Objective Low-intensity transcranial focused ultrasound (tFUS) has emerged as a promising non-invasive brain stimulation modality with high spatial selectivity and the ability to reach deep brain areas. The present study aimed to investigate the safety and effectiveness of low-intensity tFUS in treating major depressive disorder.Methods Participants were recruited in an outpatient clinic and randomly assigned to either the verum tFUS or sham stimulation group. The intervention group received six sessions of tFUS stimulation to the left dorsolateral prefrontal cortex over two weeks. Neuropsychological assessments were conducted before and after the sessions. Resting-state functional magnetic resonance imaging (rsfMRI) was also performed to evaluate changes in functional connectivity (FC). The primary outcome measure was the change in depressive symptoms, assessed with the Montgomery–Åsberg Depression Rating Scale (MADRS).Results The tFUS stimulation sessions were well tolerated without any undesirable side effects. The analysis revealed a significant main effect of session sequence on the MADRS scores and significant interactions between the session sequences and groups. The rsfMRI analysis showed a higher FC correlation between the right superior part of the subgenual anterior cingulate cortex (sgACC) and several other brain regions in the verum group compared with the sham group.Conclusion Our results reveal that tFUS stimulation clinically improved MADRS scores with network-level modulation of a sgACC subregion. This randomized, sham-controlled clinical trial, the first study of its kind, demonstrated the safety and probable efficacy of tFUS stimulation for the treatment of depression.

Alzheimer’s disease (AD) is the most common type of dementia, and depression is a risk factor for developing AD. Epidemiological studies provide a clinical correlation between late-life depression (LLD) and AD. Depression patients generally remit with no residual symptoms, but LLD patients demonstrate residual cognitive impairment. Due to the lack of effective treatments, understanding how risk factors affect the course of AD is essential to manage AD. Advances in neuroimaging, including resting-state functional MRI (fMRI), have been used to address neural systems that contribute to clinical symptoms and functional changes across various psychiatric disorders. Resting-state fMRI studies have contributed to understanding each of the two diseases, but the link between LLD and AD has not been fully elucidated. This review focuses on three crucial and well-established networks in AD and LLD and discusses the impacts on cognitive decline, clinical symptoms, and prognosis. Three networks are the (1) default mode network, (2) executive control network, and (3) salience network. The multiple properties emphasized here, relevant for the hypothesis of the linkage between LLD and AD, will be further developed by ongoing future studies.

Junhyung Kim, Hyun-Ghang Jeong, Moon‑Soo Lee, Seung-Hoon Lee, Sang-Won Jeon, Changsu Han. Clin Psychopharmacol Neurosci 2023;21:732-41. https://doi.org/10.9758/cpn.23.1049

Objective Enhancing subjective well-being is an effective way to improve mental health. This study aimed to validate a virtual realitybased interactive feedback program as an intervention tool for promoting subjective well-being. Methods Thirty-six males participated in this program, consisting of three tasks constructed based on the theories of positive psychology: 'Experience-based problem recognition task', 'Future self-based success story expression task', and 'Strength expression task'. Participants rated visual analog scores associated with each of the tasks contents. The concurrent validity of task scores was evaluated by correlations with the psychological scale scores. Results The total task score was positively correlated with scores of Mental Health Continuum-Short Form (MHC-SF) emotional wellbeing and psychological well-being, Rosenberg's Self-Esteem Scale, Dispositional Hope Scale agency dimension and pathways dimension, and Life Orientation Test Revised, but not with MHC-SF social well-being scores. After controlling for the effects of the other task scores, the task scores had linear relationships with certain psychological assessments. Conclusion Since the task scores are closely related to indicators of well-being, self-esteem, hope, and optimism, the program contents are well associated with certain aspects of subjective well-being and thus may be available for training that improves subjective well-being through interactive feedback.

Junhyung Kim, Hyun-Ghang Jeong, Moon-Soo Lee, Chi-Un Pae, Ashwin A. Patkar, Sang Won Jeon, Cheolmin Shin, Changsu Han. Clin Psychopharmacol Neurosci 2024;22:253-62. https://doi.org/10.9758/cpn.23.1070

This study assesses the early effectiveness of esketamine nasal spray (ESK) in adults with treatment-resistant depression (TRD) 1 day after the first administration, as monitored through self-assessment via the mobile application, Esketamine Continuing Assessment for Relapse Prevention (EsCARe). In this multi-center, open-label, single-arm study, adults aged 18–65 years diagnosed with TRD after failing at least two antidepressant therapies were enrolled from five tertiary hospitals in South Korea. During the induction period, participants self-administered ESK twice weekly and used the EsCARe app daily to record mood, sleep, and somatic symptoms. Key clinical assessments, the Patient Health Questionnaire-9 (PHQ-9), the Hamilton Depression Rating Scale (HAMD), and the Generalized Anxiety Disorder Scale (GAD-7), were measured at baseline and at weeks 2 and 4. The reliability and validity of EsCARe was assessed. The treatment results indicated significant improvements in depressive and anxiety symptoms, with notable reductions in the PHQ-9 and the GAD-7 by week 2, and the HAMD by week 4. The EsCARe app reliably and validly monitored depressive symptoms and demonstrated a significant reduction in depressive symptoms 1 day after the first administration of ESK. Using ESK, complemented by mobile self-monitoring, effectively reduces the symptoms of TRD early in the treatment course. Integrating mobile health technology into the therapeutic regimen highlights a significant advancement in managing TRD, offering patients and clinicians immediate feedback on treatment efficacy.