Motivation levels and white matter microstructure in children living with HIV.

Central nervous system involvement in HIV infection leads to neurobehavioural sequelae. Although apathy is a well-recognised symptom in adults living with HIV linked to alterations in brain structure, there is scarce research examining motivation in children living with HIV (CLWH). We used the Children's Motivation Scale (CMS; normative mean = 50, SD = 10) to assess motivation levels in 76 CLWH aged 6-16 years (63 on antiretroviral therapy [ART]; 13 ART-naïve slow progressors) in South Africa. Overall, CLWH scored low on the CMS (mean = 35.70 [SD = 5.87]). Motivation levels were significantly reduced in children taking ART compared to ART-naïve slow progressors (p = 0.02), but were not correlated with markers of HIV disease (CD4 + cell count or viral load), or neurocognitive function (p > 0.05). CMS scores were correlated with diffusion tensor imaging metrics of white matter microstructure in specific frontostriatal brain regions (p < 0.05). On multiple regression, associations with the anterior limb of the internal capsule, a subcortical white matter region, remained significant after adjusting for potential confounders. These findings suggest that reduced motivation may be an important neurobehavioural symptom in CLWH and may reflect changes in white matter microstructure of frontostriatal brain regions.

Shape analysis of subcortical structures in obsessive-compulsive disorder and the relationship with comorbid anxiety, depression, and medication use: A meta-analysis by the OCD Brain Imaging Consortium.

OBJECTIVE: Neuroimaging studies of obsessive-compulsive disorder (OCD) patients have highlighted the important role of deep gray matter structures. Less work has however focused on subcortical shape in OCD patients. METHODS: Here we pooled brain MRI scans from 412 OCD patients and 368 controls to perform a meta-analysis utilizing the ENIGMA-Shape protocol. In addition, we investigated modulating effects of medication status, comorbid anxiety or depression, and disease duration on subcortical shape. RESULTS: There was no significant difference in shape thickness or surface area between OCD patients and healthy controls. For the subgroup analyses, OCD patients with comorbid depression or anxiety had lower thickness of the hippocampus and caudate nucleus and higher thickness of the putamen and pallidum compared to controls. OCD patients with comorbid depression had lower shape surface area in the thalamus, caudate nucleus, putamen, hippocampus, and nucleus accumbens and higher shape surface area in the pallidum. OCD patients with comorbid anxiety had lower shape surface area in the putamen and the left caudate nucleus and higher shape surface area in the pallidum and the right caudate nucleus. Further, OCD patients on medication had lower shape thickness of the putamen, thalamus, and hippocampus and higher thickness of the pallidum and caudate nucleus, as well as lower shape surface area in the hippocampus and amygdala and higher surface area in the putamen, pallidum, and caudate nucleus compared to controls. There were no significant differences between OCD patients without co-morbid anxiety and/or depression and healthy controls on shape measures. In addition, there were also no significant differences between OCD patients not using medication and healthy controls. CONCLUSIONS: The findings here are partly consistent with prior work on brain volumes in OCD, insofar as they emphasize that alterations in subcortical brain morphology are associated with comorbidity and medication status. Further work is needed to understand the biological processes contributing to subcortical shape.

Childhood Trauma and Mental Health in the Cape Town Adolescent Antiretroviral Cohort.

This study aimed to assess the association of childhood trauma, stressful life events and HIV stigma with mental health in South African adolescents from the Cape Town Adolescent Antiretroviral Cohort (CTAAC). The Childhood Trauma Questionnaire, Life Events Questionnaire and the HIV Stigma Scale for South African Adolescents Living with HIV was used to assess childhood trauma, stressful life events and stigma in adolescents living with perinatally acquired HIV and healthy controls enrolled in the CTAAC. These measures were associated with mental health outcomes including the Beck-Youth Inventories, Child Behaviour Checklist, Columbian Impairment Scale, Childrens Motivation Scale, Conners Scale for Attention Deficit Hyperactivity Disorder using Pearson correlations and self-reported alcohol use, using Spearman-rank correlation. 63.7% of adolescents reported at least one childhood trauma on the CTQ. Significant associations were reported between CTQ measures and Beck-Youth Inventories. Emotional abuse was associated with anxiety, anger, depression and disruptive behaviour. Emotional neglect was associated with poor self-concept and disruptive behaviour. LEQ total score was significantly associated with Beck-Youth Inventories including anxiety, depression, anger and disruptive behaviour scales. HIV stigma was significantly associated with Beck-Youth Inventories including depression, anger and disruptive behaviour. Childhood trauma, stressful life events and HIV stigma in South African adolescents are associated with anxiety, depression, anger, disruptive-behaviour and poor self-concept. This study highlights the importance of enquiring about exposure to a variety of traumas, particularly those commonly experienced by South African adolescents. In addition, it is important to understand the impact of trauma exposure on each individuals mental health and functioning.

Limited evidence for a moderating effect of HIV status on brain age in heavy episodic drinkers.

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

Global Systematic Review of Common Mental Health Disorders in Adults Living with HIV.

PURPOSE OF THE REVIEW: By reviewing the most recent common mental health disorders (CMHD) studies in people living with HIV (PLWH) (2018-2020), this review discusses the prevalence of CMHD, factors associated with CMHD in PLWH, mental health in PLWH from vulnerable groups, the impact of CMHD on HIV disease progression and adherence to antiretroviral therapy and the efficacy of different treatment approaches. RECENT FINDINGS: After screening for eligibility 142 studies were included in the final systematic review. Only 27% of studies were conducted in Sub-Saharan Africa, which carries the highest burn of HIV disease globally. Despite the well-established increased risk of CMHD in PLWH, the current prevalence remains high, with studies reporting 28%-62% of PLWH having mental health symptoms. CONCLUSION: Despite the significant challenges that CMHDs present to successful HIV treatment, there are many mental health treatments and interventions which can improve outcomes in PLWH and opportunities to task-shift and integrate mental health care with HIV care.

Association of maternal and infant inflammation with neurodevelopment in HIV-exposed uninfected children in a South African birth cohort.

HIV-exposed uninfected (HEU) children may have altered immune regulation and poorer neurodevelopment outcomes compared to their HIV-unexposed (HU) counterparts. However, studies investigating the association of maternal and infant inflammation with neurodevelopment in HEU children are limited and longitudinal data are lacking. This study investigated serum inflammatory markers in women living with HIV vs. HIV-uninfected women during pregnancy and in their children, as well as associations with neurodevelopmental outcomes at two years of age in an African birth cohort study. A sub-group of mother-child dyads from the Drakenstein Child Health Study had serum inflammatory markers measured at ≈26 week's gestation (n = 77 HIV-infected mothers; n = 190 HIV-uninfected mothers), at 6-10 weeks (n = 63 HEU infants and n = 159 HU infants) and at 24-28 months (n = 77 HEU children and n = 190 HU children). Serum inflammatory markers [granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ), interleukin IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor-α (TNF-α), neutrophil gelatinase-associated lipocalin (NGAL) and metalloproteinase-9 (MMP-9)] were analyzed with a multiplex bead array and ELISA assays. The Bayley Scales of Infant and Toddler Development, third edition, was used to assess neurodevelopment at 24-28 months. After correcting for multiple comparisons, HIV infection during pregnancy was associated with lower serum levels of inflammatory markers in mothers at 26 weeks gestation (GM-CSF and MMP-9, p < 0.05) and HEU children at 6-10 weeks (IFN-γ and IL-1ß, p < 0.01), and at 24-28 months (IFN-γ, IL-1ß, IL-2 and IL-4, p < 0.05) compared to HIV-uninfected mothers and HU children. In HEU infants at 6-10 weeks, inflammatory markers (GM-CSF, IFN-γ, IL-10, IL-12p70, IL-1ß, IL-2, IL-4, IL-6 and NGAL, all p < 0.05) were associated with poorer motor function at two years of age. This is the first study to evaluate the associations of follow-up immune markers in HEU children with neurodevelopment. These findings suggest that maternal HIV infection is associated with immune dysregulation in mothers and their children through two years of age. An altered immune system in HEU infants is associated with poorer follow-up motor neurodevelopment. These data highlight the important role of the immune system in early neurodevelopment and provide a foundation for future research.

Welfare and Scientific Considerations of Tattooing and Ear Tagging for Mouse Identification.

Ear tagging is perceived as less painful or stressful than tattooing and therefore is generally considered less harmful or costly to welfare. However, ear tags are more difficult to read than tattoos and can fall out, and mice usually require restraint for the tag numbers to be read accurately. We assessed the welfare and scientific implications of tattooing by using a commercial device compared with restraint in a device versus ear tagging. Male and female BALB/c mice (n = 32) underwent procedures after 1 wk of tail or nonaversive (tunnel) handling to determine whether tunnel handling reduced anxiety. Pain was evaluated using both the Mouse Grimace Scale (MGS) and manual and automated behavior analyses; light-dark preference testing and voluntary interaction with the handler's hand were used to assess anxiety. Tail inflammation after tattooing was quantified using bioluminescent imaging, and ear tag and tattoo misidentification rates were estimated from volunteer staff records. Tunnel handling reduced anxiety compared with tail handling. According to the MGS, tattooing was not more painful than ear tagging but caused significant tail inflammation and more agitation and anxiety. However, all tattoos were read correctly without handling, whereas all ear tagged mice needed restraint, and at least 25% of the tag codes were misread. Handling stress together with identification errors at this rate represent potentially serious concerns regarding the scientific integrity of data from studies using ear tagging. These concerns are unlikely to arise with tattooing. Although tattooing was stressful, so were restraint and ear tagging. However, considering the other major advantages of tattooing, the total costs associated with tattooing were not substantially greater than for ear tagging.