Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).

PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

The macro-social and environmental conditions in which people live, such as the level of a country’s development or inequality, are associated with brain-related disorders. However, the relationship between these systemic environmental factors and the brain remains unclear. We aimed to determine the association between the level of development and inequality of a country and the brain structure of healthy adults.

We conducted a cross-sectional study pooling brain imaging (T1-based) data from 145 magnetic resonance imaging (MRI) studies in 7,962 healthy adults (4,110 women) in 29 different countries. We used a meta-regression approach to relate the brain structure to the country’s level of development and inequality.

Higher human development was consistently associated with larger hippocampi and more expanded global cortical surface area, particularly in frontal areas. Increased inequality was most consistently associated with smaller hippocampal volume and thinner cortical thickness across the brain.

Our results suggest that the macro-economic conditions of a country are reflected in its inhabitants’ brains and may explain the different incidence of brain disorders across the world. The observed variability of brain structure in health across countries should be considered when developing tools in the field of personalized or precision medicine that are intended to be used across the world.

Compulsive-like rigidity may be associated with hyposerotonergia and increased kynurenine (KYN) pathway activity. Conversion of tryptophan (TRP) to KYN, which may contribute to hyposerotonergia, is bolstered by inflammation and could be related to altered gut microbiota composition. Here, we studied these mechanisms in a naturalistic animal model of compulsive-like behavioural rigidity, that is, large nest building (LNB) in deer mice (Peromyscus sp.).

Twenty-four (24) normal nest building (NNB) and 24 LNB mice (both sexes) were chronically administered either escitalopram (a selective serotonin reuptake inhibitor; 50 mg/kg/day) or a control solution, with nesting behaviour analysed before and after intervention. After endpoint euthanising, frontal cortices and striata were analysed for TRP and its metabolites, plasma for microbiota-derived lipopolysaccharide (LPS) and its binding protein (lipopolysaccharide binding protein), and stool samples for microbial DNA.

LNB, but not NNB, decreased after escitalopram exposure. At baseline, LNB was associated with reduced frontal cortical TRP concentrations and hyposerotonergia that was unrelated to altered KYN pathway activity. In LNB mice, escitalopram significantly increased frontal-cortical and striatal TRP without altering serotonin concentrations. Treated LNB, compared to untreated LNB and treated NNB mice, had significantly reduced plasma LPS as well as a microbiome showing a decreased inferred potential to synthesise short-chain fatty acids and degrade TRP.

These findings support the role of altered serotonergic mechanisms, inflammatory processes, and gut microbiome involvement in compulsive-like behavioural rigidity. Our results also highlight the importance of gut-brain crosstalk mechanisms at the level of TRP metabolism in the spontaneous development of such behaviour.

Around the world, people living in objectively difficult circumstances who experience symptoms of generalized anxiety disorder (GAD) do not qualify for a diagnosis because their worry is not ‘excessive’ relative to the context. We carried out the first large-scale, cross-national study to explore the implications of removing this excessiveness requirement.

Data come from the World Health Organization World Mental Health Survey Initiative. A total of 133 614 adults from 12 surveys in Low- or Middle-Income Countries (LMICs) and 16 surveys in High-Income Countries (HICs) were assessed with the Composite International Diagnostic Interview. Non-excessive worriers meeting all other DSM-5 criteria for GAD were compared to respondents meeting all criteria for GAD, and to respondents without GAD, on clinically-relevant correlates.

Removing the excessiveness requirement increases the global lifetime prevalence of GAD from 2.6% to 4.0%, with larger increases in LMICs than HICs. Non-excessive and excessive GAD cases worry about many of the same things, although non-excessive cases worry more about health/welfare of loved ones, and less about personal or non-specific concerns, than excessive cases. Non-excessive cases closely resemble excessive cases in socio-demographic characteristics, family history of GAD, and risk of temporally secondary comorbidity and suicidality. Although non-excessive cases are less severe on average, they report impairment comparable to excessive cases and often seek treatment for GAD symptoms.

Individuals with non-excessive worry who meet all other DSM-5 criteria for GAD are clinically significant cases. Eliminating the excessiveness requirement would lead to a more defensible GAD diagnosis.

Despite their documented efficacy, substantial proportions of patients discontinue antidepressant medication (ADM) without a doctor's recommendation. The current report integrates data on patient-reported reasons into an investigation of patterns and predictors of ADM discontinuation.

Face-to-face interviews with community samples from 13 countries (n = 30 697) in the World Mental Health (WMH) Surveys included n = 1890 respondents who used ADMs within the past 12 months.

10.9% of 12-month ADM users reported discontinuation-based on recommendation of the prescriber while 15.7% discontinued in the absence of prescriber recommendation. The main patient-reported reason for discontinuation was feeling better (46.6%), which was reported by a higher proportion of patients who discontinued within the first 2 weeks of treatment than later. Perceived ineffectiveness (18.5%), predisposing factors (e.g. fear of dependence) (20.0%), and enabling factors (e.g. inability to afford treatment cost) (5.0%) were much less commonly reported reasons. Discontinuation in the absence of prescriber recommendation was associated with low country income level, being employed, and having above average personal income. Age, prior history of psychotropic medication use, and being prescribed treatment from a psychiatrist rather than from a general medical practitioner, in comparison, were associated with a lower probability of this type of discontinuation. However, these predictors varied substantially depending on patient-reported reasons for discontinuation.

Dropping out early is not necessarily negative with almost half of individuals noting they felt better. The study underscores the diverse reasons given for dropping out and the need to evaluate how and whether dropping out influences short- or long-term functioning.

The corpus callosum (CC) is a brain structure with a high heritability and potential role in psychiatric disorders. However, the genetic architecture of the CC and the genetic link with psychiatric disorders remain largely unclear. We investigated the genetic architectures of the volume of the CC and its subregions and the genetic overlap with psychiatric disorders.

We applied multivariate genome-wide association study (GWAS) to genetic and T1-weighted magnetic resonance imaging (MRI) data of 40,894 individuals from the UK Biobank, aiming to boost genetic discovery and to assess the pleiotropic effects across volumes of the five subregions of the CC (posterior, mid-posterior, central, mid-anterior and anterior) obtained by FreeSurfer 7.1. Multivariate GWAS was run combining all subregions, co-varying for relevant variables. Gene-set enrichment analyses were performed using MAGMA. Linkage disequilibrium score regression (LDSC) was used to determine Single nucleotide polymorphism (SNP)-based heritability of total CC volume and volumes of its subregions as well as their genetic correlations with relevant psychiatric traits.

We identified 70 independent loci with distributed effects across the five subregions of the CC (p < 5 × 10−8). Additionally, we identified 33 significant loci in the anterior subregion, 23 in the mid-anterior, 29 in the central, 7 in the mid-posterior and 56 in the posterior subregion. Gene-set analysis revealed 156 significant genes contributing to volume of the CC subregions (p < 2.6 × 10−6). LDSC estimated the heritability of CC to (h2SNP = 0.38, SE = 0.03) and subregions ranging from 0.22 (SE = 0.02) to 0.37 (SE = 0.03). We found significant genetic correlations of total CC volume with bipolar disorder (BD, rg = −0.09, SE = 0.03; p = 5.9 × 10−3) and drinks consumed per week (rg = −0.09, SE = 0.02; p = 4.8 × 10−4), and volume of the mid-anterior subregion with BD (rg = −0.12, SE = 0.02; p = 2.5 × 10−4), major depressive disorder (MDD) (rg = −0.12, SE = 0.04; p = 3.6 × 10−3), drinks consumed per week (rg = −0.13, SE = 0.04; p = 1.8 × 10−3) and cannabis use (rg = −0.09, SE = 0.03; p = 8.4 × 10−3).

Our results demonstrate that the CC has a polygenic architecture implicating multiple genes and show that CC subregion volumes are heritable. We found that distinct genetic factors are involved in the development of anterior and posterior subregions, consistent with their divergent functional specialisation. Significant genetic correlation between volumes of the CC and BD, drinks per week, MDD and cannabis consumption subregion volumes with psychiatric traits is noteworthy and deserving of further investigation.

Cognitive dysfunction in schizophrenia may be assessed by measuring within-individual variability (WIV) in performance across a range of cognitive tests. Previous studies have found increased WIV in people with schizophrenia, but no studies have been conducted in low- to middle-income countries where the different sociocultural context may affect WIV. We sought to address this gap by exploring the relationship between WIV and a range of clinical and demographic variables in a large study of people with schizophrenia and matched controls in South Africa.

544 people with schizophrenia and 861 matched controls completed an adapted version of The University of Pennsylvania Computerized Neurocognitive Battery (PennCNB). Demographic and clinical information was collected using the Structured Clinical Interview for DSM-IV Diagnoses. Across-task WIV for performance speed and accuracy on the PennCNB was calculated. Multivariate linear regression was used to assess the relationship between WIV and a diagnosis of schizophrenia in the whole sample, and WIV and selected demographic and clinical variables in people with schizophrenia.

Increased WIV of performance speed across cognitive tests was significantly associated with a diagnosis of schizophrenia. In people with schizophrenia, increased speed WIV was associated with older age, a lower level of education and a lower score on the Global Assessment of Functioning scale. Increased accuracy WIV was significantly associated with a younger age in people with schizophrenia.

Measurements of WIV of performance speed can add to the knowledge gained from studies of cognitive dysfunction in schizophrenia in resource-limited settings.

The Mini International Neuropsychiatric Interview 7.0.2 (MINI-7) is a widely used tool and known to have sound psychometric properties; but very little is known about its use in low and middle-income countries (LMICs). This study aimed to examine the psychometric properties of the MINI-7 psychosis items in a sample of 8609 participants across four countries in Sub-Saharan Africa.

We examined the latent factor structure and the item difficulty of the MINI-7 psychosis items in the full sample and across four countries.

Multiple group confirmatory factor analyses (CFAs) revealed an adequate fitting unidimensional model for the full sample; however, single group CFAs at the country level revealed that the underlying latent structure of psychosis was not invariant. Specifically, although the unidimensional structure was an adequate model fit for Ethiopia, Kenya, and South Africa, it was a poor fit for Uganda. Instead, a 2-factor latent structure of the MINI-7 psychosis items provided the optimal fit for Uganda. Examination of item difficulties revealed that MINI-7 item K7, measuring visual hallucinations, had the lowest difficulty across the four countries. In contrast, the items with the highest difficulty were different across the four countries, suggesting that MINI-7 items that are the most predictive of being high on the latent factor of psychosis are different for each country.

The present study is the first to provide evidence that the factor structure and item functioning of the MINI-7 psychosis vary across different settings and populations in Africa.

Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.

We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.

BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.

We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

The ENhancing Assessment of Common Therapeutic factors (ENACT) tool measures a set of therapeutic competencies required for the effective psychological intervention, including delivery by non-specialists. This paper describes the systematic adaptation of the ENACT for the South African (SA) context and presents the tool's initial psychometric properties.

We employed a four-step process: (1) Item generation: 204 therapeutic factors were generated by SA psychologists and drawn from the original ENACT as potential items; (2) Item relevance: SA therapists identified 96 items that were thematically coded according to their relationship to one another and were assigned to six domains; (3) Item utility: The ENACT-SA scale was piloted by rating recordings of psychological therapy sessions and stakeholder input; and (4) Psychometric properties: Internal consistency and inter-rater reliability of the final 12-item ENACT-SA were explored using Cronbach's alpha and intraclass correlation co-efficient (ICC) for both clinical psychologists and registered counsellors.

Although the original ENACT provided a framework for developing a tool for use in SA, several modifications were made to improve the applicability of the tool for the SA context, and optimise its adaptability other contexts. The adapted 12-item tool's internal consistency was good, while the inter-rater reliability was acceptable for both clinical psychologists and registered counsellors.

The ENACT-SA is a reliable tool to assess common factors in psychological treatments. It is recommended that the tool be used in conjunction with assessment protocols and treatment-specific competency measures to fully assess implementation fidelity and potential mechanisms of therapeutic change.

Behaviors typical of body-focused repetitive behavior disorders such as trichotillomania (TTM) and skin-picking disorder (SPD) are often associated with pleasure or relief, and with little or no physical pain, suggesting aberrant pain perception. Conclusive evidence about pain perception and correlates in these conditions is, however, lacking.

A multisite international study examined pain perception and its physiological correlates in adults with TTM (n = 31), SPD (n = 24), and healthy controls (HCs; n = 26). The cold pressor test was administered, and measurements of pain perception and cardiovascular parameters were taken every 15 seconds. Pain perception, latency to pain tolerance, cardiovascular parameters and associations with illness severity, and comorbid depression, as well as interaction effects (group × time interval), were investigated across groups.

There were no group differences in pain ratings over time (P = .8) or latency to pain tolerance (P = .8). Illness severity was not associated with pain ratings (all P > .05). In terms of diastolic blood pressure (DBP), the main effect of group was statistically significant (P = .01), with post hoc analyses indicating higher mean DBP in TTM (95% confidence intervals [CI], 84.0-93.5) compared to SPD (95% CI, 73.5-84.2; P = .01), and HCs (95% CI, 75.6-86.0; P = .03). Pain perception did not differ between those with and those without depression (TTM: P = .2, SPD: P = .4).

The study findings were mostly negative suggesting that general pain perception aberration is not involved in TTM and SPD. Other underlying drivers of hair-pulling and skin-picking behavior (eg, abnormal reward processing) should be investigated.

This study investigates associations of several dimensions of childhood adversities (CAs) with lifetime mental disorders, 12-month disorder persistence, and impairment among incoming college students.

Data come from the World Mental Health International College Student Initiative (WMH-ICS). Web-based surveys conducted in nine countries (n = 20 427) assessed lifetime and 12-month mental disorders, 12-month role impairment, and seven types of CAs occurring before the age of 18: parental psychopathology, emotional, physical, and sexual abuse, neglect, bullying victimization, and dating violence. Poisson regressions estimated associations using three dimensions of CA exposure: type, number, and frequency.

Overall, 75.8% of students reported exposure to at least one CA. In multivariate regression models, lifetime onset and 12-month mood, anxiety, and substance use disorders were all associated with either the type, number, or frequency of CAs. In contrast, none of these associations was significant when predicting disorder persistence. Of the three CA dimensions examined, only frequency was associated with severe role impairment among students with 12-month disorders. Population-attributable risk simulations suggest that 18.7–57.5% of 12-month disorders and 16.3% of severe role impairment among those with disorders were associated with these CAs.

CAs are associated with an elevated risk of onset and impairment among 12-month cases of diverse mental disorders but are not involved in disorder persistence. Future research on the associations of CAs with psychopathology should include fine-grained assessments of CA exposure and attempt to trace out modifiable intervention targets linked to mechanisms of associations with lifetime psychopathology and burden of 12-month mental disorders.

Major depressive disorder (MDD) is characterised by a recurrent course and high comorbidity rates. A lifespan perspective may therefore provide important information regarding health outcomes. The aim of the present study is to examine mental disorders that preceded 12-month MDD diagnosis and the impact of these disorders on depression outcomes.

Data came from 29 cross-sectional community epidemiological surveys of adults in 27 countries (n = 80 190). The Composite International Diagnostic Interview (CIDI) was used to assess 12-month MDD and lifetime DSM-IV disorders with onset prior to the respondent's age at interview. Disorders were grouped into depressive distress disorders, non-depressivedistress disorders, fear disorders and externalising disorders. Depression outcomes included 12-month suicidality, days out of role and impairment in role functioning.

Among respondents with 12-month MDD, 94.9% (s.e. = 0.4) had at least one prior disorder (including previous MDD), and 64.6% (s.e. = 0.9) had at least one prior, non-MDD disorder. Previous non-depressive distress, fear and externalising disorders, but not depressive distress disorders, predicted higher impairment (OR = 1.4–1.6) and suicidality (OR = 1.5–2.5), after adjustment for sociodemographic variables. Further adjustment for MDD characteristics weakened, but did not eliminate, these associations. Associations were largely driven by current comorbidities, but both remitted and current externalising disorders predicted suicidality among respondents with 12-month MDD.

These results illustrate the importance of careful psychiatric history taking regarding current anxiety disorders and lifetime externalising disorders in individuals with MDD.