Acta Neuropsychiatrica最新文献

Objectives: 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.

Methods: 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.

Results: 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.

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

Objective: Psychotic disorders are characterized by abnormalities in the synchronization of neuronal responses. A 40 Hz gamma band deficit during auditory steady-state response (ASSR) measured by electroencephalogram (EEG) is a robust observation in psychosis and is associated with symptoms and functional deficits. However, the majority of ASSR studies focus on specific electrode sites, while whole scalp analysis using all channels, and the association with clinical symptoms, are rare.

Methods: In this study, we use whole-scalp 40 Hz ASSR EEG measurements-power and phase locking factor-to establish deficits in early-stage psychosis (ESP) subjects, classify ESP status using an ensemble of machine learning techniques, identify correlates with principal components obtained from clinical/demographic/functioning variables, and correlate functional outcome after a short-term follow-up.

Results: We identified significant spatially-distributed group level differences for power and phase locking. The performance of different machine learning techniques and interpretation of the extracted feature importance indicate that phase locking has a more predictive and parsimonious pattern than power. Phase locking is also associated with principal components composed of measures of cognitive processes. Short-term functional outcome is associated with baseline 40 Hz ASSR signals from the FCz and other channels in both phase locking and power.

Conclusion: This whole scalp EEG study provides additional evidence to link deficits in 40 Hz ASSRs with cognition and functioning in ESP, and corroborates with prior studies of phase locking from a subset of EEG channels. Confirming 40 Hz ASSR deficits serves as a candidate phenotype to identify circuit dysfunctions and a biomarker for clinical outcomes in psychosis.

Objective: 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.

Methods: 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.

Results: 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.

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

Objectives: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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.