Ketogenic Diet: A Dietary Modification as an Anxiolytic Approach?

Anxiety disorders comprise persistent, disabling conditions that are distributed across the globe, and are associated with the high medical and socioeconomic burden of the disease. Within the array of biopsychosocial treatment modalities-including monoaminergic antidepressants, benzodiazepines, and CBT-there is an unmet need for the effective treatment of anxiety disorders resulting in full remission and recovery. Nutritional intervention may be hypothesized as a promising treatment strategy; in particular, it facilitates relapse prevention. Low-carbohydrate high-fat diets (LCHF) may provide a rewarding outcome for some anxiety disorders; more research is needed before this regimen can be recommended to patients on a daily basis, but the evidence mentioned in this paper should encourage researchers and clinicians to consider LCHF as a piece of advice somewhere between psychotherapy and pharmacology, or as an add-on to those two.

From probiotics to psychobiotics - the gut-brain axis in psychiatric disorders.

This review aims to present a comprehensive state-of-the-art analysis of the bidirectional crosstalk between gut microbiota and the central nervous system (CNS). The literature concerning the potential effects of gut microbiota on psychiatric disorders through neural pathways comprising the 'gut-brain axis' were gathered. In addition, the influence of probiotics and prebiotics and dairy-rich diets combined with the intake of probiotics and prebiotics on gut microbiota and the subsequent relationship with brain function was reviewed. However, a meta-analysis on the effectiveness of probiotic supplementation in psychiatric disorders is lacking. Therefore, a systematic search of PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases from January 1969 to December 2019 was conducted. It led to the identification of a total of 844 research articles. Of these, a total of 23 studies met the meta-analysis criteria. Statistical analysis revealed that there was no significant difference in the symptoms of schizophrenia, stress, and anxiety between probiotic and placebo groups, post-intervention. Probiotic administration reduced depressive symptoms among patients with depression in a statistically significant manner (standardised mean difference (SMD) = -0.87; 95% confidence interval (95% confidence interval): -1.66, -0.99; P=0.03). Further evidence from larger and more rigorous studies with longer duration of probiotic administration, as well as well-defined populations, homogenous probiotic intervention and outcome measures, are needed to clarify the potential therapeutic effects of probiotics on psychiatric symptoms. Based on the current literature, it seems that not all probiotic-/prebiotic-/dairy-rich diet-based treatments exhibited a psychobiotic effect on the CNS. Among the parameters determining the success of the given treatment, the most significant were probiotic composition (multi-strain formulation), the quantity of ingested psychobiotics and the duration of the study.

Fermented foods, the gut and mental health: a mechanistic overview with implications for depression and anxiety.

Mental disorders including depression and anxiety are often comorbid with gut problems, suggesting a bidirectional relationship between mental health and gut function. Several mechanisms might explain this comorbidity, such as inflammation and immune activation; intestinal permeability; perturbations in the hypothalamic-pituitary-adrenal axis; neurotransmitter/neuropeptide dysregulation; dietary deficiencies; and disturbed gut microbiome composition. The potential of modulating the microbiome-gut-brain axis, and subsequently mental health, through the use of functional foods, is an emerging and novel topic of interest. Fermented foods are considered functional foods due to their putative health benefits. The process of microbial fermentation converts food substrates into more nutritionally and functionally rich products, resulting in functional microorganisms (probiotics), substrates that enhance proliferation of beneficial bacteria in the gut (prebiotics), and bioactive components (biogenics). These functional ingredients act biologically in the gastrointestinal tract and have the ability to modify the gut microbiota, influence translocation of endotoxins and subsequent immune activation, and promote host nutrition. This narrative review explores the theoretical potential of the functional components present in fermented foods to alter gut physiology and to impact the biological mechanisms thought to underpin depression and anxiety. Pre-clinical studies indicate the benefits of fermented foods in relieving perturbed gut function and for animal models of depression and anxiety. However, in humans, the literature relating to the relevance of fermented food for treating or preventing depression and anxiety is sparse, heterogeneous and has significant limitations. This review identifies a critical research gap for further evaluation of fermented foods in the management of depression anxiety in humans.

Adherence to the MIND diet and prevalence of psychological disorders in adults.

BACKGROUND: There is no study that examined the association of the MIND diet and odds of psychological disorders. We investigated the association between adherence to the MIND diet and odds of psychological disorders. METHODS: A total of 3176 adults were included in this cross-sectional study. Dietary intakes of study participants were collected using a validated dish-based 106-item semi-quantitative food frequency questionnaire (DS-FFQ). The MIND diet score was calculated based on participants' dietary intakes obtained from DS-FFQ. To assess depression and anxiety, the Iranian validated version of Hospital Anxiety and Depression Scale (HADS) was used. Psychological distress was examined using General Health Questionnaire (GHQ). RESULTS: After taking potential confounders into account, participants in the highest quartile of the MIND diet score had a lower odds of depression (OR: 0.68; 95% CI: 0.53-0.89) and psychological distress (OR: 0.68; 95% CI: 0.52-0.89) than those in the lowest quartile. No significant association was observed between consumption of MIND diet and odds of anxiety (OR: 0.72; 95% CI: 0.51-1.03). When we did gender-stratified analyses, no significant association was seen between adherence to the MIND diet and odds of psychological disorders in men; however, women in the top quartile of the MIND diet score had lower odds of depression (OR: 0.60; 95% CI: 0.45-0.81) and psychological distress (OR: 0.66; 95% CI: 0.48-0.90) than those in the bottom quartile. CONCLUSION: We found that greater adherence to the MIND diet was inversely associated with odds of depression and psychological distress. No significant association was observed between consumption of MIND diet and odds of anxiety.

Prebiotics and probiotics for depression and anxiety: A systematic review and meta-analysis of controlled clinical trials.

With growing interest in the gut microbiome, prebiotics and probiotics have received considerable attention as potential treatments for depression and anxiety. We conducted a random-effects meta-analysis of 34 controlled clinical trials evaluating the effects of prebiotics and probiotics on depression and anxiety. Prebiotics did not differ from placebo for depression (d = -.08, p = .51) or anxiety (d = .12, p = .11). Probiotics yielded small but significant effects for depression (d = -.24, p < .01) and anxiety (d = -.10, p = .03). Sample type was a moderator for probiotics and depression, with a larger effect observed for clinical/medical samples (d = -.45, p < .001) than community ones. This effect increased to medium-to-large in a preliminary analysis restricted to psychiatric samples (d = -.73, p < .001). There is general support for antidepressant and anxiolytic effects of probiotics, but the pooled effects were reduced by the paucity of trials with clinical samples. Additional randomized clinical trials with psychiatric samples are necessary fully to evaluate their therapeutic potential.

The Effects of Dietary Improvement on Symptoms of Depression and Anxiety: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Poor diet can be detrimental to mental health. However, the overall evidence for the effects of dietary interventions on mood and mental well-being has yet to be assessed. We conducted a systematic review and meta-analysis examining effects of dietary interventions on symptoms of depression and anxiety. METHODS: Major electronic databases were searched through March 2018 for all randomized controlled trials of dietary interventions reporting changes in symptoms of depression and/or anxiety in clinical and nonclinical populations. Random-effects meta-analyses were conducted to determine effect sizes (Hedges' g with 95% confidence intervals [CI]) for dietary interventions compared with control conditions. Potential sources of heterogeneity were explored using subgroups and meta-regression analyses. RESULTS: Results: Sixteen eligible randomized controlled trials (published in English) with outcome data for 45,826 participants were included; the majority of which examined samples with nonclinical depression (n = 15 studies). Nonetheless, dietary interventions significantly reduced depressive symptoms (g = 0.162, 95% CI = 0.055 to 0.269, p = 0.003). Similar effects were observed among high-quality trials (g = 0.171, 95% C.I.=0.057 to 0.286, p=0.003) and when compared with both inactive (g = 0.114, 95% C.I.=0.008 to 0.219, p=0.035) and active controls (g = 0.224, 95% C.I.= 0.052 to 0.397, p = 0.011). No effect of dietary interventions was observed for anxiety (k = 11, n = 2270, g = 0.085, 95% C.I. = -0.031 to 0.202, p=0.151). Studies with female samples observed significantly greater benefits from dietary interventions, for symptoms of both depression and anxiety. CONCLUSIONS: Dietary interventions hold promise as a novel intervention for reducing symptoms of depression across the population. Future research is required to determine the specific components of dietary interventions that improve mental health, explore underlying mechanisms, and establish effective schemes for delivering these interventions in clinical and public health settings. REGISTRATION: PROSPERO Online Protocol: CRD42018091256.

Examining Parental Medication Adherence as a Predictor of Child Medication Adherence in Pediatric Anxiety Disorders.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are the recommended first-line pharmacotherapy for pediatric anxiety disorders but adherence remains difficult to predict. OBJECTIVES: To estimate SSRI adherence in children with anxiety disorders and determine if prior parental medication adherence is predictive of child high SSRI adherence. METHODS: We identified children (3-17 y) initiating SSRI treatment after an anxiety disorder diagnosis in a commercial claims database (2005-2014). We evaluated parent SSRI, statin, and antihypertensive adherence [6-mo proportion days covered (PDC), high adherence=PDC≥0.80] in the year before child SSRI initiation. We estimated risk differences (RD) of child high SSRI adherence (6-mo PDC) stratified by parent adherence and multivariable risk ratios using modified Poisson regression. We estimated change in c-statistic and risk reclassification when adding parent-level covariates with child-level covariates to predict child adherence. RESULTS: In 70,979 children with an anxiety disorder (59%=female, 14=median age), the mean 6-month SSRI PDC was 0.72, with variation by anxiety disorder. Overall 64% of children had high adherence if their parent had high SSRI adherence versus 53% of children with parents with low SSRI adherence (RD, 12%; multivariable risk ratios, 1.17; 95% confidence interval, 1.14-1.20). Findings were similar for parent statin (RD=10%) and antihypertensive adherence (RD=8%) and when stratified by child age and parent sex. There was minor improvement in risk reclassification and the c-statistic after adding parent adherence and parent-level covariates. CONCLUSIONS: Parental medication adherence could help providers identify children at risk of nonadherence to inform the treatment decision, reduce unnecessary medication switches, and lead to broader effective interventions.

Mechanisms underlying the effects of n-3 polyunsaturated fatty acids on fear memory processing and their hypothetical effects on fear of cancer recurrence in cancer survivors.

The relationship of n-3 polyunsaturated fatty acids (PUFAs) and gut microbiota with brain function has been extensively reported. Here, we review how n-3 polyunsaturated fatty acids affect fear memory processing. n-3 PUFAs may improve dysfunctional fear memory processing via immunomodulation/anti-inflammation, increased BDNF, upregulated adult neurogenesis, modulated signal transduction, and microbiota-gut-brain axis normalization. We emphasize how n-3 PUFAs affect this axis and also focus on the hypothetical effects of PUFAs in fear of cancer recurrence (FCR), the primary psychological unmet need of cancer survivors. Its pathophysiology may be similar to that of post-traumatic stress disorder (PTSD), which involves dysfunctional fear memory processing. Due to fewer adverse effects than psychotropic drugs, nutritional interventions involving n-3 PUFAs should be acceptable for physically vulnerable cancer survivors. We are currently studying the relationship of FCR with n-3 PUFAs and gut microbiota in cancer survivors to provide them with a nutritional intervention that protects against FCR.

Nutritional supplements in Anxiety Disorder.

In recent years, a direct relation between the occurrence of anxiety disorders, sleep disturbances, and mood disorders has been observed as a consequence of poor or inadequate diet. Eating habits in Western societies have greatly changed in recent decades, with an increase in the consumption of foods low in vitamin and mineral content, high in caloric value, and rapidly prepared and easily consumed. It may be that the new lifestyles that directly affect family organization and planning interfere with following a proper diet. However, with increasing frequency, especially among young adults, there is interest in healthy and balanced nutrition, as well as learning culinary techniques. We reviewed the literature for this study, and describe the concept of anxiety and its existence in relation to dietary disorders, as well as alternatives for the treatment of these symptoms. The characteristics of these disorders and their impact on patients are analyzed. The information used in this work was obtained mainly from PubMed, PsycARTICLES, PsycCRITIQUES, and PsycINFO. It was retrieved using the keywords “mental health”, “nutrition”, “diet”, “phytotherapy”, “natural alternatives”, “anxiety”, “mood”, and “sleep disturbance”.

A comparison of structural connectivity in anxious depression versus non-anxious depression.

BACKGROUND: Major depressive disorder (MDD) and anxiety disorders are highly co-morbid. Research has shown conflicting evidence for white matter alteration and amygdala volume reduction in mood and anxiety disorders. To date, no studies have examined differences in structural connectivity between anxious depressed and non-anxious depressed individuals. This study compared fractional anisotropy (FA) and density of selected white matter tracts and amygdala volume between anxious depressed and non-anxious depressed individuals. METHODS: 64- direction DTI and T1 scans were collected from 110 unmedicated subjects with MDD, 39 of whom had a co-morbid anxiety disorder diagnosis. Region of interest (ROI) and tractography methods were performed to calculate amygdala volume and FA in the uncinate fasciculus, respectively. Diffusion connectometry was performed to identify whole brain group differences in white matter health. Correlations were computed between biological and clinical measures. RESULTS: Tractography and ROI analyses showed no significant differences between bilateral FA values or bilateral amygdala volumes when comparing the anxious depressed and non-anxious depressed groups. The diffusion connectometry analysis showed no significant differences in anisotropy between the groups. Furthermore, there were no significant relationships between MRI-based and clinical measures. CONCLUSION: The lack of group differences could indicate that structural connectivity and amygdalae volumes of those with anxious-depression are not significantly altered by a co-morbid anxiety disorder. Improving understanding of anxiety co-morbid with MDD would facilitate development of treatments that more accurately target the underlying networks.

Epigenetic and genetic variants in the HTR1B gene and clinical improvement in children and adolescents treated with fluoxetine.

The serotonin 1B receptor (5-HT1B) is important to both the pathogenesis of major depressive disorder and the antidepressant effects of selective serotonin reuptake inhibitors. Although fluoxetine has been shown to be effective and safe in children and adolescents, not all patients experience a proper clinical response, which has led to further study into the main factors involved in this inter-individual variability. Our aim was to study the effect of epigenetic and genetic factors that could affect 5-hydroxytryptamine receptor 1B (HTR1B) gene expression, and thereby response to fluoxetine. A total of 83 children and adolescents were clinically assessed 12weeks after of initiating an antidepressant treatment with fluoxetine for the first time. We evaluated the influence of single nucleotide polymorphisms (SNPs) specifically located in transcription factor binding sites (TFBSs) on their clinical improvement. A combined genetic analysis considering the significant SNPs together with the functional variant rs130058 previously associated in our population was also performed. Moreover, we assessed, for the first time in the literature, whether methylation levels of the HTR1B promoter region could be associated with the pharmacological response. Two, rs9361233 and rs9361235, were significantly associated with clinical improvement after treatment with fluoxetine. The heterozygous genotype combination analysis showed a negative correlation with clinical improvement. The lowest improvement was experienced by patients who were heterozygous for all three SNPs. Moreover, a negative correlation was found between clinical improvement and the average methylation level of the HTR1B promoter. These results give new evidence for the role of epigenetic and genetic factors which could modulate HTR1B expression in the pharmacological response to antidepressants.

Suplementos nutricionales en el trastorno de ansiedad / Nutritional supplements in Anxiety Disorder

No disponible

The effects of dietary tryptophan on affective disorders.

Using a randomized crossover study design, 25 healthy young adults were examined for differences in anxiety, depression, and mood after consuming a high tryptophan and a low tryptophan diet for 4days each. There was a 2week washout between the diets. A within-subjects analysis of the participants' mood indicated significantly (p<.01) more positive affect scores after consuming a high tryptophan diet as compared to a low tryptophan diet. Negative affect differences between the diets were not statistically significant (p>.05). Also, consuming more dietary tryptophan resulted in (p<.05) less depressive symptoms and decreased anxiety.

Interaction between 5-HTTLPR genotype and cognitive stress vulnerability on sleep quality: effects of sub-chronic tryptophan administration.

BACKGROUND: Abundant evidence suggests that allelic variation in the serotonin transporter-linked polymorphic region (5-HTTLPR) influences susceptibility to stress and its affective consequences due to brain serotonergic vulnerability. Based on recent assumptions, the present study examined whether the 5-HTTLPR genotype may also interact with a vulnerability to chronic stress experience (conceptualized by trait neuroticism) in order to influence sleep quality and, additionally, whether this is influenced by brain serotonergic manipulations. METHODS: In a well-balanced experimental design, homozygous S-allele (n = 57) and L-allele (n = 54) genotypes with high and low chronic stress vulnerability (neuroticism) were first assessed for general past sleep quality during a month before onset of the experiment. Then subjects were assessed for sleep quality following 7 days of tryptophan (3.0g/day) or placebo intake. RESULTS: Although high neuroticism was significantly related to a higher frequency of stressful life events and daily hassles, it did not interact with the 5-HTTLPR genotype on general past sleep quality. However, as expected, a 7 day period of tryptophan administration was exclusively associated with better sleep quality scores in the S'/S' genotype with high trait neuroticism. CONCLUSIONS: Current findings suggest that 5-HTTLPR does not directly interact with stress vulnerability in order to influence sleep quality. Instead, based on current and previous findings, it is suggested that the S'/S' 5-HTTLPR genotype promotes the risk for stress-related sleep disturbances because of an increased susceptibility to the depressogenic consequences of stress. Accordingly, by way of reducing depressive symptomatology, tryptophan augmentation may particularly improve sleep quality in stress-vulnerable individuals carrying the 5-HTTLPR S-allele.

Brain membrane lipids in major depression and anxiety disorders.

Major depression and anxiety disorders have high prevalence rates and are frequently comorbid. The neurobiological bases for these disorders are not fully understood, and available treatments are not always effective. Current models assume that dysfunctions in neuronal proteins and peptide activities are the primary causes of these disorders. Brain lipids determine the localization and function of proteins in the cell membrane and in doing so regulate synaptic throughput in neurons. Lipids may also leave the membrane as transmitters and relay signals from the membrane to intracellular compartments or to other cells. Here we review how membrane lipids, which play roles in the membrane's function as a barrier and a signaling medium for classical transmitter signaling, contribute to depression and anxiety disorders and how this role may provide targets for lipid-based treatment approaches. Preclinical findings have suggested a crucial role for the membrane-forming n-3 polyunsaturated fatty acids, glycerolipids, glycerophospholipids, and sphingolipids in the induction of depression- and anxiety-related behaviors. These polyunsaturated fatty acids also offer new treatment options such as targeted dietary supplementation or pharmacological interference with lipid-regulating enzymes. While clinical trials support this view, effective lipid-based therapies may need more individualized approaches. Altogether, accumulating evidence suggests a crucial role for membrane lipids in the pathogenesis of depression and anxiety disorders; these lipids could be exploited for improved prevention and treatment. This article is part of a Special Issue entitled Brain Lipids.

The impact of whole-of-diet interventions on depression and anxiety: a systematic review of randomised controlled trials.

OBJECTIVE: Non-pharmacological approaches to the treatment of depression and anxiety are of increasing importance, with emerging evidence supporting a role for lifestyle factors in the development of these disorders. Observational evidence supports a relationship between habitual diet quality and depression. Less is known about the causative effects of diet on mental health outcomes. Therefore a systematic review was undertaken of randomised controlled trials of dietary interventions that used depression and/or anxiety outcomes and sought to identify characteristics of programme success. DESIGN: A systematic search of the Cochrane, MEDLINE, EMBASE, CINAHL, PubMed and PyscInfo databases was conducted for articles published between April 1971 and May 2014. RESULTS: Of the 1274 articles identified, seventeen met eligibility criteria and were included. All reported depression outcomes and ten reported anxiety or total mood disturbance. Compared with a control condition, almost half (47%) of the studies observed significant effects on depression scores in favour of the treatment group. The remaining studies reported a null effect. Effective dietary interventions were based on a single delivery mode, employed a dietitian and were less likely to recommend reducing red meat intake, select leaner meat products or follow a low-cholesterol diet. CONCLUSIONS: Although there was a high level of heterogeneity, we found some evidence for dietary interventions improving depression outcomes. However, as only one trial specifically investigated the impact of a dietary intervention in individuals with clinical depression, appropriately powered trials that examine the effects of dietary improvement on mental health outcomes in those with clinical disorders are required.

Análisis de la mejora de la calidad del sueño y la ansiedad en estudiantes universitarios, bajo estrés, mediante el consumo de cerveza sin alcohol / Analysis of improved sleep quality and anxiety in college students under stress by consuming non-alcoholic beer

Fundamentos: La cerveza sin alcohol es una bebida saludable. Esta contiene lúpulo que junto a sus polifenoles: myrcenol y xanthumol aportan a la cerveza propiedades sedantes. Nuestro objetivo es determinar la influencia de la cerveza sin alcohol sobre la ansiedad y la calidad del sueño nocturno, en una población de estudiantes sometidos a estrés. Métodos: Se reclutó una población de 31 estudiantes. Se les analizó el sueño mediante Activimetría por Actiwatch®, durante 3 semanas. Y se les realizaron el Cuestionario de sueño Pittsburgh y Cuestionario de ansiedad STAI. Las 2 últimas semanas se ingirió una cerveza sin alcohol en la cena. Resultados: En Activimetría se mostraron diferencias significativas (p<0,05) en cuanto a la disminución de la Latencia de sueño tras la ingesta de cerveza sin alcohol (16,67±17,62 min), frente al grupo control (22,19±21,34 min). También se observaron diferencias en el Cuestionario de sueño Pittsburgh, siendo estadísticamente significativas en la segunda semana de tratamiento (7,07±4,37) frente a la Semana Control (9,03±6,31). Además del Cuestionario de Ansiedad/Estado STAI, que mostró disminución. Conclusión: La Latencia de sueño analizada por Activimetría mejora tras la toma de una cerveza sin alcohol en la cena. El Índice de sueño de Pittsburgh constata dicha mejoría en el sueño nocturno. Así como la disminución de la Ansiedad/Estado por STAI (AU)

Introduction: Non-alcoholic beer it is a healthy beverage. Its contains hop, and polyphenols: myrcenol and xanthoumol giving beer sedative properties. Our aim is to determine the influence of non-alcoholic beer on anxiety and sleep quality in a student population under stress. Methods: A population of 31 students. Sleep data were collected through Actimetry (Actiwatch®) for 3 weeks. Participants filled out the Pittsburgh Sleep Questionnaire and STAI Anxiety Questionnaire. Last 2 weeks volunteers ingested a non-alcoholic beer at dinner. Results: Results showed significant differences (p<0.05) of reduction in Sleep latency after ingesting non-alcoholic beer (16.67±17.62 min) versus the control group (22.19±21.34 min). Statistically significant differences were showed in the Pittsburgh Sleep Questionnaire in the second week of treatment (7.07±4.37) compared to the Control week (9.03±6.31). Regarding the STAI Anxiety Questionnaire, it was observed a decrease. Conclusion: There is a decrease in Sleep latency after ingesting non-alcoholic beer at dinner. The Pittsburgh Sleep Index found that improvement in nighttime sleep. And the Anxiety/State by the STAI improves (AU)

Dietary inhibitors of monoamine oxidase A.

Inhibition of monoamine oxidase is one way to treat depression and anxiety. The information now available on the pharmacokinetics of flavonoids and of the components of tobacco prompted an exploration of whether a healthy diet (with or without smoking) provides active compounds in amounts sufficient to partially inhibit monoamine oxidase. A literature search was used to identify dietary monoamine oxidase inhibitors, the levels of these compounds in foods, the pharmacokinetics of the absorption and distribution, and tissue levels observed. An estimated daily intake and the expected tissue concentrations were compared with the measured efficacies of the compounds as inhibitors of monoamine oxidases. Norharman, harman and quercetin dietary presence, pharmacokinetics, and tissue levels were consistent with significant levels reaching neuronal monoamine oxidase from the diet or smoking; 1,2,3,4-tetrahydroisoquinoline, eugenol, 1-piperoylpiperidine, and coumarin were not. Quercetin was equipotent with norharman as a monoamine oxidase A inhibitor and its metabolite, isorhamnetin, also inhibits. Total quercetin was the highest of the compounds in the sample diet. Although bioavailability was variable depending on the source, a healthy diet contains amounts of quercetin that might give sufficient amounts in brain to induce, by monoamine oxidase A inhibition, a small decrease in neurotransmitter breakdown.