Clinical Psychopharmacology and Neuroscience最新文献

Objective: This study aimed to investigate the moderating effects of interleukin-1β (IL-1β) on the relationship between stressful life events (SLEs) and antidepressant treatment outcomes over 12 weeks in patients with depressive disorders.

Methods: Baseline assessments of SLEs, IL-1β levels, and other covariates were conducted for 1,094 depressive outpatients with 1,086 followed up for 12 weeks. Antidepressant treatment was tailored according to clinician recommendations and patient preferences, with outcomes evaluated at 12 weeks using the Hamilton depression rating scale. Logistic regression analyses explored the individual and interactive effects of SLEs and IL-1β on depression remission.

Results: SLEs alone did not predict 12-week remission (OR = 0.93, 95% CI [0.82, 1.06]). However, IL-1β levels significantly influenced outcomes (OR = 0.67, 95% CI [0.53, 0.87]), particularly in conjunction with high SLE exposure (Wald = 13.29, p < 0.001). Higher IL-1β levels were associated with lower odds of achieving remission in the group with two or more SLEs (OR = 0.46, 95% CI [0.33, 0.65]), whereas in the group with fewer than two SLEs, the odds were not significantly different (OR = 1.13, 95% CI [0.77, 1.65]).

Conclusion: These findings highlight the critical role of both biological markers and environmental stressors in antidepressant treatment. IL-1β could serve as a biomarker for customizing antidepressant strategies, particularly in patients experiencing high SLE exposure, thereby enhancing treatment efficacy and personalized care. Future studies should include longitudinal assessments of IL-1β to further elucidate its dynamic role in depression pathology and treatment response.

Objective: Autistic spectrum disorders (ASD) are a heterogeneous collection of neurodevelopmental disorders with an unknown etiology. Erythropoietin is a versatile growth factor that plays a crucial role in the nervous system, exhibiting high expression in various regions of the brain, including neurons, glial cells and endothelial cells. Recent animal studies have demonstrated that Epo exerts neuroprotective and neurotrophic effects. The objective of this study was to examine the levels of erythropoietin-(Epo) and its receptor-(EpoR) in children with ASD and to elucidate the potential effects of Epo in the disorder.

Methods: The study involved 50 children diagnosed with ASD based on the 5th Edition of the Diagnostic and Statistical Manual of Mental Disorders criteria, with ASD severity assessed using the Childhood Autism Rating Scale. Additionally, a control group of 50 healthy children was included. Serum samples were collected from both groups, and levels of Epo and its EpoR.

Results: There were no statistically significant differences between the age and sex distributions of the ASD and control groups (p > 0.05). However, analysis of the serum samples revealed a statistically significant reduction in Epo levels in the ASD cohort compared to the control.

Conclusion: The results of our study indicate that Epo may have potential as an adjunctive therapy for children with ASD. The observed decrease in Epo levels and increase in EpoR levels in children with ASD suggest a dysregulation in the Epo-EpoR axis that may contribute to the pathophysiology of ASD. Further research is required to investigate the therapeutic effects of modulating Epo levels in ASD and to elucidate the mechanisms underlying these changes.

Objective: The brain-derived neurotrophic factor (BDNF) playing a crucial role in neuron survival and function, particularly in neurodegenerative diseases like Alzheimer's disease (AD). Our study seeks to explore polymorphisms in miRNAs that regulate the BDNF gene in individuals with AD, and to reveal the relationship between these polymorphisms and APOE genotypes.

Methods: Seventy AD patients who applied to the Psychiatry outpatient clinic were recruited for the study as well as 70 healthy individuals in the same age. The cases were examined for 5 miRNAs regulating BDNF and 2 APOE SNPs using the SNPType method on the Fluidigm platform.

Results: In comparisons of the genotype distributions for three polymorphisms (miR-206 rs16882131, miR-30e rs112439044, miR-26b rs188612260) (p < 0.01 all) and the allele frequencies for two polymorphisms (miR-30e rs112439044, miR-26b rs188612260) (p < 0.01) detected significant differences between groups. While the APOE e4/e4 genotype was detected in 4.50% of the AD group, no individual with this genotype was observed in the control group. When the correlation between miRNA polymorphisms and APOE genotypic distributions were investigated, the miR-30e rs10489167 polymorphism showed a statistically significant positive correlation with the ε2/ε2 genotype and a statistically significant negative correlation with the e2/e3 genotype (p < 0.08 and p < 0.001, respectively). On the other hand, the miR-30e rs112439044 polymorphism exhibited a statistically significant positive correlation with the e2/e2 and ε2/ε2 genotypes (p < 0.03 and p < 0.07, respectively).

Conclusion: These findings could potentially offer insights into the mechanisms underlying AD.

Recent advances in the application of transcranial direct current stimulation in psychiatry include providing about five sessions of stimulation in a short period of time with an inter-session interval of 20 minutes. Such "accelerated" protocols may reduce treatment duration and have differential neurophysiological benefits. In this narrative review, we discuss the potential impact of such protocols on the temporal aspects of metaplasticity of the neurons, non-linear behaviour of the neuronal population and brain criticality. We discuss the potential neurophysiological mechanisms involved and how to translate these mechanisms to specific stimulation parameters like duration of session, inter-session interval and number of sessions in a day. The expected benefits and necessary precautions required for accelerated protocols are also discussed.

Objective: Transcranial magnetic stimulation is an effective treatment modality for obsessive-compulsive disorder (OCD). In this large case series, we attempted to discuss various factors that might have a bearing on therapeutic response in OCD.

Methods: This study included patients with OCD receiving continuous theta burst stimulation over the supplementary motor area attending a tertiary care centre between April and December 2023.

Results: Our study evaluated 11 patients, of which seven showed a significant reduction in their symptoms (based on reduction in Yale-Brown Obsessive-Compulsive Scale score) by more than 35% from the baseline, indicating a positive response to the treatment. We found that patients who received twice-daily sessions had a higher response rate (four out of five patients or 80%). However, four patients reported experiencing a transient headache during the sessions, with two patients being from the twice-daily sessions group and the other two from the once-daily sessions group. In our case series, even patients with early onset, multiple obsessions, treatment resistance, chronic illness, and psychiatric comorbidities responded to add-on continuous theta burst stimulation (cTBS).

Conclusion: cTBS is a potentially promising add-on treatment modality in OCD that warrants further investigation and the presence of predictors of poor response should not discourage its use.

Objective: Aripiprazole long-acting injection (LAI) is both effective and widely used in clinical practice. Notably, no previous studies have examined the factors affecting the continuation of aripiprazole LAI within the Korean population. This study aims to identify real-world factors contributing to the continuation of aripiprazole LAI.

Methods: A 1-year retrospective cohort study was conducted on 68 patients initiating aripiprazole LAI at Inha University Hospital, Korea. Patient medical records were reviewed to assess continuation rates, the duration from initiation to discontinuation, and reasons for discontinuation.

Results: Overall, 27.9% of patients discontinued aripiprazole LAI within 12 months. The predominant reasons for discontinuation were insufficient efficacy (42.1%), adverse effects (31.6%), and preference for oral medication (21.1%). Univariate analysis revealed associations between discontinuation and patient compliance. After adjustment for sociodemographic factors, patient compliance and transitioning from paliperidone LAI to aripiprazole LAI were associated with the continuation of aripiprazole LAI. Multiple logistic regression analysis, adjusted for sociodemographic variables and compliance, identified significant associations between discontinuation and compliance.

Conclusion: This study supports the clinical effectiveness of aripiprazole LAI, demonstrated by a reduced one-year discontinuation rate compared to that observed in a paliperidone LAI study with a similar design. Large-scale, long-term prospective studies are essential to definitively ascertain the factors associated with LAI discontinuation.

Dystonia presents as a complex neurological disorder that can be challenging to manage, often impacting specific parts of the body and involving dysfunction in the cortico-subcortical loop, particularly the basal ganglia. Emerging evidence points to heightened motor cortex excitability, hyperplasticity of the sensorimotor cortex, and abnormal sensorimotor integration as pivotal factors contributing to dystonia. Consistent research findings underscore the significance of contralateral motor cortex hyper-excitability in the progression of focal dystonia. Therefore, neuromodulation techniques like repetitive transcranial magnetic stimulation hold promise in modulating focal cortical activity and addressing dystonia. This case study details the treatment of a 70-year-old male patient with progressive left upper limb dystonia and associated pain. The patient received all recommended treatments for hand dystonia, including botulinum toxin injections. Accelerated continuous theta burst stimulation (acTBS) was used to mitigate the challenges posed by the condition. This case underscores the potential advantages of neuromodulation techniques, such as acTBS and transcutaneous electrical nerve stimulation (TENS), in managing upper limb dystonia and its related pain symptoms. It highlights the promise of non-invasive interventions in enhancing function and quality of life for individuals with similar conditions.

Objective: Despite the prevalence of music listening among individuals performing tasks that require sustained attention, the impact of various components of rhythmic auditory stimulation on concentration remains inconclusive. The aim of this pilot study was to determine the efficacy of a novel specific rhythmic auditory stimulation (SAS) on attentional performance, including vigilance, orientation, and executive control, in healthy adults in comparison with other auditory stimulation and silence conditions.

Methods: This block-randomized study included 27 male and 27 female participants with a mean age of 31.52 years. Participants underwent the Attention Network Test (ANT) and the Frankfurt Attention Inventory (FAIR) under three auditory stimulation conditions: SAS, traditional rhythmic auditory stimulation (TAS), and a control condition of silence (CON). To assess potential sex differences in attentional abilities in response to auditory stimuli, nine participants were grouped into each sex-specific condition. All data collected were subjected to statistical analysis.

Results: The results showed that SAS resulted in significantly different mean reaction times, alerting and orienting effects on the ANT and P scores, and the percentage of Q and C scores on the FAIR test compared to TAS and CON (p < 0.05). However, no differences were found between males and females for any of the variables of the ANT and FAIR test under the same auditory stimulus conditions.

Conclusion: It is suggested that the new auditory stimuli used in this study may be more effective in improving attention than TAS or CON in healthy adults, irrespective of sex.

Schizophrenia is a chronic and severe mental illness associated with substantial morbidity and mortality. Antipsychotics primarily rely on direct dopamine blockade, leading to potential life-interfering adverse events. The purpose of this review is to describe the safety and efficacy of xanomeline-trospium (Cobenfy^TM), a Food and Drug Administration approved treatment for schizophrenia in adults. Xanomeline has a novel mechanism of action for the treatment of schizophrenia acting as a dual muscarinic-1 and muscarinic-4 preferring receptor agonist. Two phase 3 trials with a xanomeline- trospium up to 125 mg/30 mg 2 times daily for patients with schizophrenia saw significant reductions in PANSS positive and negative subscales, PANSS Marder negative factors, and CGI-S scale scores compared to placebo. The Cohen's d effect for the primary endpoint was around 0.60 in both trials. The medication was well-tolerated in all clinical trials with the most common adverse events being rated as mild-to-moderate. Two long-term, open-label studies with xanomeline-trospium showed that after 52 weeks of treatment more than 75% of participants achieved a > 30% improvement on PANSS total score with a mean decrease in score by 33.3 points. Other improvements were reductions in PANSS positive and negative subscales, PANSS Marder negative factor score, and CGI-S score. In both long-term studies, patients previously in the placebo groups during either phase 2 or phase 3 trials achieved a statistically significant improvement on all efficacy measures starting at week 2. These data suggest that xanomeline-trospium is an effective and well tolerated treatment for schizophrenia with a novel mechanism of action.

Objective: Psychosocial and genetic factors are considered to play roles in the etiological mechanisms of major depressive disorder (MDD). The involvement of miRNAs in the etiopathogenesis of depression and childhood traumas is still unclear. This study aims to reveal potential differences in miRNA levels between patients with depression and healthy individuals and assess their connection to childhood traumas.

Methods: This study included fifty patients with MDD and 33 healthy controls. The targeting of the 3'UTR regions of the BDNF, SLC6A4/SERT/5-HTT, HTR1a, and HTR2a genes by 8 miRNAs was analyzed to explore their potential involvement in depression and childhood traumas. The Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Childhood Trauma Questionnaire-28 were administered to the participants.

Results: Patients with MDD exhibited significantly lower expression levels of miR-335 and miR-4775, as well as significantly higher expression levels of miR-15, miR-16, miR-17, miR-92, miR-182, and miR-206, when compared to healthy controls using the 2^-(ΔΔCt) method. Only miR-17 and miR-92 were associated with childhood traumas in the patients with depression.

Conclusion: Our research reveals a possible involvement of miRNAs in the pathophysiology of depression and highlights a potential relationship between childhood traumas and specific miRNAs in depressed patients.