Clinical Psychopharmacology and Neuroscience最新文献

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.

Objective: Suicide is a significant public health issue, particularly among older adults, where the risk is heightened. Early identification of individuals at risk for suicidal ideation is essential for timely interventions, greatly improving prevention efforts. This study aimed to develop a predictive model for suicidal ideation in community-dwelling older adults using psychiatric self-report scales and machine learning classifiers.

Methods: A total of 238 older adults were assessed using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7, Perceived Stress Scale-10, and World Health Organization Quality of Life Scale - Abbreviated Version. A nested 5-fold cross-validation procedure repeated 100 times was used for feature selection and model evaluation. Various classifiers-including support vector machines, random forest, logistic regression, linear discriminant analysis, and gradient boosting-were employed.

Results: As the number of PHQ-9 items increased from two to six, the area under the curve (AUC) rose from 0.835 to 0.892. When a set of nine features-selected based on feature stability across iterations-was used, the AUC further improved to 0.904. This progression indicates that inclusion of additional informative items enhances classification performance.

Conclusion: This study demonstrates that psychiatric self-report scales can effectively predict suicidal ideation risk in community-dwelling older adults. By utilizing efficient features, the predictive accuracy of the model can be enhanced, offering valuable insights for developing early identification systems for high-risk groups. These findings suggest that a community-based suicide prevention program could be promoted by implementing a screening system to identify individuals at high risk for suicidal ideation among the elderly.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique used to treat major depressive disorder (MDD), particularly in patients with treatment resistant depression. More recently, accelerated transcranial magnetic stimulation (aTMS) has shown comparable efficacy while offering a faster treatment option. This review assesses whether aTMS is non-inferior to rTMS. This systematic review compared aTMS and rTMS protocols for MDD treatment. Studies were identified through PubMed, Cochrane Library, and Web of Science (September 2024). Non-MDD populations and non-aTMS techniques were excluded, such as studies that did not qualify as clinical trials, cohort or randomized controlled trial. Inclusion criteria required direct protocol comparisons and a minimum sample of 10 participants. Bias assessment followed the Cochrane Collaboration's robvis tool. Four studies were included, encompassing a total sample of 219 patients. Results showed symptom improvement across all groups, with accelerated protocols demonstrating faster response in some cases. However, long-term efficacy varied, and no study provided conclusive superiority of one protocol over the other. This study reveals the variability in aTMS protocols and the inconsistency in the depression rating scales selected across studies, noting that the lack of standardised assessment methods limits meta-analytical potential. Short follow-up durations contrast with antidepressant studies, restricting long-term efficacy evaluation. Additionally, improvements in sham methodologies have increased placebo responses, further influencing treatment outcome interpretation. This systematic review highlights the efficacy, tolerability, and cost-effectiveness of aTMS, suggesting its non-inferiority to rTMS and underscoring the need for further research to define the optimal accelerated protocol.

Objective: This study aimed to explore treatment outcomes and pharmacological treatment intensities across major depressive disorder (MDD) subtypes over a 24-month period in a naturalistic clinical setting.

Methods: A total of 1,079 MDD patients were classified into melancholic (n = 182; 16.9%), atypical (n = 68; 6.3%), and unspecified (n = 829; 76.8%) subtypes and followed in a longitudinal cohort study. Treatment intensity and outcomes, including 12-week and 12-month remission and 24-month relapse rates, were measured using the Hamilton Depression Rating Scale.

Results: There were no significant differences in remission or relapse rates across subtypes at 12 weeks, 12 months, or 24 months. However, melancholic and atypical subtypes received more intensive pharmacological treatments compared to the unspecified subtype, particularly during the initial 12-week treatment phase. This increased treatment intensity was associated with equivalent outcomes across subtypes.

Conclusion: Despite similar long-term outcomes across MDD subtypes, variations in treatment intensity were crucial for achieving these results. Our findings suggest that tailoring treatment plans according to depressive subtype severity and characteristics is essential for effective management. Future research should investigate the genetic and biomolecular bases of these subtypes to further optimize treatment strategies.

Objective: Body scan meditation is a popular mindfulness practice in which a person directs their attention toward internal bodily sensations. Although its neural mechanisms have been investigated using functional magnetic resonance imaging, few studies have used functional near-infrared spectroscopy (fNIRS) to directly measure prefrontal networks during body scan meditation.

Methods: In this study, symptoms of depression and anxiety were measured in 40 healthy young adults without prior meditation experience. Participants' prefrontal networks were evaluated using fNIRS during body scan meditation and resting with nature sounds.

Results: Analyses of fNIRS data revealed significant positive prefrontal network connectivity in both conditions, with greater connectivity between the dorsolateral prefrontal cortex and medial prefrontal cortex observed when participants were resting with nature sounds than during body scan meditation. Correlation analyses showed that the left dorsolateral superior frontal gyrus-right medial superior frontal gyrus connectivity during body scan meditation was negatively associated with depressive and anxiety symptoms and positively associated with emotion regulation abilities.

Conclusion: Enhanced prefrontal networks induced by meditation may have therapeutic implications for mental health. The fNIRS findings, which measured direct changes in prefrontal networks during body scan meditation, could serve as a cornerstone for understanding the neural correlates.

Objective: 3,4-Methylenedioxymethamphetamine (MDMA) is widely used recreationally but also modulates serotonergic signaling in the gut, potentially influencing the microbiota. Because low bone mineral density (BMD) is common in depression and other psychiatric disorders, we tested whether repeated, intermittent MDMA attenuates BMD loss in ovariectomized (OVX) mice.

Methods: OVX mice received MDMA (10 mg/kg) three times per week for six weeks. BMD was measured, and untargeted metabolomics of plasma samples along with gut microbiota profiling of fecal samples were performed.

Results: Compared with vehicle, MDMA increased whole-body and femoral BMD and shifted circulating bone-remodeling markers toward an antiresorptive profile-lower receptor activator of nuclear factor-κB ligand (RANKL) and higher osteoprotegerin. Gut microbiota profiling and untargeted metabolomics showed reduced Clostridia and enrichment of Bacilli, along with a marked decrease in plasma β-D-allose, a metabolite linked to Lactobacillus johnsonii.

Conclusion: These findings suggest that intermittent MDMA may mitigate OVX-induced BMD loss in association with remodeling of a gut microbiota-bone axis. Future studies should define causal microbial and metabolic mediators and evaluate generalizability across additional bone-loss models.

Depression is increasingly conceptualized as a disorder of impaired synaptic plasticity and excitation-inhibition imbalance within corticolimbic circuits. Two rapid-acting therapeutic classes, NMDA receptor modulators (ketamine, esketamine) and neuroactive-steroid GABA-A positive allosteric modulators (brexanolone, zuranolone), offer complementary approaches to restore circuit function. Clinically, intravenous ketamine and intranasal esketamine show superiority over placebo and active comparators in treatment-resistant depression (TRD), with esketamine supported for continuation-phase relapse prevention and, in the United States, is approved both as adjunctive therapy and as monotherapy in adults with TRD. Evidence of efficacy extends to bipolar depression with careful mood-stabilizer coverage. Both agents reduce suicidal ideation within hours to days, although effects on suicidal behavior have not been demonstrated. Safety profiles include dissociation and hemodynamic changes; concerns with prolonged or high-cumulative exposure include cystitis and misuse liability. Neurosteroid GABA-A modulators are effective in post partum depression with some preliminary evidence in major depression, particularly in combination with antidepressants, while adverse events are mainly dose-dependent sedation. Brexanolone requires monitored infusion, whereas zuranolone enables a 14-day outpatient course. Patient selection should integrate diagnosis, comorbidity, concomitant medications (e.g. benzodiazepines), logistics, and perinatal goals. Robust efficacy/tolerability predictors remain limited, though early symptomatic change is clinically informative. In conclusion, NMDA receptor modulators and neuroactive-steroid GABA-A positive allosteric modulators have improved the treatment for mood disorders and accelerated a transition to mechanism-driven care.

Objective: The choice of emotion regulation (ER) strategies depends on contextual characteristics, and the flexible choice of ER strategies based on context is essential for psychological health, including depression. Focusing on reappraisal, this study examined how perceived reappraisal affordances (the inherent potential of a situation for semantic reappraisal) -a reappraisal-related situational factor-are linked to the success of reappraisal use via reappraisal choice and investigated the role of depression in this mediation.

Methods: Eighty participants (40 individuals with major depressive disorder [MDD] and 40 non-depressed controls) read eight vignettes describing negative-emotion-evoking situations and reported reappraisal affordance, the likelihood of choosing reappraisal, and negative emotional responses for each vignette. Then, they were asked to implement reappraisal for each situation, followed by reporting their negative emotional responses again.

Results: Reappraisal affordance predicted greater reductions in negative emotions following reappraisal use (i.e., greater success) via an increased choice of the strategy. Group moderated the affordance-choice relationship, with a significant positive relationship observed only in the MDD group, while the relationship was not significant in the controls.

Conclusion: These results support the idea that considering contextual factors is crucial in understanding ER; however, adjusting ER choice based on situational factors may not always reflect flexible ER, as indicated by the significant affordance-choice link only in the MDD group.