The antidepressant effect of whole-body hyperthermia is associated with the classical interleukin-6 signaling pathway.

There is urgent need for novel antidepressant treatments that confer therapeutic benefits via engagement with identified mechanistic targets. The objective of the study was to determine whether activation of the classical anti-inflammatory interleukin-6 signaling pathways is associated with the antidepressant effects of whole-body hyperthermia. A 6-week, randomized, double-blind study compared whole-body hyperthermia with a sham condition in a university-based medical center. Medically healthy participants aged 18-65 years who met criteria for major depressive disorder, were free of psychotropic medication use, and had a baseline 17-item Hamilton Depression Rating Scale score ≥ 16 were randomized with 1-to-1 allocation in blocks of 6 to receive whole-body hyperthermia or sham. Of 338 individuals screened, 34 were randomized, 30 received interventions and 26 had ≥ 2 blood draws and depressive symptom assessments. Secondary data analysis examined change in the ratio of IL-6:soluble IL-6 receptor pre-intervention, post-intervention, and at weeks 1 and 4. Hierarchical linear modeling tested whether increased IL-6:soluble IL-6 receptor ratio post-intervention was associated with decreased depressive symptom at weeks 1, 2, 4 and 6 for those randomized to whole-body hyperthermia. Twenty-six individuals were randomized to whole-body hyperthermia [n = 12; 75 % female; age = 37.9 years (SD = 15.3) or sham [n = 14; 57.1 % female; age = 41.1 years (SD = 12.5). When compared to the sham condition, active whole-body hyperthermia only increased the IL-6:soluble IL-6 receptor ratio post-treatment [F(3,72) = 11.73,p < .001], but not pre-intervention or at weeks 1 and 4. Using hierarchical linear modeling, increased IL-6:sIL-6R ratio following whole-body hyperthermia moderated depressive symptoms at weeks 1, 2, 4 and 6, such that increases in the IL-6:soluble IL-6 receptor ratio were associated with decreased depressive symptoms at weeks 1, 2, 4 and 6 for those receiving the active whole-body hyperthermia compared to sham treatment (B = -229.44, t = -3.82,p < .001). Acute activation of classical intereukin-6 signaling might emerge as a heretofore unrecognized novel mechanism that could be harnessed to expand the antidepressant armamentarium.

Yoga-Based Interventions in Low-Income Populations: A Scoping Review.

Introduction: The popularity of yoga has surged in recent years; however, yoga practitioners have remained a largely homogenous population. Research reflects that most practitioners are of a higher socioeconomic status. There are access barriers to yoga for lower income individuals, likely due to factors such as financial constraints and logistical challenges. The primary goal of this review was to synthesize literature on yoga research among low-income populations and better understand the feasibility and acceptability of such interventions. A secondary goal was to assess the consistency of metrics for reporting feasibility and acceptability across such studies using the CheckList Standardizing the Reporting of Interventions for Yoga (CLARIFY) guidelines as a framework. Third, the authors sought to propose additional standardized CLARIFY guidelines that may enhance reporting on the diversity of yoga research populations, adherence, and retention. Methods: The electronic databases PubMed, PsycINFO, Cochrane Central Register of Controlled Trials, and Google Scholar were searched in May 2022 using a prespecified search string. Articles assessing a yoga intervention in predominantly low-income adult populations were deemed eligible for inclusion. Results: The search resulted in 512 potential articles. Eleven were deemed eligible for inclusion. The included studies reported mostly positive effects of yoga on the target outcome (i.e., pain/disability, quality of life/wellness, and psychiatric symptoms). Recruitment and retention data showed generally good attendance and high study completion rates. Common study design components included recruitment embedded within preexisting medical settings, proximal yoga locations, and mitigation of yoga-related costs. Finally, the authors noted inconsistency in the reporting of adherence, retention, and other sociodemographic characteristics of participants and yoga instructors (e.g., race, ethnicity, and income). Discussion: Yoga may promote physical and mental health for low-income individuals. Important facilitators to access are noted, such as proximal study settings, as well as barriers such as the need for childcare that can be addressed in future research. In addition, several study design considerations could help address the specific needs of low-income participants in yoga research, such as compensating participants, recruiting within existing medical settings, and providing yoga-related equipment at no cost. Finally, the authors suggest specific ways to enhance reporting of study metrics related to socioeconomic diversity, by adding to the preexisting CLARIFY guidelines.

Predictors of the placebo response in a nutraceutical randomized controlled trial for depression.

OBJECTIVE: The placebo response in depression studies is the change in symptoms amongst those who receive an inactive treatment. Many well-designed randomized controlled trials (RCTs) of depression have a high proportion of placebo responders, with little understanding as to why. The present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo responders. METHODS: This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo (n = 69 in placebo group). We investigated participant characteristics such as socio-demographics, clinical features, and recruitment methods, and their association with the placebo response. Monoaminergic genetic polymorphisms were also assessed. Placebo response was measured based on change in Montgomery-Asberg Depression Rating Scale score. The association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects models. RESULTS: Greater levels of education, particularly pursuing post-high school education, better self-reported general health, marriage/de facto, greater improvement in the first trial week, and more failed antidepressant therapies in the current depressive episode were associated with greater placebo response. An increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant therapy. Single nucleotide polymorphisms from the tryptophan hydroxylase 1 (TPH1) gene (A779C and A218C) were weakly associated with greater placebo response, although the evidence was attenuated after accounting for multiple comparisons. CONCLUSION: This is, to our knowledge, the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo response. Several variables appeared to predict the placebo response. Such findings may encourage future trial designs which could dampen placebo response, improve assay sensitivity, and allow for treatment effects to be potentially more detectable. Please cite this article as: Arnold R, Murphy-Smith J, Ng CH, Mischoulon D, Byrne GJ, Bousman CA, Stough C, Berk M, Sarris J. Predictors of the placebo response in a nutraceutical randomized controlled trial for depression. J Integr Med. 2024; 22(1): 46-53.

Apolipoprotein E and Its Association With Cognitive Change and Modification of Treatment Effects of Vitamin D3 and Omega-3s on Cognitive Change: Results From the In-Clinic Subset of a Randomized Clinical Trial.

BACKGROUND: Apolipoprotein E (APOE)-ε4 allele is associated with cognitive decline; however, its potential to modify effects of vitamin D3 and omega-3s supplementation on later-life cognition is unclear. Our objectives were to estimate among the in-clinic subset of a randomized trial: (1) associations between APOE-ε4 and global and domain-specific cognitive change, with exploration of potential sex and race differences; and (2) modification by APOE-ε4 of effects of vitamin D3 and omega-3s supplementation on cognitive change. METHODS: From an ancillary study of depression prevention within a completed 2 × 2 factorial trial testing vitamin D3 (2 000 IU per day), omega-3s (1 g per day), and/or placebos, we included 743 older adults with baseline in-person neuropsychiatric assessments and APOE genotyping data. The primary outcome was change in global cognition (averaging z-scores of 9 tests) over 2 years. Secondarily, episodic memory and executive function/attention z-scores were examined. General linear models of response profiles with multiplicative interaction terms were constructed; stratified results were reported. RESULTS: Mean age (standard deviation) was 67.1 (5.3) years; 50.6% were females; 24.9% were APOE-ε4 carriers. Compared to noncarriers, APOE-ε4 carriers had worse 2-year change in global cognition and episodic memory; differences were more apparent among females than males. There was no variation by race in APOE-ε4 associations with cognition. APOE-ε4 did not significantly modify effects of vitamin D3 or omega-3s, compared to placebo, on change in global cognition, episodic memory, or executive function/attention. CONCLUSIONS: APOE-ε4 was associated with worse cognition but did not modify overall effects of vitamin D3 or omega-3 supplementation on cognition over 2 years.

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.

A Brief Review on the Potential of Psychedelics for Treating Alzheimer's Disease and Related Depression.

Alzheimer's disease (AD), the most common form of senile dementia, is poised to place an even greater societal and healthcare burden as the population ages. With few treatment options for the symptomatic relief of the disease and its unknown etiopathology, more research into AD is urgently needed. Psychedelic drugs target AD-related psychological pathology and symptoms such as depression. Using microdosing, psychedelic drugs may prove to help combat this devastating disease by eliciting psychiatric benefits via acting through various mechanisms of action such as serotonin and dopamine pathways. Herein, we review the studied benefits of a few psychedelic compounds that may show promise in treating AD and attenuating its related depressive symptoms. We used the listed keywords to search through PubMed for relevant preclinical, clinical research, and review articles. The putative mechanism of action (MOA) for psychedelics is that they act mainly as serotonin receptor agonists and induce potential beneficial effects for treating AD and related depression.

Individuals with depression exhibiting a pro-inflammatory phenotype receiving omega-3 polyunsaturated fatty acids experience improved motivation-related cognitive function: Preliminary results from a randomized controlled trial.

Cognitive impairment related to major depressive disorder (MDD) is highly prevalent, debilitating and is lacking in effective treatments; dysregulated inflammatory physiology is a putative mechanism and may represent a therapeutic target. In depressed individuals exhibiting a pro-inflammatory phenotype who were enrolled in a 12-week randomized placebo-controlled trial of 3 doses of omega-3 polyunsaturated fatty acids (ω-3-FA), we examined: (i) the relationship between dysregulated inflammatory physiology and baseline cognitive impairment; (ii) improvement in cognitive impairment following treatment; and (iii) the association between baseline inflammatory biomarkers and change in cognitive impairment for those receiving treatment. We randomized 61 unmedicated adults aged 45.50 years (75% female) with DSM-5 MDD, body mass index >25 kg/m2, and C-reactive protein (CRP) ≥3.0 mg/L to three doses of ω-3-FA (1, 2, or 4 g daily) or matching placebo. Analyses focused on 45 study completers who had inflammatory biomarkers assessed [circulating CRP, interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) as well as lipopolysaccharide (LPS)-stimulated concentrations of IL-6 and TNFα in peripheral blood mononuclear cells (PBMC)] and on the highest dose ω-3-FA (4 g daily; n = 11) compared to placebo (n = 10). Impairment in motivational symptoms (e.g., alertness, energy, enthusiasm) and higher-order cognitive functions (e.g., word-finding, memory) were assessed by a validated self-report measure. Among all 45 participants at baseline, lower concentrations of IL-6 in LPS-stimulated PBMC were associated with greater impairment in higher-order cognitive functions (r = -0.35, p = .02). Based on hierarchical linear modeling, individuals receiving 4 g/day of ω-3-FA reported significant improvement in motivational symptoms compared to placebo (B = -0.07, p = .03); in the 4 g/day group, lower baseline concentrations of TNFα in LPS-stimulated PBMC were associated with significant improvement in motivational symptoms (Ρ = .71, p = .02) following treatment. In this exploratory clinical trial, daily supplementation with 4 g of ω-3-FA improves motivational symptoms in depressed individuals exhibiting an inflammatory phenotype.

Evaluation, Treatment, and Referral of Treatment-Resistant Depression in Primary Care.

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. 2023;25(4):22f03438. Author affiliations are listed at the end of this article.

Relation of serum BDNF to major depression and exploration of mechanistic roles of serum BDNF in a study of vitamin D3 and omega-3 supplements for late-life depression prevention.

This study: 1) examined cross-sectional and longitudinal relations of serum brain-derived neurotrophic factor (BDNF) to late-life depression (LLD); 2) tested effects of vitamin D3 and omega-3s on change in BDNF; 3) explored modifying or mediating roles of BDNF on effects of vitamin D3 and omega-3s for LLD. We selected 400 adults from a completed trial of vitamin D3 and omega-3 supplements for LLD prevention. BDNF was measured using an enzyme-linked immunosorbent assay. We administered semi-structured diagnostic interviews and Patient Health Questionnaire [PHQ]-9 to ascertain outcomes at baseline (depression caseness vs. non-caseness; PHQ-9) and at 2-year follow-up among baseline non-depressed individuals (incident vs. no incident MDD; change in PHQ-9). At baseline, while there were no significant differences in mean serum BDNF comparing depression cases and non-cases, being in the lowest vs. highest serum BDNF quartile was significantly associated with worse depressive symptoms. There were no significant longitudinal associations between serum BDNF and LLD. Neither supplement significantly affected change in BDNF; serum BDNF did not appear to modify or mediate treatment effects on LLD. In conclusion, we observed significant cross-sectional but not longitudinal associations between serum BDNF levels and LLD. Vitamin D3 or omega-3s did not alter serum BDNF over 2 years.

Effects of Vitamin D3 and Marine Omega-3 Fatty Acids Supplementation on Indicated and Selective Prevention of Depression in Older Adults: Results From the Clinical Center Sub-Cohort of the VITamin D and OmegA-3 TriaL (VITAL).

Objective: To test vitamin D3 and omega-3 fatty acids (omega-3s) for late-life depression prevention under the National Academy of Medicine framework for indicated (targeting subthreshold depression) and selective (targeting presence of high-risk factors) prevention.Methods: The VITamin D and OmegA-3 TriaL (VITAL) is a 2 × 2 factorial trial of vitamin D3 (2,000 IU/d) and/or omega-3s (1 g/d) for cardiovascular and cancer prevention (enrollment: November 2011-March 2014; end date: December 31, 2017). In this targeted prevention study, we included 720 VITAL clinical sub-cohort participants who completed neurobehavioral assessments at baseline and 2 years (91.9% retention). High-risk factors were subthreshold or clinical anxiety, impaired activities of daily living, physical/functional limitation, medical comorbidity, cognitive impairment, caregiving burden, problem drinking, and low psychosocial support. Coprimary outcomes were incident major depressive disorder (MDD), adjudicated using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), and change in mood (Patient Health Questionnaire-9 [PHQ-9]). We used exact tests to determine treatment effects on MDD incidence and repeated-measures models to determine treatment effects on PHQ-9.Results: A total of 11.1% had subthreshold depression, 60.8% had ≥ 1 high-risk factor, MDD incidence was 4.7% (5.1% among completers), and mean PHQ-9 score change was 0.02 points. Among those with subthreshold depression, the MDD risk ratio (95% confidence interval) was 0.36 (0.06 to 1.28) for vitamin D3 and 0.85 (0.25 to 2.92) for omega-3s, compared to placebo; results were also null among those with ≥ 1 high-risk factor (vitamin D3 vs placebo: 0.63 [0.25 to 1.53]; omega-3s vs placebo: 1.08 [0.46 to 2.71]). There were no significant differences in PHQ-9 score change comparing either supplement with placebo.Conclusions: Neither vitamin D3 nor omega-3s showed benefits for indicated and selective prevention of late-life depression; statistical power was limited.Trial Registration: ClinicalTrials.gov identifier: NCT01696435.

Personalized Medicine of Omega-3 Fatty Acids in Depression Treatment in Obese and Metabolically Dysregulated Patients.

The co-occurrence of depression and obesity has become a significant public health concern worldwide. Recent studies have shown that metabolic dysfunction, which is commonly observed in obese individuals and is characterized by inflammation, insulin resistance, leptin resistance, and hypertension, is a critical risk factor for depression. This dysfunction may induce structural and functional changes in the brain, ultimately contributing to depression's development. Given that obesity and depression mutually increase each other's risk of development by 50-60%, there is a need for effective interventions that address both conditions. The comorbidity of depression with obesity and metabolic dysregulation is thought to be related to chronic low-grade inflammation, characterized by increased circulating levels of pro-inflammatory cytokines and C-reactive protein (CRP). As pharmacotherapy fails in at least 30-40% of cases to adequately treat major depressive disorder, a nutritional approach is emerging as a promising alternative. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are a promising dietary intervention that can reduce inflammatory biomarkers, particularly in patients with high levels of inflammation, including pregnant women with gestational diabetes, patients with type 2 diabetes mellitus, and overweight individuals with major depressive disorder. Further efforts directed at implementing these strategies in clinical practice could contribute to improved outcomes in patients with depression, comorbid obesity, and/or metabolic dysregulation.

Pilot Study of Second-Generation DNA Methylation Epigenetic Markers in Relation to Cognitive and Neuropsychiatric Symptoms in Older Adults.

BACKGROUND: Associations between epigenetic aging with cognitive aging and neuropsychiatric measures are not well-understood. OBJECTIVE: 1) To assess cross-sectional correlations between second-generation DNA methylation (DNAm)-based clocks of healthspan and lifespan (i.e., GrimAge, PhenoAge, and DNAm-based estimator of telomere length [DNAmTL]) and cognitive and neuropsychiatric measures; 2) To examine longitudinal associations between change in DNAm markers and change in cognition over 2 years. METHODS: Participants were members of VITAL-DEP (VITamin D and OmegA-3 TriaL- Depression Endpoint Prevention) study. From previously ascertained cognitive groups (i.e., cognitively normal and mild cognitive impairment), we randomly selected 45 participants, aged≥60 years, who completed in-person neuropsychiatric assessments at baseline and 2 years. The primary outcome was global cognitive score (averaging z-scores of 9 tests). Neuropsychiatric Inventory severity scores were mapped from neuropsychiatric symptoms (NPS) from psychological scales and structured diagnostic interviews. DNAm was assayed using Illumina MethylationEPIC 850K BeadChip at baseline and 2 years. We calculated baseline partial Spearman correlations between DNAm markers and cognitive and NPS measures. We constructed multivariable linear regression models to examine longitudinal relations between DNAm markers and cognition. RESULTS: At baseline, we observed a suggestive negative correlation between GrimAge clock markers and global cognition but no signal between DNAm markers and NPS measures. Over 2 years: each 1-year increase in DNAmGrimAge was significantly associated with faster declines in global cognition; each 100-base pair increase in DNAmTL was significantly associated with better global cognition. CONCLUSION: We found preliminary evidence of cross-sectional and longitudinal associations between DNAm markers and global cognition.

Ages at menarche and menopause, hormone therapy, and the risk of depression.

OBJECTIVE: To examine the association between female reproductive factors and the risk of depression. METHOD: A retrospective cohort study was performed using a national database in South Korea. Among 945,729 eligible postmenopausal women, the associations between female reproductive factors including the age at menarche, age at menopause, parity, duration of oral contraceptive (OC) use, duration of breastfeeding, and use of menopausal hormone therapy (MHT), and the occurrence of depression were investigated. RESULTS: Compared to women with menarche at the age of ≤12 years, those with menarche at the age of ≥15 showed an increased risk of depression [adjusted hazard ratio (aHR) of 1.09 for 15-16 years and 1.18 for ≥17 years]. Compared to women with menopause at the age of 50-54, those with menopause at an earlier age showed an increased risk of depression (aHR of 1.20 for <40 years), and those with menopause at a later age showed a decreased risk of depression (aHR of 0.94 for ≥55 years). Use of MHT was associated with an increased risk of depression (aHR of 1.30 for ≥5 years). Duration of breastfeeding and duration of OC use had U-shaped but weak associations with depression. Whereas parity did not show a significant association with depression. CONCLUSION: Late menarche, early menopause, and the use of MHT were associated with an increased risk of depression in postmenopausal women.

Virtual mentalizing imagery therapy for Spanish language Latino family dementia caregivers: A feasibility and acceptability study.

Spanish speaking family caregivers of people living with dementia have limited supportive resources in Spanish. There are few validated, culturally acceptable virtual interventions for reducing these caregivers' psychological distress. We investigated the feasibility of a Spanish language adaptation of a virtual Mentalizing Imagery Therapy (MIT) program, which provides guided imagery and mindfulness training to reduce depression, increase mentalizing, and promote well-being. 12 Spanish-speaking family dementia caregivers received a 4-week virtual MIT program. Follow-up was obtained post group and at 4 months post baseline assessment. Feasibility, acceptability, and satisfaction with MIT were assessed. The primary psychological outcome was depressive symptoms; secondary outcomes included caregiver burden, dispositional mindfulness, perceived stress, well-being, interpersonal support, and neurological quality of life. Statistical analysis was performed with mixed linear models. Caregivers were 52 ± 8 (mean ± SD) years of age. 60% had a high school education or less. Participation in weekly group meetings was 100%. Home practice was performed on average 4 ± 1 times per week [range 2-5]. Satisfaction with MIT reached 19 ± 2 of a possible 20 points. Reduction in depression from baseline was observed by week three (p = 0.01) and maintained at 4 month follow-up (p = 0.05). There were significant improvements in mindfulness post-group, and in caregiver burden and well-being at 4 months. MIT was successfully adapted for Latino Spanish language family dementia caregivers within a virtual group environment. MIT is feasible and acceptable and may help reduce depressive symptoms and improve subjective well-being. Larger, randomized controlled trials of MIT should determine durability of effects and validate efficacy in this population.

The descriptive analysis of depressive symptoms and White Blood Cell (WBC) count between the sexual minorities and heterosexual identifying individuals in a nationally representative sample: 2005-2014.

BACKGROUND: Sexual minorities are at a higher risk of suffering from depressive symptoms compared with heterosexual individuals. Only a few studies have examined the conditions of having depressive symptoms within different sexual minority groups, especially people with sexual orientation uncertainty in a nationally representative sample. Furthermore, few studies have explored whether the mean white blood count (WBC) is different between people with and without depressive symptoms among different sexual minority groups in a nationally representative sample. METHODS: We analyzed the National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2014 with a sample of 14,090 subjects. We compared the prevalence of depressive symptoms in subpopulations stratified by sex, sexual minority status, and race. We also examined the difference in mean WBC count between depressed and non-depressed people among heterosexual individuals and different sexual minority groups. Additionally, two multivariable logistic regression models were used to explore the association between sexual minority status and depressive symptoms, treating sexual minority status as both a binary and categorical variable. RESULTS: Female sex (OR: 1.96, 95% CI: 1.72-2.22) and sexual minority status (OR: 1.79, 95% CI: 1.47-2.17) were both independently associated with depressive symptoms. Within the sexual minority population, subjects who were unsure about their sexual identities had the highest odds of having depressive symptoms (OR: 2.56, 95% CI: 1.40-4.68). In the subgroup analysis considering intersectionality, black sexual minority females had the highest rate of depressive symptoms (19.4%, 95% CI: 7.72-40.98). Finally, the mean WBC count differed significantly between people with and without depressive symptoms among male heterosexual individuals, female heterosexual individuals, and female sexual minorities, but not among male sexual minorities. CONCLUSIONS: Based on sex, race, and sexual minority status, black females of sexual minority status had the highest rate of depressive symptoms. Within sexual minority groups, participants who were unsure about their sexual identities had the highest odds of having depressive symptoms. Finally, the mean WBC count was significantly higher among people with depressive symptoms than those without depressive symptoms only among male heterosexuals, female heterosexuals, and female sexual minorities, but not among male sexual minorities. Future research should investigate the social and biological mechanisms of the differences.

Clinical response to EPA supplementation in patients with major depressive disorder is associated with higher plasma concentrations of pro-resolving lipid mediators.

Chronic inflammation has been implicated in the pathophysiology of major depressive disorder (MDD). Activating the resolution of inflammation through ω-3 fatty acid supplementation may prove to be a successful therapeutic strategy for the treatment of MDD. Patients with MDD, body mass index >25 kg/m2, and plasma high-sensitivity C-reactive protein ≥3 µg/mL (n = 61) were enrolled in a 12-week randomized trial consisting of 4 parallel arms: EPA 1, 2, and 4 g/d, and placebo. The supplement contained EPA and DHA in a 3.9:1 ratio. Depression symptoms were assessed using the IDS-C30 scale. Plasma fatty acids and pro-resolving lipid mediators (SPMs) were measured in 42 study completers at baseline and at the end of treatment by liquid chromatography/mass spectrometry. The response rate (≥50% reduction in IDS-30 score) was higher in the 4 g/d EPA arm than placebo (Cohen d = 0.53). In the 4 g/d EPA arm, responders had significantly greater increases in 18-hydroxyeicosapentaenoic acid (18-HEPE) and 13-hydroxydocosahexaenoic acid (13-HDHA) than non-responders (p < 0.05). Within the 4 g/d EPA arm, the increase in 18-HEPE was significantly associated with reductions in plasma hs-CRP concentrations (p < 0.05) and IDS-C30 scores (p < 0.01). In summary, response rates were greater among patients with MDD randomized to EPA 4 g/d supplementation and in those who showed a greater ability to activate the synthesis of 18-HEPE. The inverse association of 18-HEPE with both systemic inflammation and symptoms of depression highlights the activation of the resolution of inflammation as a likely mechanism in the treatment of MDD with ω-3 fatty acid supplementation.

Does the association between Herpes Simplex 2 infection and depressive symptoms vary among different sexual minority statuses and sex groups? Findings from a nationally representative sample.

BACKGROUND: Herpes Simplex Virus Type 2 (HSV-2) has been associated with depression, but the relationship has yet to be explored with respect to gender and sexual orientation in a nationally representative sample to help identify individuals at higher risk for depression. METHODS: A dataset from National Health and Nutrition Examination Survey 2009-2014 was used in this study. Multivariable logistic regression models were constructed to test effect modification on both the multiplicative and additive scale using a sample of 57,684 subjects. RESULTS: Effect modification by sexual minority status was not significant on either the multiplicative scale (Ratio of ORs: 0.74, 95 % CI: 0.37-1.50, p = 0.395) or the additive scale (RERI: -0.22, 95%CI: -2.27-1.84, p = 0.833). Meanwhile, biological sex assigned at birth was a significant modifier only on the additive scale (RERI: 0.82, 95 % CI: 0.004-1.64, P = 0.049). Specifically, females (OR: 1.43, 95 % CI: 1.03-1.97, P = 0.032) had greater odds of having depressive symptoms compared with males (OR: 1.20, 95 % CI: 0.69-2.08, p = 0.509) after the HSV-2 infection. LIMITATIONS: The analysis was based on a cross-sectional study; further investigation using longitudinal datasets might be beneficial. CONCLUSIONS: Sexual minority status did not modify the association between HSV-2 infection and having depressive symptoms. However, biological sex assigned at birth was a modifier only on the additive but not the multiplicative scale. Health workers should be alert for depression symptoms in females with HSV-2 infection.

High body weight variability is associated with increased risk of depression: a nationwide cohort study in South Korea.

BACKGROUND: Body weight variability (BWV) negatively affects the incidence and outcomes of various diseases, but the nature of the association between BWV and depression remains unclear. In this study, we aimed to test the hypothesis that BWV is associated with the risk of new-onset depression. METHODS: Data from a nationwide population-based cohort in the Korean National Health Insurance Service database were analyzed for 6 598 570 adults with no history of depression and reports of at least three health examinations. BWV was estimated using variability independent of the mean indices and divided into quartiles (Q1 lowest, Q4 highest BWV). Cox proportional hazard models were applied to assess the risk of depression according to the quartile of BWV. RESULTS: The incident rate for depression from Q1 to Q4 of BWV was 20.7, 20.3, 20.8, and 22.2 per 1000 person-years, respectively. BWV, especially high BWV, was associated with an increased risk of depression after adjusting for age, sex, smoking, alcohol consumption, physical activity, income, diabetes mellitus, hypertension, and dyslipidemia. The hazard ratio (HR) of new-onset depression was highest in Q4 relative to Q1 in the total population (HR 1.12, p < 0.0001) and was higher in women than in men (HR 1.72 v. 1.16, p < 0.0001). In stratified analyses, regardless of obesity or weight change status at baseline, the risk of depression was increased when bodyweight fluctuated highly during follow-up. CONCLUSIONS: High BWV was associated with an increased risk of depression. Further studies need to evaluate the role of high BWV with respect to the onset of depression.