Biology of Perseverative Negative Thinking: The Role of Timing and Folate Intake.

Past-oriented rumination and future-oriented worry are two aspects of perseverative negative thinking related to the neuroticism endophenotype and associated with depression and anxiety. Our present aim was to investigate the genomic background of these two aspects of perseverative negative thinking within separate groups of individuals with suboptimal versus optimal folate intake. We conducted a genome-wide association study in the UK Biobank database (n = 72,621) on the "rumination" and "worry" items of the Eysenck Personality Inventory Neuroticism scale in these separate groups. Optimal folate intake was related to lower worry, but unrelated to rumination. In contrast, genetic associations for worry did not implicate specific biological processes, while past-oriented rumination had a more specific genetic background, emphasizing its endophenotypic nature. Furthermore, biological pathways leading to rumination appeared to differ according to folate intake: purinergic signaling and circadian regulator gene ARNTL emerged in the whole sample, blastocyst development, DNA replication, and C-C chemokines in the suboptimal folate group, and prostaglandin response and K+ channel subunit gene KCNH3 in the optimal folate group. Our results point to possible benefits of folate in anxiety disorders, and to the importance of simultaneously taking into account genetic and environmental factors to determine personalized intervention in polygenic and multifactorial disorders.

Anxiolytic effect of chronic intake of supplemental magnesium chloride in rat.

Evidence suggest that magnesium dietary supplementation has several health benefits including lowering blood pressure, reducing insulin resistance, and improving symptoms of depression, anxiety, and migraine. Here, we aimed to study the effect of chronic magnesium supplementation on anxiety-like behavior in rats by supplementing with magnesium their drinking water for 30 days. Anxiety-like behavior was induced by subcutaneous injection of veratrin 30 min before performing elevated plus maze and open field tests to measure anxiety levels and locomotion, respectively. We quantify the concentration of magnesium in plasma and cerebrospinal fluid. We used diazepam to compare the efficacy of magnesium supplementation as an anxiolytic agent. Our results show that rats supplemented with magnesium had a statistically significant decrease in anxiety levels with not effects on locomotion and a statistically significant increase in concentration of magnesium in plasma and cerebrospinal fluid. However, the anxiolytic effect of magnesium supplementation washes-out in 12 days. We discuss the advantages of using supplemental magnesium as anxiolytic.

Obesity Prevents S-Adenosylmethionine-Mediated Improvements in Age-Related Peripheral and Hippocampal Outcomes.

BACKGROUND: Age predisposes individuals to a myriad of disorders involving inflammation; this includes stress-related neuropsychiatric disorders such as depression and anxiety, and neurodegenerative diseases. Obesity can further exacerbate these effects in the brain. We investigated whether an inexpensive dietary supplement, s-adenosylmethionine (SAMe), could improve age- and/or obesity-related inflammatory and affective measures in the hippocampus. METHODS: Mice were placed on their diets at six weeks of age and then aged to 14 months, receiving SAMe (0.1 g/kg of food) for the final six weeks of the experiment. Prior to tissue collection, mice were tested for anxiety-like behaviors in the open field test and for metabolic outcomes related to type 2 diabetes. RESULTS: SAMe treatment significantly improved outcomes in aged control mice, where fasting glucose decreased, liver glutathione levels increased, and hippocampal microglia morphology improved. SAMe increased transforming growth factor ß-1 mRNA in both control mice, potentially accounting for improved microglial outcomes. Obese mice demonstrated increased anxiety-like behavior, where SAMe improved some, but not all, open field measures. CONCLUSIONS: In summary, SAMe boosted antioxidant levels, improved diabetic measures, and hippocampal inflammatory and behavioral outcomes in aged mice. The effects of SAMe in obese mice were more subdued, but it could still provide some positive outcomes for obese individuals dealing with anxiety and having difficulty changing their behaviors to improve health outcomes.

Broad spectrum micronutrient formulas for the treatment of symptoms of depression, stress, and/or anxiety: a systematic review.

Introduction: Vitamin and mineral nutritional supplements are becoming increasingly popular as alternative treatments for anxiety and depression, as issues such as side effects from medication, failure to respond to psychotherapy and workforce limitations pose barriers for successful treatment.Areas covered: This review covered double-blind, randomized controlled trials (DBRCTs) testing formulas including at least four vitamins and/or minerals used for the treatment of symptoms of anxiety, stress, or depression in adults not currently taking medication for psychiatric difficulties.Expert opinion: The majority of the 23 trials reviewed were conducted on people without psychological difficulties, limiting the generalizability of the results in people with diagnosed mood and anxiety difficulties. Sixteen studies demonstrated positive effects for symptoms of anxiety, depression, or stress. Micronutrient supplementation in healthy nonclinical adults has limited benefits for mood and anxiety symptoms, although may convey some subtle general improvements. The evidence for adults with physical or mental ill health is more positive although limited by small samples and variability in nutrients studied. Broad-spectrum nutrient products may be more effective than a selected few. While an effect of micronutrients cannot be dismissed, the variability of the studies makes it extremely challenging to identify specific treatment benefits.

The Impact of Coconut Oil and Epigallocatechin Gallate on the Levels of IL-6, Anxiety and Disability in Multiple Sclerosis Patients.

BACKGROUND: Due to the inflammatory nature of multiple sclerosis (MS), interleukin 6 (IL-6) is high in blood levels, and it also increases the levels of anxiety related to functional disability. Epigallocatechin gallate (EGCG) decreases IL-6, which could be enhanced by the anti-inflammatory effect of high ketone bodies after administering coconut oil (both of which are an anxiolytic). Therefore, the aim of this study was to assess the impact of coconut oil and EGCG on the levels of IL-6, anxiety and functional disability in patients with MS. METHODS: A pilot study was conducted for four months with 51 MS patients who were randomly divided into an intervention group and a control group. The intervention group received 800 mg of EGCG and 60 mL of coconut oil, and the control group was prescribed a placebo. Both groups followed the same isocaloric Mediterranean diet. State and trait anxiety were determined before and after the study by means of the State-Trait Anxiety Inventory (STAI). In addition, IL-6 in serum was measured using the ELISA technique and functional capacity was determined with the Expanded Disability Status Scale (EDSS) and the body mass index (BMI). RESULTS: State anxiety and functional capacity decreased in the intervention group and IL-6 decreased in both groups. CONCLUSIONS: EGCG and coconut oil improve state anxiety and functional capacity. In addition, a decrease in IL-6 is observed in patients with MS, possibly due to the antioxidant capacity of the Mediterranean diet and its impact on improving BMI.

Strain specific stress-modulating effects of candidate probiotics: A systematic screening in a mouse model of chronic restraint stress.

BACKGROUND: Changes in the gut microbiota have been implicated in mood and cognition. In rodents, supplementation with certain bacteria have been shown to alleviate adverse effects of stress on gut microbiota composition and behaviour, but little is known of how the performance of different strains compare to each other. We took a systematic approach to test the efficacy of twelve candidate probiotic strains from ten species/sub-species of Bifidobacterium and Lactobacillus on behaviours and neuroendocrine responses of chronically stressed mice. METHODS: The strains were tested in four screening experiments with non-stressed and chronically stressed vehicle groups. The three most efficacious strains were re-tested to validate the results. Mice were administered a daily oral gavage containing either 1 × 109 colony forming units (CFU) of selected candidate probiotic or saline solution for one week prior to and for three weeks during daily chronic restraint stress. Behavioural tests including the elevated plus maze, open field, novel object recognition, and forced swim test were applied during week five. Corticosterone and adrenocorticotropic hormone (ACTH) were analysed to measure the neuroendocrine response to stress. Plasma and tissue samples were collected for biomarker analyses. RESULTS: Of the twelve candidate probiotics, Lactobacillus paracasei Lpc-37, Lactobacillus plantarum LP12407, Lactobacillus plantarum LP12418 and Lactobacillus plantarum LP12151 prevented stress-associated anxiety and depression-related behaviours from developing compared with chronically stressed vehicle mice. In addition, Lpc-37 improved cognition. CONCLUSION: This systematic screening indicates species- and strain-dependent effects on behavioural outcomes related to stress and further suggests that strains differ from each other in their effects on potential mechanistic outcomes.

Omega-3 fatty acids and anxiety: A systematic review of the possible mechanisms at play.

Introduction: Anxiety is prevalent, costly, and associated with significant adverse outcomes. The importance of nutrition is underestimated in the management of mental health disorders. In particular, omega-3 fatty acids (ω-3 FAs) are a critical component for healthy development and have been shown to reduce anxiety symptoms. Objective: This paper reviews the current state of the research to identify potential mechanisms underlying the relationship between ω-3 FAs and anxiety reduction. Method: Studies were identified using PubMed, PsycINFO, and CINAHL databases. Results: Of the 197 full-text studies screened, six met criteria for inclusion. Four mechanisms were identified based on primary outcomes reported by each study, Inflammatory Response, Brain-Derived Neurotrophic Factor (BDNF), Cortisol, and Cardiovascular Activity. Conclusion: Five key recommendations are provided to guide future research examining ω-3 FAs and anxiety. They include: (1) standardization of dosage and duration of ω-3 supplementation, (2) more rigorous measurement of variables, (3) effective blinding of participants, (4) designing experiments that test mediation, and (5) increasing sample diversity.

Choline Supplementation Ameliorates Behavioral Deficits and Alzheimer's Disease-Like Pathology in Transgenic APP/PS1 Mice.

SCOPE: Alzheimer's disease (AD) is a detrimental neurodegenerative disease and has no known effective treatment. The essential nutrient choline potentially plays an important role in cognition. Perinatal choline supplementation (CS) is critical for memory performance. Findings have shown that postnatal choline-containing compounds enhance memory functions in populations with memory impairments. However, whether CS can be targeted to decelerate the progression of AD remains unknown. METHODS AND RESULTS: APP/PS1 mice and their wild-type littermates are fed either a control or CS diet from 2 to 11 months of age. As compared to WT mice, APP/PS1 mice on the control diet are characterized by the reduction in the number of cholinergic neurons in the basal forebrain, reduced cholinergic fiber staining intensity in the amygdala, and reduced hippocampal and cerebral cortical levels of choline and acetylcholine. CS partially prevents these changes and ameliorates cognitive deficits and anxiety. Furthermore, amyloid-ß deposition and microgliosis are decreased in the APP/PS1 mice fed a CS diet. These effects may have been due to inhibition of NLRP3 inflammasome activation and restoration of synapse membrane formation. CONCLUSION: These findings reveal a beneficial effect of CS on AD progression during adulthood and provide a likely therapeutic intervention for AD patients.

Vitamin D as potential antidepressant in outpatients with musculoskeletal pain
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OBJECTIVE: To determine the incidence of vitamin D deficiency, anxiety, and depression disorders in an outpatient population with musculoskeletal pain (MSP), and to evaluate the effects of correcting a vitamin D deficiency on MSP and psychological symptoms. MATERIALS AND METHODS: A total of 261 outpatients with MSP and 100 controls were involved. The Hospital Anxiety and Depression Scale (HADS) was used to assess psychological symptoms. Serum vitamin D was measured. Outpatients with vitamin D insufficiency and deficiency received oral vitamin D supplementation. Pain severity and psychological symptoms were evaluated before and after vitamin D supplementation plus dairy products. RESULTS: Vitamin D deficiency was found in 88.7% of participants in the MSP group and 69% of controls. Clinical anxiety was reported by 38.3% of participants in the MSP group and 9% of controls, while clinical depression was reported by 31.8% of participants in the MSP group and 2% of controls. Multisite pain was significantly and positively associated with anxiety, depression, and pain severity, and was inversely associated with daily calcium intake. Anxiety was inversely associated with vitamin D level, daily calcium intake, and age. A similar pattern was observed for depression. MSP was the most significant independent predictor of anxiety (OR = 7.84) and depression (OR = 5.89). Relative to baseline, all measured outcome parameters significantly improved after vitamin D supplementation plus increased intake of dairy products. CONCLUSION: Low serum vitamin D is associated with MSP along with low calcium intake, depression, and anxiety. Supplementation with vitamin D improved MSP and associated disorders.
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Medium chain triglyceride diet reduces anxiety-like behaviors and enhances social competitiveness in rats.

Medium-chain triglycerides (MCT) are emerging as unique dietary supplements that are potentially relevant for the amelioration of brain dysfunctions. MCT are converted into ketones and free medium chain fatty acids that, in the brain, are highly effective energy sources to mitochondria and potentially less harmful than glucose metabolism to neurons. Given the recently established link between mitochondrial dysfunction and high anxiety and depression, we performed this study to investigate the effectiveness of an MCT-enriched diet to ameliorate anxiety- and depression-related behaviors in rats. Male rats were distributed into groups, according to their anxiety-like behaviors in the elevated plus maze. Each group was given either MCT-supplemented diet or an isocaloric control diet for fifteen days. Starting from the eighth day of diet, rats were exposed to different behavioral tests. MCT-fed rats exhibited reduced anxiety-like behaviors and enhanced social competitiveness, while their coping responses in the forced swim test were not affected by the treatment. When evaluated at the end of the two-week MCT diet, mitochondrial respiration was reduced in the medial prefrontal cortex (mPFC) while unchanged in the nucleus accumbens. In the mPFC, enzymes related to glycolysis and oxidative phosphorylation were also decreased by MCT diet, while proteins controlling glucose and glutamate transport were increased. Altogether, our findings strongly suggest the effectiveness of MCT diet to exert anxiolytic effects. In the brain, our results point to the mPFC as a brain region in which MCT supplementation improves transport and control of energy substrates.

Hyperglycemia elicits anxiety-like behaviors in zebrafish: Protective role of dietary diphenyl diselenide.

Diabetes mellitus (DM) is a chronic metabolic disease that may comorbid with various psychiatric disorders, such as anxiety and depression. The search for effective therapeutics to alleviate hyperglycemia and complications resulting from DM is continuous. Here we investigate the effects of diphenyl diselenide (DD), an organoselenium compound with several pharmacological properties, in a zebrafish model of hyperglycemia. Fish were fed for 74 days with a diet containing 3 mg/Kg DD, a concentration chosen after experiments based in a dose-response curve (DD 1, 2 and 3 mg/Kg) that did not cause overt toxicity (mortality, weight loss and neurobehavioral deficits). In the last 14 days of the experimental period, fish were concomitantly exposed to a glucose solution (111 mM). Afterwards, blood glucose levels, brain selenium (Se) content, and behavioral analysis aiming to assess anxiety-like behaviors and locomotor/exploratory activities were performed. In the novel tank diving test, glucose decreased vertical exploration and fish spent less time in the lit area when tested in the light-dark test, suggesting increased anxiety-like behavior. Moreover, DD decreased blood glucose levels in hyperglycemic fish as well as prevented the development of anxiety-related symptoms. DD diet alone did not change glycemia and behavioral parameters, but increased Se levels in the brain without affecting the cellular viability. Collectively, our findings highlight the growing utility of this zebrafish hyperglycemia model as a valuable strategy for further research in DM field and neuroprotective approaches.

The effects of vitamin D and probiotic co-supplementation on mental health parameters and metabolic status in type 2 diabetic patients with coronary heart disease: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: This study was carried out to evaluate the effects of vitamin D and probiotic co-supplementation on mental health parameters and metabolic status in diabetic people with coronary heart disease (CHD). METHODS: This randomized, double-blind, placebo-controlled trial was carried out among 60 diabetic people with CHD, aged 45-85 years old. Subjects were randomly allocated into two groups to receive either 50,000 IU vitamin D every 2 weeks plus 8 × 109 CFU/g probiotic of Lactocare Zisttakhmir Co (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were obtained at baseline and after the 12-week intervention to determine metabolic profiles. RESULTS: After the 12-week intervention, compared with the placebo, vitamin D and probiotic co-supplementation resulted in significant improvements in beck depression inventory total score (-2.8 ±â€¯3.8 vs. -0.9 ±â€¯2.1, P = 0.01), beck anxiety inventory scores (-2.1 ±â€¯2.3 vs. -0.8 ±â€¯1.4, P = 0.009) and general health questionnaire scores (-3.9 ±â€¯4.1 vs. -1.1 ±â€¯3.4, P = 0.005). Compared with the placebo, vitamin D and probiotic co-supplementation resulted in significant reductions in serum insulin levels (-2.8 ±â€¯3.8 vs. +0.2 ±â€¯4.9 µIU/mL, P = 0.009), homeostasis model of assessment-estimated insulin resistance (-1.0 ±â€¯1.6 vs. -0.1 ±â€¯1.5, P = 0.02), and a significant increase in serum 25-OH-vitamin D (+11.8 ±â€¯5.9 vs. +0.1 ±â€¯1.4 ng/mL, P < 0.001), the quantitative insulin sensitivity check index (+0.03 ±â€¯0.04 vs. -0.001 ±â€¯0.01, P = 0.003) and serum HDL-cholesterol levels (+2.3 ±â€¯3.5 vs. -0.5 ±â€¯3.8 mg/dL, P = 0.004). In addition, changes in serum high sensitivity C-reactive protein (hs-CRP) (-950.0 ±â€¯1811.2 vs. +260.5 ±â€¯2298.2 ng/mL, P = 0.02), plasma nitric oxide (NO) (+1.7 ±â€¯4.0 vs. -1.4 ±â€¯6.7 µmol/L, P = 0.03) and plasma total antioxidant capacity (TAC) (+12.6 ±â€¯41.6 vs. -116.9 ±â€¯324.2 mmol/L, P = 0.03) in the supplemented group were significantly different from the changes in these indicators in the placebo group. CONCLUSIONS: Overall, vitamin D and probiotic co-supplementation after 12 weeks among diabetic people with CHD had beneficial effects on mental health parameters, serum hs-CRP, plasma NO, TAC, glycemic control and HDL-cholesterol levels. CLINICAL TRIAL REGISTRATION NUMBER: http://www.irct.ir: IRCT2017073033941N4.

Comparison of myo-inositol and metformin on mental health parameters and biomarkers of oxidative stress in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Data on comparison of myo-inositol and metformin on mental health parameters and biomarkers of oxidative stress in subjects with polycystic ovary syndrome (PCOS) are scarce. This purpose of this study was to compare of myo-inositol and metformin on mental health parameters and biomarkers of oxidative stress in subjects with PCOS. METHODS: This randomized controlled trial was conducted among 60 subjects diagnosed with PCOS according to the Rotterdam criteria. Subjects were randomly assigned into two groups to intake either myo-inositol (n = 30) or metformin (n = 30) for 12 weeks. Parameters of mental health were recorded at baseline and after the 12-week intervention. Fasting blood samples were obtained at baseline and the end of the study to determine biomarkers of biomarkers of oxidative stress. RESULTS: After the 12-week intervention, changes in beck depression inventory total score (-1.0 ± 1.7 vs. -0.3 ± 0.7, p = 0.03), general health questionnaire scores (-1.7 ± 2.9 vs. -0.5 ± 1.2, p = 0.02), depression anxiety and stress scale scores (-3.9 ± 6.4 vs. -0.9 ± 1.9, p = 0.01) and plasma total antioxidant capacity (TAC) concentrations (+106.1 ± 69.6 vs. +2.1 ± 132.4 mmol/L, p < 0.001) in the myo-inositol group were significantly different from the changes in these indicators in the metformin group. Myo-inositol supplementation for 12 weeks among patients with PCOS did not affect plasma glutathione and malondialdehyde levels. CONCLUSIONS: Overall, our data supported that myo-inositol supplementation for 12 weeks among patients with PCOS had favorable effects on parameters of mental health and plasma TAC levels.

Effects of the prebiotic mannan-oligosaccharide on the stress response of feed deprived zebrafish (Danio rerio).

Feed deprivation has deleterious effects on fish behavior and stress physiology which may susceptible them to disease outbreak. Functional ingredients in diets may substantially impact the physiology and stress responses of host organisms. Here, we hypothesized that the administration of a dietary prebiotic might attenuate the negative influences of feed deprivation on the behavioral profile of anxiety and physiological responses to stress in zebrafish (Danio rerio). Fish were fed with either basal or mannan-oligosaccharide supplemented (0.4% MOS/kg diet) diets, once per day (normal-control: CN, and normal-prebiotic: PN) or once every other day (starved-control: CS, and starved-prebiotic: PS) for 8weeks. Afterwards, fish were subjected to a novel tank test to measure anxiety. Fish from the CS treatment exhibited more pronounced bottom-dwelling behavior than the other treatments. The number of transitions from the bottom to the top third of the novel tank was significantly higher in PN fish than the CS specimens. No significant differences were found between the CN and PS treatments in all of the anxiety behaviors. CS fish showed higher baseline cortisol levels than the other treatments, which was in line with higher expression of CRH gene in fish subjected to this treatment. Cortisol levels and CRH gene expression of the subjects were also measured after induction of two routine aquaculture stressors. CN and PS fish exhibited similar patterns of cortisol responses at most of the sampling times after stress, and PN specimens showed a significantly lower concentration of cortisol than the other treatments in most cases. Expression of the CRH gene was higher in feed deprived fish immediately after stress induction. Overall, the results show that feed deprivation in some cases influenced anxiety-like behaviors and elevated stress response in zebrafish juveniles; however, the addition of MOS to the diet helped deprived fish exhibit behaviors more typical of normally fed animals.

A double-blind, randomized, placebo-controlled trial of Lactobacillus helveticus and Bifidobacterium longum for the symptoms of depression.

OBJECTIVES: This trial investigated whether probiotics improved mood, stress and anxiety in a sample selected for low mood. We also tested whether the presence or severity of irritable bowel syndrome symptoms, and levels of proinflammatory cytokines, brain-derived neurotrophic factor and other blood markers, would predict or impact treatment response. METHOD: Seventy-nine participants (10 dropouts) not currently taking psychotropic medications with at least moderate scores on self-report mood measures were randomly allocated to receive either a probiotic preparation (containing Lactobacillus helveticus and Bifidobacterium longum) or a matched placebo, in a double-blind trial for 8 weeks. Data were analysed as intent-to-treat. RESULTS: No significant difference was found between the probiotic and placebo groups on any psychological outcome measure (Cohen's d range = 0.07-0.16) or any blood-based biomarker. At end-point, 9 (23%) of those in the probiotic group showed a ⩾60% change on the Montgomery-Åsberg Depression Rating Scale (responders), compared to 10 (26%) of those in the placebo group ([Formula: see text], p = ns). Baseline vitamin D level was found to moderate treatment effect on several outcome measures. Dry mouth and sleep disruption were reported more frequently in the placebo group. CONCLUSIONS: This study found no evidence that the probiotic formulation is effective in treating low mood, or in moderating the levels of inflammatory and other biomarkers. The lack of observed effect on mood symptoms may be due to the severity, chronicity or treatment resistance of the sample; recruiting an antidepressant-naive sample experiencing mild, acute symptoms of low mood, may well yield a different result. Future studies taking a preventative approach or using probiotics as an adjuvant treatment may also be more effective. Vitamin D levels should be monitored in future studies in the area. The results of this trial are preliminary; future studies in the area should not be discouraged.

Dietary omega-3 polyunsaturated fatty acid supplementation in an animal model of anxiety.

A large body of evidence suggests that dietary supplementation with omega-3 fatty acids may ameliorate depressed mood. The magnitude of the effect varies between studies, however, ranging from none at all to being of clinical significance. Given that substantial comorbidity occurs between mood and anxiety disorders, suggesting that they have one or more pathophysiological mechanisms in common, we hypothesized that omega-3 fatty acids may be acting primarily to reduce anxiety rather than depression per se, a possibility which could underlie their variable effects on mood. To test this hypothesis rats were fed for 8 weeks with diets containing one of three types of omega-3 fatty acids, alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid, as well as a low omega-3 fatty acid control diet. Although brain omega-3 fatty acid concentrations were altered by dietary supplementation with eicospentaenoic acid and docosahexaenoic acid, no significant change in anxiety related behaviors were observed compared to the control group as assessed by the elevated-plus maze test. Our data therefore do not support an anxiolytic effect of omega-3 fatty acids and suggest that any effect of these lipids on mood likely occurs by a mechanism unrelated to reducing anxiety.

The effects of magnesium supplementation on subjective anxiety.

Experimental studies of anxiety in animal models, and evidence of efficacious outcomes of magnesium (Mg) supplementation in the treatment of acute clinical affective disorders, has increased interest in Mg as a potential novel treatment for symptoms of mild/moderate subjective anxiety. This short review examines the existing evidence for the effects of Mg supplementation on subjective anxiety in humans. Additionally, evidence from three unpublished studies that examined Mg and vitamin B6 intake on subjective anxiety is summarised to supplement the existing literature. CONCLUSIONS: The efficacy of Mg in the treatment of anxiety in the mildly anxious and those reporting premenstrual syndrome-related anxiety is suggestive of a beneficial effect of Mg intake. Further randomised controlled trials are warranted to further establish the efficacy of Mg as a novel treatment for subjective anxiety.

Experimental Verification of the Effects on Normal Domestic Cats by Feeding Prescription Diet for Decreasing Stress.

The objective of this study was to evaluate the effects of diet on the feline stress response by measuring plasma and urinary cortisol. A study diet was developed with a unique combination of nutrients that supports the management of stressful situations. The specific formulation of the diet included alpha-casozepine, which is believed to have an anxiolytic effect, and tryptophan supplementation. Tryptophan is the precursor for the synthesis of the neurotransmitter serotonin. Twenty-one indoor cats were fed with the study diet (n = 10) or a control diet (n = 11) for 8 weeks, after which physiological responses were evaluated. The study diet significantly increased the ratio of plasma tryptophan to large neutral amino acids and decreased urinary cortisol concentrations after being consumed daily for 8 weeks, but there was no effect on plasma cortisol levels following a stressful event (veterinary examination and blood draw). Further studies, such as behavioral analyses, are needed to clarify the effects of the study diet.

Effects of a phyto complex on well-being of climacteric women.

AIM: The aim of this study was to assess the effects of a phyto complex on menopausal symptoms. MATERIAL AND METHODS: A total of 151 women aged 42-67 years were enrolled. They were in spontaneous or surgical menopause by at least 12 months, reporting symptoms referable to the climacteric syndrome. Two validated and standardized tests were given to the whole sample at the entrance of the study (T0) and after 6 months of treatment (T6): the Greene Climacteric Scale (GCS) and the Beck Depression Inventory (BDI). Interim evaluations were carried out at 1-3 months (T1 and T3) on five symptoms selected from the GCS. The phyto complex was given to each enrolled woman, from the T0 to T6 time-points, for a total of 180 days. RESULTS: At the T0 time-point, the average scores were: GCS, 28.98 (standard deviation [SD] ± 10.71); BDI, 14.48 (SD ± 6.5). At the T1 time-point, five parameters of the GCS were assessed with a reduction of 36.25% in symptoms (5.69, SD ± 3.53). At the T6 time-point the assessment was completed: average GCS results were 11.54 (SD ± 8.01) with a 60.17% improvement; and average BDI results were 6.11 (SD ± 4.6) with a 58.91% improvement in the depressive symptoms. CONCLUSIONS: The phyto complex under consideration is an effective tool to counter, in a quick and long-lasting manner, the most common and nagging symptoms of the climacteric syndrome, such as hot flushes, insomnia and depression.

Interactive actions of Bdnf methylation and cell metabolism for building neural resilience under the influence of diet.

Quality nutrition during the period of brain formation is a predictor of brain functional capacity and plasticity during adulthood; however it is not clear how this conferred plasticity imparts long-term neural resilience. Here we report that early exposure to dietary omega-3 fatty acids orchestrates key interactions between metabolic signals and Bdnf methylation creating a reservoir of neuroplasticity that can protect the brain against the deleterious effects of switching to a Western diet (WD). We observed that the switch to a WD increased Bdnf methylation specific to exon IV, in proportion to anxiety-like behavior, in Sprague Dawley rats reared in low omega-3 fatty acid diet, and these effects were abolished by the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine. Blocking methylation also counteracted the reducing action of WD on the transcription regulator CTCF binding to Bdnf promoter IV. In vitro studies confirmed that CTCF binding to Bdnf promoter IV is essential for the action of DHA on BDNF regulation. Diet is also intrinsically associated to cell metabolism, and here we show that the switch to WD downregulated cell metabolism (NAD/NADH ratio and SIRT1). The fact that DNA methyltransferase inhibitor did not alter these parameters suggests they occur upstream to methylation. In turn, the methylation inhibitor counteracted the action of WD on PGC-1α, a mitochondrial transcription co-activator and BDNF regulator, suggesting that PGC-1α is an effector of Bdnf methylation. Results support a model in which diet can build an "epigenetic memory" during brain formation that confers resilience to metabolic perturbations occurring in adulthood.