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.

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.

Childhood sexual abuse (CSA) and emotional maltreatment are salient risk factors for the development of major depressive disorder (MDD) in women. However, the type- and timing-specific effects of emotional maltreatment experienced during adolescence on future depressive symptomatology in women with CSA have not been explored. The goal of this study was to fill this gap.

In total, 203 women (ages 20–32) with current depressive symptoms and CSA (MDD/CSA), remitted depressive symptoms and CSA (rMDD/CSA), and current depressive symptoms without CSA (MDD/no CSA) were recruited from the community and completed self-report measures. Depressive symptoms were assessed using the Beck Depression Inventory (BDI-II) and a detailed maltreatment history was collected using the Maltreatment and Abuse Chronology of Exposure (MACE). Differences in maltreatment exposure characteristics, including multiplicity and severity of maltreatment, as well as the chronologies of emotional maltreatment subtypes were compared among groups. A random forest machine-learning algorithm was utilized to assess the impact of exposure to emotional maltreatment subtypes at specific ages on current depressive symptoms.

MDD/CSA women reported greater prevalence and severity of emotional maltreatment relative to rMDD/CSA and MDD/no CSA women [F(2,196) = 9.33, p < 0.001], specifically from ages 12 to 18. The strongest predictor of current depressive symptoms was parental verbal abuse at age 18 for both MDD/CSA women (variable importance [VI] = 1.08, p = 0.006) and MDD/no CSA women (VI = 0.68, p = 0.004).

Targeting emotional maltreatment during late adolescence might prove beneficial for future intervention efforts for MDD following CSA.

Multiplex polymerase chain reaction (PCR) panels for stool testing may be used to diagnose Clostridioides difficile, which can circumvent more appropriate targeted C. difficile testing, resulting in treatment of incidentally detected colonization. We sought to reduce C. difficile diagnosis via a gastrointestinal pathogen panel (GIPP).

Quasi-experimental, pre/post, retrospective cohort study from January 1, 2022, to January 31, 2024.

Mayo Clinic Arizona—a single academic medical center and associated clinics.

Adult patients receiving C. difficile testing and/or treatment.

Preferred C. difficile testing consisted of glutamate dehydrogenase and toxin antigen immunoassay, followed by toxin gene testing for discrepant results. The GIPP contained 22 targets during the baseline period with C. difficile removed during the postintervention period. Surveys were provided to provider and nursing groups, separately, to identify C. difficile ordering practices and knowledge gaps.

At baseline, from January 1, 2022, to January 31, 2023, 2,772 GIPPs were completed for 2,307 unique patients (∼7 per day), primarily for outpatients (1,805 of 2,772, 65%). The most common positive target was C. difficile (517 of 1,018, 51%), which resulted in treatment for C. difficile infection in 94.9% (337 of 355) of cases. Following GIPP C. difficile target removal, GIPP orders decreased from 3.23 to 2.7 per 1,000 patient visits (P < .001). Prescribing of C. difficile treatments decreased in the postintervention period in inpatient and outpatient settings. There were no cases of delayed C. difficile diagnosis during the postintervention period.

Removing C. difficile from the GIPP resulted in effective diagnostic and antimicrobial stewardship without resulting in delayed diagnoses.

People with psychotic disorders often experience neurocognitive deficits, such as neurocognitive impairment (NCI), which can negatively affect their daily activities (e.g., performing independent tasks) and recovery. Because of this, the American Psychology Association advocates integrating neurocognitive testing into routine care for people living with psychotic disorders, especially those in their first episode, to inform treatment and improve clinical outcomes. However, in low-and-middle income countries (LMICs), such as Uganda where the current study took place, administering neurocognitive tests in healthcare settings presents numerous challenges. In Uganda there are few resources (e.g., trained clinical staff, and culturally relevant and normed tests) to routinely offer testing in healthcare settings. NeuroScreen is a brief, highly automated, tablet-based neurocognitive testing tool that can be administered by all levels of healthcare staff and has been translated into indigenous Ugandan languages. To examine the psychometric properties of NeuroScreen, we measured convergent and criterion validity of the NeuroScreen tests by comparing performance on them to performance on a traditional battery of neurocognitive tests widely used to assess neurocognition in people with psychotic disorders, the Matric Consensus Cognitive Battery (MCCB).

Sixty-five patients admitted into Butabika Mental Referral Hospital in Uganda after experiencing a psychotic episode and forty-seven demographically similar control participants completed two neurocognitive test batteries: the MCCB and NeuroScreen. Both batteries include tests measuring the neurocognitive domains of executive functioning, working memory, verbal learning, and processing speed. Prior to completing each battery, patients were medically stabilized and could not exhibit any positive symptoms on the day of testing. On the day of testing, medication dosages were scheduled so that patients would not experience sedative effects while testing. To examine convergent validity, we examined correlations between overall performance on NeuroScreen and the MCCB, as well as tests that measured the same neurocognitive domains. To examine criterion validity, an ROC curve was computed to examine the sensitivity and specificity of NeuroScreen to detect NCI as defined by the MCCB.

There was a large correlation between overall performance on NeuroScreen and the MCCB battery of tests, r(110) = .65, p < .001. Correlations of various strengths were found among tests measuring the same neurocognitive domains in each battery: executive functioning [r(110) = .56 p <.001], processing speed [r(110) = .44, p <.001)], working memory [r(110) = .29, p<.01], and verbal learning [r(110) = .22, p < .01]. ROC analysis of the ability of NeuroScreen to detect MCCB defined NCI showed an area under curve of .798 and optimal sensitivity and specificity of 83% and 60%, respectively.

Overall test performance between the NeuroScreen and MCCB test batteries was similar in this sample of Ugandans with and without a psychotic disorder, with the strongest correlations in tests of executive functioning and processing speed. ROC analysis provided criterion validity evidence of NeuroScreen to detect MCCB defined NCI. These results provide support for use of NeuroScreen to assess neurocognitive functioning among patients with psychotic disorders in Uganda, however more work needs to be to determine how well it can be implemented in this setting. Future directions include assessing cultural acceptability of NeuroScreen and generating normative data from a larger population of Ugandan test-takers.

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.

Treatment-resistant schizophrenia (TRS) is associated with high levels of functional impairment, healthcare usage and societal costs. Cross-sectional studies may overestimate TRS rates because of selection bias.

We aimed to quantify TRS rates by using first-episode cohorts to improve resource allocation and clozapine access.

We undertook a systematic review of TRS rates among people with first-episode psychosis and schizophrenia, with a minimum follow-up of 8 weeks. We searched PubMed, PsycINFO, EMBASE, CINAHL and the Cochrane Database of Systematic Reviews, and meta-analysed TRS rates from included studies.

Twelve studies were included, totalling 11 958 participants; six studies were of high quality. The rate of TRS was 22.8% (95% CI 19.1–27.0%, P < 0.001) among all first-episode cohorts and 24.4% (95% CI 19.5–30.0%, P < 0.001) among first-episode schizophrenia cohorts. Subgroup sensitivity analyses by location of recruitment, TRS definition, study quality, time of data collection and retrospective versus prospective data collection did not lead to statistically significant differences in heterogeneity. In a meta-regression, duration of follow-up and percentage drop-out did not significantly affect the overall TRS rate. Men were 1.57 times more likely to develop TRS than women (95% CI 1.11–2.21, P = 0.010).

Almost a quarter of people with first-episode psychosis or schizophrenia will develop TRS in the early stages of treatment. When including people with schizophrenia who relapse despite initial response and continuous treatment, rates of TRS may be as high as a third. These high rates of TRS highlight the need for improved access to clozapine and psychosocial supports.