Recent studies have shown that the distribution of the tryptophan/kynurenine pathway (KP) plays a role in the development of obsessive-compulsive disorder (OCD). We aimed to reveal the relationship between CYP1A1 rs464903 and aryl hydrocarbon receptor (AhR) rs10249788 associated with the KP and interferon gamma (IFN γ) and oxidative stress in OCD.

In our study, the serum and DNAs of 150 samples, including 100 OCD patients and 50 controls, were used. The activity of glutathione peroxidase (GSH-Px), and the levels of IFN γ, thiobarbituric acid reactive substances (TBARS), tryptophan, and kynurenine were determined by biochemical methods. AhR rs10249788 and cytochrome P450 family CYP1A1 rs4646903, which interact directly with the KP, were analysed by polymerase chain reaction followed by restriction fragment length polymorphism. P < 0.05 was considered statistically significant.

There were no significant differences between groups in CYP1A1 rs4646903 and AhR rs10249788 while tryptophan and IFN γ were found to be higher in controls (p < 0.001, for both), and TBARS and indolamine-2,3-dioxygenase were found to be higher in OCD (p < 0.001, for both). There were significant correlations between IFN γ and TBARS and GSH-Px (p = 0.028, p = 0.020, respectively) in the OCD group.

For the first time studied in OCD, it has been shown that IFN γ, tryptophan, oxidative stress parameters, and gene variants of CYP1A1 rs4646903 anAhR rs10249788 are shown effective on the KP.

The cause of cognitive side effects after electroconvulsive therapy (ECT) is largely unknown. Alterations in the blood–brain barrier (BBB) have been considered in several recent ECT studies. We therefore found it worthwhile to perform a systematic review of the literature to examine if electrically induced seizures affect the permeability of the BBB.

PubMed/MEDLINE and Embase were searched 16 November 2022. Studies with a direct measurement of BBB permeability in animals treated with modified electroconvulsive stimulation (ECS) and in humans treated with ECT were included. Synthesis of results was narrative due to the low number of studies and differences in study designs.

Four animal and two human (31 participants) studies were included. In animals, two studies found increased BBB permeability to some smaller molecules after modified ECS, while the two other studies found marginally increased or unchanged permeability to albumin after treatment. In contrast, the human studies did not find increased BBB permeability to smaller molecules or albumin after ECT.

Animal but not human studies support increased BBB permeability to some smaller molecules after electrically induced seizures. However, this conclusion is confined by the low number of studies and the lack of studies applying state-of-the-art methods. More studies using modern approaches to measuring of BBB permeability are warranted.

The study was founded by Mental Health Services in the Capital Region of Denmark (grant number 61151-05) and was registered on PROSPERO before data extraction was initiated (CRD42022331385).

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.

Although disconnectivity among brain regions has been one of the main hypotheses for schizophrenia, the superficial white matter (SWM) has received less attention in schizophrenia research than the deep white matter (DWM) owing to the challenge of consistent reconstruction across subjects.

We obtained the diffusion magnetic resonance imaging (dMRI) data of 223 healthy controls and 143 patients with schizophrenia. After harmonising the raw dMRIs from three different studies, we performed whole-brain two-tensor tractography and fibre clustering on the tractography data. We compared the fractional anisotropy (FA) of white matter tracts between healthy controls and patients with schizophrenia. Spearman’s rho was adopted for the associations with clinical symptoms measured by the Positive and Negative Syndrome Scale (PANSS). The Bonferroni correction was used to adjust multiple testing.

Among the 33 DWM and 8 SWM tracts, patients with schizophrenia had a lower FA in 14 DWM and 4 SWM tracts than healthy controls, with small effect sizes. In the patient group, the FA deviations of the corticospinal and superficial–occipital tracts were negatively correlated with the PANSS negative score; however, this correlation was not evident after adjusting for multiple testing.

We observed the structural impairments of both the DWM and SWM tracts in patients with schizophrenia. The SWM could be a potential target of interest in future research on neural biomarkers for schizophrenia.

In sub-Saharan Africa, there are no validated screening tools for delirium in older adults, despite the known vulnerability of older people to delirium and the associated adverse outcomes. This study aimed to assess the effectiveness of a brief smartphone-based assessment of arousal and attention (DelApp) in the identification of delirium amongst older adults admitted to the medical department of a tertiary referral hospital in Northern Tanzania.

Consecutive admissions were screened using the DelApp during a larger study of delirium prevalence and risk factors. All participants subsequently underwent detailed clinical assessment for delirium by a research doctor. Delirium and dementia were identified against DSM-5 criteria by consensus.

Complete data for 66 individuals were collected of whom 15 (22.7%) had delirium, 24.5% had dementia without delirium, and 10.6% had delirium superimposed on dementia. Sensitivity and specificity of the DelApp for delirium were 0.87 and 0.62, respectively (AUROC 0.77) and 0.88 and 0.73 (AUROC 0.85) for major cognitive impairment (dementia and delirium combined). Lower DelApp score was associated with age, significant visual impairment (<6/60 acuity), illness severity, reduced arousal and DSM-5 delirium on univariable analysis, but on multivariable logistic regression only arousal remained significant.

In this setting, the DelApp performed well in identifying delirium and major cognitive impairment but did not differentiate delirium and dementia. Performance is likely to have been affected by confounders including uncorrected visual impairment and reduced level of arousal without delirium. Negative predictive value was nevertheless high, indicating excellent ‘rule out’ value in this setting.

Empathy is a key factor to examine in development, because of its predictive associations with both aggression and successful prosocial behaviour. However, established measures of empathy for Low-to-Middle Income Countries, including South Africa, are lacking. In children, parent-report measures are key. However, a local study examining empathy and aggression (Malcolm-Smith et al., 2015) found poor psychometric performance for a widely used parent-report measure of dispositional empathy, the Griffith Empathy Measure (GEM). We thus investigated which of two questionnaires measuring dispositional cognitive and affective empathy perform better in this context.

We contrasted internal consistency reliability of a simplified version of the GEM (SGEM; n = 160) and a parent-report version of the Questionnaire of Cognitive and Affective Empathy (QCAE; n = 440) in a low-mid socio-economic status sample. Convergence between the measures and factor structure were also assessed.

The parent-report version of the QCAE performed well as a measure of child dispositional cognitive and affective empathy, with good reliability (overall α = 0.90 vs. SGEM α = .63), and confirmatory factor analysis supporting the two-factor structure. The SGEM’s reliability and failure to correlate with QCAE indicated poor psychometric performance.

This is the first psychometric evaluation of the QCAE as a parent-report measure, and our results indicate that it should prove useful for future assessments of dispositional empathy in children across a variety of contexts.

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.

To test the hypothesis that exposure to peer self-harm induces adolescents’ urges to self-harm and that this is influenced by individual suggestibility.

We recruited 97 UK-based adults aged 18–25 years with a recent history of self-harm, measuring baseline suggestibility (Resistance to Peer Influence; RPI) and perceived ability to control urges to self-harm (using an adapted item from the Self-Efficacy to Resist Suicidal Action scale; SEASA) before and after two self-harm vignettes featuring named peers from the participant’s social network (to simulate exposure to peer non-suicidal self-harm) and after a wash-out exposure. We used paired t-tests to compare mean SEASA scores pre- and post-exposure, and linear regression to test for an association between RPI and change in SEASA scores pre- and post-exposure.

Perceived ability to control urges to self-harm was significantly reduced following exposure to peer self-harm (t(96) = 4.02, p < 0.001, mean difference = 0.61; 95% CI = 0.31, 0.91), but was not significantly different from baseline after exposure to a wash-out. We found no association between suggestibility and change in urges to self-harm after exposure to peer self-harm.

Our findings support social influences on self-harm in a sample of young adults, regardless of their individual degree of suggestibility.

Monoamine neurotransmitters play a role in aggression, especially when altered by illicit substances. However, some literature suggests that not all illicit substances may lead to aggression, notably psychedelics. This narrative review investigates the associations between serotonergic psychedelics and MDMA on aggressive behaviour.

PubMed and PsycINFO were searched for original, peer-reviewed articles evaluating the effects of serotonergic psychedelics and 3,4-methyl enedioxy methamphetamine (MDMA) on violent and aggressive behaviour using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

After removing duplicates, a total of 555 articles were screened, with 16 meeting the inclusion criteria. One additional article was obtained through reference screening bringing the total to 17 articles. Of these 17 articles, 14 studies focused on MDMA and three on serotonergic psychedelics. Findings were mixed, with some results demonstrating increased aggression following psychedelics and others suggesting protective effects. Limitations in the current literature include varied definitions of psychedelics, lack of standardised objective outcome measures and failure to control for confounding.

As psychedelic research continues to expand, further assessment on the effects of serotonergic psychedelics and MDMA on aggressive behaviour is required.

Psychiatric research applies statistical methods that can be divided in two frameworks: causal inference and prediction. Recent proposals suggest a down-prioritisation of causal inference and argue that prediction paves the road to ‘precision psychiatry’ (i.e., individualised treatment). In this perspective, we critically appraise these proposals.

We outline strengths and weaknesses of causal inference and prediction frameworks and describe the link between clinical decision-making and counterfactual predictions (i.e., causality). We describe three key causal structures that, if not handled correctly, may cause erroneous interpretations, and three pitfalls in prediction research.

Prediction and causal inference are both needed in psychiatric research and their relative importance is context-dependent. When individualised treatment decisions are needed, causal inference is necessary.

This perspective defends the importance of causal inference for precision psychiatry.

Bipolar disorder (BD) is a recurrent chronic disorder characterised by fluctuations in mood and energy disposition. Diseases could lead to degenerative alterations in brain structures such as corpus callosum (CC). Studies demonstrated that abnormalities in CC are associated with BD symptoms. The present study aims to analyse the CC of the patients with statistical shape analysis (SSA) and compare the findings with healthy controls.

Forty-one BD patients and 41 healthy individuals in similar age groups, which included 23 female and 18 male subjects, participated in the study. CC was marked with landmarks on the mid-sagittal images of each individual. The mean ‘Procrustes’ point was calculated, and shape deformations were analysed with thin-plate spline analysis.

Significant differences were observed in the shape of CC between the two groups, where maximum CC deformation was observed in posterior region marks in BD patients. There was no significant difference between the CC area of the BD patients and controls.

CC analysis conducted with SSA revealed significant differences between patients and healthy controls. The study findings emphasised the abnormal distribution of white matter in CC and the variable subregional nature of CC in BD patients. This study may enable the development of more targeted and effective treatment strategies by taking into account biological factors and understanding the differences in the brain regions of individuals with BD.

Tools based on generative artificial intelligence (AI) such as ChatGPT have the potential to transform modern society, including the field of medicine. Due to the prominent role of language in psychiatry, e.g., for diagnostic assessment and psychotherapy, these tools may be particularly useful within this medical field. Therefore, the aim of this study was to systematically review the literature on generative AI applications in psychiatry and mental health.

We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search was conducted across three databases, and the resulting articles were screened independently by two researchers. The content, themes, and findings of the articles were qualitatively assessed.

The search and screening process resulted in the inclusion of 40 studies. The median year of publication was 2023. The themes covered in the articles were mainly mental health and well-being in general – with less emphasis on specific mental disorders (substance use disorder being the most prevalent). The majority of studies were conducted as prompt experiments, with the remaining studies comprising surveys, pilot studies, and case reports. Most studies focused on models that generate language, ChatGPT in particular.

Generative AI in psychiatry and mental health is a nascent but quickly expanding field. The literature mainly focuses on applications of ChatGPT, and finds that generative AI performs well, but notes that it is limited by significant safety and ethical concerns. Future research should strive to enhance transparency of methods, use experimental designs, ensure clinical relevance, and involve users/patients in the design phase.

No drugs are currently approved for the treatment of borderline personality disorder (BPD). These studies (a randomised study and its open-label extension) aimed to evaluate the efficacy, safety and tolerability of brexpiprazole for the treatment of BPD.

The Phase 2, multicentre, randomised, double-blind, placebo-controlled, parallel-group study enrolled adult outpatients with BPD. After a 1-week placebo run-in, patients were randomised 1:1 to brexpiprazole 2–3 mg/day (flexible dose) or placebo for 11 weeks. The primary endpoint was change in Zanarini Rating Scale for BPD total score from randomisation (Week 1) to Week 10 (timing of randomisation and endpoint blinded to investigators and patients). The Phase 2/3, multicentre, open-label extension study enrolled patients who completed the randomised study; all patients received brexpiprazole 2–3 mg/day (flexible dose) for 12 weeks. Safety assessments included treatment-emergent adverse events (TEAEs).

Brexpiprazole was not statistically significantly different from placebo on the primary endpoint of the randomised study (N = 324 randomised; N = 110 analysed per treatment group; least squares mean difference −1.02; 95% confidence limits −2.75, 0.70; p = 0.24). Numerical efficacy advantages for brexpiprazole were observed at other time points. The most common TEAE in the randomised study was akathisia (brexpiprazole, 14.0%; placebo, 1.2%); data from the open-label study (N = 199 analysed) suggested that TEAEs were transient.

The primary endpoint of the randomised study was not met. Further research on brexpiprazole in BPD is warranted based on possible efficacy signals at other time points and its safety profile.

ClinicalTrials.gov identifiers: NCT04100096, NCT04186403. Funding: Otsuka, Lundbeck.

Placebo and nocebo effects are widely reported across psychiatric conditions, yet have seldom been examined in the context of gambling disorder. Through meta-analysis, we examined placebo effects, their moderating factors, and nocebo effects, from available randomised, controlled pharmacological clinical trials in gambling disorder.

We searched, up to 19 February 2024, a broad range of databases, for double-blind randomised controlled trials (RCTs) of medications for gambling disorder. Outcomes were gambling symptom severity and quality of life (for efficacy), and drop outs due to medication side effects in the placebo arms.

We included 16 RCTs (n = 833) in the meta-analysis. The overall effect size for gambling severity reduction in the placebo arms was 1.18 (95%CI 0.91–1.46) and for quality of life improvement was 0.63 (0.42-0.83). Medication class, study sponsorship, trial duration, baseline severity of gambling and publication year significantly moderated effect sizes for at least some of these outcome measures. Author conflict of interest, placebo run-in, gender split, severity scale choice, age of participants or unbalanced randomisation did not moderate effect sizes. Nocebo effects leading to drop out from the trial were observed in 6% of participants in trials involving antipsychotics, while this was less for other medication types.

Placebo effects in trials of pharmacological treatment of gambling disorder are large, and there are several moderators of this effect. Nocebo effects were measureable and may be influenced by medication class being studied. Practical implications of these new findings for the field are discussed, along with recommendations for future clinical trials.