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BACKGROUND: This study examined the cumulative risk of unhealthy lifestyle behaviors and the associations between overall lifestyle and common mental disorders (CMDs), insomnia, stress, health-related quality of life (HRQOL), and functional impairment. Additionally, the treatment preferences for managing CMDs and insomnia were examined. METHODS: A survey was conducted on 1487 Chinese Hong Kong adults, assessing their lifestyle behaviors (i.e., diet and nutrition, substance use, physical activity, stress management, restorative sleep, social support, and environmental exposures), mental health-related outcomes, and treatment preferences via a vignette. RESULTS: The findings revealed significant additive relationships between the number of 'worse' lifestyle domains and the risk of all outcomes. A healthier overall lifestyle was significantly associated with reduced risks of all outcomes (AORs = 0.88 to 0.93). Having healthier practices in diet and nutrition, substance use, stress management, restorative sleep, and social support domains were significantly associated with lower risks of all outcomes (AORs = 0.93 to 0.98), except that substance use was not significantly associated with stress. Physical activity was inversely associated with only depressive symptoms (AOR = 0.98), anxiety symptoms (AOR = 0.99), and stress (AOR = 0.99). Environmental exposures were not significantly associated with functional impairment but with all other outcomes (AORs = 0.98 to 0.99). Besides, lifestyle interventions (55 %) were significantly more preferred for managing CMDs and insomnia relative to psychotherapy (35.4 %) and pharmacotherapy (9.6 %). CONCLUSIONS: Our findings underscore the importance of considering lifestyle factors when managing CMDs, insomnia, stress, HRQOL, and functional impairment, with a particular emphasis on adopting a multicomponent treatment approach.

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 find

OBJECTIVE: To prevent the exacerbation of mental health burdens, a growing body of research has recommended a balanced approach that emphasizes both the delivery of mental health treatments to individuals with common mental disorders (CMDs) and the strengthening of protective factors for CMDs among nonclinical populations. This randomized controlled trial (RCT) evaluated the efficacy of a smartphone-delivered multicomponent lifestyle medicine (LM) intervention, Lifestyle Hub, for improving mental health among a nonclinical population of Chinese adults. METHODS: A total of 106 participants with Patient Health Questionnaire-9 total score < 10 and Generalized Anxiety Disorder 7-Item Scale <8 were randomly assigned to either the Lifestyle Hub intervention group (LH, n = 53) or the waitlist control group (WL, n = 53). Lifestyle Hub is an 8-week smartphone-delivered multicomponent LM intervention developed based on the transtheoretical model. The intervention components included lifestyle psychoeducation, physical activity, diet and nutrition, stress management, sleep management, and motivation and goal-setting techniques. Assessments were conducted at baseline, immediate post-intervention, and 1-month follow-up (LH only). RESULTS: The linear mixed effect model based on the intention-to-treat principle indicated that Lifestyle Hub significantly improved overall mental health, depressive symptoms, anxiety symptoms, stress, insomnia severity, overall health-promoting behaviors, dietary quality, and stress management compared to the WL group at immediate post-intervention (d = 0.13-0.56). No significant between-group differences were observed in terms of functional impairment, health-related quality of life, health responsibility, physical activity level, spiritual growth, and interpersonal relations. The intervention gains in the LH group were maintained at 1-month follow-up. The LH participants indicated that Lifestyle Hub was an acceptable intervention for improving menta

Generalised Anxiety Disorder (GAD) is a prevalent, chronic mental health disorder. The measurement of regional brain gamma-aminobutyric acid (GABA) offers insight into its role in anxiety and is a potential biomarker for treatment response. Research literature suggests Piper methysticum (Kava) is efficacious as an anxiety treatment, but no study has assessed its effects on central GABA levels. This study investigated dorsal anterior cingulate (dACC) GABA levels in 37 adult participants with GAD. GABA was measured using proton magnetic resonance spectroscopy (1H-MRS) at baseline and following an eight-week administration of Kava (standardised to 120 mg kavalactones twice daily) (n = 20) or placebo (n = 17). This study was part of the Kava for the Treatment of GAD (KGAD; ClinicalTrials.gov: NCT02219880), a 16-week intervention study. Compared with the placebo group, the Kava group had a significant reduction in dACC GABA (p = 0.049) at eight weeks. Baseline anxiety scores on the HAM-A were positively correlated with GABA levels but were not significantly related to treatment. Central GABA reductions following Kava treatment may signal an inhibitory effect, which, if considered efficacious, suggests that GABA levels are modulated by Kava, independent of reported anxiety symptoms. dACC GABA patterns suggest a functional role of higher levels in clinical anxiety but warrants further research for symptom benefit. Findings suggest that dACC GABA levels previously un-examined in GAD could serve as a biomarker for diagnosis and treatment response.

OBJECTIVES: Randomized controlled trials (RCTs) on the efficacy of multicomponent lifestyle medicine (LM) interventions for improving sleep quality have yielded inconsistent findings. This study marks the first meta-analysis to evaluate the efficacy of multicomponent LM interventions in improving sleep quality. METHODS: We searched six online databases for RCTs that compared multicomponent LM interventions to an active or inactive control group in an adult population and assessed subjective sleep quality as a primary or secondary outcome using validated sleep measures at any post-intervention time-point. RESULTS: A total of 23 RCTs with 26 comparisons involving 2534 participants were included in the meta-analysis. After excluding outliers, the analysis revealed that multicomponent LM interventions significantly improved sleep quality at immediate post-intervention (d = 0.45) and at short-term follow-up (i.e.,

BACKGROUND: Preliminary evidence supports the use of dietary interventions and gut microbiota-targeted interventions such as probiotic or prebiotic supplementation for improving mental health. We report on the first randomised controlled trial (RCT) to examine the effects of a high-prebiotic dietary intervention and probiotic supplements on mental health. METHODS: "Gut Feelings" was an 8-week, 2 × 2 factorial RCT of 119 adults with moderate psychological distress and low prebiotic food intake. Treatment arms: (1) probiotic supplement and diet-as-usual (probiotic group); (2) high-prebiotic diet and placebo supplement (prebiotic diet group); (3) probiotic supplement and high-prebiotic diet (synbiotic group); and (4) placebo supplement and diet-as-usual (placebo group). The primary outcome was assessment of total mood disturbance (TMD; Profile of Mood States Short Form) from baseline to 8 weeks. Secondary outcomes included anxiety, depression, stress, sleep, and wellbeing measures. RESULTS: A modified intention-to-treat analysis using linear mixed effects models revealed that the prebiotic diet reduced TMD relative to placebo at 8 weeks [Cohen's d = -0.60, 95% confidence interval (CI) = -1.18, -0.03; p = 0.039]. There was no evidence of symptom improvement from the probiotic (d = -0.19, 95% CI = -0.75, 0.38; p = 0.51) or synbiotic treatments (d = -0.03, 95% CI = -0.59, 0.53; p = 0.92). Improved anxiety, stress, and sleep were noted in response to the prebiotic diet while the probiotic tentatively improved wellbeing, relative to placebo. No benefit was found in response to the synbiotic intervention. All treatments were well tolerated with few adverse events. CONCLUSION: A high-prebiotic dietary intervention may improve mood, anxiety, stress, and sleep in adults with moderate psychological distress and low prebiotic intake. A synbiotic combination of high-prebiotic diet and probiotic supplement does not appear to have a beneficial effect on mental health outcomes, thoug

Ayahuasca is a psychoactive Amazonian plant brew. It is usually made from the Banisteriopsis caapi vine (Spruce ex Griseb. Morton, Malpighiaceae), which contains three primary harmala alkaloids, along with the leaves of Psychotria viridis (Ruiz et Pavon, Rubiaceae) in which the potent psychedelic dimethyltryptamine (DMT) is found. DMT-harmaloid concoctions have gained popularity in recent years, due to growing anecdotal and scientific reports of therapeutic benefits associated with their consumption. Ayahuasca is now ingested in a variety of different settings across the globe, from traditional ethnobotanical to so called "neo-shamanic" ceremonies. Furthermore, related preparations involving alternative sources of DMT and harmala alkaloids are becoming increasingly common as knowledge of ayahuasca continues to spread internationally. This article reviews the existing literature and draws on original qualitative data from a large cross-sectional study of ayahuasca drinkers, to propose a model of psychotherapeutic processes associated with the consumption of ayahuasca. We assert that it is these processes, facilitated by a range of neurobiological effects, that lead to beneficial mental health and wellbeing outcomes. Our proposed model identifies five key psychotherapeutic processes or effects inherent to the ayahuasca experience; somatic effects; introspection and emotional processing; increased Self-connection; increased spiritual connection, and finally the gaining of insights and new perspectives. We note some important differences in these processes compared with other classic psychedelics as well as the implications of the model for the therapeutic use of ayahuasca. Improved understanding of the psychotherapeutic processes involved with the ayahuasca experience will better equip practitioners to work with this potentially transformative concoction and enable the optimization of therapeutic treatment models for potential clinical use.

Objectives The therapeutic use of nutrient-based ‘nutraceuticals’ and plant-based ‘phytoceuticals’ for the treatment of mental disorders is common; however, despite recent research progress, there have not been any updated global clinical guidelines since 2015. To address this, the World Federation of Societies of Biological Psychiatry (WFSBP) and the Canadian Network for Mood and Anxiety Disorders (CANMAT) convened an international taskforce involving 31 leading academics and clinicians from 15 countries, between 2019 and 2021. These guidelines are aimed at providing a definitive evidence-informed approach to assist clinicians in making decisions around the use of such agents for major psychiatric disorders. We also provide detail on safety and tolerability, and clinical advice regarding prescription (e.g. indications, dosage), in addition to consideration for use in specialised populations. Methods The methodology was based on the WFSBP guidelines development process. Evidence was assessed based on the WFSBP grading of evidence (and was modified to focus on Grade A level evidence – meta-analysis or two or more RCTs – due to the breadth of data available across all nutraceuticals and phytoceuticals across major psychiatric disorders). The taskforce assessed both the ‘level of evidence’ (LoE) (i.e. meta-analyses or RCTs) and the assessment of the direction of the evidence, to determine whether the intervention was ‘Recommended’ (+++), ‘Provisionally Recommended’ (++), ‘Weakly Recommended’ (+), ‘Not Currently Recommended’ (+/−), or ‘Not Recommended’ (−) for a particular condition. Due to the number of clinical trials now available in the field, we firstly examined the data from our two meta-reviews of meta-analyses (nutraceuticals conducted in 2019, and phytoceuticals in 2020). We then performed a search of additional relevant RCTs and reported on both these data as the primary drivers supporting our clinical recommendations. Lower levels of evidence, including isola

OBJECTIVE: There is often a shortfall in recovery following treatment for an episode of bipolar disorder (BD). Exploration of participant's experience provides vital information to enhance statistical outcomes for novel therapy trials. This study used mixed-methods to explore participants' experience of a trial testing N -acetyl cysteine (NAC) and mitochondrially active nutraceuticals for BD depression. CASE: report forms from a randomised controlled trial (RCT) of BD depression (n = 148) were analysed using a pragmatic adaption of grounded theory and thematic analysis. RESULTS: Thematic analysis of 148 study participants indicated numerous changes in participant experience over time. For example, perceived environmental stressors reported by participants decreased over the trial in both treatment groups. Quantitative analysis of the themes revealed more positive theme reports in the combination treatment arm compared to the placebo arm and there were more negative themes identified in the placebo arm, compared to the NAC arm. CONCLUSION: This approach revealed additional results not elucidated in the primary quantitative analysis. This emphasises the value of mixed-methods research in capturing participants' experiences in RCTs and detecting possible latent benefits and risks. Such methods can detect latent target signals in novel therapy trials conducted in BD and generate novel hypotheses.

Disruptive innovation is a cornerstone of various disciplines, particularly in the business world, where paradigm-altering approaches are often lauded. As a construct, disruptive psychiatry can be considered to embody such an approach by the pursuit of innovations within the field which test boundaries and shake up the status quo. Given the importance of addressing the current mental health pandemic, and the deficit of highly effective pharmacological treatments for various conditions, innovative disruptive thinking is required. Significant promise exists via the provision of potentially more effective innovative therapeutic options, including digital interventions, psychedelic medicines, microbiome-altering treatments, brain stimulation technology, and nanotechnology-based delivery systems. These approaches may be further advanced by individualization of the treatments using computational technology (including quantum computing, machine learning, and artificial intelligence) and genomics.

Background: Naturalistic and placebo-controlled studies suggest ayahuasca, a potent psychedelic beverage originating from Indigenous Amazonian tradition, may improve mental health, alter personality structure, and reduce alcohol and drug intake. To better understand ayahuasca's therapeutic potential and to identify factors that influence therapeutic efficacy, we conducted a naturalistic, longitudinal study of facilitated ayahuasca consumption in naïve participants using a comprehensive battery of self-report questionnaires. Materials and Methods: Ayahuasca naive individuals registering for ayahuasca ceremonies were asked to complete a range of validated questionnaires assessing mental health, alcohol/cannabis use, relationships, personality, and connection to self and spirituality, prior to and 1 month after attending an ayahuasca ceremony. Data for two mental health measures (the DASS-21 and PANAS) and acute subjective effects via the MEQ-30 were also assessed 7 days post-ceremony. Repeated measures ANOVA were used to examine pre-to-post changes, and Pearson correlations explored predictors of improvement in outcomes. Results: Fifty-three attendees (32 women, 21 men) completed pre and post ayahuasca assessments with 55.6% of the sample reporting a complete mystical experience based on the MEQ-30. One-month post-ayahuasca, significant reductions were identified in depression, anxiety, stress, alcohol and cannabis use, body dissociation, accepting external influence, self-alienation, impulsivity, and negative affect/emotionality. Significant increases were identified in positive mood, self-efficacy, authentic living, extraversion, agreeableness, open-mindedness, spirituality, and satisfaction with relationships. While facets of the mystical experience held little predictive validity on outcome measures, baseline traits, particularly high negative emotionality and body dissociation, and low sense of self-efficacy, robustly predicted improvements in mental health and a

BACKGROUND: Lifestyle medicine (LM) is gaining increasing attention as a treatment option for anxiety, but the current state of evidence has not yet been systematically examined. METHODS: Six electronic databases were systematically searched from inception to February 2022. Randomized controlled trials (RCTs) comparing the effects of multicomponent LM interventions on anxiety symptoms with either care-as-usual, waitlist, no intervention, or attention control group on anxiety symptoms were identified. RESULTS: A total of 53 RCTs with 18,894 participants were included for qualitative synthesis, in which 45 RCTs with data available were included for meta-analysis. Multicomponent LM intervention was significantly more effective than the control groups in reducing anxiety symptoms at immediate posttreatment (d = 0.19, p < .001) and at short-term follow-up (d = 0.29, p < .001). However, no significant difference at medium-term was found (p = .14), whereas more studies are needed to study the long-term effects. The subgroup analyses suggested that baseline anxiety symptoms was a significant moderator, suggesting that those with moderate level of baseline anxiety symptoms appeared to have greater improvements (d = 0.66, p < .05). LIMITATIONS: Minimal anxiety symptoms at baseline contributed to the floor effect and influenced the degree of improvement. The included RCTs had a high risk of bias in general with potential publication bias detected. CONCLUSION: The findings of this meta-analysis provided support for the positive effects of multicomponent LM interventions for anxiety symptoms. Future research is needed to determine the long-term effects of multicimponent LM and the optimal baseline anxiety severity.

INTRODUCTION: The understanding of biological responses to psychedelics with antidepressant potential is imperative. Here we report how a set of acute parameters, namely emotional (depressive symptoms), cognitive (psychedelic experience), and physiological (salivary cortisol), recorded during an ayahuasca dosing session, modulated serum brain-derived neurotrophic factor (BDNF), serum cortisol (SC), serum interleukin 6 (IL-6), plasma C-reactive protein (CRP), and salivary cortisol awakening response (CAR). METHODS: Results were analyzed 2 days after the psychedelic intervention (ayahuasca) versus placebo in both patients with treatment-resistant depression and healthy volunteers. These measures were assessed as part of a randomized double-blinded, placebo-controlled trial (n = 72). RESULTS: Results revealed that larger reductions of depressive symptoms during the dosing session significantly moderated higher levels of SC in patients. Whereas lesser changes in salivary cortisol levels during the ayahuasca intervention were related to higher BDNF levels in patients with a larger clinical response in the reduction in depressive symptoms. No moderator was found for patient's CAR, IL-6, and CRP responses to ayahuasca and for all biomarker responses to ayahuasca in healthy controls and in the placebo group. DISCUSSION: In summary, some specific emotional and physiological parameters during experimental ayahuasca session were revealed as critical moderators of the improvement of major depression biomarkers, mainly BDNF and SC two days after ayahuasca intake. These findings contribute to paving the way for future studies investigating the biological antidepressant response to psychedelic therapy.

The current study investigated the efficacy of extract of Bacopa monnieri (BM; CDRI 08®) in reducing levels of inattention and hyperactivity in young children. BM has demonstrated improvements in cognitive outcomes in adults, yet little research is available on its effects in younger populations. A 14-week randomized, double-blind, placebo-controlled clinical trial, with placebo run-in and run-out phases, investigated the effects of BM on behavioural, cognitive, mood, and sleep effects in male children aged 6 to 14 years against placebo. One-hundred and twelve participants were recruited into the trial, with 93 datasets available for analysis. No significant behavioural differences were noted between treatment groups. Cognitive outcomes indicated decreased error-making in children taking CDRI 08® (p = .04) and increased speed of reaction time in those taking placebo (p = .04) at study end. Improvements in cognitive flexibility (p = .01), executive functioning (p = .04), interpersonal problems (p = .02), and sleep routine (p = .04) were noted in those consuming CDRI 08® over placebo. CDRI 08® did not improve behavioural outcomes, but may have cognitive, mood and sleep benefits in children aged 6 to 14 years. Further study is required to support the findings presented here.

Objectives: Plant-based medicines have had a long-standing history of use in psychiatric disorders. Highly quantified and standardized extracts or isolates may be termed “phytoceuticals,” in a similar way that medicinal nutrients are termed as “nutraceuticals.” Over the past 2 decades, several meta-analyses have examined the data for a range of plant-based medicines in the treatment of psychiatric disorders. The aim of this international project is to provide a “meta-review” of this top-tier evidence. Methods: We identified, synthesized, and appraised all available up to date meta-analyses... of randomized controlled trials (RCTs) reporting on the efficacy and effectiveness of individual phytoceuticals across all major psychiatric disorders. Results: Our systematic search identified 9 relevant meta-analyses of RCTs, with primary analyses including outcome data from 5,927 individuals. Supportive meta-analytic evidence was found for St John’s wort for major depressive disorder (MDD); curcumin and saffron for MDD or depression symptoms, and ginkgo for total and negative symptoms in schizophrenia. Kava was not effective in treating diagnosed anxiety disorders. We also provide details on 22 traditional Chinese herbal medicine formulas’ meta-analyses (primarily for depression studies), all of which revealed highly significant and large effect sizes. Their methodology, reporting, and potential publication bias were, however, of marked concern. The same caveat was noted for the curcumin, ginkgo, and saffron meta-analyses, which may also have significant publication bias. Conclusions: More rigorous international studies are required to validate the efficacy of these phytoceuticals before treatment recommendations can be made. In conclusion, the breadth of data tentatively supports several phytoceuticals which may be effective for mental disorders alongside pharmaceutical, psychological therapies, and standard lifestyle recommendations.

Background: Certain nutrient supplements (nutraceuticals) may target neurobiological pathways perturbed in bipolar disorder (BD) such as inflammation, oxidative stress, and mitochondrial dysfunction. Nutraceuticals thus may have a potential role as adjunctive treatments for BD. Methods: A search of Embase via embase.com, PubMed via PubMed, Cumulated index to nursing and allied health literature (CINAHL) Complete via EBSCO, and Cochrane Central Register of Controlled Clinical Trials via cochranelibrary.com was conducted to identify published randomized controlled trials assessing the efficacy of nutraceuticals on mood symptomatology in adults with BD. Search terms for BD, nutraceuticals, and clinical trials (total search terms = 75) were used to search from inception to February 20, 2020. The Cochrane Collaboration’s tool for assessing the risk of bias in randomized trials was used to assess the risk of bias. Results: A total of 1,712 studies were identified through the search. After rigorous screening, 22 studies were included in the review. There was large variability across the studies with 15 different nutraceutical agents assessed and as such insufficient homogeneity for a meta-analysis to be conducted ( I 2 > 50%). Studies revealed promising, albeit conflicting, evidence for omega-3 fatty acids and N-acetylcysteine. Isolated positive results were reported for coenzyme Q10. Conclusion: Given nutraceuticals are tolerable and accessible, they may be useful as potential adjunctive treatments for BD. Nutraceuticals targeting neuroinflammation or mitochondrial activity may have the most potential for the depressive phase. However, further studies are required to determine efficacy.

Abstract Rationale Major depressive disorder is one of the leading global causes of disability, for which the classic serotonergic psychedelics have recently reemerged as a potential therapeutic treatment option. Objective We present the first meta-analytic review evaluating the clinical effects of classic serotonergic psychedelics vs placebo for mood state and symptoms of depression in both healthy and clinical populations (separately). Results Our search revealed 12 eligible studies (n = 257; 124 healthy participants, and 133 patients with mood disorders), with data from randomized controlled trials involving psilocybin (n = 8), lysergic acid diethylamide ([LSD]; n = 3), and ayahuasca (n = 1). The meta-analyses of acute mood outcomes (3 h to 1 day after treatment) for healthy volunteers and patients revealed improvements with moderate significant effect sizes in favor of psychedelics, as well as for the longer-term (16 to 60 days after treatments) mood state of patients. For patients with mood disorder, significant effect sizes were detected on the acute, medium (2–7 days after treatment), and longer-term outcomes favoring psychedelics on the reduction of depressive symptoms. Conclusion Despite the concerns over unblinding and expectancy, the strength of the effect sizes, fast onset, and enduring therapeutic effects of these psychotherapeutic agents encourage further double-blind, placebo-controlled clinical trials assessing them for management of negative mood and depressive symptom

BACKGROUND: Obsessive-compulsive disorder (OCD) is often challenging to treat and resistant to psychological interventions and prescribed medications. The adjunctive use of nutraceuticals with potential neuromodulatory effects on underpinning pathways such as the glutamatergic and serotonergic systems is one novel approach. OBJECTIVE: To assess the effectiveness and safety of a purpose-formulated combination of nutraceuticals in treating OCD: N-acetyl cysteine, L-theanine, zinc, magnesium, pyridoxal-5' phosphate, and selenium. METHODS: A 20-week open label proof-of-concept study was undertaken involving 28 participants with treatment-resistant DSM-5-diagnosed OCD, during 2017 to 2020. The primary outcome measure was the Yale-Brown Obsessive-Compulsive Scale (YBOCS), administered every 4 weeks. RESULTS: An intention-to-treat analysis revealed an estimated mean reduction across time (baseline to week-20) on the YBOCS total score of -7.13 (95% confidence interval = -9.24, -5.01), with a mean reduction of -1.21 points per post-baseline visit (P ≤ .001). At 20-weeks, 23% of the participants were considered "responders" (YBOCS ≥35% reduction and "very much" or "much improved" on the Clinical Global Impression-Improvement scale). Statistically significant improvements were also revealed on all secondary outcomes (eg, mood, anxiety, and quality of life). Notably, treatment response on OCD outcome scales (eg, YBOCS) was greatest in those with lower baseline symptom levels, while response was limited in those with relatively more severe OCD. CONCLUSIONS: While this pilot study lacks placebo-control, the significant time effect in this treatment-resistant OCD population is encouraging and suggests potential utility especially for those with lower symptom levels. Our findings need to be confirmed or refuted via a follow-up placebo-controlled study.

INTRODUCTION: Emerging evidence suggests that psychedelic compounds, including the Amazonian botanical decoction ayahuasca, may provide clinical benefit in the treatment of alcohol or other drug use disorders. This study investigates associations between ayahuasca consumption in naturalistic settings and current alcohol and other drug use. METHODS: Online cross-sectional study of people who have consumed ayahuasca in religious, traditional and non-traditional settings in over 40 countries. A total of 8629 participants (53% male, average age 40 years) were included in the analysis. Logistic regressions were used to explore associations between ayahuasca drinking variables and the current use of alcohol and other drugs, as well as the influence of confounding factors, such as church or community membership. RESULTS: The number of times ayahuasca had been consumed was strongly associated with increased odds of never or rarely drinking alcohol, never or rarely engaging in 'risky drinking' and having not consumed a range of drugs in the past month, with these effects greater for those with a prior substance use disorder compared to those without. The strength of ayahuasca drinkers subjective spiritual experience, number of personal self-insights obtained and drinking ayahuasca with an ayahuasca church were also associated with lower substance use in some models. DISCUSSION AND CONCLUSIONS: Consumption of ayahuasca in naturalistic settings is associated with lower self-reported current consumption of alcohol and other drugs for those with and without prior substance use disorders, with such effects present after adjusting for religious or social group effects.

Objective: to perform a systematic literature review to examine the effects of high-dose, B-complex multivitamin/mineral supplementation on physical, mental, and energy outcomes in healthy and 'at-risk' (suboptimal nutritional status/subclinical symptoms at baseline) adult populations. Methods: PubMed was searched for relevant randomized controlled trials until January 2020. Results: overall, 136 publications were identified. In the seven randomised, double-blind, placebo-controlled studies considered eligible for inclusion, supplementation in healthy populations predominantly showed improvements in perceived stress, physical stamina, concentration, and general mental health, and significant reductions in anxiety and improvements in self-reported vigour. However, not all of these outcomes were significant, and statistical correction for multiple outcomes was not commonly employed. Studies investigating brain mapping following supplementation indicated increased functional activity in brain regions related to processing of attention, executive control, and working memory during cognitive tasks. Conclusions: while there is certainly a need for further studies on the neurocognitive and physical benefits of micronutrient supplementation, this review provides generally supportive evidence for the benefits of a high-dose, B-complex multivitamin/mineral supplement in healthy and at-risk populations in terms of physical, mental, and energy outcomes.

BACKGROUND: Molecular biomarkers are promising tools to be routinely used in clinical psychiatry. Among psychiatric diseases, major depression disorder (MDD) has gotten attention due to its growing prevalence and morbidity. METHODS: We tested some peripheral molecular parameters such as serum mature Brain-Derived Neurotrophic Factor (mBDNF), plasma C-Reactive Protein (CRP), serum cortisol (SC), and the salivary Cortisol Awakening Response (CAR), as well as the Pittsburgh sleep quality inventory (PSQI), as part of a multibiomarker panel for potential use in MDD diagnosis and evaluation of disease's chronicity using regression models, and ROC curve. RESULTS: For diagnosis model, two groups were analyzed: patients in the first episode of major depression (MD: n = 30) and a healthy control (CG: n = 32). None of those diagnosis models tested had greater power than Hamilton Depression Rating Scale-6. For MDD chronicity, a group of patients with treatment-resistant major depression (TRD: n = 28) was tested across the MD group. The best chronicity model (p < 0.05) that discriminated between MD and TRD included four parameters, namely PSQI, CAR, SC, and mBDNF (AUC ROC = 0.99), with 96% of sensitivity and 93% of specificity. CONCLUSION: These results indicate that changes in specific biomarkers (CAR, SC, mBDNF and PSQI) have potential on the evaluation of MDD chronicity, but not for its diagnosis. Therefore, these findings can contribute for further studies aiming the development of a stronger model to be commercially available and used in psychiatry clinical practice.

The last 20 years have seen major developments in the understanding of how childhood trauma (negative events that cause distress and overwhelm a person’s ability to cope) can have long-term effects on the health and well-being of adults who have experienced this. Child sexual abuse was first included in global burden of disease and disability estimates in 2004, and there has been a steady accumulation of research and evidence identifying the public health issues and costs associated with various traumatic childhood experiences. Much of this research has used the framework of adverse childhood experiences or ACEs, which encompass emotional, physical, and sexual abuse, as well as various other adverse events, including growing up in a household in which there is domestic violence, alcohol or drug abuse, or a member with mental illness; criminal behavior or incarceration of a family member; caregiver separation or divorce; and neglect, both physical and emotional. Such experiences have been found to be associated with higher rates of physical and mental illness, disability, and premature death in adulthood.

BACKGROUND: The use of cannabis for symptoms of endometriosis was investigated utilising retrospective archival data from Strainprint Technologies Ltd., a Canadian data technology company with a mobile phone application that tracks a range of data including dose, mode of administration, chemovar and their effects on various self-reported outcomes, including pelvic pain. METHODS: A retrospective, electronic record-based cohort study of StrainprintTM users with self-reported endometriosis was conducted. Self-rated cannabis efficacy, defined as a function of initial and final symptom ratings, was investigated across the included symptom clusters of cramps, pelvic pain, gastrointestinal pain, nausea, depression, and low libido. Cannabis dosage form, dose and cannabinoid ratio information was also recorded. RESULTS: A total number of 252 participants identifying as suffering endometriosis recorded 16193 sessions using cannabis between April 2017 and February 2020. The most common method of ingestion was inhalation (n = 10914, 67.4%), with pain as the most common reported symptom being treated by cannabis (n = 9281, 57.3%). Gastrointestinal symptoms, though a less common reason for cannabis usage (15.2%), had the greatest self-reported improvement after use. Inhaled forms had higher efficacy for pain, while oral forms were superior for mood and gastrointestinal symptoms. Dosage varied across ingestion methods, with a median dose of 9 inhalations (IQR 5 to 11) for inhaled dosage forms and 1 mg/mL (IQR 0.5 to 2) for other ingested dosage forms. The ratio of THC to CBD had a statistically significant, yet clinically small, differential effect on efficacy, depending on method of ingestion. CONCLUSIONS: Cannabis appears to be effective for pelvic pain, gastrointestinal issues and mood, with effectiveness differing based on method of ingestion. The greater propensity for use of an inhaled dosage delivery may be due to the rapid onset of pain-relieving effects versus the slower

OBJECTIVE: Cancer and its treatment can lead to a variety of physical and emotional concerns impacting on those affected, including subclinical or clinical depression and anxiety, which in turn have a significant impact on wellbeing, quality of life and survival. The aim of this review was to evaluate the effect of yoga-based interventions on self-reported depression and anxiety symptoms in people with cancer in randomized controlled trials. METHOD: Six databases were searched to identify relevant studies. Systematic review procedures were followed including a quality assessment. Meta-analysis of suitable studies was conducted. RESULTS: 26 studies from our search criteria were eligible for inclusion for depressive and 16 for anxiety symptoms. Meta-analyses revealed evidence for significant medium effects of yoga on depression symptoms (N = 1,486, g = -0.419, 95% confidence interval [CI] = -0.558 to -0.281, p < 0.001) and anxiety (N = 977, g = -0.347, 95% CI = -0.473 to -0.221, p < 0.001) compared to controls. Subgroup analyses for depressive symptoms revealed significant effects for all analyses performed (type of cancer, type of control, treatment status, duration of intervention or frequency of yoga sessions), with effect sizes being comparable between subgroups. Similar findings were found for anxiety symptoms except for treatment status, where the only significant effect was found when yoga was delivered during active treatment. CONCLUSIONS: This review provides evidence that in people with cancer, yoga-based interventions are associated with amelioration of depression and anxiety symptoms and therefore a promising therapeutic modality for their management. However, the potential for risk of bias together with control group design challenges means the results should be interpreted with caution.

Given the growing evidence that a range of lifestyle factors are involved in the etiology of depression, a 'lifestyle medicine' approach can be potentially safe and cost-effective to prevent or treat depression. To examine the effects and acceptability of a group-based, integrative lifestyle medicine intervention as a standalone treatment for managing depressive symptoms, a pilot randomized controlled trial (RCT) was conducted in a Chinese adult population in 2018. Participants (n = 31) with PHQ-9 score above the cut-off of ≥ 10, which was indicative of moderate to severe depression, were recruited from the general community in Hong Kong and randomly assigned to lifestyle medicine group (LM group) or care-as-usual group (CAU group) in a ratio of 1:1. Participants in the LM group received 2-hour group sessions once per week for six consecutive weeks, which covered diet, exercise, mindfulness, psychoeducation, and sleep management. Linear mixed-effects model analyses showed that the LM group had a significant reduction in PHQ-9 scores compared to the CAU group at immediate posttreatment and 12-week posttreatment follow-up (d = 0.69 and 0.73, respectively). Moreover, there were significantly greater improvements in anxiety, stress, and insomnia symptoms (measured by DASS-21 and ISI) at all time points in the LM group (d = 0.42-1.16). The results suggests that our 6-week group-based, integrative lifestyle intervention program is effective in lowering depressive, anxiety, stress, and insomnia symptoms in the Chinese population. Further studies in clinical populations with a larger sample size and longer follow-up are warranted.

Background Ayahuasca is a psychoactive Amazonian brew which has emerging data indicating that it has antidepressant and anxiolytic properties. Methods This paper uses data from the Global Ayahuasca Project (GAP), which was undertaken across 2017-2020 and involved 11912 people, to examine the perceived effects of ayahuasca consumption on affective symptoms. The study focused on the subsample reporting depression or anxiety diagnoses at time of Ayahuasca consumption (n = 2011). Results Of participants reporting depression (n=1571) or anxiety (n=1125) at the time of consuming Ayahuasca, 78% reported that their depression was either ‘very much’ improved (46%), or ‘completely resolved’ (32%); while 70% of those with anxiety reported that their symptoms were ‘very much’ improved (54%), or ‘completely resolved’ (16%). A range of factors were associated with greater reported affective symptoms improvement, including subjective mystical experience, number of Ayahuasca sessions, and number of personal psychological insights experienced. 2.7% and 4.5% of drinkers with depression or anxiety, respectively, reported worsening of symptoms. Limitations This study is recognized as a cross-sectional analysis which cannot assess treatment efficacy. Selection bias may exist due to survey-respondents with favorable experience being potentially biased towards participation. Conclusions Drinkers of Ayahuasca in naturalistic settings perceived remarkable benefits for their affective symptoms in this survey assessment. There is no obvious evidence of negative mental health effects being associated with long-term consumption. Additional randomized controlled trial evidence is required to establish the efficacy of Ayahuasca in affective disorders, and to understand the worsened symptoms reported by a small percentage of drinkers.

The comprehension of the pathophysiology of the major depressive disorder (MDD) is essential to the strengthening of precision psychiatry. In order to determine the relationship between the pathophysiology of the MDD and its clinical progression, analyzed by severity of the depressive symptoms and sleep quality, we conducted a study assessing different peripheral molecular biomarkers, including the levels of plasma C-reactive protein (CRP), serum mature brain-derived neurotrophic factor (mBDNF), serum cortisol (SC), and salivary cortisol awakening response (CAR), of patients with MDD (n = 58) and a control group of healthy volunteers (n = 62). Patients with the first episode of MDD (n = 30) had significantly higher levels of CAR and SC than controls (n = 32) and similar levels of mBDNF of controls. Patients with treatment-resistant depression (TRD, n = 28) presented significantly lower levels of SC and CAR, and higher levels of mBDNF and CRP than controls (n = 30). An increased severity of depressive symptoms and worse sleep quality were correlated with levels low of SC and CAR, and with high levels of mBDNF. These results point out a strong relationship between the stages clinical of MDD and changes in a range of relevant biological markers. This can assist in the development of precision psychiatry and future research on the biological tests for depression.

Emerging evidence is showing nutrition as a crucial factor in the high prevalence and incidence of neurodegenerative mental disorders. Preventive interventions on neuroinflammation seem to be able to interfere with neurodegeneration. Supplementation of essential nutrients, such as long-chain-polyunsaturated fatty acids, vitamin E and mineral elements, may minimize inflammation, enhancing antioxidative defense, and lowering the risk and incidence of age-related diseases, such as cardiovascular diseases and neurodegenerative diseases. This manuscript reviews the current evidence on the role of neuroinflammation in the pathophysiology of neurodegenerative and mental disorders, and preventive strategies for food supplementation in these neuropsychiatric diseases. Dietary supplementation-based strategies have been demonstrated to be effective in subjects with mild cognitive impairment, while weaker results have been obtained in patients with advance neurodegenerative disease. Adjunctive supplementation has also been demonstrated to improve depression, this being of marked benefit considering the comorbidity between cognitive impairment/dementia and depression. Further research is needed to improve the prescriptive precision of supplementation in patients, and to better understand potential interactions with clinical and pharmacokinetic factors.

Background There is now evolving data exploring the relationship between depression and various individual lifestyle factors such as diet, physical activity, sleep, alcohol intake, and tobacco smoking. While this data is compelling, there is a paucity of longitudinal research examining how multiple lifestyle factors relate to depressed mood, and how these relations may differ in individuals with major depressive disorder (MDD) and those without a depressive disorder, as ‘healthy controls’ (HC). Methods To this end, we assessed the relationships between 6 key lifestyle factors (measured via self-report) and depressed mood (measured via a relevant item from the Patient Health Questionnaire) in individuals with a history of or current MDD and healthy controls (HCs). Cross-sectional analyses were performed in the UK Biobank baseline sample, and longitudinal analyses were conducted in those who completed the Mental Health Follow-up. Results Cross-sectional analysis of 84,860 participants showed that in both MDD and HCs, physical activity, healthy diet, and optimal sleep duration were associated with less frequency of depressed mood (all p < 0.001; ORs 0.62 to 0.94), whereas screen time and also tobacco smoking were associated with higher frequency of depressed mood (both p < 0.0001; ORs 1.09 to 1.36). In the longitudinal analysis, the lifestyle factors which were protective of depressed mood in both MDD and HCs were optimal sleep duration (MDD OR = 1.10; p < 0.001, HC OR = 1.08; p < 0.001) and lower screen time (MDD OR = 0.71; p < 0.001, HC OR = 0.80; p < 0.001). There was also a significant interaction between healthy diet and MDD status (p = 0.024), while a better-quality diet was indicated to be protective of depressed mood in HCs (OR = 0.92; p&thi

Background Many individuals with mental health problems have comorbid physical conditions, or may present with substance/alcohol misuse or abuse issues. This results in complex treatment challenges that may not be adequately addressed by a model of care that is solely delivered by an individual clinician using a sole intervention. Mainstream pharmacotherapeutic treatment of mental health problems often have limited effectiveness in completely resolving symptoms, and may cause adverse side effects. Adjunctive treatment approaches, including nutraceuticals, lifestyle and behaviour change interventions, are widely used to assist with treatment of mental health problems. However, whilst these can be generally safer with fewer side effects, they have varying levels of evidentiary support. These circumstances warrant reframing the current treatment approach towards a more evidence-based integrative model which may better address the real-world challenges of psychiatric disorders and comorbid physical conditions. In essence, this means developing an integrative model of care which embodies an evidence-informed, personalized stepwise approach using both conventional pharmacological treatments alongside novel adjunctive treatments (where applicable) via the application of a collaborative care approach. Discussion In order to inform this position, a brief review of findings on common patterns of comorbidity in mental illness is presented, followed by identification of limitations of conventional treatments, and potential applications of integrative medicine interventions. Advantages and challenges of integrative mental health care, collaborative models of care, review of research highlights of select integrative approaches, and comment on potential cost advantages are then discussed. Summary We propose that a collaborative care model incorporating evidence-based integrative medicine interventions may more adequately address mental health problems with comorbid medical conditi

BACKGROUND: Medicinal cannabis has received increased research attention over recent years due to loosening global regulatory changes. Medicinal cannabis has been reported to have potential efficacy in reducing pain, muscle spasticity, chemotherapy-induced nausea and vomiting, and intractable childhood epilepsy. Yet its potential application in the field of psychiatry is lesser known. METHODS: The first clinically-focused systematic review on the emerging medical application of cannabis across all major psychiatric disorders was conducted. Current evidence regarding whole plant formulations and plant-derived cannabinoid isolates in mood, anxiety, sleep, psychotic disorders and attention deficit/hyperactivity disorder (ADHD) is discussed; while also detailing clinical prescription considerations (including pharmacogenomics), occupational and public health elements, and future research recommendations. The systematic review of the literature was conducted during 2019, assessing the data from all case studies and clinical trials involving medicinal cannabis or plant-derived isolates for all major psychiatric disorders (neurological conditions and pain were omitted). RESULTS: The present evidence in the emerging field of cannabinoid therapeutics in psychiatry is nascent, and thereby it is currently premature to recommend cannabinoid-based interventions. Isolated positive studies have, however, revealed tentative support for cannabinoids (namely cannabidiol; CBD) for reducing social anxiety; with mixed (mainly positive) evidence for adjunctive use in schizophrenia. Case studies suggest that medicinal cannabis may be beneficial for improving sleep and post-traumatic stress disorder, however evidence is currently weak. Preliminary research findings indicate no benefit for depression from high delta-9 tetrahydrocannabinol (THC) therapeutics, or for CBD in mania. One isolated study indicates some potential efficacy for an oral cannabinoid/terpene combination in ADHD. Clinica

OBJECTIVE: The effects of chronic cannabis consumption on physiological parameters of athletic performance are investigated to determine whether chronic cannabis consumption negatively affects athletic performance; improves performance, potentially via enhanced recovery; or has no effect at all. METHODS: A systematic review of the literature (cross-sectional, longitudinal, and intervention studies) concerning the effects of cannabis consumption on sports performance outcomes, e.g. VO2Max (maximal oxygen uptake), PWC (physical work capacity) up to January 2020 was conducted using the PubMed, CINAHL, Medline, PsycArticles, PsycInfo, SPORTDiscus, Psychology and Behavioural Sciences Collection, and Health Source: Nursing/Academic Edition databases. After screening and additional forward searching, four articles were found to fit the inclusion criteria. RESULTS: Resting heart rate was the only physiological measure that significantly differed between groups, and only in one of the four studies included herein. The strongest predictors of athletic performance (VO2Max and PWC) were not found to be significantly different between groups in any of the included studies. Chronic cannabis consumption had no significant effect on athletic performance. The included studies did not assess other elements, such as recovery or endurance. CONCLUSION: No evidence exists for ergogenic or ergolytic effects from chronic cannabis consumption. In some sports, advantages may plausibly be conveyed by psychotropic enhancement or pain reduction. Further research (particularly longitudinal or interventional studies) is required to determine whether cannabis, or constituents thereof, may provide indirect supplemental benefits to athletes.

OBJECTIVE: Emerging evidence suggests that handgrip strength (a proxy for muscular fitness) is associated with better cognitive performance in people with major depressive disorder (MDD). The underlying processes are unclear, although hippocampal volume (HCV) reductions and white matter hyperintensities (WMHs) have been implicated. Therefore, we investigated the associations between handgrip strength and various brain region volumes and WMHs in MDD and healthy controls (HCs). METHODS: This study is a cross-sectional analysis of handgrip strength and neuroimaging data from the UK Biobank. Generalized linear models were used to assess the relationship between grip strength and gray matter, white matter, total brain volume, left and right hippocampus volume, and WMHs in MDD and HCs, adjusting for age, sex, education, and body weight. RESULTS: The sample included 527 people with MDD (54.3 ± 7.3 years, 37.2% male) and 1764 HCs (56.6 ± 7.2 years, 53% male). In MDD, stronger handgrip was significantly associated with increased left (coefficient ± SE = 108.1 ± 27.6, t = 3.92) and right (76.8 ± 30.4, t = 2.53) HCV. In HCs, only right HCV related to handgrip strength (44.8 ± 18.1, t = 2.47). Interaction analyses found stronger associations between grip strength and HCV in MDD compared with HCs, for both hippocampal regions. Stronger handgrip was associated with reduced WMHs in people with MDD (-0.24 ± 0.07, t = -3.24) and HCs (-0.11 ± 0.04, t = -2.47). Maximal handgrip strength was not associated with gray matter, white matter, or total brain volumes in either group. CONCLUSIONS: Stronger grip strength is associated with greater left and right HCV and reduced WMHs in MDD. Future research should investigate directionality and consider if interventions targeting strength/muscular fitness can improve brain health and reduce the neurocognitive abnormalities associated with MDD.

Obsessive-compulsive disorder (OCD) is a relatively prevalent mental disorder that poses significant health burdens on the community. Although current conventional medications have good efficacy for many patients, they can elicit a range of associated adverse effects. Plant-based compounds have been evaluated for different mental disorders, with a range of anxiolytic properties revealed. To determine the current evidence in the area, we conducted a systematic review using the electronic databases including PubMed, Scopus, and the Cochrane Library up to June 12, 2019, for pharmacological and clinical evidence of herbal medicines and phytochemicals with antiobsessive-compulsive effects. Additional search criteria were employed for locating research on the underpinning mechanisms of action. Results revealed that tentative low-quality evidence exists for several plant medicines, including Crocus sativus, Silybum marianum, Echium amoenum, Hypericum perforatum, and Withania somnifera, along with several natural molecules, including crocin, cannabidiol, and curcumin. Although more research is needed to confirm effectiveness, present preclinical studies indicate that monoamine pathway modulation (in particular serotonin reuptake inhibition) may be the most important anti-OCD mechanism among the studied natural compounds.

There is increasing academic and clinical interest in how "lifestyle factors" traditionally associated with physical health may also relate to mental health and psychological well-being. In response, international and national health bodies are producing guidelines to address health behaviors in the prevention and treatment of mental illness. However, the current evidence for the causal role of lifestyle factors in the onset and prognosis of mental disorders is unclear. We performed a systematic meta-review of the top-tier evidence examining how physical activity, sleep, dietary patterns and tobacco smoking impact on the risk and treatment outcomes across a range of mental disorders. Results from 29 meta-analyses of prospective/cohort studies, 12 Mendelian randomization studies, two meta-reviews, and two meta-analyses of randomized controlled trials were synthesized to generate overviews of the evidence for targeting each of the specific lifestyle factors in the prevention and treatment of depression, anxiety and stress-related disorders, schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. Standout findings include: a) convergent evidence indicating the use of physical activity in primary prevention and clinical treatment across a spectrum of mental disorders; b) emerging evidence implicating tobacco smoking as a causal factor in onset of both common and severe mental illness; c) the need to clearly establish causal relations between dietary patterns and risk of mental illness, and how diet should be best addressed within mental health care; and d) poor sleep as a risk factor for mental illness, although with further research required to understand the complex, bidirectional relations and the benefits of non-pharmacological sleep-focused interventions. The potentially shared neurobiological pathways between multiple lifestyle factors and mental health are discussed, along with directions for future research, and recommendations for the imp

BACKGROUND: There is now evolving data exploring the relationship between depression and various individual lifestyle factors such as diet, physical activity, sleep, alcohol intake, and tobacco smoking. While this data is compelling, there is a paucity of longitudinal research examining how multiple lifestyle factors relate to depressed mood, and how these relations may differ in individuals with major depressive disorder (MDD) and those without a depressive disorder, as 'healthy controls' (HC). METHODS: To this end, we assessed the relationships between 6 key lifestyle factors (measured via self-report) and depressed mood (measured via a relevant item from the Patient Health Questionnaire) in individuals with a history of or current MDD and healthy controls (HCs). Cross-sectional analyses were performed in the UK Biobank baseline sample, and longitudinal analyses were conducted in those who completed the Mental Health Follow-up. RESULTS: Cross-sectional analysis of 84,860 participants showed that in both MDD and HCs, physical activity, healthy diet, and optimal sleep duration were associated with less frequency of depressed mood (all p < 0.001; ORs 0.62 to 0.94), whereas screen time and also tobacco smoking were associated with higher frequency of depressed mood (both p < 0.0001; ORs 1.09 to 1.36). In the longitudinal analysis, the lifestyle factors which were protective of depressed mood in both MDD and HCs were optimal sleep duration (MDD OR = 1.10; p < 0.001, HC OR = 1.08; p < 0.001) and lower screen time (MDD OR = 0.71; p < 0.001, HC OR = 0.80; p < 0.001). There was also a significant interaction between healthy diet and MDD status (p = 0.024), while a better-quality diet was indicated to be protective of depressed mood in HCs (OR = 0.92; p = 0.045) but was not associated with depressed mood in the MDD sample. In a cross-sectional (OR = 0.91; p < 0.0001) analysis, higher frequency of alcohol consumption was surprisingly associated with reduced frequency of depr