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

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

Depression is a debilitating mood disorder that is among the top causes of disability worldwide. It can be characterized by a set of somatic, emotional, and behavioral symptoms, one of which is a high risk of suicide. This work presents a hypothesis that depression may be caused by the convergence of two factors: (A) A lifestyle that lacks certain physiological stressors that have been experienced by primates through millions of years of evolution, such as brief changes in body temperature (e.g. cold swim), and this lack of"thermal exercise"may cause inadequate functioning of the brain. (B) Genetic makeup that predisposes an individual to be affected by the above condition more seriously than other people. To test the hypothesis, an approach to treating depression is proposed that consists of adapted cold showers (20 degrees C, 2-3 min, preceded by a 5-min gradual adaptation to make the procedure less shocking) performed once or twice daily. The proposed duration of treatment is several weeks to several months. The following evidence appears to support the hypothesis: Exposure to cold is known to activate the sympathetic nervous system and increase the blood level of beta-endorphin and noradrenaline and to increase synaptic release of noradrenaline in the brain as well. Additionally, due to the high density of cold receptors in the skin, a cold shower is expected to send an overwhelming amount of electrical impulses from peripheral nerve endings to the brain, which could result in an anti-depressive effect. Practical testing by a statistically insignificant number of people, who did not have sufficient symptoms to be diagnosed with depression, showed that the cold hydrotherapy can relieve depressive symptoms rather effectively. The therapy was also found to have a significant analgesic effect and it does not appear to have noticeable side effects or cause dependence. In conclusion, wider and more rigorous studies would be needed to test the validity of the hypothesis.

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

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

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

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

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

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

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

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

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

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

Curcumin, a yellow pigment extracted from rhizomes of the plant Curcuma longa (turmeric), has been widely used as food additive and also as a herbal medicine throughout Asia. The present study was designed to study the pharmacological, biochemical and neurochemical effects of daily administration of curcumin to rats subjected to chronic unpredictable stress. Curcumin treatment (20 and 40 mg/kg, i.p., 21 days) significantly reversed the chronic unpredictable stress-induced behavioral (increase immobility period), biochemical (increase monoamine oxidase activity) and neurochemical (depletion of brain monoamine levels) alterations. The combination of piperine (2.5 mg/kg, i.p., 21 days), a bioavailability enhancer, with curcumin (20 and 40 mg/kg, i.p., 21 days) showed significant potentiation of its anti-immobility, neurotransmitter enhancing (serotonin and dopamine) and monoamine oxidase inhibitory (MAO-A) effects as compared to curcumin effect per se. This study provided a scientific rationale for the use of curcumin and its co-administration with piperine in the treatment of depressive disorders.

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

BACKGROUND:Major depressive disorder (MDD) is a highly prevalent, heterogeneous and systemic medical condition. Treatment options are limited, and recent studies have suggested that physical exercise can play an important role in the therapeutics of MDD. The aim of this study was to evaluate the antidepressant efficacy of adjunctive aerobic activity in association with pharmacotherapy (selective serotonin reuptake inhibitor) in symptomatic MDD as well as its association with physiological biomarkers.

METHODS:In this randomized, single-blind, add-on, controlled clinical trial, 57 patients (18-55 years of age) were followed-up for 28 days. All patients were drug-free, had been diagnosed with symptomatic MDD and received flexible dose of sertraline during the trial. Patients were randomized to either a 4-week program (4x/week) of add-on aerobic exercise (exercise group, N = 29) or no activity (control group, N = 28). Depression severity was assessed using the Hamilton Rating Scale for Depression (HAM-D) as the primary outcome. At baseline and endpoint, all patients underwent a comprehensive metabolic/cardiopulmonary exercise testing-including determination of maximal oxygen uptake (VO2max), VO2 at the second ventilatory threshold (VO2-VT2), and oxygen pulse (O2 pulse).

RESULTS:Depression scores significantly decreased in both groups after intervention. Importantly, patients in the aerobic exercise group required lower sertraline dose compared to the control group (sertraline monotherapy). The VO2max and O2 pulse parameters increased over time only in the exercise group and remained unchanged in the control group.

CONCLUSIONS:The present findings suggest that a 4-week training of aerobic exercise significantly improves functional capacity in patients with MDD and may be associated with antidepressant efficacy. This approach may also decrease the need for higher doses of antidepressants to achieve response. Further studies in unmedicated and treatment-resistant MDD patients are needed in order to confirm the utility of short-term aerobic exercise as an alternative therapeutic approach in MDD.

TRIAL REGISTRATION:ClinicalTrials.gov NCT02427789.

Physical exercise has been shown to exert antidepressant effects, but the mechanisms underlying this effect are not completely elucidated. Therefore, we aimed at investigating the antidepressant, pro-neurogenic, and neuroprotective effects of physical exercise and the possible role of FNDC5/irisin for this effect. Treadmill running was used as a protocol of physical exercise (45 min/day/5 days/week for 4 weeks) in female Swiss mice. Immobility time was registered in the tail suspension test (TST) and forced swim test (FST). Immunohistochemical analyses to evaluate hippocampal cell proliferation, neuronal survival, and neuronal commitment and maturation, as well as expression of FNDC5 C-terminal fragment were performed in the entire, dorsal, and ventral dentate gyrus (DG) of the hippocampus. Fluoro-Jade B staining was performed to evaluate degenerating neurons in DG. FNDC5 C-terminal and FNDC5/irisin immunocontents were analyzed by western blot. Exposure to physical exercise reduced the immobility time both in the TST and the FST. This antidepressant-like effect was accompanied by an increase in hippocampal cell proliferation, hippocampal neuronal differentiation, and neuronal survival in the dorsal and ventral DG. Fluoro-Jade B staining was reduced in entireand dorsal DG in exercised mice. Finally, physical exercise also resulted in increased number of FNDC5-positive cells in the hippocampal DG as well as elevated FNDC5 C-terminal and FNDC5/irisin immunocontent in the entire hippocampus. The results suggest that the FNDC5 C-terminal fragment/irisin pathway may be implicated in the antidepressant-like, pro-neurogenic, and neuroprotective effects of treadmill running.

BACKGROUND:The extracellular signal-regulated kinase (ERK) signaling pathway is considered to be associated with the pathogenesis and treatment of depression. Acupuncture has been demonstrated to ameliorate depression-related behavior and promote neurogenesis. In this study, we explored the role of the ERK signaling pathway in the antidepressant-like effects of acupuncture in rats exposed to chronic unpredictable mild stress (CUMS).

METHODS:Eighty male Sprague-Dawley rats were randomly divided into eight groups: control group, model group, model + Acupuncture group (Acu group), model + fluoxetine group (FLX group), model + DMSO group (DMSO group), model + PD98059 group (PD group), model + Acupuncture + PD98059 group (Acu + PD group) and model + fluoxetine + PD98059 group (FLX + PD group). Except forthe control group, all rats were subjected to 3 weeks of CUMS protocols to induce depression. Acupuncture was carried out for 10 min at acupoints of Baihui (GV-20) and Yintang (GV-29) each day during the experimental procedure. The ERK signaling pathway was inhibited using PD98059 through intracerebroventricular injection. The depression-like behaviors were evaluated using the sucrose intake and open-field tests. The protein levels of ERK1/2, phosphor (p)-ERK1/2, cAMP response element-binding protein (CREB), p-CREB and brain-derived neurotrophic factor (BDNF) in the hippocampus were examined using western blot.

RESULTS:Acupuncture ameliorated the depression-like behaviors and dysfunction of the ERK signaling pathway in the hippocampus of CUMS rats. PD98059 pretreatment inhibited the improvements brought about by acupuncture on the ERK signaling pathway.

CONCLUSIONS:Taken together, our results indicated that acupuncture had a significant antidepressant-like effect on CUMS-induced depression model rats, and the ERK signaling pathway was implicated in this effect.

Although blended essential oils are increasingly being used for the improvement of the quality of life and for the relief of various symptoms in patients, the scientific evaluation of the aroma-therapeutic effects of blended essential oils in humans is rather scarce. In this study, we hypothesized that applying blended essential oil would provide a synergistic effect that would have a chance for success in treating depression or anxiety. Therefore, the main objective of this study was to investigate the effects of the blended essential oil on autonomic parameters and on emotional responses in humans following transdermal absorption. The blended essential oil consisted of lavender and bergamot oils. Human autonomic parameters, i.e. blood pressure, pulse rate, breathing rate, and skin temperature, were recorded as indicators of the arousal level of the autonomic nervous system. In addition, subjects had to rate their emotional condition in terms of relaxation, vigor, calmness, attentiveness, mood, and alertness in order to assess subjective behavioral arousal. Forty healthy volunteers participated in the experiments. Blended essential oil was applied topically to the skin of the abdomen of each subject. Compared with placebo, blended essential oil caused significant decreases of pulse rate, and systolic and diastolic blood pressure, which indicated a decrease of autonomic arousal. At the emotional level, subjects in the blended essential oil group rated themselves as 'more calm' and 'more relaxed' than subjects in the control group. This finding suggests a decrease of subjective behavioral arousal. In conclusion, our investigation demonstrates the relaxing effect of a mixture of lavender and bergamot oils. This synergistic blend provides evidence for its use in medicine for treating depression or anxiety in humans.

INTRODUCTION:Cancer patients are particularly vulnerable to depression and anxiety, with fatigue as the most prevalent symptom of those undergoing treatment. The purpose of this study was to determine whether improvement in depression, anxiety or fatigue during chemotherapy following anthroposophy art therapy intervention is substantial enough to warrant a controlled trial.

MATERIAL AND METHODS:Sixty cancer patients on chemotherapy and willing to participate in once-weekly art therapy sessions (painting with water-based paints) were accrued for the study. Nineteen patients who participated in>or =4 sessions were evaluated as the intervention group, and 41 patients who participated in

RESULTS:BFI scores were higher in the participant group (p=0.06). In the intervention group, the median HADS score for depression was 9 at the beginning and 7 after the fourth appointment (p=0.021). The median BFI score changed from 5.7 to 4.1 (p=0.24). The anxiety score was in the normal range from the beginning.

CONCLUSION:Anthroposophical art therapy is worthy of further study in the treatment of cancer patients with depression or fatigue during chemotherapy treatment.

ETHNOPHARMACOLOGICAL RELEVANCE:Withania somnifera (Family: Solanaceae), commonly known as Ashwagandha or Indian ginseng is distributed widely in India, Nepal, China and Yemen. The roots of plant consist of active phytoconstituents mainly withanolides, alkaloids and sitoindosides and are conventionally used for the treatment of multiple brain disorders.

AIM OF THE REVIEW:This review aims to critically assess and summarize the current state and implication of Ashwagandha in brain disorders. We have mainly focussed on the reported neuroactive phytoconstituents, available marketed products, pharmacological studies, mechanism of action and recent patents published related to neuroprotective effects of Ashwagandha in brain disorders.

MATERIALS AND METHODS:All the information and data was collected on Ashwagandha using keywords"Ashwagandha"along with"Phytoconstituents","Ayurvedic, Unani and Homeopathy marketed formulation","Brain disorders","Mechanism"and"Patents". Following sources were searched for data collection: electronic scientific databases such as Science Direct, Google Scholar, Elsevier, PubMed, Wiley On-line Library, Taylor and Francis, Springer; books such as AYUSH Pharmacopoeia; authentic textbooks and formularies.

RESULTS:Identified neuroprotective phytoconstituents of Ashwagandha are sitoindosides VII-X, withaferin A, withanosides IV, withanols, withanolide A, withanolide B, anaferine, beta-sitosterol, withanolide D with key pharmacological effects in brain disorders mainly anxiety, Alzheimer's, Parkinson's, Schizophrenia, Huntington's disease, dyslexia, depression, autism, addiction, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder and bipolar disorders. The literature survey does not highlight any toxic effects of Ashwagandha. Further, multiple available marketed products and patents recognized its beneficial role in various brain disorders; however, very few data is available on mechanistic pathway and clinical studies of Ashwagandha for various brain disorders is scarce and not promising.

CONCLUSION:The review concludes the results of recent studies on Ashwagandha suggesting its extensive potential as neuroprotective in various brain disorders as supported by preclinical studies, clinical trials and published patents. However vague understanding of the mechanistic pathways involved in imparting the neuroprotective effect of Ashwagandha warrants further study to promote it as a promising drug candidate.

CONTEXT: Adherence to the Mediterranean dietary pattern (MDP) is thought to reduce inflammatory, vascular, and metabolic processes that may be involved in the risk of clinical depression.

OBJECTIVE: To assess the association between adherence to the MDP and the incidence of clinical depression.

DESIGN: Prospective study that uses a validated 136-item food frequency questionnaire to assess adherence to the MDP. The MDP score positively weighted the consumption of vegetables, fruit and nuts, cereal, legumes, and fish; the monounsaturated- to saturated-fatty-acids ratio; and moderate alcohol consumption, whereas meat or meat products and whole-fat dairy were negatively weighted.

SETTING: A dynamic cohort of university graduates (Seguimiento Universidad de Navarra/University of Navarra Follow-up [SUN] Project). PARTICIPANTS: A total of 10 094 initially healthy Spanish participants from the SUN Project participated in the study. Recruitment began on December 21, 1999, and is ongoing.

MAIN OUTCOME MEASURE: Participants were classified as having incident depression if they were free of depression and antidepressant medication at baseline and reported a physician-made diagnosis of clinical depression and/or antidepressant medication use during follow-up.

RESULTS: After a median follow-up of 4.4 years, 480 new cases of depression were identified. The multiple adjusted hazard ratios (95% confidence intervals) of depression for the 4 upper successive categories of adherence to the MDP (taking the category of lowest adherence as reference) were 0.74 (0.57-0.98), 0.66 (0.50-0.86), 0.49 (0.36-0.67), and 0.58 (0.44-0.77) (P for trend<.001). Inverse dose-response relationships were found for fruit and nuts, the monounsaturated- to saturated-fatty-acids ratio, and legumes.

CONCLUSIONS: Our results suggest a potential protective role of the MDP with regard to the prevention of depressive disorders; additional longitudinal studies and trials are needed to confirm these findings.

Interruptions to time spent sitting can ameliorate detrimental metabolic-health consequences of high volumes of sedentary time, but their potential mental health benefits have not been examined. We used the Swedish Health Profile Assessment database, a general health assessment offered to all employees working for companies or organisations connected to occupational and health services. Cross-sectional analyses examined data from 40,550 employees (60% male, mean age = 42 years), collected in 2017-2019. Participants reported the proportion of time (almost always; 75% of the time; 50% of the time; 25% of the time; and almost never) usually spent in leisure-time sedentary behaviours; and, separately, the frequency (never; rarely; sometimes; often; and very often) of interruptions (every 30 min) to sedentary time. Logistic regression models assessed associations of sedentary time, and the frequency of interruptions to sedentary time, with depression/anxiety symptoms. Fully adjusted models included physical exercise. Compared to those in the lowest sedentary time category, those in the medium and high categories had 1.52 (95% confidence interval (CI) = 1.40-1.66) and 3.11 (95% CI = 2.82-3.42) higher odds of frequent depression/anxiety symptoms, respectively. Compared to those who never/rarely interrupted their sedentary time, those who reported interruptions sometimes, often and very often had 0.72 (95% CI = 0.65-0.80), 0.59 (95% CI = 0.53-0.65), and 0.53 (95% CI = 0.46-0.59) lower odds of depression/anxiety symptoms, respectively. In stratified analyses, more frequent interruptions to sedentary time were associated withlower odds of depression/anxiety symptoms, except among those in the lowest interruptions categories (never/25% of the time). More regularly interrupting sitting during leisure-time may reduce the odds of experiencing symptoms of depression and anxiety.

OBJECTIVES:We investigated the clinical benefits of bright light therapy (BLT) as an adjunct treatment to ongoing psychopharmacotherapy, both in unipolar and bipolar difficult-to-treat depressed (DTD) outpatients.

METHODS:In an open-label study, 31 depressed outpatients (16 unipolar and 15 bipolar) were included to undergo 3 weeks of BLT. Twenty-five completed the treatment and 5-week follow-up.

MAIN OUTCOME MEASURES:Clinical outcomes were evaluated by the Hamilton Depression Rating Scale (HDRS). The Snaith-Hamilton Pleasure Scale and the Depression Retardation Rating Scale were used to assess changes in anhedonia and psychomotor retardation, respectively.

RESULTS:The adjunctive BLT seemed to influence the course of the depressive episode, and a statistically significant reduction in HDRS scores was reported since the first week of therapy. The treatment was well-tolerated, and no patients presented clinical signs of (hypo)manic switch during the overall treatment period. At the end of the study (after 5 weeks from BLT discontinuation), nine patients (36%, eight unipolar and one bipolar) still showed a treatment response. BLT augmentation also led to a significant improvement of psychomotor retardation.

CONCLUSION:BLT combined with the ongoing pharmacological treatment offers a simple approach, and it might be effective in rapidly ameliorating depressive core symptoms of vulnerable DTD outpatients. These preliminary results need to be confirmed in placebo-controlled, randomized, double-blind clinical trial on larger samples.