Clinical Psychopharmacology and Neuroscience最新文献

Objective: The efficacy of antidepressants is influenced by a combination of genetic, individual, and environmental factors. This study aimed to investigate the association between the miR-182 rs76481776 polymorphism and the response to antidepressant treatment in major depressive disorder (MDD) patients, and its underlying molecular mechanisms.

Methods: This study enrolled 180 MDD patients and 180 healthy controls. The rs76481776 genotype was determined using TaqMan-based qPCR. The severity of depression and treatment response were assessed using the Hamilton Depression Rating Scale (HAMD). The expression of miR-182 and BDNF was measured using RT-qPCR. The regulatory relationship between miR-182 and BDNF was confirmed through a luciferase reporter gene assay. The correlation between miR-182 and BDNF expression was evaluated using the Pearson correlation coefficient.

Results: The T allele of rs76481776 was a significant risk factor for MDD (OR = 2.182, 95% CI: 1.424-3.345, p < 0.001) and was significantly associated with higher baseline scores on the HAMD. Moreover, individuals carrying the T allele (CT/TT genotype) exhibited a significantly poorer response to antidepressant treatment and a lower remission rate within 12 months compared to those with the CC genotype (p < 0.05). Mechanistically, miR-182 was highly expressed in patients with MDD (p < 0.05), and its expression was even higher in T allele carriers (p < 0.05). miR-182 could directly target and suppress BDNF , leading to decreased BDNF expression in MDD patients, and its expression was significantly and inversely correlated with BDNF expression.

Conclusion: The T allele of rs76481776 diminished the therapeutic efficacy of antidepressants by up-regulating miR-182 expression and subsequently suppressing BDNF expression.

Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR encephalitis) is an autoimmune encephalopathy increasingly recognized in the pediatric population. Although conventional immunotherapy-focused treatments have significantly improved outcomes, a substantial proportion of patients experience enduring neuropsychiatric and cognitive sequelae. Here, we present a three-year longitudinal follow-up report of a female case with confirmed anti-NMDAR encephalitis, focusing on the neuropsychiatric trajectory and cognitive sequelae management with memantine. A previously healthy 10-year-old girl presented with acute-onset psychotic, affective and cataplexy-like features, primarily such as severe irritability and dysphoria, mixed-type mood fluctuation, affective lability, disorganized speaking and thinking, mutism, visual hallucinations, cognitive regression, dysgraphia, and impulsive behavioral dysregulation. The patient received immunotherapy including intravenous methylprednisolone, intravenous immunoglobulin, and rituximab, as well as concurrent psychotropics, including valproate and olanzapine/aripiprazole. Despite psychiatric improvement in 6 months, she showed persistent deficits in memory, executive function, and impulse control, even after 18th month of conventional therapies. Despite appropriate immunotherapy and psychotropic treatments, exhibited persistent deficits in attention, memory, and executive functioning (dysfunction in language and learning), without any severe adverse events. Memantine, a non-competitive NMDAR antagonist with documented neuroprotective properties, was initiated during the chronic phase as complementary to psychotropic medications. While 20 mg/day dose of memantine was administering during 6 months, marked improvement was observed in her verbal fluency, academic functioning, and social engagement, that may be associated with post-acute initiation of memantine alongside conventional treatments. This case highlights the evolving understanding of post-autoimmune cognitive rehabilitation and discusses current evidence and theoretical rationale supporting memantine use in complementary treatment of prolonged cognitive dysfunction in the pediatric anti-NMDAR encephalitis.

Objective: Attention-deficit/hyperactivity disorder is one of the most common psychiatric disorders in childhood. This study aims to examine blood levels of glial cell line-derived neurotrophic factor and neuron-specific enolase in children with attention-deficit/hyperactivity disorder, and to explore their relationships with sleep patterns, eating behaviors, and attention-deficit/hyperactivity disorder symptoms.

Methods: A total of 51 patients diagnosed with attention-deficit/hyperactivity disorder and 20 healthy controls were included in the study. The Children's Sleep Habits Questionnaire and Eating Behavior Assessment Scale for Children were administered. Glial cell line-derived neurotrophic factor and neuron-specific enolase levels were measured using the Bioassay Technology Laboratory Human ELISA Kit.

Results: When comparing the serum glial cell line-derived neurotrophic factor levels between groups, no statistically significant difference was found in the distribution of glial cell line-derived neurotrophic factor levels (p = 0.645). The serum neuron-specific enolase levels in the attention-deficit/hyperactivity disorder group were found to be higher than the control group (p = 0.038). Correlation analysis demonstrated a negative correlation between glial cell line-derived neurotrophic factor levels and total scores on the eating scale (r = -0.309, p = 0.026).

Conclusion: These results highlight the possible involvement of glial cell line-derived neurotrophic factor in the regulation of eating patterns among children diagnosed with attention-deficit/hyperactivity disorder. Higher serum neuron-specific enolase levels were observed as discriminative between healthy and attention-deficit/hyperactivity disorder children.

Objective: This study aimed to investigate the relationship between zonulin and intestinal fatty acid-binding protein (I-FABP), biomarkers of intestinal permeability, and cognitive functions in patients with bipolar disorder (BD) compared to healthy controls (HCs).

Methods: The study included 40 individuals diagnosed with BD and HCs. Cognitive functions were evaluated using the Stroop Test, Trail Making Test, Öktem Verbal Memory Processes Test, Wisconsin Card Sorting Test, and Digit Span Test. Serum zonulin and I-FABP levels were measured.

Results: Zonulin and I-FABP levels were significantly higher in the BD group than in HCs (p < 0.001). After correction for multiple comparisons, significant associations remained between zonulin levels and cognitive performance measures, including the Stroop effect (r = 0.46, p < 0.001), delayed recall (r = -0.41, p < 0.001), and recognition performance (r = 0.42, p < 0.001). No significant correlations were found between I-FABP levels and cognitive test results.

Conclusion: The observed associations between zonulin levels and cognitive performance suggests a potential relationship of intestinal barrier integrity and gut microbiota with cognitive functions in BD. These findings should be interpreted as associative rather than causal, and future longitudinal studies are required to explore the direction of these relationships.

Objective: This study aimed to assess the prevalence of drug use-related problems in a Korean community sample and to examine the association between drug use-related problems and health-related quality of life (HRQOL).

Methods: Data were collected from 500 community-dwelling adults residing in Jeju, Korea. Drug use-related problems were assessed using the Drug Abuse Screening Test-10, and HRQOL was measured using the 26-item abbreviated version of the World Health Organization Quality of Life instrument.

Results: A total of 25 participants (5.0%) reported experiencing drug use-related problems in the previous 12 months. Multivariate analysis revealed that drug use-related problems were significantly associated with lower scores in all HRQOL domains, i.e., physical health, psychological health, social relationships, and environment, even after adjusting for relevant covariates.

Conclusion: Drug use-related problems were strongly associated with poorer HRQOL. These findings imply that clinicians should pay close attention to HRQOL when evaluating and treating individuals with illicit drug use.

Objective: This study compared the effects of personalized exercise versus acupuncture on multidimensional cognitive function in individuals at high risk for stroke with mild cognitive impairment (MCI).

Methods: A randomized controlled trial enrolled 200 stroke-risk adults aged 50-80 years. Ninety participants diagnosed with MCI (MMSE, HIS, CDR criteria) were randomly assigned to exercise (n = 30), acupuncture (n = 30), or control (n = 30) groups. Interventions lasted 6 months. Cognitive outcomes (MMSE, Raven's Progressive Matrices, Digit Symbol Substitution Test, Animal Fluency, Rey-Osterrieth test, Stroop test) were assessed before and after intervention. Multivariate regression identified risk factors for MCI. ANOVA was used for group comparisons.

Results: Hypertension (aOR = 1.5) and diabetes (aOR = 1.3) were significant risk factors for MCI. After intervention, the exercise group showed the largest MMSE improvement (Δ = 5.0), compared with acupuncture (Δ = 3.0) and control (Δ = 1.0) (p < 0.001). Exercise produced greater gains in non-verbal reasoning (31.8% vs. 26.1% in acupuncture, p < 0.01). Acupuncture more effectively enhanced processing speed and attention (DSST: Δ = 26 vs. Δ = 20 in exercise, p = 0.03) and executive function (Stroop interference time: Δ = 16 vs. Δ = 15 seconds in exercise, p = 0.04). Both interventions significantly improved verbal fluency (p < 0.001), with larger benefits in those with baseline MMSE ≤ 20.

Conclusion: Hypertension and diabetes are key risk factors for MCI in stroke-prone individuals. Exercise yields greater improvement in global cognition and memory, whereas acupuncture is more effective for enhancing attention and executive function. Both modalities benefit verbal fluency, particularly in lower-functioning participants.

Delirium is a common acute neuropsychiatric syndrome, and its early detection may improve clinical outcomes. This narrative review synthesized findings from 11 original studies and two systematic reviews that employed wearable sensors (actigraphy) to predict or detect delirium. In surgical, intensive care unit, and geriatric populations, delirium has consistently been associated with disrupted rest-activity rhythms, including lower daytime activity, increased nighttime activity, and fragmented sleep-wake cycles. Characteristic motor patterns also differed based on the motor subtype (hyperactive vs. hypoactive). Several studies have demonstrated that continuous wrist accelerometry can objectively detect the onset of delirium and classify motor subtypes. Notably, one machine learning model showed improved prediction accuracy, increasing from approximately 62% to 74% when motion features were included. Overall, continuous motion monitoring appears feasible and may serve as a promising non-invasive tool for early delirium detection and risk stratification. However, the findings remain heterogeneous, and motion-based algorithms alone show only moderate sensitivity. Further validation in larger and more diverse cohorts, as well as integration with clinical risk factors, is required before clinical implementation.

Objective: Youths with disruptive behavior disorders (DBDs) and a history of trauma exposure often exhibit deficits in neural mechanisms related to reward anticipation and assessment. This preliminary investigation examines the potential of a serotonergic agent (fluoxetine) to modulate neural activity in reward-related pathways for this population.

Methods: Three participant groups were: (i) youth with DBDs and trauma exposure who received fluoxetine treatment for 8 weeks (n = 12); (ii) a matched group of youth with DBDs and trauma exposure who received routine regular follow-up in an outpatient clinic (n = 9); and (iii) typically developing youth (n = 19). All participants completed a passive avoidance fMRI task twice, 8 weeks apart (pre-treatment and post treatment for youth with DBDs).

Results: Youth with DBDs and trauma exposure who received fluoxetine treatment compared to the other two groups showed: (i) significant improvement in externalizing, oppositional defiant disorder, irritability, anxiety-depression, and trauma-related symptoms; (ii) significantly increased recruitment of regions implicated in reward expectation (e.g., ventral tegmental area, nucleus accumbens), monitoring prediction error (e.g., dorsolateral prefrontal cortex, posterior parietal cortex), and inhibitory control (e.g., anterior insula, pre-supplementary motor area, anterior prefrontal cortex.

Conclusion: We provide preliminary data suggesting that a serotonergic medication can correct reward processing and provide symptom improvement in youth with DBDs and a history of trauma exposure. Given the small sample size, more rigorous studies with larger sample size are needed to confirm these results. The findings of this study could aid future clinical research and treatment for this challenging population.

The decision to use multiple long-acting injectable antipsychotics (LAIAs) is difficult since there is no evidence base for their use in treatment guidelines. In this case series, we aimed to present our experiences with the use of triple LAIAs in four patients diagnosed with schizophrenia. The study included four treatment-resistant schizophrenia cases who were followed in the inpatient ward of a university hospital, who could not use clozapine due to non-compliance with treatment, who did not benefit from multiple electroconvulsive therapy procedures, who did not respond to dual antipsychotic treatments and who were using triple LAIAs. The clinical histories of the cases were analysed retrospectively by experienced psychiatrists. All patients responded to the treatment with a decrease in their psychotic symptoms and the number of hospitalizations without any significant side effects. Also, improvement in daily functioning and adherence to treatment was observed in all cases. Based on these results, the use of multiple LAIAs can be safely applied, especially in appropriate treatment-resistant schizophrenia patients and with close follow-up by a clinician.

The sixth edition of the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) was published in 2025. This review compared KMAP-DD 2025 with four major international clinical practice guidelines: Canadian Network for Mood and Anxiety Treatments Clinical Guidelines for the Management of Major Depressive Disorders, National Institute for Health and Care Excellence Depression Guideline, Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines for Mood Disorders, and British Association for Psychopharmacology Guideline. While KMAP-DD is based on expert consensus, and others on evidence-based methods, overall treatment strategies for depressive episodes were fairly consistent. Especially, KMAP-DD 2025 offers more structured recommendations in areas lacking strong evidence, such as premenstrual dysphoric disorder, perinatal depression, and depression with medical comorbidities. KMAP-DD 2025 also reflected Korean clinical practice patterns emphasizing rapid symptom relief and early use of combination strategies. Despite limitations as a consensus-based guideline, KMAP-DD 2025 complements evidence-based approaches and provides practical, situation-specific guidance for real-world clinical decision-making in Korea.