Clinical Psychopharmacology and Neuroscience最新文献

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.

Objective: Epothilone D (EpoD), microtubule (MT) stabilizing agent, demonstrated promising results in the animal models of Alzheimer's disease, Parkinson's disease and schizophrenia. The present study sought to investigate preventive effects of EpoD on altered changes of MT related proteins and endoplasmic reticulum (ER) stress proteins induced by social defeat stress (SDS).

Methods: We measured protein expression levels of α-tubulin and its post-translational modifications, MT-associated protein 2, stathmin1 and 2 with their phosphorylated forms, and ER stress markers, 78-kDa glucose-regulated protein (GRP-78) and CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) in the prefrontal cortex (PFC) and hippocampus (HIP) of C57BL/6J strain mice treated with EpoD (2 mg/kg) or its vehicle, dimethylsulfoxide (DMSO), and exposed to SDS.

Results: We observed lower levels of acetylated α-tubulin, MAP2, p-STMN (Ser16), and GRP-78 in the PFC of the EpoD-Con group when compared to the DMSO-Con group. On the other hand, in the HIP, there were significantly higher levels of tyrosinated α-tubulin and GRP-78 in the EpoD-Defeat group compared to the DMSO-Defeat group. Furthermore, the level of MAP2 in the HIP was found to be lower in the EpoD-Con group compared to the DMSO-Con group.

Conclusion: Our results suggest that EpoD exhibits a dual impact, manifesting both beneficial and detrimental effects on the aberrant changes of MT-related proteins and ER stress proteins induced by SDS, depending on the brain regions. These findings underscore the complexity of EpoD's effects, necessitating further exploration to understand its intricate mechanisms in cellular pathways linked to SDS.

Objective: Language disorder, a prevalent developmental disorder, impedes children's communication skills, with genetic and environmental factors playing pivotal roles in its pathomechanism. This study aims to investigate the involvement of sequence variations in SETBP1 and CNTNAP2 genes, along with environmental variables, in language disorder's etiology.

Methods: Between September 2022 and March 2023, thirty children aged 2-7 diagnosed with language disorders according to DSM-5 criteria, and evaluated using the Ankara Developmental Screening Inventory, were studied to identify genetic and environmental factors contributing to etiology.Thirty healthy children with similar age were included as a control group. DNA samples isolated from peripheral blood of both groups were analyzed for SETBP1 and CNTNAP2 genes using next-generation sequencing (custom design panel). The frequencies and clinical significance of the identified variants was evaluated, and variant verification and segregation analyses were performed by Sanger sequencing. The obtained data were compared using appropriate statistical methods.

Results: Language disorder showed a male-dominant distribution. The SETBP1 rs11082414-CC genotype frequency was significantly higher in patients (p = 0.024), and two rare variants (CNTNAP2: c.973C>G:p.P325A; CNTNAP2: c.2236 G>A:p.D746N) were exclusive to cases. In silico analyses yielded conflicting results for rare variants, inherited paternally from unaffected parents. Among non-genetic factors, patients had higher birth weights (p = 0.043) and shorter lactation durations (p = 0.044).

Conclusion: Homozygosity for SETBP1 rs11082414 polymorphic variant increases language disorder susceptibility. This study underscores the genetic dimension of language disorder, urging physicians' awareness and early intervention strategies to mitigate its impact.

Rabbit syndrome (RS), characterized by fine, rapid, rhythmic movements along the mouth's vertical axis, is typically linked to prolonged antipsychotic medication use. Emerging evidence suggests newer antipsychotics' involvement in RS, prompting investigation into its association with long-acting injectable antipsychotics (LAIs) for schizophrenia or bipolar disorder. We report a case of RS observed in a patient diagnosed with bipolar I disorder and treated with Abilify Maintena, highlighting the importance of vigilance in monitoring adverse effects. The patient, a 53-year-old male, experienced persistent manic episodes despite prior treatments. Upon initiation of Abilify Maintena 400 mg, RS symptoms manifested seven months later, remaining resistant to medication adjustments. This case emphasizes the significance of RS in LAIs-treated patients and emphasizes the need for further research into its mechanisms and optimal management strategies. Additionally, an updated review of RS associated with newer generation antipsychotics is provided to enhance understanding and clinical management.