Clinical Psychopharmacology and Neuroscience最新文献

Objective: Spontaneous remission may influence the outcome of clinical trials and evaluation of antidepressant efficacy, as it is associated with placebo effects and false remission rates. However, the characteristics of spontaneous remission and its biological mechanisms remain poorly understood. This study aimed to explore the metabolic signatures and underlying biological mechanisms of spontaneous remission using metabolomics.

Methods: This study conducted untargeted and targeted metabolomic analyses in a discovery cohort (n = 16) comprising patients with major depressive disorder (MDD) and those who were spontaneously remitted without medication. Findings were validated in an independent cohort (n = 185), comprising drug-treated patients and healthy controls.

Results: Acetylcarnitine levels were significantly increased in spontaneous remission compared to depression, whereas glycerophosphocholine levels were decreased in spontaneous remission. Both metabolites showed the highest concentration in the control group, followed by the remission group, and the lowest concentration in the depression group, regardless of medication status. These changes suggest alterations in mitochondrial and membrane lipid metabolism.

Conclusion: Altered levels in acetylcarnitine and glycerophosphocholine may reflect key pathogenic mechanisms of MDD. These findings offer new insight into spontaneous remission as a distinct clinical subtype of depression and may highlight the potential of these metabolites as biomarkers for treatment monitoring in MDD.

Objective: This study aimed to determine the molecular repercussions of chronic treatment and potential biomarker candidates by comparing the expression profiles of 34 selected miRNAs in peripheral plasma of patients with bipolar disorder receiving pharmacotherapy for at least one year with healthy controls.

Methods: The study included 40 patients with bipolar disorder and 40 age- and sex-matched healthy controls. The miRNA fraction was obtained from plasma samples isolated from peripheral blood. 34 target miRNAs were quantified on the Biomark Real-Time PCR Dynamic Array^TM IFC platform. Control and bipolar groups were compared based on ΔCt values.

Results: After applying multiple comparison corrections, we found that the following miRNAs significantly decreased in the bipolar group: hsa-miR-222-3p, hsa-miR-574-3p, hsa-miR-145-5p, and hsa-miR-195-5p. Conversely, hsa-miR-25-3p exhibited an increase. The most notable increases were seen in hsa-miR-92a-3p, with a fold change of 1.25 (p < 0.001; q = 0.009), and hsa-miR-486-5p, with a fold change of 1.67 (p = 0.002; q = 0.033). Additionally, other miRNAs showed raw p values less than 0.05, but they lost statistical significance after false discovery rate correction.

Conclusion: Peripheral plasma miRNA profiles in chronic bipolar disorder revealed elevated miR-92a-3p and miR-486-5p and decreased miR-222-3p, miR-574-3p, miR-145-5p and miR-195-5p. These miRNAs may be suitable for evaluation as minimally invasive biomarker candidates in bipolar disorder, and their potential clinical use in diagnosis, prognosis, and treatment monitoring should be investigated with further studies.

Objective: Post-traumatic stress disorder (PTSD) is a serious mental health challenge that usually lacks effective responses to conventional therapies. High-definition transcranial alternating current stimulation (HD-tACS) is gaining attention as a potential therapeutic approach for neuropsychiatric disorders. This study aimed to investigate the effects of 1-Hz tACS on PTSD symptoms.

Methods: A randomized controlled trial involving 40 PTSD patients was designed. Patients were randomly divided into sham and real stimulation groups and underwent 10 HD-tACS sessions. We used 1-Hz HD-tACS with the central anode positioned at T8 and the ring cathodes at P8, C4, F8 and EX10 (targeting right lateral temporal cortex). Clinical symptoms of patients were evaluated through the PTSD Checklist for DSM-5 (PCL-5). Also, we measured salivary cortisol levels and serum brain-derived neurotrophic factor (BDNF) levels before and after treatment.

Results: The real stimulation resulted in a more significant reduction in PTSD symptoms as measured by the mean PCL-5 score (56.25 ± 12.13 to 39.40 ± 13.91) compared to the sham stimulation (p < 0.05). The mean salivary cortisol level increased significantly in the real stimulation group (0.053 ± 0.04 μg/dl to 0.10 ± 0.07 μg/dl) compared to the sham (p < 0.001). In contrast, serum BDNF levels showed no significant changes in either group.

Conclusion: Preliminary findings suggest that HD-tACS in delta band can significantly alleviate PTSD symptoms, indicating its potential as a therapeutic intervention for PTSD.

A complex bidirectional relationship exists between human immunodeficiency virus (HIV) infection and psychotic disorders. The co-occurrence of both conditions is associated with higher morbidity and mortality than their individual occurrence. In this case report, we discuss a 36-year-old people with HIV and first-episode psychotic disorder who benefited from the two-injection start regimen of long-acting aripiprazole without side effects in the context with relevant literature. In people with HIV and psychotic symptoms, a thorough evaluation is required to exclude other known causes of psychosis. With a multidisciplinary approach, proper diagnosis and appropriate treatment can reduce morbidity and mortality as well as improve functionality and quality of life. Especially in patients with poor oral medication adherence, the use of the two-injection start regimen of long-acting aripiprazole while considering potential drug-drug interactions and extrapyramidal symptoms may improve treatment compliance and reduce the exacerbation risk of psychotic symptoms caused by medication discontinuation.

Objective: The current meta-analysis aimed at updating evidence regarding the therapeutic potential of probiotics against autism spectrum disorder (ASD) symptoms and identifying outcome confounders.

Methods: Following PRISMA guidelines, randomized placebo-controlled trials retrieved from PubMed, Embase, Cochrane CENTRAL, and ScienceDirect were analyzed for effect size of primary outcomes (i.e., overall behavioral symptom changes) expressed as standardized mean difference (SMD) and odds ratios (ORs) for continuous and categorical variables, respectively, with 95% confidence interval (CI).

Results: Meta-analysis of eight studies (465 participants, mean age: 6.03, range: 1.5-45, female: 17.4%) revealed total ASD symptom improvements in the probiotic group compared to placebos (SMD: -0.19, 95% CI: -0.38 to -0.01, p = 0.04, I² = 0%, eight studies, 465 participants, certainty of evidence [COE]: low). Subgroup analyses showed probiotics-associated improvements only in studies recruiting predominantly preschool children (SMD: -0.30, 95% CI: -0.59 to -0.01, p = 0.04, three studies, 191 participants) or those using probiotics for over three months (SMD: -0.39, 95% CI: -0.73 to -0.06, p = 0.04, three studies, 144 participants) without difference between multiple-and single-strain probiotics. No difference was noted in overall dropouts between individuals treated with probiotics and those taking placebos (OR: 0.98, p = 0.94, eight studies, I² = 0%, 464 participants, COE: low). Despite a low risk of bias in most studies, COE was deemed low from limited trials and inconsistencies on sensitivity analysis.

Conclusion: The current study showed an association between probiotics use and an improvement in ASD symptoms, mainly in those aged below six or over three-month treatments. More large-scale investigations are warranted to support our findings.

Objective: Benzodiazepine receptor agonists (BZRAs) are still prescribed for insomnia to many patients in clinical practice, even though dual orexin receptor antagonists (DORAs) are an effective insomnia pharmacotherapy. It is important to establish appropriate methods of switching from BZRAs to DORAs for insomnia treatment.

Methods: We performed a secondary analysis of our prior retrospective study of the rate of DORA (suvorexant or lemborexant) continuance at 3 months after the introduction of these agents in 210 patients under long-term BZRA treatment. We investigated the effects of the classes of BZRAs (which are based on half-life lengths) on the DORA continuation rate and the decreased BZRA ratio.

Results: Our analyses revealed a significantly lower rate of failure of switching to a DORA in the patients who were being treated with ultra-short/short-acting BZRAs. Two logistic regression analyses of successful switching to DORAs identified the following as predictors of a 3-month continuation of a DORA: (i) a higher-dose BZRA at baseline (Exp(B): 1.570, 95% CI: 1.090-2.262), (ii) shorter-term BZRA use (Exp(B): 0.991, 95% CI: 0.985-0.997), and (iii) BZRA with ultra-short/short half-lives (Exp(B): 7.335, 95% CI: 2.054-26.188). The analyses identified higher BZRA dose at baseline (Exp(B): 1.801, 95% CI: 1.008-3.216) as a predictor of both DORA continuation and BZRA tapering.

Conclusion: These findings suggest that in efforts to switch a patient's insomnia medication to a DORA, the tapering of ultra-short/short-acting BZRAs can lead to the successful switch to a DORA among patients under high-dose BZRA treatment, whereas careful switching is necessary for patients under long-term BZRA treatment.

The study aims to report that a lower dose of aripiprazole ameliorates restless legs syndrome (RLS) induced by antidepressants. We report 3 cases of RLS associated with antidepressants. We differentiated the symptoms from akathisia due to diurnal variation and focused sensation in the legs and evaluated them using the International Restless Legs Syndrome Severity Rating Scale. In all cases, the symptoms deteriorated under antidepressant treatment. In one case, this may have been due to discontinuation of aripiprazole. According to the presented cases and literature, we concluded that aripiprazole has efficacy for secondary RLS induced by antidepressants.

Objective: The escalating global mental health crisis necessitates innovative solutions to address traditional service limitations such as high costs and professional shortages. This review examines the emerging role of artificial intelligence (AI) chatbots in digital psychiatry, analyzing their clinical efficacy, ethical challenges, and future directions.

Methods: This narrative review synthesizes evidence from recent randomized controlled trials, meta-analyses, and scholarly publications on AI chatbots for mental health. It also discusses the ethical and social implications, including data privacy, algorithmic bias, and cognitive effects, and provides a forward-looking roadmap for regulation and development.

Results: Chatbots grounded in evidence-based principles like cognitive-behavioral therapy demonstrate clinical effectiveness in reducing symptoms of depression and anxiety, with some studies reporting a strong "therapeutic alliance" comparable to that with human therapists. AI models also show promise in diagnostic and predictive roles by analyzing selfreport questionnaires and physiological data. However, critical risks include inappropriate responses in crisis situations, potential for AI psychosis, and the erosion of cognitive abilities due to over-reliance.

Conclusion: The future of digital psychiatry lies in a blended care model that combines the accessibility of AI with the indispensable empathy and professional judgment of human clinicians. A collaborative roadmap is essential, mandating safety protocols, strengthened data governance, expert involvement, and ethical design to ensure AI acts as a transformative and responsible tool.

Objective: Essential development of the frontal lobe occurs during childhood and adolescence, affecting various executive function (EF) domains. Of the frontal areas, the supplementary motor area (SMA) located in the medial frontal cortex, is involved in various high-order EFs which include inhibition, working memory, and cognitive flexibility. However, it remains unclear how the functional network of the SMA is associated with EF development.

Methods: We assessed Wisconsin Card Sorting Test (WCST) score and resting state functional magnetic resonance imaging data from 6- to 17-year-old children and adolescents to identify age differences in SMA functional connectivity (FC) associated with EF.

Results: A total of 112 children and adolescents (62 males; mean [standard deviation] age, 12.21 [2.98] years) were included. After adjusting for sex, we discovered significant evidence in the older group that 300 FCs between the SMA and numerous regions of the brain, including the frontal, occipital, parietal, temporal, limbic, and cerebellar areas, were negatively correlated with the WCST subcategories (false discovery rate < 0.05).

Conclusion: This finding underscores the SMA's pivotal role in executive dysfunction during developmental stages. Interestingly, this significant connectivity was absent in younger participants, highlighting the age range of 11-12 as a critical turning point for brain functional alterations involved in EF development. Since the crucial role of SMA in refining EF development has been underappreciated, this work has the potential to provide insight into both the nature of the functional alteration of SMA and the differences in individuals' EF development trajectories.

Objective: Since its development in 2002 by the Korean College of Neuropsychopharmacology and the Korean Society for Affective Disorders, the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) has undergone five revisions.

Methods: To improve survey efficiency, reflect general clinical practice, and facilitate comparisons with previous KMAP-DD revisions, the overall structure of the questionnaire was retained. The six sections of the questionnaire were as follows: 1) pharmacological treatment strategies for major depressive disorder with and without psychotic features; 2) pharmacological treatment strategies for persistent depressive disorder and other depressive disorder subtypes; 3) consensus on treatment-resistant depression; 4) selection of an antidepressant in consideration of safety, adverse effects, and comorbid physical conditions; 5) treatment strategies for special populations (children/adolescents, elderly, and women); and 6) non-pharmacological biological therapies. First-, second-, and third-line treatment recommendations were statistically derived.

Results: Compared to KMAP-DD 2021, only minor changes were noted, due to the limited introduction of new medications or treatment modalities. Nonetheless, notable shifts included an increased preference for atypical antipsychotics (AAPs), and higher preference of combination strategies involving AAPs and mood stabilizers, indicating a more proactive and intensive treatment trend in Korea.

Conclusion: KMAP-DD is expected to serve as a valuable clinical resource by providing expert consensus-based recommendations on specific treatment strategies and pharmacological options for major depressive disorders, thereby supporting the integration of real-world clinical practice with evidence-based medicine.