World Journal of Biological Psychiatry最新文献

Background: Although the brain is not the only source of circulating endocannabinoids and their levels can be affected by many factors, it is underlined that serum endocannabinoid levels can be used as a biomarker in psychiatric disorders. In this study, we aimed to examine whether serum endocannabinoid and N-acylethanolamine concentrations reflect their brain levels.

Methods: In the present study acute immobilisation (AIS) and post-traumatic stress (PTSD) models were applied to Wistar albino male rats. Rota rod performance, forced swim, open field and elevated plus maze tests were performed. Endocannabinoid and N-acylethanolamine levels in serum and hippocampus, amygdala and cortex were assessed using LC-MS/MS.

Results: We observed significant increases in anandamide (AEA), palmitoylethanolamide (PEA) and oleoethylethanolamide (OEA) levels in the amygdala and hippocampus in both models except PEA in amygdala in the AIS group, while 2-AG levels decreased. There was no change in serum AEA and 2-AG levels in all groups; in the PTSD group serum PEA levels were higher whereas OEA levels were lower in both the AIS and the PTSD groups.

Conclusion: Our results show that there is no correlation in endocannabinoid and N-acylethanolamine levels between serum and specific brain regions in two stress models of rat.

Objectives: There is only limited knowledge about the impact of sex on the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in depressive disorders. Here, we analysed a large real-world sample of depressive patients with respect to potential sex-specific effects of rTMS treatment.

Methods: Data of 984 patients (539 females/445 males) were analysed. Patients received various antidepressant TMS protocols, most of them 10Hz, 20 Hz, Theta burst or accelerated protocols over the left dorsolateral prefrontal cortex. Changes in Hamilton Depression Scale (HAMD) and Major Depression Inventory (MDI) scores as well as response and remission rates were compared between female and male patients.

Results: There were no significant differences in any outcome between female and male patients. Response rates according to the HAMD-21 scores were 34.3% for females and 30.1% for males, according to the MDI 33.1% and 33.5% respectively. In an additional explorative analysis there was a tendency towards better outcome for females for the 20 Hz protocol.

Conclusions: The antidepressive effectiveness of rTMS does not differ between men and women.

Objectives: Knowledge on how sunlight impacts SERT activity via SLC6A4 promoter methylation in Seasonal Affective Disorder (SAD) remains limited. This study aimed to investigate the effect of daily sunshine duration on SLC6A4 promoter methylation in 28 patients with SAD and 40 healthy controls (HC).

Methods: Daily sunlight data for Vienna, Austria (mean of 28 days before blood sampling), were obtained from ©GeoSphere Austria. A general linear model analysed SLC6A4 promoter methylation as the dependent variable, with sunlight hours as the independent variable, and group (SAD, HC), age, sex, and 5-HTTLPR/rs25531 as covariates. Exploratory analyses examined the effects of sunlight hours and methylation on Beck Depression Inventory (BDI) scores.

Results: Sunlight had a significant effect on SLC6A4 promoter methylation (p = 0.03), with more sunlight hours resulting in lower methylation (r = -0.25). However, the interaction between sunlight and group was non-significant, suggesting a rather general effect across both groups. Sunlight also influenced BDI scores (p < 0.01), with fewer sunlight hours leading to higher scores (r = -0.25), which aligns with previous research. SLC6A4 promoter methylation had no significant effect on BDI scores.

Conclusions: Our findings suggest that sunlight influences SLC6A4 methylation without SAD specificity.

Background: Mild dementia is distressing for patients and their relatives. Due to its chronic and progressive nature, healthcare systems are at risk of being overwhelmed by the increasing number of affected patients. Thus, there is a need for safe and well-tolerated treatments that can be initiated at the earliest stages.

Objectives: This meta-analysis of clinical trials aimed to assess the treatment effects of Ginkgo biloba extract EGb 761 in patients with mild dementia.

Methods: Eligible randomised placebo-controlled trials were included in this meta-analysis. Data of patients with mild dementia (defined as the SKT Short Cognitive Performance Test total scores from 9 to 15) were selected.

Results: The meta-analysis was performed with pooled data from four eligible trials comprising 782 patients with mild dementia. Treatment with 240 mg EGb 761 daily was significantly superior to placebo in cognition (p = 0.04), global assessment (p = 0.01), activities of daily living (p = 0.01) and quality of life (p = 0.02). Standardised effects were medium to large. The frequency of adverse events was alike in patients treated with EGb 761 and placebo (p = 0.66).

Conclusions: The meta-analysis demonstrates that patients with mild dementia benefit from EGb 761 in terms of cognition, activities of daily living, global assessment and quality of life.

Focal adhesions and their dynamic nature are essential for various physiological processes, including the formation of neurites, synaptic function and plasticity. Alterations in these processes have been associated with schizophrenia and bipolar disorder.

Objectives: This study aimed to explore the impact of pharmacological treatments used for bipolar disorder and schizophrenia on the expression of genes involved in the focal adhesion pathway, addressing a gap in understanding the interaction between medication effects and disease pathophysiology.

Methods: NT2-N (neuron-like) cells were exposed to treatment with amisulpride, aripiprazole, chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone, or vehicle for 24 h. Genome-wide mRNA expression was analysed using gene set enrichment analysis.

Results: The analysis revealed that seven out of the eight drugs widely prescribed for bipolar disorder and schizophrenia downregulate the expression of genes associated with the focal adhesions pathway. Focal adhesion was the pathway with the most negative normalised enrichment score across all treatments.

Conclusions: Our results support the hypothesis that focal adhesion pathways may play a role in the pathophysiology of bipolar disorder and schizophrenia. Moreover, the data underscore the importance of differentiating medication effects from disease mechanisms in psychiatric research, a challenge compounded by the medicated state of most study participants.

Background: Genes associated with global developmental delay (GDD) and intellectual disability (ID) are increasingly being identified through next-generation sequencing (NGS) technologies. This study aimed to identify novel mutations in GDD/ID phenotypes through whole-exome sequencing (WES) and additional in silico analyses.

Material and methods: WES was performed on 27 subjects, among whom 18 were screened for potential novel mutations. In silico analyses included protein-protein interactions (PPIs), gene-miRNA interactions (GMIs), and enrichment analyses. The identified novel variants were further modelled using I-Tasser-MTD and SWISS-MODEL, with structural superimposition performed.

Results: Novel mutations were detected in 18 patients, with 10 variants reported for the first time. Among these, three were classified as pathogenic (DNMT1:c.856dup, KCNQ2:c.1635_1636insT, and TMEM94:c.2598_2599insC), and six were likely pathogenic. DNMT1 and MRE11 were highlighted as key players in PPIs and GMIs. GMIs analysis emphasised the roles of hsa-miR-30a-5p and hsa-miR-185-5p. The top-scoring pathways included the neuronal system (R-HSA-112316, p = 7.73E-04) and negative regulation of the smooth muscle cell apoptotic process (p = 3.37E-06). Homology modelling and superimposition revealed a significant functional loss in the mutated DNMT1 enzyme structure.

Conclusion: This study identified 10 novel pathogenic/likely pathogenic variants associated with GDD/ID, supported by clinical findings and in silico analyses focused on DNMT1 mutations.

Objectives: Our group conducted a single-blind, controlled, multi-site trial, wherein participants with treatment-resistant depression were randomised to standard 10 Hz rTMS, applied to the left dorsolateral prefrontal cortex (DLPFC), or accelerated bilateral TBS (aBLTBS), applied sequentially to the right then left DLPFC. We present a secondary analysis of this trial, investigating clinical predictors for treatment response.

Methods: Logistic regression analysis explored the relationship between TMS response and, adjusted for baseline depressive symptom severity: suicidality, current episode duration, age, sex, and presence of melancholia and psychosis. The relationship between self-reported past ECT response and current rTMS treatment response was evaluated with McNemar's test.

Results: Adjusted response status to aBLTBS, but not standard rTMS, is influenced by duration of current episode (aBLTBS OR 0.9945, p = 0.0417 vs. rTMS OR 0.9973, p = 0.2870). No other differential response predictors were identified.

Conclusions: There are no clinically significant differential response predictors to standard rTMS or accelerated TBS treatment protocols. Accelerated TBS or standard rTMS may be effective in treatment-resistant depression, including in patients with previous ECT non-response, and psychosis may lower the odds of treatment response. Given the overall time efficiency in delivering accelerated TBS, this may further strengthen the argument for its broader clinical adoption.

Objectives: Exercise might restore morphine-induced behavioural and molecular changes, but related evidence is inconsistent. We conducted a systematic review and meta-analysis of animal studies to elucidate the contribution of brain-derived neurotrophic factor (BDNF) to exercise effects on morphine addiction.

Methods: We searched papers published until May 25, 2024, in databases, manually searched related references, screened eligible studies, and extracted relevant data. The risk of bias was assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE)'s risk bias tool. Subsequently, we summarised study characteristics, reported risks of bias, and conducted a meta-analysis. Subgroup and sensitivity analyses were also conducted.

Results: The meta-analysis showed that exercise increased BDNF levels in morphine-addicted male animals, regardless of the exercise type and intensity. Under morphine addiction, voluntary exercise (running wheel) affected BDNF levels in males, whilst forced exercise (treadmill exercise) did not. Furthermore, different exercise intensities did not affect BDNF levels in males. The sensitivity analysis determined that the results were robust.

Conclusions: Exercise increased BDNF levels in male but not in female animals. BDNF level changes might be related to the type of exercise but not its intensity. Therefore, BDNF might serve as a biomarker for the effects of different exercise types.