Background:Adolescent depression necessitates the development of novel therapeutic approaches. Temporal interference stimulation (TIS) is a promising noninvasive neuromodulation technique capable of modulating deep-brain circuits; however, its feasibility in adolescent populations has not yet been established. This open-label pilot study evaluated the feasibility, safety, and tolerability of a five-day TIS protocol targeting the right amygdala in adolescents with depression. Clinical outcomes and neuroimaging findings were assessed as exploratory, hypothesis-generating objectives. Methods:Twelve adolescents with depression received five consecutive daily sessions of TIS (2000 Hz carrier frequency with a 100 Hz difference frequency; 20 min/day) targeting the right amygdala. Feasibility was evaluated on the basis of tolerability and adherence rates. Clinical outcomes were assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17), Montgomery-Åsberg Depression Rating Scale (MADRS), 14-item Hamilton Anxiety Rating Scale (HAMA-14), and the THINC-integrated tool (THINC-it) at baseline, post-treatment, and at one-week and four-week follow-up assessments. Exploratory resting-state functional magnetic resonance imaging (fMRI) was performed to investigate neuromodulatory effects. Results:Nine participants completed the study, corresponding to a completion rate of 75%, with a tolerability rate of 100%. No device-related adverse events were reported. Trends toward improvement were observed in depressive symptoms, anxiety symptoms, and subjective cognitive functioning. From baseline to post-treatment, HAMD-17 and HAMA-14 scores decreased by 52.0% and 56.7%, respectively, and these improvements were maintained at the four-week follow-up, with a 53.3% reduction in depression severity. Exploratory fMRI analyses demonstrated acute increases in functional connectivity between the right amygdala and sensorimotor cortical regions during the first stimulation session. Conclusions:A five-day course of right amygdala-targeted TIS was feasible, safe, and well tolerated in adolescents with depression. The observed improvements in depressive and anxiety symptoms, together with acute alterations in amygdala-cortical functional connectivity, provide hypothesis-generating signals that warrant further investigation in rigorously designed sham-controlled trials. However, given the open-label and uncontrolled nature of the study, these improvements cannot be causally attributed to the intervention. Clinical Trial Registration:The study has been registered on https://clinicaltrials.gov/ (registration number: No: NCT06452849; registration link: https://clinicaltrials.gov/study/NCT06452849).
Background:Anxiety-related symptoms are frequently reported in patients with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitor (TKI) therapy. However, the role of TKIs, including imatinib, in development of anxiety remains unclear. The prefrontal cortex (PFC) is closely associated with anxiety-like behaviors, and its metabolic components, particularly lipid- and myelin-related metabolites, are involved in their regulation. Whether imatinib affects brain metabolism remains unknown. This study aimed to evaluate the effects of imatinib on anxiety-like behaviors and to investigate associated metabolic alterations in the PFC. Methods:Anxiety-like behaviors were assessed using a battery of behavioral assays in imatinib-treated mice. PFC tissues from imatinib-treated and control mice were subjected to untargeted metabolomic analysis. Results:Imatinib-treated mice exhibited selective alterations in anxiety-like behaviors. Metabolomic analysis revealed distinct metabolic profiles between the two groups, with significant changes in lipid-related pathways, particularly sphingolipid metabolism. These findings extend the current understanding of the metabolic basis of anxiety-like behaviors and suggest that TKI treatment may influence neuropsychiatric processes through metabolic remodeling of the PFC. Conclusions:This study highlights a potential link between TKI therapy and brain metabolism and provides a framework for understanding the neurobiological basis of anxiety-related effects. These findings may inform future research on the neuropsychiatric consequences of targeted cancer therapies.
Background:Artificial intelligence (AI) integration offers significant potential to improve mental healthcare, however, the reliability of large language models (LLMs) in performing nuanced clinical tasks remains an important and largely unanswered question. This study aimed to evaluate ChatGPT's performance in scoring the Hamilton Depression Rating Scale (HAMD-21) compared with expert raters using standardized patients (SPs). Methods:Three senior mental health experts created and portrayed scenarios for ten SPs representing diverse depressive symptom profiles. Recorded interviews were transcribed and used as input for ChatGPT-4o. HAMD-21 scores generated by ChatGPT were compared with those assigned by expert raters and with predefined script-based reference scores. Inter-rater reliability was assessed using intraclass correlation coefficient (ICC), and differences between raters were evaluated using Steiger's tests. Results:ChatGPT and the expert raters achieved good-to-excellent reliability for total HAMD-21 scores (experts: ICC = 0.9921; ChatGPT: ICC = 0.9739). However, expert raters achieved perfect ICCs on 11 individual items, whereas ChatGPT achieved perfect agreement on only 2 items. Steiger's test demonstrated that experts significantly outperformed ChatGPT on 10 individual items as well as on total scores (Z = 1.931, p = 0.0268). Qualitative review revealed that ChatGPT tended to overestimate scores on items related to insomnia and somatic symptoms (items 4-6 and 13) and frequently miscalculated total scores. Conclusions:ChatGPT demonstrated excellent agreement on total HAMD-21 scores in structured, text-based depression assessments, supporting the potential role of LLMs as adjunctive tools for standardized depression severity evaluation. However, item-level discrepancies and systematic scoring errors indicate that human oversight remains essential for clinically nuanced interpretation.
Background:The interrelationships among the negative symptoms of schizophrenia and factors affecting quality of life remain unclear. To address this gap, the present study explores the complex interrelationships among anhedonia, self-stigma, self-esteem, psychological resilience, and social support in individuals with schizophrenia. Methods:A comprehensive battery of measures was used to assess 447 patients with schizophrenia. Undirected network analysis was employed to examine the centrality of various factors, and Bayesian network analysis was used to explore the indirect influence of upstream variables on anhedonia through psychological factors. Results:Self-stigma was identified as the most central factor. Among the subdimensions of anhedonia, abstract anticipatory pleasure and contextual consummatory pleasure demonstrated the highest centrality. Negative symptoms of schizophrenia and social support were found to indirectly influence different aspects of anhedonia through psychological factors such as self-esteem and resilience. In one of the identified pathways, social support influenced psychological resilience, which in turn affected abstract anticipatory pleasure, contextual consummatory pleasure, and contextual anticipatory pleasure. Conclusions:Our findings suggest that social support is associated with pleasure experiences partly through psychological resilience and underscore the potential mediating role of psychological factors in linking clinical symptoms, social resources, and hedonic capacity in schizophrenia.
Background:Although the global burden of mental disorders has been extensively documented, systematic assessments of cross-country inequalities, particularly regarding how this burden varies across levels of socio-demographic development, remain limited. Methods:Data on disability-adjusted life-years (DALYs) attributable to mental disorders and the socio-demographic index (SDI) were obtained from the 2021 Global Burden of Disease Study. Absolute and relative inequalities were assessed using the slope index of inequality (SII) and concentration index (CI). Results:Between 1990 and 2021, the total number of DALYs attributable to mental disorders increased by 73.4%, with the largest increase observed among adults aged 30 to 54 years. Age-standardized DALY rates increased by 9.4%, primarily driven by anxiety disorders, eating disorders, and depressive disorders. Females exhibited higher age-standardized rates of depressive disorders, anxiety disorders, bipolar disorder, and eating disorders, whereas males had higher rates of schizophrenia, autism spectrum disorder, conduct disorder, attention-deficit/hyperactivity disorder (ADHD), and other mental disorders. Anxiety disorders and depressive disorders were the primary contributors to the increasing burden, particularly among women and adolescents. In 2021, the burden of mental disorders showed substantial geographical variation across countries and territories. Inequality analyses demonstrated that the SII for overall mental disorders increased from 69 to 243, whereas relative inequality remained stable over time. Across SDI strata, high-SDI countries experienced a greater burden of eating disorders, ADHD, schizophrenia, and anxiety disorders, while low-SDI countries experienced a greater burden of depressive disorders and idiopathic developmental intellectual disability. Conclusions:The burden of mental disorders remains substantial and unequally distributed worldwide. Persistent and widening disparities over the past three decades highlight the urgent need for strengthened global health policies and coordinated multilevel interventions aimed at reducing inequalities across countries with differing levels of socio-demographic development.
