Acta Neuropsychiatrica最新文献

Objective: To ascertain whether psychotherapies combined with medication are more efficacious than those without medication and determine which combinations yield the best results.

Methods: We conducted a network meta-analysis of randomised controlled trials (RCTs) comparing behavioural activation (BA), psychoanalytic/psychodynamic psychotherapy (DYN), interpersonal psychotherapy (IPT), individual face-to-face cognitive behavioural therapy (CBT (ftf)), group cognitive behavioural therapy (gCBT), and computerised or internet cognitive behavioural therapy (iCBT) with each other, or with treatment-as-usual (TAU) and wait list control (WLC) among adults formally diagnosed with depression. The psychotherapy arms were categorised as either psychotherapy alone or psychotherapy combined with medication (+ p). Treatment efficacy was assessed based on depression severity. We used a random-effects model to conduct a pairwise meta-analysis.

Results: A total of 100 RCTs with 9,873 participants were included. The most common treatment was CBT (ftf) alone. All treatment arms were compared with TAU. Most psychotherapies combined with medication were superior to psychotherapy alone. In the subgroup analyses according to the baseline severity of depression, most psychotherapies combined with medication were more effective than psychotherapy alone in moderate-to-severe depression, whereas in mild depression, such differences were not observed. Among psychotherapies with medication, gCBT + p was significantly more effective than TAU and other psychotherapies in both the main and subgroup analyses.

Conclusion: The efficacy of depression treatment varied depending on the severity of the depressive condition. Notably, gCBT + p was identified as the most effective approach for treating adult depression.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Objective: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Objective: Associations between leptin (LEP) and leptin receptor (LEPR) gene polymorphisms and mood disorders have been found but not yet confirmed in multiple studies. The aim of our study was to study the associations between LEP and LEPR single nucleotide polymorphisms (SNPs) and treatment response of depression. Associations between leptin levels and depression severity were also investigated.

Methods: The data included 242 depressed patients in secondary psychiatric care. Symptoms of depression were assessed with the Montgomery–Åsberg Depression Rating Scale (MADRS). Previously found LEP and LEPR SNPs associated with depression and other mood disorders were studied. Furthermore, all available LEP and LEPR SNPs were clumped using proxy SNPs to represent gene areas in r² > 0.2 linkage disequilibrium and their association with treatment response was analysed with logistic regression.

Results: Two proxy SNPs of LEPR gene, rs12564738 and rs12029311, were associated with MADRS response at 6 weeks (p adjusted = 0.024, p adjusted = 0.024). SNPs from previous studies were not associated with MADRS response, but LEPR rs12145690 from a previous study was strongly associated with rs12564738 (r² = 0.94). The positive association between leptin levels and MADRS score at baseline after adjusting with age, sex, body mass index (BMI), Alcohol Use Disorders Identification Test score, and smoking was found (p = 0.011).

Conclusion: Our findings suggest that LEPR polymorphisms are associated with depression treatment response. We also found associations between leptin levels and depression independently of BMI. Further studies and meta-analyses are needed to confirm the significance of found SNPs and the role of leptin in depression.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Objective: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Childhood trauma can cause deficits in emotional regulation. However, few studies have investigated childhood trauma and emotional regulation skills in patients with mood disorders. We aimed to investigate how childhood trauma and Emotion Regulation Skills Questionnaire (ERSQ) scores are associated with mood disorders.This study included 779 patients with mood disorders (major depressive disorder [MDD, n = 240], bipolar I disorder [BDI, n = 121], and bipolar II disorder [BDII, n = 418]). We used their Childhood Trauma Questionnaire-Short Form (CTQ) and ERSQ scores for the evaluation.The between-group differences in CTQ and ERSQ scores were examined. The CTQ and ERSQ total scores were negatively correlated. Among the CTQ subscales, emotional neglect showed a significant correlation with the ERSQ total score, whereas acceptance and tolerance showed higher negative correlations with the CTQ than with the other ERSQ subscales. The negative relationship between emotional regulation and childhood trauma varied significantly depending on the group, with the BDI group showing a more prominent association than the other groups.Based on various mood disorders, we observed associations between childhood trauma and emotional regulation skills. Consequently, our study offers notable insights for future research on the impact of childhood trauma on ERSQ.

Though commonly used to model affective disorders, zebrafish display notable differences in terms of the structure and function of the brain serotonin system, including responses to pharmacological interventions, as compared to mammals. For example, elevation of brain serotonin following acute administration of serotonin reuptake inhibitors (SRIs) generally has anxiogenic effects, both in the clinical situation and in rodent models of anxiety, but previous research has indicated the opposite in zebrafish. However, several issues remain unresolved. We conducted a systematic review of SRI effects in zebrafish models of anxiety and, on the basis of these results, performed a series of experiments further investigating the influence of serotonin-releasing agents on anxiety-like behaviour in zebrafish, with sex-segregated wild-type animals being administered either escitalopram, or the serotonin releaser fenfluramine, in the light-dark test. In the systematic review, we find that the available literature indicates an anxiolytic-like effect of SRIs in the novel-tank diving test. Regarding the light-dark test, most studies reported no behavioural effects of SRIs, although the few that did generally saw anxiolytic-like responses. In the experimental studies, consistent anxiolytic-like effects were observed with neither sex nor habituation influencing treatment response. We find that the general effect of acute SRI administration in zebrafish indeed appears to be anxiolytic-like, indicating, at least partly, differences in the functioning of the serotonin system as compared to mammals and that caution is advised when using zebrafish to model affective disorders.

From a neuroscientific point of view, one of the unique archetypes of substance use disorders is its road to relapse, in which the reward system plays a crucial role. Studies on the neurobiology of substance use disorders have highlighted the central role of a protein belonging to the Fos family of transcription factors, ΔFosB. Relying on the roles ΔFosB plays in the pathophysiology of substance use disorders, we endeavour to present some evidence demonstrating that N-acetylcysteine, a low-cost and well-tolerated over-the-counter medicine, may influence the downstream pathway of ΔFosB, thereby serving as a treatment strategy to mitigate the risk of relapse in cases of substance use.