Country-level gender inequality is associated with structural differences in the brains of women and men.

Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality.

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup.

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. These findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in higher-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

Fronto-limbic white matter microstructural changes in psychiatrically healthy adults with childhood trauma.

Childhood trauma (CT) may influence brain white matter microstructure; however, few studies have examined the differential impact of distinct CT types on white matter microstructure in psychiatrically healthy adults living in a developing country. In adults without significant medical or psychiatric disorders, we investigated the association(s) between CT, including abuse and neglect, and fractional anisotropy (FA) of limbic tracts previously shown to be associated with CT. Participants underwent diffusion tensor imaging and completed the Childhood Trauma Questionnaire. Multivariate analysis of variance models were used to test the effects of total overall CT, as well as CT subtypes, on FA in six fronto-limbic tracts, adjusting for age, sex, and educational level. The final sample included 69 adults (age 47 ± 17 years; 70% female). Overall, CT had a significant main effect on FA for tracts of interest (p < .001). Greater CT severity was associated with lower FA for the bilateral and left stria terminalis (uncorrected) as well as the bilateral, left, and right anterior limb of the internal capsule (ALIC; corrected). Exposure to total non-violent/deprivational trauma specifically was associated with lower FA of the bilateral, left, and right ALIC, suggesting that distinct types of CT are associated with differential white matter changes in apparently healthy adults. The ALIC predominantly carries fibers connecting the thalamus with prefrontal cortical regions. Microstructural alterations in the ALIC may be associated with functional brain changes, which may be adaptive or increase the risk of accelerated age-related cognitive decline, maladaptive behaviors, and subsyndromal psychiatric symptoms.

Antipsychotic treatment effects and structural MRI brain changes in schizophrenia.

BACKGROUND: Progressive brain structural MRI changes are described in schizophrenia and have been ascribed to both illness progression and antipsychotic treatment. We investigated treatment effects, in terms of total cumulative antipsychotic dose, efficacy and tolerability, on brain structural changes over the first 24 months of treatment in schizophrenia. METHODS: A prospective, 24-month, single-site cohort study in 99 minimally treated patients with first-episode schizophrenia, schizophreniform and schizoaffective disorder, and 98 matched healthy controls. We treated the patients according to a fixed protocol with flupenthixol decanoate, a long-acting injectable antipsychotic. We assessed psychopathology, cognition, extrapyramidal symptoms and BMI, and acquired MRI scans at months 0, 12 and 24. We selected global cortical thickness, white matter volume and basal ganglia volume as the regions of interest. RESULTS: The only significant group × time interaction was for basal ganglia volumes. However, patients, but not controls, displayed cortical thickness reductions and increases in white matter and basal ganglia volumes. Cortical thickness reductions were unrelated to treatment. White matter volume increases were associated with lower cumulative antipsychotic dose, greater improvements in psychopathology and cognition, and more extrapyramidal symptoms. Basal ganglia volume increases were associated with greater improvements in psychopathology, greater increases in BMI and more extrapyramidal symptoms. CONCLUSIONS: We provide evidence for plasticity in white matter and basal ganglia associated with antipsychotic treatment in schizophrenia, most likely linked to the dopamine blocking actions of these agents. Cortical changes may be more closely related to the neurodevelopmental, non-dopaminergic aspects of the illness.

Obesity and brain structure in schizophrenia - ENIGMA study in 3021 individuals.

Schizophrenia is frequently associated with obesity, which is linked with neurostructural alterations. Yet, we do not understand how the brain correlates of obesity map onto the brain changes in schizophrenia. We obtained MRI-derived brain cortical and subcortical measures and body mass index (BMI) from 1260 individuals with schizophrenia and 1761 controls from 12 independent research sites within the ENIGMA-Schizophrenia Working Group. We jointly modeled the statistical effects of schizophrenia and BMI using mixed effects. BMI was additively associated with structure of many of the same brain regions as schizophrenia, but the cortical and subcortical alterations in schizophrenia were more widespread and pronounced. Both BMI and schizophrenia were primarily associated with changes in cortical thickness, with fewer correlates in surface area. While, BMI was negatively associated with cortical thickness, the significant associations between BMI and surface area or subcortical volumes were positive. Lastly, the brain correlates of obesity were replicated among large studies and closely resembled neurostructural changes in major depressive disorders. We confirmed widespread associations between BMI and brain structure in individuals with schizophrenia. People with both obesity and schizophrenia showed more pronounced brain alterations than people with only one of these conditions. Obesity appears to be a relevant factor which could account for heterogeneity of brain imaging findings and for differences in brain imaging outcomes among people with schizophrenia.

The Effect of Statins on Male Reproductive Parameters: A Mechanism Involving Dysregulation of Gonadal Hormone Receptors and TRPV1.

Statins have been shown to cause diverse male reproductive function impairment, and in some cases, orchialgia. Therefore, the current study investigated the possible mechanisms through which statins may alter male reproductive parameters. Thirty adult male Wistar rats (200-250 g) were divided into three groups. The animals were orally administered rosuvastatin (50 mg/kg), simvastatin (50 mg/kg), or 0.5% carboxy methyl cellulose (control), for a 30-day period. Spermatozoa were retrieved from the caudal epididymis for sperm analysis. The testis was used for all biochemical assays and immunofluorescent localization of biomarkers of interest. Rosuvastatin-treated animals presented with a significant decrease in sperm concentration when compared to both the control and simvastatin groups (p < 0.005). While no significant difference was observed between the simvastatin and the control group. The Sertoli cells, Leydig cells and whole testicular tissue homogenate expressed transcripts of solute carrier organic anion transporters (SLCO1B1 and SLCO1B3). There was a significant decrease in the testicular protein expression of the luteinizing hormone receptor, follicle stimulating hormone receptor, and transient receptor potential vanilloid 1 in the rosuvastatin and simvastatin-treated animals compared to the control. The expression of SLCO1B1, SLCO1B2, and SLCO1B3 in the different spermatogenic cells portray that un-bio transformed statin can be transported into the testicular microenvironment, which can subsequently alter the regulation of the gonadal hormone receptors, dysregulate pain-inflammatory biomarkers, and consequently impair sperm concentration.

Childhood trauma exposure and reward processing in healthy adults: A functional neuroimaging study.

The association between childhood trauma exposure and risk of developing psychopathology may in part be mediated by the effects of chronic stress on dopaminergic neurotransmission. However, little is known about the differential effects of distinct trauma types on reward processing, particularly in adults without concurrent medical or psychiatric disorders. We examined the association of childhood trauma exposure, including the differential effects of abuse and neglect, with reward processing in healthy adults (n = 114). Functional magnetic resonance imaging during a monetary incentive delay task was used to assess neural activity in the ventral striatum and orbitofrontal cortex in relation to reward anticipation and reward outcome, respectively. Exposure to childhood trauma, including abuse and neglect, was assessed using the Childhood Trauma Questionnaire-Short Form. We found a significant effect for abuse on ventral striatal activation during reward anticipation, adjusting for age, sex, scanner site, educational level, and household monthly income. There were no effects for abuse or neglect, independently or combined, on orbitofrontal cortex activation during reward outcome. Our findings suggest differential effects of childhood abuse on ventral striatum activation during reward anticipation in healthy adults.

Hazardous or harmful alcohol use and reward processing in people with HIV.

The intersecting epidemics of HIV and hazardous or harmful alcohol use (HAU) can have significant detrimental consequences. Both HIV and HAU have independent negative influences on executive function. Dysfunction in reward processing may play a role in these co-occurring epidemics. In this cross-sectional case-control study, we investigated the association of HAU with reward processing amongst people with HIV (PWH). We investigated the function of the ventral-striatal reward system using a functional MRI (fMRI) monetary incentive delay (MID) task in a sample of 60 South African adults (mean age 32.7 years): 42 living with HIV and on ART (21 with harmful alcohol use [HIV + HAU], 21 without [HIV-HAU]) and 18 healthy controls, matched for age, gender, and resident community. Education significantly influenced task performance, with those with a secondary level of education demonstrating a greater increase in reaction time (p = 0.048) and accuracy (p = 0.002) than those without. There were no significant differences in reward anticipation in the ventral striatum (VS) between HIV + HAU, HIV-HAU, and healthy controls when controlling for level of education. There were also no significant differences in reward outcome in the orbitofrontal cortex (OFC) between HIV + HAU, HIV-HAU, and healthy controls when controlling for level of education. In a sample of South African adults, we did not demonstrate significant differences in reward anticipation in the VS and reward outcome in the OFC in PWH, with and without HAU, and controls. Factors, such as task performance, education, and depression may have influenced our results. Further studies are needed to better delineate the potential links between HIV, HAU, and depression and reward system function.

Standards in semen examination: publishing reproducible and reliable data based on high-quality methodology.

Biomedical science is rapidly developing in terms of more transparency, openness and reproducibility of scientific publications. This is even more important for all studies that are based on results from basic semen examination. Recently two concordant documents have been published: the 6th edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, and the International Standard ISO 23162:2021. With these tools, we propose that authors should be instructed to follow these laboratory methods in order to publish studies in peer-reviewed journals, preferable by using a checklist as suggested in an Appendix to this article.

Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium.

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d = -0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.

Bisphenol A and Male Infertility: Role of Oxidative Stress.

Bisphenol A (BPA) is an endocrine-disrupting chemical that is capable of mimicking, antagonizing, and interfering with the normal biological functioning of the endocrine system. BPA is used in diverse industries, hence its vast sources of exposure. Although the half-life of BPA is relatively short (<24 hours), studies have reported its detection in the urine of different populations. It, therefore, became important to investigate its effect on general health, including male reproductive health. The adverse effects of BPA on male fertility have been evaluated and reported from both in vivo and in vitro studies. Up to date, reports from randomized controlled trials remain controversial, as some revealed decreased sperm quality, sperm concentration, and total sperm count, while others reported that no adverse effect was seen after exposure. Findings from animal model studies and in vitro experiments have shown that exposure to BPA led to a reduction in sperm quality and increased sperm DNA fragmentation, and some even revealed altered expression of the gene that encodes gonadotropin-releasing hormone. This shows that BPA not only may adversely affect male fertility by acting as an endocrine disruptor but also can potentially impact male fertility via its possible contribution to oxidative stress. Therefore, this book chapter aims to identify and elucidate the effect of BPA exposure on male fertility, and to as well illustrate the mechanisms through which this occurs, while emphasizing the role of oxidative stress as a potential pathway.

Computational Analysis of Short Linear Motifs in the Spike Protein of SARS-CoV-2 Variants Provides Possible Clues into the Immune Hijack and Evasion Mechanisms of Omicron Variant.

Short linear motifs (SLiMs) are short linear sequences that can mediate protein-protein interaction. Mimicking eukaryotic SLiMs to compete with extra- or intracellular binding partners, or to sequester host proteins is the crucial strategy of viruses to pervert the host system. Evolved proteins in viruses facilitate minimal protein-protein interactions that significantly affect intracellular signaling networks. Unfortunately, very little information about SARS-CoV-2 SLiMs is known, especially across SARS-CoV-2 variants. Through the ELM database-based sequence analysis of spike proteins from all the major SARS-CoV-2 variants, we identified four overriding SLiMs in the SARS-CoV-2 Omicron variant, namely, LIG_TRFH_1, LIG_REV1ctd_RIR_1, LIG_CaM_NSCaTE_8, and MOD_LATS_1. These SLiMs are highly likely to interfere with various immune functions, interact with host intracellular proteins, regulate cellular pathways, and lubricate viral infection and transmission. These cellular interactions possibly serve as potential therapeutic targets for these variants, and this approach can be further exploited to combat emerging SARS-CoV-2 variants.

Guinness World Record: Personal Experience and Physiological Responses of a Non-Professional Athlete Successfully Covering 620 Km in 7-Days by Foot Across the United Arab Emirates.

Ultra-endurance record-breaking attempts place significant metabolic, cardiovascular, and mechanical stress on the athlete. This research explores the personal experience and physiological responses of a non-professional athlete attempting the Guinness World Record of covering 620 km on foot across the United Arab Emirates in 7-days or less. The participant wore a smartwatch throughout the challenge to collect heart rate, activity, and environmental temperature data. Anthropometric, body composition, and inflammatory, haematological, and endocrine biomarkers measurements were completed pre- and post-event. A pre- and post-event interview was conducted to collect data on training and preparation, and self-reported experiences during the challenge. Despite episodes of diarrhoea, vomiting, and muscle cramps due to hypohydration during the first days of the challenge, the participant successfully completed 619.01 km in six days, 21 hours, and 47 minutes (average pace 10.11 min/km) achieving a new Guinness World Record. Body mass remained unchanged, fat mass decreased, and fat-free mass especially in the legs increased over the seven days, most likely due to water retention. Biomarkers of stress, cell damage, and inflammation increased. Haematological markers related to red blood cells decreased probably due to exercise-induced increases in plasma volume with the participant classified with mild anaemia post-event. This case study reinforces the importance of amateur athletes attempting similar ultra-endurance events adhering to a pre-planned hydration and nutrition strategy to maximise performance and minimise the risk of injury.

Fertility and pregnancy outcome among women undergoing assisted reproductive technology treatment in Windhoek, Namibia.

PURPOSE: Infertility has been defined as a couple's failure to conceive after regular and unprotected coitus for 1 year or six months, depending on the age of the female counterpart. Although infertility can result from both the male and/or the female, often the female partner faces pressure since it is believed in some African cultures that a woman without children is like a tree without leaves. The aim of this study was to determine the prevalence of successful pregnancy outcomes among infertile women undergoing assisted reproductive technology (ART) treatment at the Cape Windhoek Fertility Clinic. METHODS: This was a prospective and descriptive cross-sectional case reference study encompassing 178 infertile women visiting the Cape Windhoek Fertility Clinic for ART treatment. RESULTS: The vast majority of the participants (81.5%) were married women. From the 178 infertile women, 96 (53.9%) suffered from primary and 82 (46.1%) from secondary infertility. The predominant cause of complications for infertility among the women studied was defective ovulation (28.7%) and the most common ART treatment administered was IVF/ICSI (52.2%). Only a third (33.1%) of the women who received ART treatment eventually fell pregnant. CONCLUSION: The outcome of this study may not give a clear indication of the prevalence of infertility among women in the entire Namibian nation due to the costs involved with ART treatment offered mainly at privately owned hospitals and/or clinics, thereby resulting in those who cannot afford treatment to be left out despite being infertile.

The Role of Selected Natural Biomolecules in Sperm Production and Functionality.

Emerging evidence from in vivo as well as in vitro studies indicates that natural biomolecules may play important roles in the prevention or management of a wide array of chronic diseases. Furthermore, the use of natural compounds in the treatment of male sub- or infertility has been proposed as a potential alternative to conventional therapeutic options. As such, we aimed to evaluate the effects of selected natural biomolecules on the sperm production, structural integrity, and functional activity. At the same time, we reviewed their possible beneficial or adverse effects on male reproductive health. Using relevant keywords, a literature search was performed to collect currently available information regarding molecular mechanisms by which selected natural biomolecules exhibit their biological effects in the context of male reproductive dysfunction. Evidence gathered from clinical trials, in vitro experiments and in vivo studies suggest that the selected natural compounds affect key targets related to sperm mitochondrial metabolism and motion behavior, oxidative stress, inflammation, DNA integrity and cell death. The majority of reports emphasize on ameliorative, stimulating and protective effects of natural biomolecules on the sperm function. Nevertheless, possible adverse and toxic behavior of natural compounds has been indicated as well, pointing out to a possible dose-dependent impact of natural biomolecules on the sperm survival and functionality. As such, further research leading to a deeper understanding of the beneficial or adverse roles of natural compounds is necessary before these can be employed for the management of male reproductive dysfunction.

Increased power by harmonizing structural MRI site differences with the ComBat batch adjustment method in ENIGMA.

A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address this heterogeneity with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether the batch adjustment method, ComBat, can further reduce site-related heterogeneity and thus increase statistical power. We conducted random-effects meta-analyses, mixed-effects mega-analyses and ComBat mega-analyses to compare cortical thickness, surface area and subcortical volumes between 2897 individuals with a diagnosis of schizophrenia and 3141 healthy controls from 33 sites. Specifically, we compared the imaging data between individuals with schizophrenia and healthy controls, covarying for age and sex. The use of ComBat substantially increased the statistical significance of the findings as compared to random-effects meta-analyses. The findings were more similar when comparing ComBat with mixed-effects mega-analysis, although ComBat still slightly increased the statistical significance. ComBat also showed increased statistical power when we repeated the analyses with fewer sites. Results were nearly identical when we applied the ComBat harmonization separately for cortical thickness, cortical surface area and subcortical volumes. Therefore, we recommend applying the ComBat function to attenuate potential effects of site in ENIGMA projects and other multi-site structural imaging work. We provide easy-to-use functions in R that work even if imaging data are partially missing in some brain regions, and they can be trained with one data set and then applied to another (a requirement for some analyses such as machine learning).

Hair cortisol levels in posttraumatic stress disorder and metabolic syndrome.

Individuals with post-traumatic stress disorder (PTSD) evidence increased rates of metabolic syndrome (MetS), and both PTSD and MetS are associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis function. Few investigations have examined the possible role of HPA-axis dysfunction in the co-occurrence of PTSD and MetS. In a case-control study, we aimed to determine whether hair cortisol concentrations (HCC) were associated with (i) PTSD caseness and severity and (ii) PTSD and MetS co-occurrence. We used the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) to determine PTSD diagnoses and severity scores in 216 females of mixed ancestry aged between 20 and 79 years (M = 43.8, SD =13.3). Hair samples, representing a three-month retrospective window of cortisol levels, were obtained and analyzed utilizing liquid chromatography-tandem mass spectrometry. We constructed multivariate linear regression models to evaluate whether PTSD diagnosis, PTSD severity, and MetS comorbidity were associated with HCC, controlling for potential confounders. HCC were significantly higher (adj ß = 0.154, p = .033; Cohen's d = 0.44) in PTSD patients (n = 110) than trauma-exposed controls (n = 106) and CAPS severity scores (adj ß = 0.207, p = .005) were significantly associated with HCC. MetS was not associated with HCC and there were no significant interactions between PTSD and MetS on HCC. This study provides evidence of a chronically dysregulated neuroendocrine mediated stress response in PTSD, with a clear dose-response relationship. HCC do not, however, appear to have specificity for the comorbidity of PTSD and MetS in this sample.LAY SUMMARYWe found that levels of the stress hormone, cortisol, measured in hair samples were significantly higher in South African women with post-traumatic stress disorder (PTSD) than in women who had also experienced trauma but did not have PTSD. Hair cortisol levels were, however, not associated with metabolic syndrome, a cluster of risk factors for heart disease, in the women studied. We thus show that South African women with PTSD have elevated long-term stress hormone levels and that this effect is related to PTSD and not solely due to trauma exposure.

SARS-CoV-2 and the testis: similarity with other viruses and routes of infection.

Since the start of the latest coronavirus (SARS-CoV-2) outbreak, the number of infected individuals and cases of coronavirus disease (COVID-19) has been increasing exponentially worldwide. Of interest is existing evidence that orchitis can develop due coronavirus infection. It is therefore not unreasonable to believe that SARS-CoV-2 could be transmitted by semen. Consequently, it is of paramount importance that individuals who could potentially be infected take all possible care to mitigate the likely risk of passing on the infection through sexual intercourse.

The Uruguayan semen donor population: A twenty-eight-year retrospective study.

Several studies have reported a global decline in seminal quality over the years. The objective of this study was to describe the semen donor population of Uruguay through comparing data of successive samples banked by the same donors and the analysis of their semen and physical characteristics, ancestry origin and educational level. A total of 3,449 ejaculated samples collected from 71 donors, cryobanked between 1989 and March 2017 at Fertilab, were analysed. Results revealed a mean age of 23.90 ± 3.98 years, an average weight of 74.95 ± 1.09 kg and a mean height of 1.78 ± 0.06 m. The majority of the donors trace their origin to Europe (74.65%, 53/71) and 66.19% (47/71) have a level of education higher than secondary school. We observed longitudinal differences in two parameters, that is sperm concentration and semen volume. Sperm concentration declined, while semen volume increased significantly over the 28-year period. The results of the present study are in accordance with that of previous articles that also reported a decline in sperm concentration over time. However, no differences were observed in total sperm number per ejaculate due to the increase in semen volume values, thus reflecting no real changes in sperm production over time.

Efavirenz is associated with altered fronto-striatal function in HIV+ adolescents.

Neurotoxicity associated with the antiretroviral efavirenz (EFV) has been documented in HIV-infected adults, but there are no data on the impact of EFV on brain function in adolescents. We investigated potential alterations in fronto-striatal function associated with EFV use in adolescents. A total of 86 adolescents underwent a Stop Signal Anticipation Task (SSAT) during functional MRI (fMRI), 39 HIV+ adolescents receiving EFV, 27 HIV+ adolescents on antiretroviral therapy without EFV (matched on age, gender, education, CD4 cell count and HIV viral load) and 20 HIV- matched controls (matched on age and gender). The task required participants to give timed GO responses with occasional STOP signals at fixed probabilities. Reactive inhibition was modelled as a correct STOP response and proactive inhibition was modelled after response slowing as the STOP probability increases. A priori mask-based regions associated with reactive and proactive inhibition were entered into two respective multivariate ANOVAs. The EFV treatment group showed significantly blunted proactive inhibitory behavioural responses compared to HIV+ adolescents not receiving EFV. There was no difference in reactive inhibition between treatment groups. We also demonstrated a significant effect of EFV treatment on BOLD signal in proactive inhibition regions. There was no difference in regions involved in reactive inhibition. We found no differences between adolescents not receiving EFV and HIV- controls, showing that functional and behavioural differences were unique to the EFV group. Here, we demonstrate for the first time a potential adverse impact of EFV on higher cortical function in young HIV+ adolescents.