Amygdala real-time fMRI neurofeedback upregulation in treatment resistant depression: Proof of concept and dose determination.

Previous work has shown that adults suffering from major depressive disorder (MDD) can increase their amygdala reactivity while recalling positive memories via real-time neurofeedback (rt-fMRI-nf) training, which is associated with reduction in depressive symptoms. This study investigated if this intervention could also be considered for patients suffering from MDD who do not respond to standard psychological and pharmacological interventions, i.e., treatment resistant (TR-MDD). 15 participants received 5 neurofeedback sessions. Outcome measures were depressive symptoms assessed by BDI scores up to 12 weeks following acute intervention, and amygdala activity changes from initial baseline to final transfer run during neurofeedback sessions (neurofeedback success). Participants succeeded in increasing their amygdala activity. A main effect of visit on BDI scores indicated a significant reduction in depressive symptomatology. Percent signal change in the amygdala showed a learning curve during the first session only. Neurofeedback success computed by session was significantly positive only during the second session. When examining the baseline amygdala response, baseline activity stabilized/asymptoted by session 3. This proof-of-concept study suggests that only two neurofeedback sessions are necessary to enable those patients to upregulate their amygdala activity, warranting a future RCT. Over the course of the rtfMRI-nf intervention, participants also reported reduced depressive symptomatology. Clinical trial registration number: NCT03428828 on ClinicalTrials.gov.

Ventromedial prefrontal cortex activation and neurofeedback modulation during episodic future thinking for individuals with suicidal thoughts and behaviors.

Individuals experiencing suicidal thoughts and behaviors (STBs) show less specificity and positivity during episodic future thinking (EFT). Here, we present findings from two studies aiming to (1) further our understanding of how STBs may relate to neural responsivity during EFT and (2) examine the feasibility of modulating EFT-related activation using real-time fMRI neurofeedback (rtfMRI-nf). Study 1 involved 30 individuals with major depressive disorder (MDD; half with STBs) who performed an EFT task during fMRI, for which they imagined personally-relevant future positive, negative, or neutral events. Positive EFT elicited greater ventromedial prefrontal cortex (vmPFC) activation compared to negative EFT. Importantly, the MDD + STB group exhibited reduced vmPFC activation across all EFT conditions compared to MDD-STB; although EFT fluency and subjective experience remained consistent across groups. Study 2 included rtfMRI-nf focused on vmPFC modulation during positive EFT for six participants with MDD + STBs. Results support the feasibility and acceptability of the rtfMRI-nf protocol and quantitative and qualitative observations are provided to help inform future, larger studies aiming to examine similar neurofeedback protocols. Results implicate vmPFC blunting as a promising treatment target for MDD + STBs and suggest rtfMRI-nf as one potential technique to explore for enhancing vmPFC engagement.

Imagery rescripting and cognitive restructuring for inpatients with moderate and severe depression - a controlled pilot study.

BACKGROUND: This controlled pilot study investigates the effect of the combined use of cognitive restructuring (CR) and imagery rescripting (IR) compared to treatment as usual among inpatients with moderate and severe depression. Alongside expert ratings and self-report tools, fitness wristbands were used as an assessment tool. METHODS: In addition to the standard inpatient care (SIC) program, 33 inpatients with moderate and severe depression were randomly assigned to an intervention group (two sessions of IR and CR) or an active treatment-as-usual (TAU) control group (two sessions of problem-solving and build-up of positive activity). Depression severity was assessed by the Hamilton Depression Rating Scale-21 (HDRS-21), the Beck Depression Inventory-II (BDI-II), and as a diagnostic adjunct daily step count via the Fitbit Charge 3™. We applied for analyses of HDRS-21 and BDI-II, 2 × 2 repeated-measures analysis of variance (ANOVA), and an asymptotic Wilcoxon test for step count. RESULTS: The main effect of time on both treatments was η2 = .402. Based on the data from the HDRS-21, patients in the intervention group achieved significantly greater improvements over time than the TAU group (η2 = .34). The BDI-II data did not demonstrate a significant interaction effect by group (η2 = .067). The daily hourly step count for participants of the intervention group was significantly higher (r = .67) than the step count for the control group. CONCLUSIONS: The findings support the utilization of imagery-based interventions for treating depression. They also provide insights into using fitness trackers as psychopathological assessment tools for depressed patients. TRIAL REGISTRATION: The trial is registered at the German Clinical Trials Register (Deutsches Register Klinischer Studien) under the registration number: DRKS00030809.

Efficacy of transcranial photobiomodulation in the treatment for major depressive disorder: A TMS-EEG and pilot study.

BACKGROUND: Major depressive disorder (MDD) was a prevalent mental condition that may be accompanied by decreased excitability of left frontal pole (FP) and abnormal brain connections. An 820 nm tPBM can induce an increase in stimulated cortical excitability. The purpose of our study was to establish how clinical symptoms and time-varying brain network connectivity of MDD were affected by transcranial photobiomodulation (tPBM). METHODS: A total of 11 patients with MDD received 820 nm tPBM targeting the left FP for 14 consecutive days. The severity of symptoms was evaluated by neuropsychological assessments at baseline, after treatment, 4-week and 8-week follow-up; 8-min transcranial magnetic stimulation combined electroencephalography (TMS-EEG) was performed for five healthy controls and five patients with MDD before and after treatment, and time-varying EEG network was analyzed using the adaptive-directed transfer function. RESULTS: All of scales scores in the 11 patients decreased significantly after 14-day tPBM (p < .01) and remained at 8-week follow-up. The time-varying brain network analysis suggested that the brain regions with enhanced connection information outflow in MDD became gradually more similar to healthy controls after treatment. CONCLUSIONS: This study showed that tPBM of the left FP could improve symptoms of patients with MDD and normalize the abnormal network connections.

Effect of exercise for depression: systematic review and network meta-analysis of randomised controlled trials.

OBJECTIVE: To identify the optimal dose and modality of exercise for treating major depressive disorder, compared with psychotherapy, antidepressants, and control conditions. DESIGN: Systematic review and network meta-analysis. METHODS: Screening, data extraction, coding, and risk of bias assessment were performed independently and in duplicate. Bayesian arm based, multilevel network meta-analyses were performed for the primary analyses. Quality of the evidence for each arm was graded using the confidence in network meta-analysis (CINeMA) online tool. DATA SOURCES: Cochrane Library, Medline, Embase, SPORTDiscus, and PsycINFO databases. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Any randomised trial with exercise arms for participants meeting clinical cut-offs for major depression. RESULTS: 218 unique studies with a total of 495 arms and 14 170 participants were included. Compared with active controls (eg, usual care, placebo tablet), moderate reductions in depression were found for walking or jogging (n=1210, κ=51, Hedges' g -0.62, 95% credible interval -0.80 to -0.45), yoga (n=1047, κ=33, g -0.55, -0.73 to -0.36), strength training (n=643, κ=22, g -0.49, -0.69 to -0.29), mixed aerobic exercises (n=1286, κ=51, g -0.43, -0.61 to -0.24), and tai chi or qigong (n=343, κ=12, g -0.42, -0.65 to -0.21). The effects of exercise were proportional to the intensity prescribed. Strength training and yoga appeared to be the most acceptable modalities. Results appeared robust to publication bias, but only one study met the Cochrane criteria for low risk of bias. As a result, confidence in accordance with CINeMA was low for walking or jogging and very low for other treatments. CONCLUSIONS: Exercise is an effective treatment for depression, with walking or jogging, yoga, and strength training more effective than other exercises, particularly when intense. Yoga and strength training were well tolerated compared with other treatments. Exercise appeared equally effective for people with and without comorbidities and with different baseline levels of depression. To mitigate expectancy effects, future studies could aim to blind participants and staff. These forms of exercise could be considered alongside psychotherapy and antidepressants as core treatments for depression. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018118040.

Cost-effectiveness of a mindful yoga intervention added to treatment as usual for young women with major depressive disorder versus treatment as usual only: Cost-effectiveness of yoga for young women with depression.

In a randomized controlled trial in the Netherlands, we studied the (cost)effectiveness of adding a mindful yoga intervention (MYI+TAU) to treatment as usual (TAU) for young women with major depressive disorder (MDD). In this paper, we present the results of the economic analyses. Societal costs and health outcomes were prospectively assessed during 15 months for all randomized participants (n = 171). Symptoms of depression (Depression Anxiety and Stress Scales; DASS) and quality adjusted life years (QALYs) were used as health outcomes in the economic analyses. Mean total societal costs during the 15 months of the study were €11.966 for the MYI+TAU group and €13.818 for the TAU group, differences in mean total societal costs were not statistically significant. Health outcomes (DASS and QALY) were slightly in favour of MYI+TAU, but differences between groups were not statistically significant. Combining costs and health outcomes in cost-effectiveness analyses indicated that MYI+TAU is likely to be cost-effective compared to TAU which was confirmed by sensitivity analyses. Although there were limitations in the cost-effectiveness analysis, findings from this study suggest that MYI+TAU warrants future attention for the potential to be cost-effective compared to TAU for young women with MDD.

The effects of swLORETA Z-score neurofeedback for patients comorbid with major depressive disorder and anxiety symptoms.

BACKGROUND: Patients with major depressive disorder (MDD) exhibit atypical brain activities in the frontal, temporal, and parietal lobes. The study aimed to investigate the effects of standardized weighted low-resolution electromagnetic tomography Z-score neurofeedback (swLZNFB) on symptoms of depression and anxiety, electroencephalography (EEG) parameters, and deep brain activities in patients with MDD. METHOD: Forty-eight patients with MDD comorbid with anxiety symptoms were assigned to the swLZNFB group and the control group. Participants completed the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI) and a 5-minute resting EEG at the pre-and post-tests. The swLZNFB group received ten sessions of one-hour treatment twice weekly. The control group received treatment as usual. The scores for BDI-II and BAI, number of EEG abnormalities, percentage of EEG abnormalities, and current source density (CSD) measured in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and amygdala were compared at pre-and post-tests between the two groups. RESULTS: There were decreased scores of BDI-II and BAI, number of EEG abnormalities, and percentage of EEG abnormalities at post-test compared with pre-test in the swLZNFB group, and lower scores of BDI-II and BAI at post-test in the swLZNFB group compared with the control group. Moreover, decreased CSD of beta1 and beta3 in the PFC, ACC, PCC, and amygdala at post-test compared to pre-test in the swLZNFB group. LIMITATIONS: Not a randomized controlled trial. CONCLUSION: Ten sessions of swLZNFB reduced clinical symptoms and atypical brain activities, it serves as a potential psychological intervention for patients with MDD.

Mindfulness plus physical activity reduces emotion dysregulation and insomnia severity among people with major depression.

BACKGROUND: As the disorder progresses, patients with depression suffer from decreased emotional stability, cognitive control and motivation. In the present study, we examined the effectiveness of three interventions on emotion dysregulation and insomnia severity: 1) mindfulness; 2) physical activity, and 3) mindfulness plus physical activity. METHOD: A total of 50 participants (mean age 33.21 ± 5.72 SD, 59% females) with major depression were randomly assigned to one of the three study conditions. Emotional dysregulation and insomnia severity were assessed at baseline, eight weeks later at study completion, and 4 weeks after that at follow-up. RESULTS: Emotion regulation and sleep quality improved over time from baseline to study completion and to follow-up. Compared to the mindfulness and physical activity alone conditions, the mindfulness plus physical activity condition led to higher emotion regulation and sleep quality. CONCLUSION: The combination of physical activity and mindfulness seems to have a beneficial effect on sleep quality and emotion regulation in those with major depression disorder and could be a valuable treatment strategy.

Perceptions of community mental health services among culturally diverse adult Singaporeans with major depressive disorder: A descriptive qualitative study.

Persons with major depressive disorder (PMDDs) often experience pernicious ramifications on the biopsychosocial aspects of their health. While community mental health services (CMHSs) in Singapore are increasingly leveraged to meet the escalating demand for mental healthcare, shortcomings such as a substantial treatment gap and the lack of holistic, culturally sensitive care have been highlighted. Of note, the perspectives of the service users, which have hardly been studied in the literature, are crucial to our understanding of their needs to continuously improve CMHSs. Accordingly, this qualitative descriptive study explored the perceptions and experiences of community-dwelling adults with major depressive disorder in their use of CMHSs in Singapore. Seventeen adults with major depressive disorder purposefully sampled from a CMHS provider were interviewed through a semi-structured guide between October and November 2021. Data analysis via Braun and Clarke's six-step thematic framework yielded five themes corresponding to three different phases: pre-CMHS encounter ((i) procrastination to seek help and (ii) factors influencing CMHS utilization); intra-CMHS encounter ((iii) incongruous perceptions of the impacts on biopsychosocial health and (iv) differing perceptions and experiences of culturally sensitive care); and post-CMHS encounter ((v) enhancing CMHSs for PMDDs based on end-users' experiences). Our findings underscore the need to improve the delivery of personalized mental healthcare services, use of settings- and culturally-specific anti-stigma strategies, and nationwide mental health literacy in symptom recognition and awareness of help-seeking resources.

Increased functional connectivity between the midbrain and frontal cortex following bright light therapy in subthreshold depression: A randomized clinical trial.

The underlying mechanisms of bright light therapy (BLT) in the prevention of individuals with subthreshold depression symptoms are yet to be elucidated. The goal of the study was to assess the correlation between midbrain monoamine-producing nuclei treatment-related functional connectivity (FC) changes and depressive symptom improvements in subthreshold depression. This double-blind, randomized, placebo-controlled clinical trial was conducted between March 2020 and June 2022. A total of 74 young adults with subthreshold depression were randomly assigned to receive 8-week BLT (N = 38) or placebo (N = 36). Depression severity was measured using the Hamilton Depression Rating Scale (HDRS). The participants underwent resting-state functional magnetic resonance imaging at baseline and after treatment. The dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and habenula seed-based whole-brain FC were analyzed. A multivariate regression model examined whether baseline brain FC was associated with changes in scores on HDRS during BLT treatment. BLT group displayed significantly decreased HDRS scores from pre- to posttreatment compared to the placebo group. BLT increased the FC between the DRN and medial prefrontal cortex (mPFC) and between the left VTA and right superior frontal gyrus (SFG). Altered VTA-SFG connectivity was associated with HDRS changes in the BLT group. Moreover, the baseline FC between DRN and mPFC could predict HDRS changes in BLT. These results suggested that BLT improves depressive symptoms and increases midbrain monoamine-producing nuclei and frontal cortex connectivity in subthreshold depression, which raises the possibility that pretreatment FC of DRN-mPFC could be used as a biomarker for improved BLT treatment in depression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Prospectively assessed summer mood status in major depression, recurrent with seasonal pattern: Evidence for SAD's construct validity.

OBJECTIVE: Seasonal patterns are often undetectable in population-based depression studies, calling into question the existence of winter seasonal affective disorder (SAD). If SAD has construct validity, individuals with SAD should show spontaneous depression remission in the summer. Data are sparse on prospectively assessed summer mood status in confirmed SAD patients. METHOD: We conducted prospective summer followup of community adults who, the winter before, were diagnosed with Major Depression, Recurrent with Seasonal Pattern on the Structured Clinical Interview for DSM-IV Axis I Disorders, developed a current SAD episode on the Structured Interview Guide for the Hamilton Rating Scale for Depression-Seasonal Affective Disorder Version (SIGH-SAD), and enrolled in a clinical trial comparing group cognitive-behavioral therapy for SAD and light therapy. In July/August after treatment, 143/153 (93.5 %) participants provided data on the SIGH-SAD, the Beck Depression Inventory-Second Edition, and the Longitudinal Interval Followup Evaluation (LIFE). RESULTS: Summer mean depression scores were in the normal range, with the substantial majority in remission across different measures. On the LIFE, 113/143 (79.0 %) experienced complete summer remission, 19/143 (13.3 %) experienced partial summer remission, and 11/143 (7.7 %) had major depression in the summer. Depression scores were significantly lower at summer than post-treatment in both treatments, indicating incomplete treatment response. LIMITATIONS: This was a single-site study with a relatively homogeneous sample. CONCLUSIONS: Supporting construct validity for SAD, the substantial majority experienced complete summer remission, with a minority in partial remission and a very small minority in episode. Both treatments left residual symptoms at treatment endpoint compared to summer.

A randomized controlled trial of mindfulness-based cognitive therapy for major depressive disorder in undergraduate students: Dose- response effect, inflammatory markers and BDNF.

To examine the dose-response effect of mindfulness-based cognitive therapy (MBCT) for college students with major depressive disorder (MDD), a randomized control trial with MBCT and a wait-list (WL) group was performed. All participants were invited to self-administer a set of questionnaires at baseline, mid-intervention (4th week), and post-intervention (8th week) by the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder scale (GAD-7), the Pittsburgh Sleep Quality Index (PSQI), the Five Facet Mindfulness Questionnaire (FFMQ), the Self-Compassion Scale (SCS). The serum levels of IL-1ß, IL-6, IL-8, TNF-α, BDNF were detected at baseline and post-intervention. After intervention, the scores of PHQ-9, GAD-7, PSQI, and the levels of IL-1ß, IL-6, IL-8 and TNF-α in the MBCT were significantly lower than those in WL group, and total scores of FFMQ, SCS, and the level of BDNF were significantly higher than those in WL group. In MBCT group, daily practice time and session numbers positively related to reduction rates of PHQ-9, GAD-7 and PSQI at post-intervention. The reduction rate of PHQ-9, GAD-7 and PSQI at post-intervention in the completers were higher significantly than those in the partial attendees. These findings suggested MBCT is effective for MDD, and the intervention has a dose-response effect. TRIAL REGISTRATION: Registration number is [ChiCTR2100044309].

Mindfulness-based real-time fMRI neurofeedback: a randomized controlled trial to optimize dosing for depressed adolescents.

BACKGROUND: Adolescence is characterized by a heightened vulnerability for Major Depressive Disorder (MDD) onset, and currently, treatments are only effective for roughly half of adolescents with MDD. Accordingly, novel interventions are urgently needed. This study aims to establish mindfulness-based real-time fMRI neurofeedback (mbNF) as a non-invasive approach to downregulate the default mode network (DMN) in order to decrease ruminatory processes and depressive symptoms. METHODS: Adolescents (N = 90) with a current diagnosis of MDD ages 13-18-years-old will be randomized in a parallel group, two-arm, superiority trial to receive either 15 or 30 min of mbNF with a 1:1 allocation ratio. Real-time neurofeedback based on activation of the frontoparietal network (FPN) relative to the DMN will be displayed to participants via the movement of a ball on a computer screen while participants practice mindfulness in the scanner. We hypothesize that within-DMN (medial prefrontal cortex [mPFC] with posterior cingulate cortex [PCC]) functional connectivity will be reduced following mbNF (Aim 1: Target Engagement). Additionally, we hypothesize that participants in the 30-min mbNF condition will show greater reductions in within-DMN functional connectivity (Aim 2: Dosing Impact on Target Engagement). Aim 1 will analyze data from all participants as a single-group, and Aim 2 will leverage the randomized assignment to analyze data as a parallel-group trial. Secondary analyses will probe changes in depressive symptoms and rumination. DISCUSSION: Results of this study will determine whether mbNF reduces functional connectivity within the DMN among adolescents with MDD, and critically, will identify the optimal dosing with respect to DMN modulation as well as reduction in depressive symptoms and rumination. TRIAL REGISTRATION: This study has been registered with clinicaltrials.gov, most recently updated on July 6, 2023 (trial identifier: NCT05617495).

Objective and subjective sleep in patients with non-seasonal major depressive disorder and eveningness - Results from a randomized controlled trial of bright light therapy.

STUDY OBJECTIVES: This study examines the (dis)agreement between objective and subjective sleep and their prospective changes in a randomized controlled trial of bright light therapy (BLT) in patients with major depressive disorder (MDD) and eveningness. METHODS: A total of 93 adults were randomized to receive either 30-min daily of 10,000 lux BLT or 50lux placebo dim red light therapy (DRL group) for a total of 5 weeks. Actigraphic data were collected at the baseline and during the last week of treatment. (Dis)Concordance of diary and actigraphic sleep parameters were assessed by partial correlations and Bland-Altman plots, and the associations between these discrepancies to depression severity was assessed by linear regression models. Changes of sleep parameters were assessed by linear mixed models. RESULTS: Significant correlations were found between subjective sleep timings and chronotype to actigraphic parameters. Discrepancies between diary- and actigraphic-measures were observed, and patients with more severe depressive symptoms were associated with a greater under-estimation of total sleep time (TST). A greater advance in the diary-based time to fall sleep and rise time were achieved in the BLT group as compared to the DRL group, while diary-based wake after sleep onset (WASO), TST and sleep efficiency (SE) comparably improved with time in both groups. There was no significant difference between the two groups in the actigraphic parameters after treatment. CONCLUSIONS: In this study, we found that depression severity influenced subjective report of sleep. BLT led to a greater advance in subjective sleep timings when compared to the placebo group.

In situ fNIRS measurements during cognitive behavioral emotion regulation training in rumination-focused therapy: A randomized-controlled trial.

Repetitive negative thinking (RNT), including rumination, plays a key role in various psychopathologies. Although several psychotherapeutic treatments have been developed to reduce RNT, the neural correlates of those specific treatments and of psychotherapy in general are largely unknown. Functional near-infrared spectroscopy (fNIRS) offers the potential to investigate the neural correlates of psychotherapeutic techniques in situ. Therefore, in this study we investigated the efficacy and neural correlates of a fNIRS adapted Mindfulness-based Emotion Regulation Training (MBERT) for the treatment of depressive rumination in 42 subjects with major depressive disorder (MDD) in a cross-over designed randomized controlled trial. Using psychometric measures, subjective ratings and fNIRS, we analyzed in situ changes in depressive symptom severity, ruminative thoughts and cortical activity in the Cognitive Control Network (CCN). Our results show that MBERT is effective in treating depressive symptoms and rumination. On a neural level, we found consistently higher cortical activation during emotion regulation training compared to control trials in the bilateral inferior frontal gyrus (IFG) and dorsolateral prefrontal cortex (DLPFC). Furthermore, cortical oxygenation decreased from session to session in the bilateral DLPFC. The relevance of the results for the psychotherapeutic treatment of MDD as well as further necessary investigations are discussed.

Predicting acupuncture efficacy for major depressive disorder using baseline clinical variables: A machine learning study.

Acupuncture is a viable treatment option for major depressive disorder (MDD). However, its effectiveness varies among patients. This study aimed to develop a model to predict the efficacy of acupuncture therapy for MDD using machine learning and baseline clinical variables. A total of 124 patients with MDD from five research centers were included in our machine learning study. All patients underwent acupuncture treatment for 6 weeks and the efficacy of the treatment was evaluated using the Hamilton Depression Scale-17 (HAMD-17). The max-relevance and min-redundancy (mRMR) algorithm and Pearson correlation analysis were used for selecting 11 significant features from 26 baseline clinical variables for model training. We compared the performance of five machine learning models, including logistic regression, support vector machine, K-nearest neighbor, random forest, and XgBoost, in predicting the effect of acupuncture in relieving major depression. Among the five models, XgBoost performed the best with an area under the receiver operating characteristic curve (AUC) of 0.835, an accuracy of 0.730, a sensitivity of 0.670, a specificity of 0.774, and an F1 score of 0.751. The key predictive variables identified were anxiety score in the self-rating depression scale (SDS), the traditional Chinese medicine syndrome of deficiency in both heart and spleen, and body mass index (BMI). The study demonstrates that the developed model can help physicians predict the patients who will benefit from acupuncture treatment, which is of positive significance for improving the clinical efficacy of acupuncture on MDD.

Developing Advanced AI Ecosystems to Enhance Diagnosis and Care for Patients with Depression.

Major Depressive Disorder (MDD) has a significant impact on the daily lives of those affected. This concept paper presents a project that aims at addressing MDD challenges through innovative therapy systems. The project consists of two use cases: a multimodal neurofeedback (NFB) therapy and an AI-based virtual therapy assistant (VTA). The multimodal NFB integrates EEG and fNIRS to comprehensively assess brain function. The goal is to develop an open-source NFB toolbox for EEG-fNIRS integration, augmented by the VTA for optimized efficacy. The VTA will be able to collect behavioral data, provide personalized feedback and support MDD patients in their daily lives. This project aims to improve depression treatment by bringing together digital therapy, AI and mobile apps to potentially improve outcomes and accessibility for people living with depression.

Illuminating the way: the role of bright light therapy in the treatment of depression.

INTRODUCTION: Despite the growing number of different therapeutic options, treatment of depression is still a challenge. A broader perspective reveals the benefits of bright light therapy (BLT). It stimulates intrinsically photosensitive retinal ganglion cells, which induces a complex cascade of events, including alterations in melatonergic, neurotrophic, GABAergic, glutamatergic, noradrenergic, serotonergic systems, and HPA axis, suggesting that BLT effects expand beyond the circadian pacemaker. AREAS COVERED: In this review, the authors present and discuss recent data of BLT in major depressive disorder, non-seasonal depression, bipolar depression or depressive phase of bipolar disorder, and seasonal affective disorder, as well as in treatment-resistant depression (TRD). The authors further highlight BLT effects in various depressive disorders compared to placebo and report data from several studies suggesting a response to BLT in TRD. Also, the authors report data showing that BLT can be used both as a monotherapy or in combination with other pharmacological treatments. EXPERT OPINION: BLT is an easy-to-use and low-budget therapy with good tolerability. Future studies should focus on clinical and biological predictors of response to BLT, on defining specific populations which may benefit from BLT and establishing treatment protocols regarding timing, frequency, and duration of BLT.

The effectiveness of mindfulness yoga on patients with major depressive disorder: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Mindfulness yoga is a type of exercise that emphasizes the integration of mindfulness or meditation into yoga. The aim of this study was to determine the effectiveness of mindfulness yoga intervention on major depressive disorder (MDD) patients. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted by searching nine databases, including PubMed, EMBASE, Web of Science, The Cochrane Library, MEDLINE, China National Knowledge Infrastructure (CNKI), Wanfang Data knowledge service platform, Chinese Biomedical Literature Database (CBM), and China Science and Technology Journal Database (VIP) from inception to April 2023. Primary outcomes included the severity of depression. Secondary outcomes included anxiety and rumination. RESULTS: Nine RCTs met our inclusion criteria (n = 581). The meta-analysis showed that mindfulness yoga significantly has a significant effect on depression (SMD = -0.53; 95%CI = -0.96 to -0.11; P < 0.05) among MDD patients. The only two RCTs involved also showed that mindfulness yoga could alleviate the anxiety level of MDD patients after intervention (SMD = -1.08; 95%CI = -1.64 to -0.52; P < 0.05). Meta-analysis did not reveal positive effects of the mindfulness yoga groups on rumination after intervention based on three RCTs (SMD = -0.33; 95%CI = -0.89 to 0.23; P > 0.05), but found a significant difference in the follow-up period based on two RCTs (MD = -7.42; 95%CI = -11.27 to -3.56; P < 0.05), compared with the control groups. CONCLUSION: Although we were unable to provide conclusive evidence to support the effectiveness of mindfulness yoga in improving symptoms in MDD patients, we found the literature included in this study indicated that mindfulness yoga might have a potential benefit for MDD patients and should be a feasible, acceptable, and promising intervention.

Plasma Brain-Derived Neurotrophic Factor Levels in First-Episode and Recurrent Major Depression and before and after Bright Light Therapy in Treatment-Resistant Depression.

Brain-derived neurotrophic factor (BDNF) is implicated in the etiology and treatment response in major depressive disorder (MDD). However, peripheral BDNF concentrations have not been compared across different MDD stages. Bright light therapy (BLT) offers some potential in treatment-resistant depression (TRD), but its effects on BDNF levels are unknown. This study included a cross-sectional analysis of plasma BDNF concentration in females with TRD, unmedicated MDD patients, and healthy controls (HC), and measurements of longitudinal BLT effects on plasma BDNF levels in TRD patients. The present study included 55 drug-naïve, first-episode patients, 25 drug-free recurrent-episode MDD patients, 71 HC participants, and 54 TRD patients. Patients were rated by Hamilton Depression Rating Scale (HAMD)-17 and the Montgomery-Åsberg Depression Rating Scale (MADRS). Patients with TRD received BLT during 4 weeks. The total HAMD-17 and MADRS scores decreased following BLT. All patient groups had lower plasma BDNF than HC, but BDNF levels did not differ between first- and recurrent-episode BDNF patients and TRD patients before or after BLT. However, responders and remitters to BLT had higher post-treatment plasma BDNF concentrations than patients who did not achieve response or remission. The changes in plasma BDNF levels may be candidates for biomarkers of treatment response to BLT in TRD patients.