Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures.

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.

Examining the association between posttraumatic stress disorder and disruptions in cortical networks identified using data-driven methods.

Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensionality reduction, we sought to conduct a well-powered study to identify vulnerable networks without regard to neuroanatomic boundaries. Moreover, this approach enabled us to avoid the excessive burden of multiple comparison correction that plagues vertex-wise methods. We derived structural covariance networks (SCNs) by applying non-negative matrix factorization (NMF) to CT data from 961 PTSD patients and 1124 trauma-exposed controls without PTSD. We used regression analyses to investigate associations between CT within SCNs and PTSD diagnosis (with and without accounting for the potential confounding effect of trauma type) and symptom severity in the full sample. We performed additional regression analyses in subsets of the data to examine associations between SCNs and comorbid depression, childhood trauma severity, and alcohol abuse. NMF identified 20 unbiased SCNs, which aligned closely with functionally defined brain networks. PTSD diagnosis was most strongly associated with diminished CT in SCNs that encompassed the bilateral superior frontal cortex, motor cortex, insular cortex, orbitofrontal cortex, medial occipital cortex, anterior cingulate cortex, and posterior cingulate cortex. CT in these networks was significantly negatively correlated with PTSD symptom severity. Collectively, these findings suggest that PTSD diagnosis is associated with widespread reductions in CT, particularly within prefrontal regulatory regions and broader emotion and sensory processing cortical regions.

Efficacy of a dialogic book-sharing intervention in a South African birth cohort: A randomized controlled trial.

OBJECTIVE: Evidence shows that dialogic book-sharing improves language development in young children in low-middle income countries (LMICs), particularly receptive and expressive language. It is unclear whether this intervention also boosts development of other neurocognitive and socio-emotional domains in children. Using a randomized controlled trial (RCT) nested in the Drakenstein Child Health Study (DCHS), a book-sharing intervention was implemented in caregivers of 3.5-year-old preschool children living in low-income South African communities. METHODS: 122 Caregivers and their children (mean age 3.5 years) were randomly assigned to an intervention group (n = 61) or waitlist control group (n = 61). A neurocognitive battery determined baseline receptive and expressive language, executive function, theory of mind, and behavior scores. RESULTS: No differences were observed between intervention and control groups on receptive and expressive language, or any of the neurocognitive or socio-emotional measures from baseline (3.5 years) to 4 months post-intervention administration (4 years). CONCLUSION: The benefits noted in prior literature of book-sharing in infants did not appear to be demonstrated at 4 months post-intervention, in children from 3.5 to 4 years of age. This suggests the importance of early intervention and emphasizes the need for further research on adaptation of book-sharing for older participants in a South African context. TRIAL REGISTRATION: retrospectively registered on 03/04/2022 PACTR202204697674974.

PTSD and comorbid MDD is associated with activation of the right frontoparietal network.

There is growing evidence of abnormalities in intrinsic functional connectivity (FC) in posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). However, there has been less work on the commonly occurring co-presentation of PTSD and MDD. Characterising intrinsic FC abnormalities in this clinical population is important for understanding how they may contribute towards impairments underpinned by different networks. Participants were mothers enroled in the Drakenstein Child Health Study from Western Cape, South Africa. Mothers between 18 and 50 years of age were recruited and divided into 4 groups: PTSD, MDD, PTSD with MDD, and healthy controls. Participants underwent resting-state fMRI at the 18-month postpartum time point. Functional connectivity within and between higher order cognitive control networks, including the salience, dorsal attention, frontoparietal, and default mode networks were compared across the 4 groups. PTSD with comorbid MDD was associated with greater intrinsic FC within the R FPAR, relative to controls and the mono-diagnostic groups. Intrinsic FC differences were observed within the default mode network for the MDD group. No group differences in connectivity between networks were observed. Differential intrinsic connectivity in participants with comorbidity are consistent with evidence that such individuals have more severe illness and require more robust intervention.

Executive function in methamphetamine users with and without psychosis.

Methamphetamine abuse is associated with cognitive deficits across a wide range of domains. It is unclear, however, whether methamphetamine-dependent individuals with co-occurring psychosis are more impaired than those without psychosis on tests assessing executive function. We therefore aimed to compare the executive function performance of three groups: methamphetamine-dependent individuals with methamphetamine-induced psychosis (MA+; n = 20), methamphetamine-dependent individuals without psychosis (MA-; n = 19), and healthy controls (HC; n = 20). All participants were administered a neuropsychological test battery that assessed executive functioning across six sub domains (problem solving, working memory, verbal generativity, inhibition, set switching, and decision making). Analyses of covariance (controlling for between-group differences in IQ) detected significant between-group differences on tests assessing verbal generativity and inhibition, with MA+ participants performing significantly more poorly than HC. The finding that methamphetamine-induced psychosis is associated with performance impairments in particular subdomains of executive function may have implications for treatment adherence and relapse prevention.

Antenatal maternal depression, early life inflammation and neurodevelopment in a South African birth cohort.

BACKGROUND: Antenatal exposure to maternal psychological adversity, including depression, increases the risk of impaired neurodevelopment in children. The underlying biological mechanisms remain unclear, especially in early life during critical windows of development and maturation. This study investigated the association of antenatal maternal depression, maternal and early life inflammatory markers and neurodevelopmental outcomes in children at 2 years of age. METHODS: A subgroup of mothers and their children (n = 255) that were enrolled in a South African birth cohort study, the Drakenstein Child Health Study, were followed from the antenatal period through to 2 years of child age. Maternal depressive symptoms were measured by the Beck Depression Inventory (BDI-II) at 26 weeks gestation. 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, tumour necrosis factor-α (TNF-α), neutrophil gelatinase-associated lipocalin (NGAL) and metalloproteinase-9 (MMP-9)] were measured in mothers at enrolment and in their children at 6-10 weeks and at 2 years. Neurodevelopment was assessed at 2 years using the Bayley Scales of Infant and Toddler Development III. RESULTS: Antenatal depressive symptoms (present in 25% of the mothers) were significantly associated with higher levels of IL-7 (p = 0.008), IL-8 (p = 0.019) and TNF-α (p = 0.031) in the mothers after correcting for sociodemographic and lifestyle factors. Serum IL-1ß and NGAL levels were significantly elevated over time in children born to mothers with depressive symptoms compared to those without depression, after controlling for maternal and child health and sociodemographic factors. Elevated infant IL-1ß at 6-10 weeks of age partially mediated the association of maternal depressive symptoms with poorer language scores at 2 years. CONCLUSION: Alterations in early life immunity, as reflected by elevated IL-1ß, is a potential pathway through which antenatal maternal depressive symptoms may impact language development in young children.

Coulrophobia: An investigation of clinical features.

BACKGROUND: Coulrophobia refers to fear or disgust elicited by clowns, or images of clowns, and may be accompanied by significant distress. The medical literature on sociodemographic and clinical features of coulrophobia is, however, sparse. AIM: This study aimed to investigate coulrophobia sociodemographic and clinical features in an online support group. SETTING: A self-administered questionnaire was distributed to an online support group for coulrophobia. METHODS: Members of the online coulrophobia support group received a link to a self-administered questionnaire. The questionnaire focused on sociodemographic and clinical features, including fear-related and disgust-related symptoms, and included DSM-5 diagnostic criteria for specific phobia. RESULTS: Of the 95 survey respondents, 79 were female respondents (mean age: 39.8 ± 12.6 years), with the mean age of onset 9 ± 6.1 years. Coulrophobia symptoms were associated with significant psychological distress and with impaired social functioning. About 7.4% of respondents reported severe anxiety with panic attacks. Comorbid disorders included major depressive disorder (9.5%), obsessive-compulsive disorder (5.3%) and panic disorder (3.2%). Individuals with fear-related symptoms were more likely to fulfil DSM-5 criteria for specific phobia. CONCLUSION: Coulrophobia is a phenomenon that warrants clinical attention, given its association with significant comorbidity, psychological distress and impaired functioning. Several sociodemographic and clinical features are consistent with a diagnosis of specific phobia, although future work employing clinician-administered diagnostic tools is needed to consolidate and extend the findings here.

Perinatal suicidality: prevalence and correlates in a South African birth cohort.

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

The neurocognitive profile of post-traumatic stress disorder (PTSD), major depressive disorder (MDD), and PTSD with comorbid MDD.

OBJECTIVE: Neurocognitive dysfunction has been associated with post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). However, although PTSD is often comorbid with MDD, there is little neurocognitive work to date on individuals who suffer from both PTSD and MDD. Here, we compared neurocognitive domains in individuals with PTSD, MDD, and comorbid PTSD and MDD with those of healthy controls. METHODS: Participants comprised of mothers enrolled in the Drakenstein Child Health Study, a study exploring child health determinants in the Drakenstein district, Western Cape. N = 175 mothers (between 18 and 50 years) were recruited and divided into 4 groups: PTSD, MDD, PTSD with MDD, and healthy controls. Participants were assessed using the computerized NIH Toolbox, and paper and pencil neurocognitive tests. Domains assessed included executive function, memory, attention, learning, and processing speed. RESULTS: Distinct patterns of neurocognitive dysfunction were observed in this sample. PTSD was associated with more intrusion errors and MDD was associated with delayed recall impairment, relative to healthy controls. PTSD with comorbid MDD was associated with processing speed impairments, relative to healthy controls, and monodiagnostic groups. No group differences were observed on measures of attention and executive function. CONCLUSION: Distinct patterns of neurocognitive dysfunction were associated with diagnoses of MDD and PTSD. Greater anticipated dysfunction and impairment in comorbid PTSD and MDD was not observed, however. Further work is needed to replicate and extend these findings.

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.

Effect of Hazardous Alcohol Use During Pregnancy on Growth Outcomes at Birth: Findings from a South African Cohort Study.

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

Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia.

BACKGROUND: Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)-Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group. METHODS: We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium. RESULTS: In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen's d = -0.17, p = .00054), and smaller amygdalae (d = -0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063). CONCLUSIONS: Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain's response to trauma.

Maternal posttraumatic stress disorder and infant developmental outcomes in a South African birth cohort study.

OBJECTIVE: To investigate the association between maternal posttraumatic stress disorder (PTSD) and infant development in a South African birth cohort. METHOD: Data from the Drakenstein Child Health Study were analyzed. Maternal psychopathology was assessed using self-report and clinician-administered interviews; and 6-month infant development using the Bayley III Scales of Infant Development. Linear regression analyses explored associations between predictor and outcome variables. RESULTS: Data from 111 mothers and 112 infants (1 set of twins) were included. Most mothers (72%) reported lifetime trauma exposure; the lifetime prevalence of PTSD was 20%. Maternal PTSD was significantly associated with poorer fine motor and adaptive behavior - motor development; the latter remaining significant when adjusted for site, alcohol dependence, and infant head-circumference-for-age z score at birth. CONCLUSION: Maternal PTSD may be associated with impaired infant neurodevelopment. Further work in low- and middle-income populations may improve early childhood development in this context. (PsycINFO Database Record

Psychological trauma and posttraumatic stress disorder: risk factors and associations with birth outcomes in the Drakenstein Child Health Study.

BACKGROUND: Prenatal and peripartum trauma may be associated with poor maternal-fetal outcomes. However, relatively few data on these associations exist from low-middle income countries, and populations in transition. OBJECTIVE: We investigated the prevalence and risk factors for maternal trauma and posttraumatic stress disorder (PTSD), and their association with adverse birth outcomes in the Drakenstein Child Health Study, a South African birth cohort study. METHODS: Pregnant women were recruited from two clinics in a peri-urban community outside Cape Town. Trauma exposure and PTSD were assessed using diagnostic interviews; validated self-report questionnaires measured other psychosocial characteristics. Gestational age at delivery was calculated and birth outcomes were assessed by trained staff. Multiple logistic regression explored risk factors for trauma and PTSD; associations with birth outcomes were investigated using linear regression. Potential confounders included study site, socioeconomic status (SES), and depression. RESULTS: A total of 544 mother-infant dyads were included. Lifetime trauma was reported in approximately two-thirds of mothers, with about a third exposed to past-year intimate partner violence (IPV). The prevalence of current/lifetime PTSD was 19%. In multiple logistic regression, recent life stressors were significantly associated with lifetime trauma, when controlling for SES, study site, and recent IPV. Childhood trauma and recent stressors were significantly associated with PTSD, controlling for SES and study site. While no association was observed between maternal PTSD and birth outcomes, maternal trauma was significantly associated with a 0.3 unit reduction (95% CI: 0.1; 0.5) in infant head-circumference-for-age z-scores (HCAZ scores) at birth in crude analysis, which remained significant when adjusted for study site and recent stressors in a multivariate regression model. CONCLUSIONS: In this exploratory study, maternal trauma and PTSD were found to be highly prevalent, and preliminary evidence suggested that trauma may adversely affect fetal growth, as measured by birth head circumference. However, these findings are limited by a number of methodological weaknesses, and further studies are required to extend findings and delineate causal links and mechanisms of association.

Risk Factors for Antenatal Depression and Associations with Infant Birth Outcomes: Results From a South African Birth Cohort Study.

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

Methamphetamine and cannabis abuse in adolescence: a quasi-experimental study on specific and long-term neurocognitive effects.

OBJECTIVES: Methamphetamine abuse affects brain structure and function. Although methamphetamine and cannabis are commonly abused together, few studies have investigated the differential neurocognitive consequences of methamphetamine abuse with or without cannabis. Furthermore, the effects of drug use on the developing adolescent brain remain poorly understood. We compared neurocognitive function between adolescents with 'pure' methamphetamine abuse, those with comorbid methamphetamine and cannabis abuse, and healthy controls at baseline and follow-up. METHODS: Individuals residing in the greater Cape Town region, between the ages of 13 and 18 years, were recruited into either Methamphetamine only group (Meth-only; n=10), Methamphetamine and cannabis group (Meth-cann; n=10) or healthy control (n=20) groups using a quasi-experimental design. All participants underwent a comprehensive neurocognitive assessment. Substance-use variables and psychiatric symptom counts were also recorded. A portion of the Meth-only and control participants completed 12-month follow-up assessments. RESULTS: While the Meth-cann group demonstrated widespread neurocognitive deficits at baseline, these deficits were restricted to the self-monitoring domain in the Meth-only group at baseline and at follow-up. CONCLUSIONS: Methamphetamine abuse with cannabis abuse is associated with significantly more neurocognitive impairment than methamphetamine abuse alone, and such deficits may be enduring.

Approach/avoidance in dreams.

The influential threat simulation theory (TST) asserts that dreaming yields adaptive advantage by providing a virtual environment in which threat-avoidance may be safely rehearsed. We have previously found the incidence of biologically threatening dreams to be around 20%, with successful threat avoidance occurring in approximately one-fifth of such dreams. TST asserts that threat avoidance is over-represented relative to other possible dream contents. To begin assessing this issue, we contrasted the incidence of 'avoidance' dreams with that of their opposite: 'approach' dreams. Because TST states that the threat-avoidance function is only fully activated in ecologically valid (biologically threatening) contexts, we also performed this contrast for populations living in both high- and low-threat environments. We find that 'approach' dreams are significantly more prevalent across both contexts. We suggest these results are more consistent with the view that dreaming is generated by reward-seeking systems than by fear-conditioning systems, although reward-seeking is clearly not the only factor determining the content of dreams.