OBJECTIVE:To evaluate feasibility, efficacy, and tolerability of Sudarshan Kriya yoga (SKY) as an adjunctive intervention in patients with major depressive disorder (MDD) with inadequate response to antidepressant treatment.

METHODS:Patients with MDD (defined by DSM-IV-TR) who were depressed despite≥ 8 weeks of antidepressant treatment were randomized to SKY or a waitlist control (delayed yoga) arm for 8 weeks. The primary efficacy end point was change in 17-item Hamilton Depression Rating Scale (HDRS-17) total score from baseline to 2 months. The key secondary efficacy end points were change in Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) total scores. Analyses of the intent-to-treat (ITT) and completer sample were performed. The study was conducted at the University of Pennsylvania between October 2014 and December 2015.

RESULTS:In the ITT sample (n = 25), the SKY arm (n = 13) showed a greater improvement in HDRS-17 total score compared to waitlist control (n = 12) (-9.77 vs 0.50, P = .0032). SKY also showed greater reduction in BDI total score versus waitlist control (-17.23 vs -1.75, P = .0101). Mean changes in BAI total score from baseline were significantly greater for SKY than waitlist (ITT mean difference: -5.19; 95% CI, -0.93 to -9.34; P = .0097; completer mean difference: -6.23; 95% CI, -1.39 to -11.07; P = .0005). No adverse events were reported.

CONCLUSIONS:Results of this randomized, waitlist-controlled pilot study suggest the feasibility and promise of an adjunctive SKY-based intervention for patients with MDD who have not responded to antidepressants.

TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT02616549.

BACKGROUND:Depression is one of the most common mental disorders. Finding effective treatments for such a disorder with higher efficiency lower side effects and affordability is an active area of research in psychiatry. This study aimed to comparatively analyze the effects of the cognitive group therapy and aerobic exercises on depression, automatic negative thoughts and dysfunctional attitudes of students at Kermanshah University of Medical Science.

METHODS:In this clinical trial, 46 associate and undergraduate students at Kermanshah University of Medical Science were randomly divided into three groups: cognitive therapy, aerobic exercise, and control. The data was gathered both before and 8 weeks after the intervention. Beck Depression Inventory (BDI-II), automatic negative thoughts (ATQ), and the Dysfunctional Attitude Scale (DAS) were used as the data collection instruments. The data were analyzed with SPSS version 15 using paired samples T-test, chi-square test, Kruskal-Wallis test, and analysis of variance (ANOVA).

RESULTS:Cognitive therapy caused a significant decrease in depression, belief in automatic negative thoughts, and dysfunctional attitudes in comparison to the control group (p<0.05). Although aerobics compared to the control group causes more reductions in the variables, however, It was only meaningful for the depression variable (p=0.049). Cognitive therapy also reduced the variables more than the aerobic exercise, but the decrease was not statistically significant.

CONCLUSIONS:Cognitive group therapy and aerobic exercise are effective in treating depression. For treating depression, aerobic exercise can be used as a therapy itself or along with cognitive-behavioral therapy and pharmacotherapy.

Despite its prevalence and significance, late life depression is underrecognized and undertreated. This study aimed to investigate the effect of a long-term exercise intervention on depressive symptoms in older Korean women. Thirty older women were assigned to exercise (n = 15, age of 80.8± 3.8 years) or control group (n = 15, age of 78.6 ± 3.2 years). The exercise group underwent a resistance exercise plus walking two times weekly on nonconsecutive days for 6 months. Post-intervention change in depressive symptoms was regarded as the primary outcome. Secondary outcomes included changes in body composition and physical performance. Repeated measures analysis of variance showed significant group by time interactions for depressive symptoms (F(1,23) = 37.540, p<0.001), percent body fat (F(1,23) = 6.122, p = 0.021), lean body mass (F(1,23) = 5.662, p = 0.026), waist circumference (F(1,23) = 4.330, p = 0.049), handgrip strength (F(1,23) = 10.114, p = 0.005), 6-min walking (F(1,23) = 28.988, p<0.001), and 2.44-m Up&Go (F(1,23) = 28.714, p<0.001). The current findings support regular exercise as a therapeutic strategy to promote overall and mental health in older Korean women with depressive symptoms.

OBJECTIVE:This pilot, randomized clinical trial investigates the effectiveness of tai chi as the primary treatment for Chinese Americans with major depressive disorder (MDD).

METHODS:67 Chinese Americans with DSM-IV MDD and no treatment for depression were recruited between March 2012 and April 2013 and randomized (1:1:1) into a tai chi intervention, an education program, or a waitlisted group for 12 weeks. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS₁₇); positive response for this outcome was defined as a decrease in total score of 50% or more, and remission was defined as HDRS₁₇ ≤ 7.

RESULTS:Participants (N = 67) were 72% female with a mean age of 54± 13 years. No serious adverse events were reported. After the end of the 12-week intervention, response rates were 25%, 21%, and 56%, and remission rates were 10%, 21%, and 50% for the waitlisted, education, and tai chi intervention groups, respectively. The tai chi group showed improved treatmentresponse when compared to both the waitlisted group (odds ratio [OR] = 2.11; 95% CI, 1.01-4.46) and to the education group (OR = 8.90; 95% CI, 1.17-67.70). Tai chi intervention showed significantly improved remission rate over the waitlisted group (OR = 3.01; 95% CI, 1.25-7.10), and a trend of improved remission compared to the education group (OR = 4.40; 95% CI, 0.78-24.17).

CONCLUSIONS:As the primary treatment, tai chi improved treatment outcomes for Chinese Americans with MDD over both passive and active control groups.

TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT01619631.

BACKGROUND:Yoga may be well suited for depressed and anxious pregnant women, given reported benefits of meditation and physical activity and pregnant women's preference for nonpharmacological treatments.

METHODS:We randomly assigned 46 pregnant women with symptoms of depression and anxiety to an 8-week yoga intervention or treatment-as-usual (TAU) in order to examine feasibility and preliminary outcomes.

RESULTS:Yoga was associated with high levels of credibility and satisfaction as an intervention for depression and anxiety during pregnancy. Participants in both conditions reported significant improvement in symptoms of depression and anxiety over time; and yoga was associated with significantly greater reduction in negative affect as compared to TAU (β = -0.53, SE = 0.20, p = .011).

CONCLUSION:Prenatal yoga was found to be a feasible and acceptable intervention and was associated with reductions in symptoms of anxiety and depression; however, prenatal yoga only significantly outperformed TAU on reduction of negative affect.

PURPOSE:To compare 2 mild-to-moderate group exercises and treatment as usual (TAU) for improvements in physical function and depressive symptoms.

METHODS:Patients with heart failure (n = 70, mean age = 66 yr, range = 45-89 yr) were randomized to 16 wk of tai chi (TC), resistance band (RB) exercise, or TAU.

RESULTS:Physical function differed by group from baseline to follow-up, measured by distance walked in the 6-min walk test (F = 3.19, P = .03). Tai chi participants demonstrated a nonsignificant decrease of 162 ft (95% confidence interval [CI], 21 to -345, P = .08) while distance walked by RB participants remained stable with a nonsignificant increase of 70 ft (95% CI, 267 to -127, P = .48). Treatment as usual group significantly decreased by 205 ft (95% CI, -35 to -374, P = .02) and no group differences occurred over time in end-systolic volume (P = .43) and left ventricular function (LVEF) (P = .67). However, groups differed over time in the Beck Depression Inventory (F = 9.2, P<.01). Both TC and RB groups improved (decreased) by 3.5 points (95% CI, 2-5, P<.01). Treatment as usual group decreased insignificantly 1 point (95% CI, -1 to 3, P = .27).

CONCLUSIONS:Tai chi and RB participants avoided a decrease in physical function decrements as seen with TAU. No groups changed in cardiac function. Both TC and RB groups saw reduced depression symptoms compared with TAU. Thus, both TC and RB groups avoided a decrease in physical function and improved their psychological function when compared with TAU.

In this pilot study, a convenience sample of 24 chronic pain patients (17 with chronic fatigue syndrome/fibromyalgia) were randomized into WHEE treatment and wait-list control groups for 6 weeks. Assessments of depression, anxiety, and pain were completed before, during, and at 1 and 3 months after treatment. Wait-listed patients then received an identical course of WHEE and assessments. WHEE decreased anxiety (P<.5) and depression (P<.05) compared with the control group. The wait-list-turned-WHEE assessments demonstrated decreased pain severity (P<.05) and depression (P<.04) but not pain interference or anxiety. WHEE appears a promising method for pain, anxiety, and depression in patients with chronic pain, compared to standard medical care alone. Though a small pilot study, the present results suggest that further research appears warranted. An incidental finding was that a majority of patients with chronic pain had suffered psychological trauma in childhood and/or adulthood.

In this pilot study, a convenience sample of 24 chronic pain patients (17 with chronic fatigue syndrome/fibromyalgia) were randomized into WHEE treatment and wait-list control groups for 6 weeks. Assessments of depression, anxiety, and pain were completed before, during, and at 1 and 3 months after treatment. Wait-listed patients then received an identical course of WHEE and assessments. WHEE decreased anxiety (P<.5) and depression (P<.05) compared with the control group. The wait-list-turned-WHEE assessments demonstrated decreased pain severity (P<.05) and depression (P<.04) but not pain interference or anxiety. WHEE appears a promising method for pain, anxiety, and depression in patients with chronic pain, compared to standard medical care alone. Though a small pilot study, the present results suggest that further research appears warranted. An incidental finding was that a majority of patients with chronic pain had suffered psychological trauma in childhood and/or adulthood.

OBJECTIVE:Affective disorder during pregnancy is a common condition requiring careful judgment to treat the depression while minimizing risk to the fetus. Following up on promising pilot trials, we studied the efficacy of light therapy.

METHOD:Twenty-seven pregnant women with nonseasonal major depressive disorder according to DSM-IV (outpatients, university polyclinic) were randomly assigned to 7,000 lux fluorescent bright white or 70 lux dim red (placebo) light administered at home in the morning upon awakening for 1 h/d in a 5-week double-blind trial carried out between October 2004 and October 2008. Clinical state was monitored weekly with the 29-item Structured Interview Guide for the Hamilton Depression Rating Scale (HDRS) with Atypical Depression Supplement (SIGH-ADS). Changes of rating scale scores over time were analyzed with the general linear model. Differences from baseline of SIGH-ADS and 17-item HDRS scores at every time point were the dependent variables, time was the within-subjects factor, and treatment was the between-subjects factor. The model also included baseline score of depression and gestational age at intervention start.

RESULTS:The superiority of bright light over dim light placebo was shown for both SIGH-ADS (R² = 0.251; F(3,23) = 3.91; P<.05) and HDRS (R² = 0.338; F(3,23) = 5.42; P<.01) when analyzing the week-by-week change from baseline, and HDRS scores showed a significant interaction of treatment with time (F(4,92) = 2.91; P<.05). Categorical analysis revealed that the response rate (HDRS≥ 50% improvement) at week 5 was significantly greater for bright light (81.3%, n = 16) than for placebo light (45.5%, n = 11) (P<.05). Remission (final score≤ 8) was attained by 68.6% versus 36.4%, respectively (P<.05). Expectation ratings did not differ significantly between groups.

CONCLUSIONS:Bright white light treatment for 5 weeks improved depression during pregnancy significantly more than placebo dim red light. The study provides evidence that light therapy, a simple, cost-effective antidepressant modality with minimal side effects for the mother and no known risk for the unborn child, may be a useful nonpharmacologic approach in this difficult situation.

TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01043289.

BACKGROUND:The aim of the study was to examine the efficacy and safety of morning bright light therapy (BLT) in the treatment of patients with a current major depressive episode (MDE) in bipolar and unipolar disorder without a seasonal pattern. It was a randomized, sham-controlled trial.

METHODS:Adults, ages 18-70 years were randomized to treatment either with BLT or a sham negative ion generator (as a placebo control). The subjects were required to be on a stable and therapeutic dose of psychotropic medication for at least 4 weeks prior to enrollment and their treatment had to be insufficiently effective. Their clinical state was monitored at the baseline and at the end of treatment. The Hamilton Depression Rating Scale-21 items (HDRS-21), Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI-II), Clinical Global Impression-Severity (CGI-S) and Patient Global Impression (PGI) were used. The results were analyzed with an intention-to-treat (ITT) analysis.

RESULTS:Ninety-five patients were enrolled (50 diagnosed with bipolar disorder and 45 with unipolar depression). Fifty-two patients were randomized to treatment with BLT and forty-three were in the placebo group (ITT population). Eighty-three subjects completed the study. There were 12 dropouts (5 in the light group and 7 in the placebo group). After 14 days of treatment, a significant improvement was found in all groups (p<0.001). The subjects treated with BLT did not significantly differ in terms of improvement in HDRS-21 scores at the endpoint when compared to patients treated with placebo (p=0.2). However, further analysis demonstrated significantly higher response (50% v. 27.9%, p=0.02) and remission rates (28.8% v. 11.6%, p=0.04) among patients treated with morning BLT when compared to placebo group. It should be noted that in the population of drug-resistant patients, BLT was more efficacious than placebo. There were no statistically significant differences between unipolar and bipolar disorders (p=0.4).

CONCLUSION:Although overall improvement in HDRS-21 scores were not superior in the BLT group, both response and remission rates were significantly higher among patients treated with BLT relative to those receiving the sham intervention. BLT was also more efficacious than placebo in the population of patients with drug-resistant depression. Further studies to define the subpopulation of patients with non-seasonal depression who may benefit the most from BLT are needed.

BACKGROUND:Qigong and Tai Chi are the two most popular traditional Chinese exercises, known as mind-body movement therapies. Previous studies suggest that Qigong and Tai Chi may be beneficial in reducing depressive symptoms. This was the first study to systematically review and compare the effects of Qigong and Tai Chi on depressive symptoms.

METHODS:A systematic search of six electronic databases was undertaken through to February 2014, for randomized controlled trials (RCTs) which reported depressive symptoms measured by a depressive symptom rating scale. The standardized mean difference in depressive symptoms score between Qigong or Tai Chi and a control group (at the end of follow-up) was extracted as a primary outcome. The secondary outcome was the standardized mean gain in symptom score (SMG) relative to the baseline from individual arms of the RCTs for various forms of care including Qigong, Tai Chi, usual care, other exercise, education and miscellaneous interventions.

RESULTS:Thirty studies with a total of 2328 participants (823 males and 1505 females) were included. A significant effect was found for the Qigong interventions (Cohen's d -0.48 95% CI -0.48 to -0.12; SMG -0.52, 95% CI -0.79 to -0.26). There was no significant effect seen for Tai Chi for the primary endpoint. No mean change in symptom scores were seen for Tai Chi, usual care, other exercises, education and the 'miscellaneous' group in pre-post assessment in single arms. The Qigong results were found to be robust in sensitivity analyses.

CONCLUSIONS:Qigong appears to be beneficial for reducing depressive symptom severity. However, given the low quality of the included studies and the documented evidence of publication bias, these results should be viewed cautiously.

BACKGROUND:Commuting routes with natural features could promote walking or cycling for commuting. Commuting through natural environments (NE) could have mental health benefits as exposure to NE can reduce stress and improve mental health, but there is little evidence. This study evaluates the association between NE and commuting, whether active or not, and the association between commuting (through NE), whether active or not, and mental health. We also evaluate the moderating effect of NE quality on the association between NE commuting and mental health.

METHODS:This cross-sectional study was based on adult respondents (n = 3599) of the Positive Health Effects of the Natural Outdoor Environment in Typical Populations in Different Regions in Europe (PHENOTYPE) project. Data were collected in four European cities in Spain, the Netherlands, Lithuania and the United Kingdom. Data on commuting behavior (active commuting at least one day/week, daily NE commuting) and mental health were collected with questionnaires. Associations were estimated with multilevel analyses including random intercepts at city- and neighborhood level.

RESULTS:Adjusted multilevel analyses showed that daily NE commuters were more often active commuters (OR 1.42; 95% CI 1.19, 1.70). There was no association between active commuting and mental health, but daily NE commuters had on average a 2.74 (95% CI 1.66, 3.82) point higher mental health score than those not commuting through NE. The association with mental health was stronger among active commuters (4.03, 95% CI 2.13, 5.94) compared to non-active commuters (2.21; 95% CI 0.90, 3.51) when daily commuting through NE, but NE quality did not have a moderating effect.

CONCLUSIONS:Daily NE commuting was associated with better mental health, especially for active commuters. Daily NE commuters were likely to be active commuters. Active commuting itself was not associated with mental health. These findings suggest that cities should invest in commuting routes with nature for cycling and walking.

Major depressive disorder (MDD) is a common disorder with a high prevalence and significant social and economic impacts. Nevertheless, the treatment of MDD is far from satisfactory. Acupuncture treatment has emerged as a promising method for treating MDD. However, the neural mechanism by which acupuncture reduces depressive symptoms is not fully understood. Studies have shown that the corticostriatal reward circuitry is associated with the pathophysiology of MDD; thus, we investigated the corticostriatal resting-state functional connectivity (rsFC) before and after real and sham acupuncture treatments combined with the antidepressant fluoxetine. Forty-six female major depressive patients were assigned to either verum acupuncture plus fluoxetine (n = 22) or sham acupuncture plus fluoxetine (n = 24) treatment for 8 weeks, and resting state functional magnetic resonance imaging (fMRI) data were collected before the first and after the last treatment sessions. The results showed that compared with sham acupuncture, the verum acupuncture group showed: (1) significantly increased rsFC between inferior ventral striatum and medial prefrontal cortex, ventral rostral putamen and amygdala/parahippocampus, as well as dorsal caudate and middle temporal gyrus; (2) significantly decreased rsFC between right ventral rostral putamen and right dorsolateral prefrontal cortex, and right dorsal caudate and bilateral cerebellar tonsil. The increased rsFC between the inferior ventral striatum and medial prefrontal cortex, ventral rostral putamen and amygdala/parahippocampus were significantly positively associated with decreased clinical scores (Montgomery-Åsberg Depression Rating Scale and Self-Rating Depression Scale scores) at the end of the eight-week treatment. Our findings suggest that acupuncture may achieve treatment effects by modulating the corticostriatal reward/motivation circuitry in MDD patients.

Major depressive disorder (MDD) is a common disorder with a high prevalence and significant social and economic impacts. Nevertheless, the treatment of MDD is far from satisfactory. Acupuncture treatment has emerged as a promising method for treating MDD. However, the neural mechanism by which acupuncture reduces depressive symptoms is not fully understood. Studies have shown that the corticostriatal reward circuitry is associated with the pathophysiology of MDD; thus, we investigated the corticostriatal resting-state functional connectivity (rsFC) before and after real and sham acupuncture treatments combined with the antidepressant fluoxetine. Forty-six female major depressive patients were assigned to either verum acupuncture plus fluoxetine (n = 22) or sham acupuncture plus fluoxetine (n = 24) treatment for 8 weeks, and resting state functional magnetic resonance imaging (fMRI) data were collected before the first and after the last treatment sessions. The results showed that compared with sham acupuncture, the verum acupuncture group showed: (1) significantly increased rsFC between inferior ventral striatum and medial prefrontal cortex, ventral rostral putamen and amygdala/parahippocampus, as well as dorsal caudate and middle temporal gyrus; (2) significantly decreased rsFC between right ventral rostral putamen and right dorsolateral prefrontal cortex, and right dorsal caudate and bilateral cerebellar tonsil. The increased rsFC between the inferior ventral striatum and medial prefrontal cortex, ventral rostral putamen and amygdala/parahippocampus were significantly positively associated with decreased clinical scores (Montgomery-Åsberg Depression Rating Scale and Self-Rating Depression Scale scores) at the end of the eight-week treatment. Our findings suggest that acupuncture may achieve treatment effects by modulating the corticostriatal reward/motivation circuitry in MDD patients.

To study the biological effects of acupuncture on depression, we hypothesized that acupuncture will exert its antidepressant effect through a bottom-up neuromodulation of the autonomic dysfunction in depression. The participants received press needle (PN) acupuncture for 72 h continuously in a sham-controlled design. Psychological assessments and Holter electrocardiography were performed before and after PN acupuncture. We evaluated their autonomic functions through the heart rate variability (HRV). As a result, following PN acupuncture participants showed significant improvement in the Beck's Depression Inventory scores (P = 0.031), systolic/diastolic blood pressures (P = 0.002/P = 0.011), and coefficient of variation of the R-R interval (P < 0.0001), compared to sham PN. The present findings showed PN acupuncture induced alterations in vagal function, blood pressure, and Beck's Depression Inventory scores. It was suggested that vagal stabilization effect by acupuncture may be associated with the therapeutic mechanism in depression.

To study the biological effects of acupuncture on depression, we hypothesized that acupuncture will exert its antidepressant effect through a bottom-up neuromodulation of the autonomic dysfunction in depression. The participants received press needle (PN) acupuncture for 72 h continuously in a sham-controlled design. Psychological assessments and Holter electrocardiography were performed before and after PN acupuncture. We evaluated their autonomic functions through the heart rate variability (HRV). As a result, following PN acupuncture participants showed significant improvement in the Beck's Depression Inventory scores (P = 0.031), systolic/diastolic blood pressures (P = 0.002/P = 0.011), and coefficient of variation of the R-R interval (P < 0.0001), compared to sham PN. The present findings showed PN acupuncture induced alterations in vagal function, blood pressure, and Beck's Depression Inventory scores. It was suggested that vagal stabilization effect by acupuncture may be associated with the therapeutic mechanism in depression.

We sought to establish the feasibility and preliminary effects of home-wearable light therapy for postpartum depression, and its effects on circadian measures. Eight women within 6 months postpartum were prescribed 60 min of daily morning light therapy for 5 weeks. The device was well tolerated. Significant improvements were observed in self-report and clinician-rated depression symptoms, with little change in objective circadian measures. Home-wearable light therapy is feasible for postpartum women and may be a promising treatment for postpartum depression. Clinicaltrials.gov Identifier: NCT02769858.

BACKGROUND:Surdashan Kriya Yoga (SKY) is a procedure that in various studies, has shown evidences of efficacy in alleviating Depression and Anxiety disorders, but in Europe and USA it has not been studied yet on a Caucasian population as an adjunct therapy for psychiatric Disorders.

METHODS:The study involved a sample of consenting women and men (n = 69) who received SKY therapy for a six-month time period. They were assessed at recruitment, after two weeks, after three months and after six months using Hamilton Rating Scale for Anxiety (HRSA), Hamilton Rating Scale for Depression (HRSD), Zung Self-Rating Anxiety Scale (ZSAS), Zung Self-Rating Depression Scale (ZSDS) and Symptom Checklist-90 (SCL-90).

RESULTS:All the analyses have shown that SKY therapy significantly reduces the scores of Anxiety and Depression. This is plain, especially after the initial SKY treatment, which is followed by a long plateau phase that seems to verge on no Anxiety/Depression scores. It was found that SKY effects lead to a significant convergence between the self-assessment (Zung Self-Rating Scale) and hetero-assessment (Hamilton Rating Scale).

LIMITATIONS:The study should be replicated on a larger clinical sample in a controlled trial to learn more about the effectiveness of SKY Protocol.

CONCLUSIONS:Participation in SKY adjunct therapy ten days intense workshop and follow-ups, coupled with daily individual and independent practice of a simplified protocol of breathing techniques (30 min), can lead to significant reduction in levels of Anxiety and Depression.

BACKGROUND:Surdashan Kriya Yoga (SKY) is a procedure that in various studies, has shown evidences of efficacy in alleviating Depression and Anxiety disorders, but in Europe and USA it has not been studied yet on a Caucasian population as an adjunct therapy for psychiatric Disorders.

METHODS:The study involved a sample of consenting women and men (n = 69) who received SKY therapy for a six-month time period. They were assessed at recruitment, after two weeks, after three months and after six months using Hamilton Rating Scale for Anxiety (HRSA), Hamilton Rating Scale for Depression (HRSD), Zung Self-Rating Anxiety Scale (ZSAS), Zung Self-Rating Depression Scale (ZSDS) and Symptom Checklist-90 (SCL-90).

RESULTS:All the analyses have shown that SKY therapy significantly reduces the scores of Anxiety and Depression. This is plain, especially after the initial SKY treatment, which is followed by a long plateau phase that seems to verge on no Anxiety/Depression scores. It was found that SKY effects lead to a significant convergence between the self-assessment (Zung Self-Rating Scale) and hetero-assessment (Hamilton Rating Scale).

LIMITATIONS:The study should be replicated on a larger clinical sample in a controlled trial to learn more about the effectiveness of SKY Protocol.

CONCLUSIONS:Participation in SKY adjunct therapy ten days intense workshop and follow-ups, coupled with daily individual and independent practice of a simplified protocol of breathing techniques (30 min), can lead to significant reduction in levels of Anxiety and Depression.

Depression is a severe neuropsychiatric disorder, of which the underlying pathological mechanisms remain unclear. The ketogenic diet (KD) has been reported to exhibit preventative effects on depressive-like behaviors in rodents. However, the therapeutic effects of KD on depressive-like behaviors have not been illustrated thus far. Here, we found that KD treatment dramatically ameliorated depressive-like behaviors in both repeated social defeat stress (R-SDS) and lipopolysaccharide (LPS) models, indicating the potential therapeutic effects of KD on depression. Our electrophysiological studies further showed that neuronal excitability was increased in the lateral habenula (LHb) of mice exposed to R-SDS or LPS, which can be reversed in the presence of KD treatment. Moreover, R-SDS and LPS were also found to induce robust microglial inflammatory activation in the LHb. Importantly, these phenotypes were rescued in mice fed with KD. In addition, we found that the protein level of innate immune receptor Trem2 in the LHb was significantly decreased in depression models. Specific knockdown of Trem2 in LHb microglia induced depressive-like behaviors, increased neuronal excitability as well as robust microglial inflammatory activation. Altogether, we demonstrated the therapeutic effects of KD on depressive-like behaviors, which are probably mediated via the restoration of microglial inflammatory activation and neuronal excitability. Besides, we also proposed an unrecognized function of Trem2 in the LHb for depression. Our study sheds light on the pathogenesis of depression and thereby offers a potential therapeutic intervention.