Cognitive function plays a pivotal role in assessing an individual’s quality of life. This research aimed to investigate how azelaic acid (AzA), a natural dicarboxylic acid with antioxidant and anti-inflammatory properties, affects aluminium chloride (AlCl3)-induced behavioural changes and biochemical alterations in the hippocampus of rats.

Thirty-two male Wistar rats divided into four groups received distilled water, AzA 50 mg/kg, AlCl3 100 mg/kg and AzA plus AlCl3, respectively, by oral gavage for 6 weeks. Behavioural changes were evaluated using open-field maze, elevated plus maze, novel object recognition (NOR), passive avoidance task, and Morris water maze (MWM) tests. Also, malondialdehyde (MDA), carbonyl protein, tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), nuclear factor-kappa B (NF-κB), C/EBP homologous protein (CHOP), glycogen synthase kinase-3 beta (GSK-3β), brain-derived neurotrophic factor (BDNF) and acetylcholinesterase (AChE) activity were examined.

AzA significantly affected AlCl3-provoked anxiety-like behaviours and learning and memory impairments. It also reduced the toxic effect of AlCl3 on MDA, carbonyl protein, TNF-α, IL-1β, NF-κB and GSK-3β status; however, its beneficial effects on AlCl3-induced changes of CHOP, BDNF and AChE activity were not significant.

These findings disclosed that AzA could improve behavioural and cognitive function and almost limit the oxidative stress and neuroinflammation caused by AlCl3.

Combining different pharmaceuticals may be beneficial when treating disorders with complex neurobiology, including alcohol use disorder (AUD). The gut-brain peptides amylin and GLP-1 may be of potential interest as they individually reduce alcohol intake in rodents. While the combination of amylin receptor (AMYR) and glucagon-like peptide-1 receptor (GLP-1R) agonists have been found to decrease feeding and body weight in obese male rats synergistically, their combined impact on alcohol intake is unknown.

Therefore, the effect of the combination of an AMYR (salmon calcitonin (sCT)) and a GLP-1R (dulaglutide) agonist on alcohol intake in rats of both sexes was explored in two separate alcohol-drinking experiments. The first alcohol-drinking experiment evaluated the potential of adding sCT to an ongoing dulaglutide treatment, whereas the second alcohol-drinking experiment examined the effect when adding sCT and dulaglutide simultaneously.

When adding sCT to an ongoing dulaglutide treatment, a reduction in alcohol intake was observed in both male and female rats. However, when combining sCT and dulaglutide simultaneously, an initial reduction in alcohol intake was observed in rats of both sexes, whereas tolerance towards treatment was observed. In both alcohol-drinking experiments, this treatment combination consistently decreased food consumption and body weight in males and females. While the treatment combination did not affect inflammatory mediators, the gene expression of AMYR or GLP-1R, it changed fat tissue morphology.

Further investigation needs to be done on the combination of AMYR and GLP-1R agonists to assess their combined effects on alcohol intake.

Clozapine is an atypical antipsychotic crucial for treatment-resistant schizophrenia, characterised by its multi-receptor targeting, including serotonin (5-HT2A, 5-HT2C) and dopamine (D1, D2, D3, D4) receptors, among others. This broad mechanism is effective against positive symptoms of schizophrenia with a lower incidence of extrapyramidal side effects. However, clozapine poses significant haematological risks, notably agranulocytosis, necessitating stringent blood monitoring protocols.

This study examined haematological parameters in 157 patients on clozapine therapy, analysing the prevalence and clinical correlations of haematological abnormalities such as leucocytosis, thrombocytosis, and alterations in red blood cell distribution width (RDW) and mean platelet volume (MPV).

The findings revealed leucocytosis in 36.9% of patients, thrombocytosis in 8.9%, and elevated RDW in 23.6%. Notably, higher clozapine doses were associated with leucocytosis, though no significant correlations were found between clozapine dose, duration of use, and changes in RDW, mean corpuscular haemoglobin concentration, or MPV.

The study’s results underscore the necessity of regular haematological monitoring to mitigate the risks of clozapine therapy while leveraging its therapeutic benefits. Additionally, the study suggests personalised dosing strategies to balance efficacy and safety, particularly in managing clozapine-induced haematological changes.

Phelan-McDermid syndrome is a rare genetic disorder characterised by various neurodevelopmental, medical, and psychiatric issues. Although bipolar disorder-like presentations and catatonia are particularly common, psychosis has also been reported but is less well described. As such, this systematic review sought to characterise the phenomenology of psychosis in Phelan-McDermid syndrome, clarify the association of psychotic symptoms with other neuropsychiatric features of the disorder, and describe antipsychotic treatment response.

A literature search was completed in July 2024 using PubMed and Scopus. Only English-language articles that reported the occurrence of psychotic symptoms in Phelan-McDermid syndrome were eligible for inclusion. 18 articles describing 35 individuals were included in the main analyses. Three additional articles of relevance are discussed separately, as they either provided limited clinical information or did not present data in a patient-specific manner.

The average age of psychosis onset was ∼17 years, and 65% of individuals developed symptoms at or before age 15. ∼69% of individuals also experienced catatonia, ∼81% experienced mood symptoms, and 50% experienced both. Visual hallucinations were the most commonly reported psychotic symptom. Where reported, ∼76% of individuals exhibited at least a partial and/or temporary response to antipsychotic therapy.

Psychotic presentations in Phelan-McDermid syndrome may qualitatively differ from schizophrenia. Although numerous antipsychotics may be efficacious in the treatment of Phelan-McDermid syndrome-associated psychosis, this review most importantly highlights the paucity of available high-quality evidence to guide treatment decisions in this respect, and as such indicates the need for more reports to be published.

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.

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.

Mechanisms of sleep disorders in fibromyalgia (FM) patients, such as insomnia, early morning awakenings and poor quality sleep, have not yet been proven and no consistent and effective treatment is yet available. The aim of this study was to investigate the pineal gland volume and the relationship between total fibre count, total fibre volume and total fibre length of the spinoreticular tract involved in regulation of sleep and wakefulness in terms of the mechanism of sleep disturbance.

This study included only female cases, 31 with fibromyalgia and 31 controls. Pittsburgh Sleep Quality Index was used to assess sleep quality. Tractography of targeted pathway from brain diffusion MR images was calculated in Diffusion Studio Imaging (DSI) Studio programme and the volume of the pineal gland was calculated in ITK-SNAP programme.

The mean volume of the pineal gland was higher in control group (218.84 ± 64.45 mm3) than in fibromyalgia group (174.77 ± 48.65 mm3), which was statistically significant (p = 0.004). However, there was no statistically significant difference between two groups in total spinoreticular tract (TSRT), total volume (TSRTV), TSRT fractional anisotropy, TSRT mean diffusion, TSRT axial diffusion and TSRT radial diffusion of spinoreticular tract, which is involved in the regulation of sleep and wakefulness (p > 0.05).

In conclusion, it is thought that the endocrine system may be more related to sleep disturbance in individuals with FM than central nervous system. Therefore, we believe that it may be more appropriate to work on the endocrine system rather than neural system in the treatment of sleep disturbance in patients with FM.

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.

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.

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.

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.

This study aims to explore the outcome with iv ketamine treatment in a real-world clinical setting, primarily measured as posttreatment days hospitalised.

The psychiatric medical records of 46 patients having received iv ketamine on a psychiatric treatment indication between 2015 and 2018 were retrospectively examined. Analysis comparing the number and duration of hospital admissions before and after ketamine treatment as well as logistic regression analysis to investigate clinical predictors of effectiveness, were performed. To assess patients’ severity of depressed symptoms records were screened for MADRS-S scores.

No significant difference between pre- and posttreatment hospital days (p = 0.170), or number of hospitalisations (p = 0.740) were found. The response rate was 31% and remission rate 21%. None of the predictors showed statistical significance in the logistic model.

Iv ketamine treatment showed effectiveness in reducing depressive symptoms even with complex patients in a real-world clinical setting. However, this did not translate to a reduction in hospitalisation. Highlighting the multifaceted challenges posed when implementing iv ketamine treatment in clinical practice.

Niemann-Pick Type C (NPC) is a genetic neurodegenerative lysosomal storage disorder commonly associated with psychiatric symptoms and delays to accurate diagnosis and treatment. This study investigated biomarker levels and diagnostic utility of plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in NPC compared to healthy controls.

Patients with NPC were recruited from a specialist assessment and management service. Data was available from an age and sex-matched healthy control group. NfL and GFAP were measured on Quanterix Simoa HD-X analysers and groups compared using generalised linear models. NfL levels were compared to, and percentiles derived from, recently developed NfL reference ranges.

Plasma NfL was significantly elevated in 11 patients with NPC compared to 25 controls (mean 17.1 vs. 7.4 pg/ml, p < 0.001), and reference ranges (all >98th percentile). NfL distinguished NPC from controls with high accuracy. GFAP levels were not elevated in NPC (66.6 vs. 75.1 pg/ml).

The study adds important evidence on the potential diagnostic utility of plasma NfL in NPC, extends the literature of NfL as a diagnostic tool to differentiate neurodegenerative from primary psychiatric disorders, and adds support to the pathology in NPC primarily involving neuronal, particularly axonal, degeneration.