Exploring gender differences in the relationship between gut microbiome and depression - a scoping review.

Background: Major depressive disorder (MDD) exhibits gender disparities, and emerging evidence suggests the involvement of the gut microbiome, necessitating exploration of sex-specific differences. Methods: A review was conducted, encompassing a thorough examination of relevant studies available in Medline via Ovid, Embase via OvidSP, CINAHL, and PsycINFO databases from their inception to June 2023. The search strategy employed specific keywords and Medical Subject Headings (MeSH) terms tailored to major depressive disorder in women, encompassing unipolar depression, depressive symptoms, and dysbiosis. Results: Five studies were included. Among the four studies, alterations in alpha (n=1) and beta diversity (n=3) in the gut microbiome of individuals with MDD were revealed compared to controls. Gender-specific differences were observed in four studies, demonstrating the abundance of specific bacterial taxa and highlighting potential sex-specific implications in MDD pathophysiology. Correlation analyses (n=4) indicated associations between certain bacterial taxa and the severity of depressive symptoms, with varying patterns between males and females. Studies (n=3) also highlighted promising findings regarding the potential utility of microbial markers in diagnosing MDD, emphasizing the crucial role of sex stratification in understanding the disease pathophysiology. Conclusions: The findings underscore the importance of recognizing gender-specific differences in the composition of the gut microbiome and its relationship with MDD. Further comprehensive robust studies are required to unravel the intricate mechanisms underlying these disparities.

Comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment resistant depression (ASCERTAIN-TRD) a randomized clinical trial.

Further research is needed to help improve both the standard of care and the outcome for patients with treatment-resistant depression. A particularly critical evidence gap exists with respect to whether pharmacological or non-pharmacological augmentation is superior to antidepressant switch, or vice-versa. The objective of this study was to compare the effectiveness of augmentation with aripiprazole or repetitive transcranial magnetic stimulation versus switching to the antidepressant venlafaxine XR (or duloxetine for those not eligible to receive venlafaxine) for treatment-resistant depression. In this multi-site, 8-week, randomized, open-label study, 278 subjects (196 females and 82 males, mean age 45.6 years (SD 15.3)) with treatment-resistant depression were assigned in a 1:1:1 fashion to treatment with either of these three interventions; 235 subjects completed the study. 260 randomized subjects with at least one post-baseline Montgomery-Asberg Depression Rating (MADRS) assessment were included in the analysis. Repetitive transcranial magnetic stimulation (score change (standard error (se)) = -17.39 (1.3) (p = 0.015) but not aripiprazole augmentation (score change (se) = -14.9 (1.1) (p = 0.069) was superior to switch (score change (se) = -13.22 (1.1)) on the MADRS. Aripiprazole (mean change (se) = -37.79 (2.9) (p = 0.003) but not repetitive transcranial magnetic stimulation augmentation (mean change (se) = -42.96 (3.6) (p = 0.031) was superior to switch (mean change (se) = -34.45 (3.0)) on the symptoms of depression questionnaire. Repetitive transcranial magnetic stimulation augmentation was shown to be more effective than switching antidepressants in treatment-resistant depression on the study primary measure. In light of these findings, clinicians should consider repetitive transcranial magnetic stimulation augmentation early-on for treatment-resistant depression.Trial registration: ClinicalTrials.gov, NCT02977299.

Associations of 24-hour movement behaviors with externalizing and internalizing problems among children and adolescents prescribed with eyeglasses/contact lenses.

Background: Emerging evidence points towards the psychological benefits of meeting 24-hour movement behavior (24-HMB) guidelines, but such associations have not yet been investigated among children and adolescents of prescribed eyeglasses/contact lenses. To this end, we examined associations of meeting 24-HMB guidelines with internalizing and externalizing challenges in this population. Methods: We used data from the 2021 National Survey of Children's Health, a cross-sectional survey including a representative sample of US children and adolescents. Data on movement behaviors (physical activity [PA], sedentary behavior operationalized via screen time [ST], and sleep duration [SL]) and internalizing and externalizing problems were collected through caregiver proxy reports. Caregivers completed questionnaires for 6030 (2799 girls) US children and adolescents of prescribed eyeglasses/contact lenses. Logistic regression analyses were conducted to determine the above-presented associations. Results: Only 7.1 % of those prescribed eyeglasses/contact lenses met all three 24-HMB guidelines, while they were more likely to meet SL guideline alone (32.1 %) in relation to other independent guidelines including PA (2.5 %) and ST (10.9 %). Compared to not meeting any of the three 24-HMB guidelines, meeting at least two guidelines (25.22 %) was significantly linked to lower odds of internalizing problems and externalizing problems. Conclusion: Meeting at least two components of the 24-HMB guidelines was beneficially linked to internalizing and externalizing problems. Thus, strategies or intervention programs that focus on meeting 24-HMB guidelines should be implemented among children and adolescents of those prescribed eyeglasses/contact lenses to foster coping with psychological issues.

Meeting 24-h movement behavior guidelines is linked to academic engagement, psychological functioning, and cognitive difficulties in youth with internalizing problems.

BACKGROUND: This study aimed to investigate associations of meeting 24-h movement behavior (24-HMB: physical activity [PA], screen time [ST] in the school-aged youth, and sleep) guidelines with indicators of academic engagement, psychological functioning, and cognitive function in a national representative sample of U.S. youth. METHODS: In this cross-sectional study, 1794 participants aged 6 to 17 years old were included for multivariable logistic regression to determine the above-mentioned associations, while adjusting for sociodemographic and health covariates. RESULTS: The proportion of participants who met 24-HMB guideline(s) varied greatly (PA+ ST+ sleep = 34 [weighted 1.17 %], PA + ST = 23 [weighted 1.72 %], PA + sleep = 52 [weighted 2.15 %], PA = 34 [weighted 2.88 %], ST = 142 [weighted 7.5 %], ST+ sleep = 209 [weighted 11.86 %], sleep = 725 [weighted 35.5 %], none = 575 [weighted 37.22 %]). Participants who met ST guideline alone and integrated (ST + Sleep and ST + sleep + PA) guidelines demonstrated the consistently beneficial associations with learning interest/curiosity, caring for school performance, completing required homework, resilience, cognitive difficulties, self-regulation (ps < 0.05). CONCLUSION: Meeting 24-HMB guidelines in an isolated or integrative manner was associated with improved academic engagement, psychological functioning, and reduced cognitive difficulties. These findings highlight the importance of the promotion of 24-HMB guidelines in youth with internalizing problems. Future longitudinal studies are needed to investigate whether changes or modifications of meeting specific 24-HMB guidelines (especially ST) is beneficial for youth with internalizing problems.

The Evaluation and Treatment of Somatic Symptom Disorder in Primary Care Practices.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.Prim Care Companion CNS Disord 2024;26(1):23f03549. Author affiliations are listed at the end of this article.

Relationships between physical activity, sleep, and screen time with academic performance and psychological functioning among US children and adolescents with depression.

OBJECTIVE: This cross-sectional study examined the relationships between adherence to 24-HMB guidelines (including physical activity [PA], screen time [ST], and sleep) with academic performance and psychological functioning among children and adolescents with depression. METHODS: This study consists of 2165 participants aged 6-17 years with depression. Independent variables were components of 24-HMB guideline adherence, while outcomes of interest were academic performance (i.e., caring about school performance and completion of required homework) and psychological functioning (i.e., resilience and self-regulation). Logistic regression analysis was conducted while adjusting for confounding variables. RESULTS: Only 1.03 % of the participants adhered to PA + ST + Sleep guidelines. Compared to non-adherence, adherence to PA + ST guidelines was significantly linked to a greater likelihood of caring about school performance (OR = 2.17), while ST + Sleep guidelines adherence was significantly linked to a greater likelihood of caring about school performance (OR = 2.02), completing homework (OR = 2.91), resilience (OR = 2.51), and self-regulation (OR = 2.51). Furthermore, adherence to PA + ST + Sleep guidelines was significantly linked to a higher likelihood of caring about school performance (OR = 5.01), resilience (OR = 2.49), and self-regulation (OR = 2.88) among these participants with depression. CONCLUSION: Adhering to 24-HMB guidelines is positively linked to academic performance and psychological functioning among children and adolescents with depression. Thus, establishing healthy lifestyle behaviors should be promoted in school settings.

A Randomized Controlled Trial of Community-Delivered Heated Hatha Yoga for Moderate-to-Severe Depression.

Objective: To evaluate feasibility, acceptability, and preliminary efficacy of heated yoga to treat moderate-to-severe depression.Design: An 8-week randomized controlled trial (RCT) of heated yoga versus waitlist control was conducted from March 2017 to August 2019.Methods: Participants in the yoga condition were asked to attend heated yoga classes at 2 community heated yoga studios at least twice weekly. We assessed acceptability and feasibility using exit interview and attendance data, respectively. The primary intervention efficacy outcome variable was change in the Inventory of Depressive Symptomatology-Clinician Rated (IDS-CR) score from baseline to post-intervention (week 8).Results: We randomized 80 participants and included 65 (mean [± SD] age 32.7 [± 11.7] years; 81.5% female) in the analyses (yoga n = 33, waitlist n = 32). The mean IDS-CR score at baseline was 35.6 (± 7.9) for the full sample, 36.9 (± 8.8) for yoga participants, and 34.4 (± 6.7) for waitlist participants. Participants attended an average of 10.3 (± 7.1) total classes over the 8-week intervention period. Yoga participants had a significantly greater pre- to post-intervention reduction in IDS-CR scores than waitlist participants (Cohen d = 1.04, P < .001). More yoga participants (59.3%; n = 16) than waitlist participants (6.3%; n = 2) evidenced larger treatment responses (IDS-CR ≥ 50% decrease in symptoms). Participants rated the heated yoga and its aftereffects positively in exit interviews.Conclusions: Approximately 1 heated yoga session per week (mean of 10.3 classes over 8 weeks) was associated with significantly greater reduction in depression symptoms than a waitlist control. Participants rated heated yoga positively. Taken together, results suggest feasibility, acceptability, and preliminary efficacy for patients with depression and warrant further research using active control conditions.Trial Registration: ClinicalTrials.gov identifier: NCT02607514.

WAPL functions as a rheostat of Protocadherin isoform diversity that controls neural wiring.

Neural type-specific expression of clustered Protocadherin (Pcdh) proteins is essential for the establishment of connectivity patterns during brain development. In mammals, deterministic expression of the same Pcdh isoform promotes minimal overlap of tiled projections of serotonergic neuron axons throughout the brain, while stochastic expression of Pcdh genes allows for convergence of tightly packed, overlapping olfactory sensory neuron axons into targeted structures. How can the same gene locus generate opposite transcriptional programs that orchestrate distinct spatial arrangements of axonal patterns? Here, we reveal that cell type-specific Pcdh expression and axonal behavior depend on the activity of cohesin and its unloader, WAPL (wings apart-like protein homolog). While cohesin erases genomic-distance biases in Pcdh choice, WAPL functions as a rheostat of cohesin processivity that determines Pcdh isoform diversity.

Pharmacotherapy and Ketamine Assisted Psychotherapy for Treatment-Resistant Depression: A Patient With Lifelong Self-Doubt and Self-Criticism.

Although consensus in the field is lacking, the most common definition for treatment-resistant depression (TRD) requires a minimum of 2 prior treatment failures with confirmed adequate dose and duration. This article presents a clinical example of TRD in a patient with a long history of depression and inadequate response to treatment. The prominent feature is the patient's persistent self-criticism that might have predisposed him to unrelenting depression symptoms, intense anger, self-doubt, and self-disapproval. We explore potential underlying causes for self-criticism, its impact on depression and help-seeking, and plausible treatment approaches.

Validation of sociocultural attitudes towards appearance questionnaire and its associations with body-related outcomes and eating disorders among Chinese adolescents.

Introduction: The Sociocultural Attitudes Towards Appearance Questionnaire-4 Revised (SATAQ-4R) has been widely used in Western countries to link body appearance that is related to eating disorders and body dissatisfaction being commonly reported by adolescents. However, a comprehensive psychometric validation of the SATAQ-4R in Chinese adolescent samples is still lacking. To this end, the aim of the current study was to validate the gender-appropriate SATAQ-4R in a sample of Chinese adolescents, following by an investigation of its associations with body-related outcomes and eating disorder symptoms. Methods: Two gender-specific studies were conducted to examine the psychometric properties of the SATAQ-4R-Female and SATAQ-4R-Male respectively among adolescent girls (Study1, N=344, with 73 participants at retest) and boys (Study2, N=335, with 64 participants at retest). Confirmatory factor analysis was employed to examine the factor structure and their test-retest reliability, the internal consistency and convergent validity were subsequently examined. Results: For the SATAQ-4R-Females, the seven-factor model has a reasonable fit, with Chi-square =1112.769 (p < 0.001), CFI = 0.91, RMSEA = 0.071, SRMR = 0.067. For the SATAR-4R-Males, an acceptable seven-factor model with Chi-square = 982.92 (p<0.001), CFI = 0.91, RMSEA = 0.08, SRMR= 0.06 was observed. With respect to test-retest reliability, the internal consistency for 7 subscales was rated as good (Cronbach's alpha =0.74 to 0.95) among female adolescents, likewise the internal consistency of the seven subscales was also rated as good (Cronbach's alpha =0.70 to 0.96) among male participants. Good convergent validity was observed, reflected by associations of the subscales of the gender-specific SATAQ-4R with muscularity-related attitude, body image-acceptance, body appearance, perceived stress level, symptoms of eating disorder and self-esteem. Discussion: For women and men, the original 7-factor structure was validated among Chinese adolescents, internal reliability coefficients for the seven subscale scores were good and test-retest reliability was acceptable. Our results also confirmed the convergent validity of the two different gender-appropriate scales.

Intimate Partner Violence Among South Asian Women During the COVID-19 Pandemic: A Cross-Sectional Survey of Prevalence and Risk Factors.

The goal of this study was to understand the prevalence of intimate partner violence (IPV) among South Asian women during COVID-19, and to identify predictors of IPV presence and severity. We recruited South Asian women (n = 132) to complete an online survey about their mood, experiences with COVID-19, and IPV. 47% of South Asian women (n = 132) reported experiencing any IPV, most commonly economic abuse. Women experiencing IPV had higher rates of COVID-19 related worry (t=-1.3, p = .001) and anxiety (t=-2.2, p = .027). The following variables were associated with greater odds of experiencing IPV: COVID-19 related worry (OR: 1.44 [1.11, 1.87]) and full-time employment status (OR: 0.13 [0.02, 0.99]). Depressive symptoms were a significant positive predictor of economic abuse severity (b = 0.80, p = .002). Future research should examine cultural and environmental factors that interact with the experience of IPV among South Asian women to better inform interventions for survivors.

What Could Highly Engaged Workers Gain From Mental Health Promotion Programs?: An Exploratory Analysis of Secondary Outcomes of Brief Daily Workplace Well-being Programs.

OBJECTIVE: The current study aims to examine the effects of mental health programs on well-being among highly engaged workers. METHODS: Participants were randomly allocated to body-mind-spiritual or peer support program. Of the whole sample, we examined participants' work engagement and positive affect from the highest quarter and the lowest quarter of work engagement at baseline. Measures were taken at baseline and 1-month intervals during 3-month programs and 3-month follow-up. RESULTS: The programs had decreasing effects on work engagement in the HWE subgroup. There is an increasing trend of positive affect on the HWE group only in the body-mind-spiritual program. The trajectories of work engagement in the HWE group moved toward a moderate level. CONCLUSION: Our results suggest that the work engagement's decrease in the HWE group could be a sign of recovery and relaxation.

Effectiveness of Mindful Self-Compassion Training Supported by Online Peer Groups in China: A Pilot Study.

Context: Self-compassion training involves the cultivation of feelings of warmth and safety, presence, and interconnectedness. Mindful Self-Compassion (MSC) training in a group setting has been found to increase self-compassion, mindfulness, and emotional well-being. Objective: The current study intended to examine the outcomes of live, online, videoconference-based MSC training with online peer-support for nonclinical populations in different cities in China. Design: The research team designed a pre-post pilot study. Setting: The study took place at Renmin University in Beijing, China. Participants: Participants were 253 Chinese individuals who were recruited from different regions in China through online advertisements. Intervention: Participants took part in online MSC training in a two-hour, group class each week for eight weeks and received support from online peer groups and through a half-day in-person retreat. Outcome Measures: Self-report outcomes were obtained at baseline and postintervention, using the Self Compassion Scale (SCS) and the Compassion for Others Scale (CS) for primary outcomes, and the Depression, Anxiety, and Stress Scale (DASS-21), the Fear of Compassion Scale (FOCS), the Satisfaction with Life Scale (SWLS), the Subjective Happiness Scale (SHS), and the Cognitive and Affective Mindfulness Scale (CAMS-R), for secondary outcomes. A fixed effects model was used to test for within-group changes in the scales. Results: The online MSC program yielded a high retention rate. Of the 206 first-time participants, 179 (86.9%) attended six or more of the eight MSC sessions, and 183 (88.8%) completed the assessments at both baseline and postintervention. Of the 183 retained participants, 97.8% were female, with an average age of 37.8 ± 7.9; 94% had college or higher education. For all scales, the within-person changes occurred in the expected direction; positive attributes and experiences increased, while negative attributes and experiences decreased. Conclusions: The study showed that first-time participants in China in an online MSC training that was supported by online peer groups had high attendance rates, high assessment completion, and favorable results. These preliminary outcomes suggest that future studies with more rigorous designs are warranted to further investigate online training with peer support as an effective and efficient approach to disseminate MSC training in China.

How family dementia caregivers perceive benefits of a 4-week Mentalizing Imagery Therapy program: a pilot study.

Background: Family caregivers of dementia patients experience high levels of interpersonal stress that often results in elevated anxiety, and depression, and negative impacts on interpersonal relationships. Changes in behaviors and the structure of relationships with the care recipient (CR) and others in the social milieu challenge the caregivers' ability to mentalize, or understand the links between mental states and behaviors. This study investigates the experiences and perceived benefits of family dementia caregivers who underwent Mentalizing Imagery Therapy (MIT), a treatment aiming to improve balanced self-other mentalizing and reduce psychological symptoms. Methods: Purposeful sampling was used to select 11 family dementia caregivers who underwent a 4-week pilot trial of MIT. Semi-structured interviews were completed post-intervention to identify subjective benefits, putative psychological mediators and perceived active components. Results: Caregivers reported improvements in well-being, mood, anxiety, and sleep, and a majority stated MIT helped with forming and maintaining healthier relationships. Some participants noted benefits extending to how they reacted to their social environment and perceived themselves more objectively from others' perspectives. Specific elements of MIT, including self-compassion, self-care, and the ability to reflect on emotionally arousing challenges, might have mediated these improvements. Conclusion: Family dementia caregivers perceived salutary benefits of MIT on multiple domains of well-being. The self reports suggest MIT holds promise for improving well-being, reducing non-mentalizing patterns of thought, and facilitating improvements in balanced mentalization within the caregivers' relationships.

Validation of the 4-Item and 10-Item Uncertainty Stress Scale in a Community-Based Sample of Chinese Adults.

Purpose: The objectives of this study were to examine the psychometric properties of the Uncertainty Stress Scale (USS) and to compare the usefulness of two versions of the scale (USS-4 and USS-10) among a large community-based sample of Chinese adults. Participants and Methods: The Uncertainty Stress Scale was validated in 904 community residents (mean age: 32.71 ± 10.99; male: 41.7%) through an online survey conducted in February 2020. Psychometric properties of reliability (Cronbach's alpha), construct validity (confirmatory factor analysis), and criterion validity (correlation and ROC curve analyses) were evaluated using established benchmarks. To validate the USS, we used the Chinese version of the Perceived Stress Scale (CPSS). In addition, sensitivity, specificity, and suitable cutoff values of the two versions of USS were determined. Results: Both versions of the USS had high internal consistency (USS-10: 0.941; USS-4: 0.851). Confirmatory factor analyses supported a one-factor structure for both measures. Both USS-4 and USS-10 scores were significantly positively correlated with CPSS scores, indicating acceptable criterion validity. Conclusion: The findings of the current study confirmed that the psychometric properties of two Chinese versions of USS are acceptable. Furthermore, the 4-item USS was as effective as the 10-item USS for the measurement of uncertainty stress in our community-based sample of Chinese adults suggesting that the USS-4 is a time-efficient alternative to the USS-10 which can be used when the circumstances require a time-efficient instrument (eg, in epidemiological studies with a large test battery).

Association of social support with negative emotions among Chinese adolescents during Omicron-related lockdown of Shenzhen City: The roles of rumination and sleep quality.

Objective: Adolescents are likely to suffer from negative emotions such as depression and anxiety due to the rapid development of biological, cognitive and social changes. Previous studies have indicated possible risk (rumination) and protective (good social support and high sleep quality) factors for depression and anxiety among this age group. The present study is the first to investigate the association between social support and negative emotions during the Outbreak of Omicron variant, on this basis, to further determine the mediating role of rumination and sleep quality on this link. Method: A total of 1,065 Chinese middle- and high-school students (51.5% female, M age = 13.80, SD = 1.20) completed a psychosocial battery, including the Social Support Rating Scale (SSRS), the Pittsburgh Sleep Quality Index (PSQI), the Ruminative Responses Scale (RRS), the Depression Anxiety Stress Scale (DASS). Serial multiple mediation analysis was conducted using PROCESS macro based on SPSS. Results: Social support, rumination, and sleep quality were significantly negatively correlated with negative emotional states (Ps < 0.05). Further, rumination and sleep quality were found to partially mediate the relationship between social support and negative emotional states. Conclusions: For early detection and prevention of depression and anxiety, providing sufficient social support is necessary for adolescents, because rumination and sleep problems are reported during stressful periods, such as the COVID-19 pandemic.

The roles of exercise tolerance and resilience in the effect of physical activity on emotional states among college students

Background/objective: Negative emotional states, such as depression, anxiety, and stress challenge health care due to their long-term consequences for mental disorders. Accumulating evidence indicates that regular physical activity (PA) can positively influence negative emotional states. Among possible candidates, resilience and exercise tolerance in particular have the potential to partly explain the positive effects of PA on negative emotional states. Thus, the aim of this study was to investigate the association between PA and negative emotional states, and further determine the mediating effects of exercise tolerance and resilience in such a relationship.Method: In total, 1117 Chinese college students (50.4% female, Mage=18.90, SD=1.25) completed a psychosocial battery, including the 21-item Depression Anxiety Stress Scale (DASS-21), the Connor-Davidson Resilience Scale (CD-RISC), the Preference for and Tolerance of the Intensity of Exercise Questionnaire (PRETIE-Q), and the International Physical Activity Questionnaire short form (IPAQ-SF). Regression analysis was used to identify the serial multiple mediation, controlling for gender, age and BMI.Results: PA, exercise intensity-tolerance, and resilience were significantly negatively correlated with negative emotional states (Ps<.05). Further, exercise tolerance and resilience partially mediated the relationship between PA and negative emotional states.Conclusions: Resilience and exercise intensity-tolerance can be achieved through regularly engaging in PA, and these newly observed variables play critical roles in prevention of mental illnesses, especially college students who face various challenges. Recommended amount of PA should be incorporated into curriculum or sport clubs within a campus environment. (AU)

Very Low-Level Transcranial Photobiomodulation for Major Depressive Disorder: The ELATED-3 Multicenter, Randomized, Sham-Controlled Trial.

Background: Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light might represent a treatment for major depressive disorder (MDD). However, the dosimetry of administered t-PBM varies widely. We tested the efficacy of t-PBM with low irradiance, low energy per session, and low number of sessions in individuals with MDD.Methods: A 2-site, double-blind, sham-controlled study was conducted of adjunct t-PBM NIR (830 nm; continuous wave; 35.8 cm2 treatment area; 54.8 mW/cm2 irradiance; 65.8 J/cm2 fluence, 20 min/session; ~2 W total power; 2.3 kJ total energy per session), delivered to the prefrontal cortex, bilaterally, twice a week for 6 weeks, in subjects diagnosed with MDD per the DSM-IV criteria. Subjects were recruited between August 2016 and May 2018. A sequential parallel comparison design was used: 18 nonresponders to sham in phase 1 (6 weeks) were re-randomized in phase 2. The primary outcome was reduction in depression severity (Hamilton Depression Rating Scale [HDRS-17] and Quick Inventory of Depressive Symptomatology-Clinician Rating [QIDS-C] scores) from baseline. Statistical analyses used R package SPCDAnalyze2, including all subjects with ≥ 1 post-randomization evaluation.Results: Of the 54 subjects recruited, we included 49 MDD subjects in the analysis (71% female, mean ± SD age 40.8 ± 16.1 years). There were no significant differences between t-PBM and sham with respect to the change in HDRS-17 (t = -0.319, P = .751) or QIDS-C (t = -0.499, P = .620) scores. The sham effect was reasonably low.Conclusions: Mostly uncontrolled studies suggest the efficacy of t-PBM for MDD; however, its optimal dose is still to be defined. A minimal dose threshold is likely necessary, similarly to other neuromodulation techniques in MDD (electroconvulsive therapy, transcranial magnetic stimulation). We established a threshold of inefficacy of t-PBM for MDD, based on combined low irradiance, low energy per session, and low number of sessions.Trial Registration: ClinicalTrials.gov identifier: NCT02959307.