex and BMIZ.This is the one of first study to investigate the association of mental health with metabolic outcomes among YLPHIV. The association of increased anger and disruptive behaviour with increased lipid concentration is a novel finding. Further longitudinal studies are needed to evaluate the causal relationships between mental health and metabolic outcomes.
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http://dx.doi.org/10.1080/09540121.2021.1950605DOI Listing
July 2021

Maternal psychosocial risk factors and child gestational epigenetic age in a South African birth cohort study.

Transl Psychiatry 2021 07 2;11(1):358. Epub 2021 Jul 2.

Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.

Accelerated epigenetic aging relative to chronological age has been found to be associated with higher risk of mortality in adults. However, little is known about whether and how in utero exposures might shape child gestational epigenetic age (EA) at birth. We aimed to explore associations between maternal psychosocial risk factors and deviation in child gestational EA at birth (i.e., greater or lower EA relative to chronological age) in a South African birth cohort study-the Drakenstein Child Health Study. Maternal psychosocial risk factors included trauma/stressor exposure; posttraumatic stress disorder (PTSD); depression; psychological distress; and alcohol/tobacco use. Child gestational EA at birth was calculated using an epigenetic clock previously devised for neonates; and gestational EA deviation was calculated as the residuals of the linear model between EA and chronological gestational age. Bivariate linear regression was then used to explore unadjusted associations between maternal/child risk factors and child gestational EA residuals at birth. Thereafter, a multivariable regression method was used to determine adjusted associations. Data from 271 maternal-child dyads were included in the current analysis. In the multivariable regression model, maternal PTSD was significantly and negatively associated with child gestational EA residuals at birth (β = -1.95; p = 0.018), controlling for study site, sex of the child, head circumference at birth, birthweight, mode of delivery, maternal estimated household income, body mass index (BMI) at enrolment, HIV status, anaemia, psychological distress, and prenatal tobacco or alcohol use. Given the novelty of this preliminary finding, and its potential translational relevance, further studies to delineate underlying biological pathways and to explore clinical implications of EA deviation are warranted.
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http://dx.doi.org/10.1038/s41398-021-01434-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253754PMC
July 2021

Central white matter integrity alterations in 2-3-year-old children following prenatal alcohol exposure.

Drug Alcohol Depend 2021 08 24;225:108826. Epub 2021 Jun 24.

Department of Pediatrics and Child Health, University of Cape Town, South Africa; Neuroscience Institute, University of Cape Town, South Africa.

Background: Prenatal alcohol exposure (PAE) remains a potentially preventable, but pervasive risk factor to neurodevelopment. Yet, evidence is lacking on the impact of alcohol on brain development in toddlers. This study aimed to investigate the impact of PAE on brain white matter integrity in 2-3-year-old children.

Methods: Children (n = 83, 30-37 months old) of the Drakenstein Child Health Study birth cohort, underwent diffusion MRI on a 3 T Siemens scanner during natural sleep. Parameters were extracted in children with PAE (n = 25, 56 % boys) and unexposed controls (n = 58, 62 % boys) using Tract-based Spatial Statistics, and compared by group. The contribution of maternal tobacco smoking to white matter differences was also explored.

Results: Children with PAE had altered fractional anisotropy, radial diffusivity and axial diffusivity in brain stem, limbic and association tracts compared to unexposed controls. Notably lower fractional anisotropy was found in the uncinate fasciculus, and lower mean and radial diffusivity were found in the fornix stria terminalis and corticospinal tract (FDR corrected p < 0.05). There was a significant interaction effect of PAE and prenatal tobacco exposure which lowered mean, radial and axial diffusivity in the corticospinal tract significantly in the PAE group but not controls.

Conclusion: Widespread altered white matter microstructural integrity at 2-3 years of age is consistent with findings in neonates in the same and other cohorts, indicating persistence of effects of PAE through early life. Findings also highlight that prenatal tobacco exposure impacts the association of PAE on white matter alterations, amplifying effects in tracts underlying motor function.
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http://dx.doi.org/10.1016/j.drugalcdep.2021.108826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299546PMC
August 2021
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