Nutraceuticals in Psychiatric Disorders: A Systematic Review.

Correct nutrition and diet are directly correlated with mental health, functions of the immune system, and gut microbiota composition. Diets with a high content of some nutrients, such as fibers, phytochemicals, and short-chain fatty acids (omega-3 fatty acids), seem to have an anti-inflammatory and protective action on the nervous system. Among nutraceuticals, supplementation of probiotics and omega-3 fatty acids plays a role in improving symptoms of several mental disorders. In this review, we collect data on the efficacy of nutraceuticals in patients with schizophrenia, autism spectrum disorders, major depression, bipolar disorder, and personality disorders. This narrative review aims to provide an overview of recent evidence obtained on this topic, pointing out the direction for future research.

Applying the Stages of Change Model in a Nutrition Education Programme for the Promotion of Fruit and Vegetable Consumption among People with Severe Mental Disorders (DIETMENT).

Despite growing evidence of the benefits of adequate intake of fruit and vegetables (F&V) and the recommendation to consume five servings daily, the adoption of these habits is poor among people with severe mental disorder (SMD). The main aim of the present study is to determine changes in the intake of F&V and motivation to do so among people with SMDs after participating in a food education programme. A community-based randomized controlled trial was conducted in Spain, with the intervention group (IG) participating in a food education programme based on the stages of change model to promote consumption of F&V and the control group (CG) receiving three informative sessions on basic healthy eating. The main outcomes were related to the intake of F&V and stages of change. Data collection was performed at baseline, post intervention, and 12-month follow-up. Seventy-four participants enrolled in the study and sixty completed the 12-month follow-up. An increase in motivation towards the intake of F&V was observed in the IG but not in the CG (McNemar's test p = 0.016, p = 0.625). No significant difference was observed for the intake of fruit, vegetables, or F&V. Basing food education strategies on the stages of change model shows positive results, increasing the awareness and disposition of people with SMD towards the intake of F&V. More research is needed to identify the most appropriate eating intervention to increase the intake of F&V.

Neuro-nutraceutical potential of Asparagus racemosus: A review.

Debilitating neuropsychiatric and neurodegenerative conditions are associated with complex multifactorial pathophysiology. Their treatment strategies often only provide symptomatic relief, delaying disease progression without giving a complete cure. Potent and safer treatment alternatives beyond symptomatic relief are sought. Herbal supplements have surely been explored due to their multiple component nature to enhance the effect of western medications. One such well-documented nutraceutical in the ancient Greek, Chinese, and Ayurvedic medicine system known for its various medicinal benefits is Asparagus racemosus. Widely used for its lactogenic properties, A. racemosus is also cited in Ayurveda as a nervine tonic. A. racemosus based nutraceuticals have shown to possess adaptogenic, neuroprotective, antioxidant, anti-inflammatory, and nootropic activity under preclinical and clinical settings without posing significant adverse effects. A. racemosus extracts restore the perturbed neurotransmitters and prevent oxidative neuronal damage. From the available neuropharmacological researches, the physiological actions of A. racemosus can ultimately be directed for either augmentation of cognitive ability or in the management of neurological conditions such as stress, anxiety, depression, epilepsy, Parkinson's, and Alzheimer's disease. The studies focus on the multi-component extract, and the lack of standardization has been a major hurdle in preventing the allotment of reported neuropharmacological activity to one of the phytoconstituent. Herbal standardization of the plant extract based on a specific biomarker can help elucidate the intricate biomolecular pathway and neurocircuitries being involved. This, followed by rigorous standardized clinical trials, fixing dosages, and determining contraindications would facilitate the translation of A. racemosus to a FDA-approved neuromedicine for neurological disorders.

Gut microbiota-derived vitamins - underrated powers of a multipotent ally in psychiatric health and disease.

Despite the well-established roles of B-vitamins and their deficiencies in health and disease, there is growing evidence indicating a key role of those nutrients in functions of the central nervous system and in psychopathology. Clinical data indicate the substantial role of B-vitamins in various psychiatric disorders, including major depression, bipolar disorder, schizophrenia, autism, and dementia, including Alzheimer's and Parkinson's diseases. As enzymatic cofactors, B-vitamins are involved in many physiological processes such as the metabolism of glucose, fatty acids and amino acids, metabolism of tryptophan in the kynurenine pathway, homocysteine metabolism, synthesis and metabolism of various neurotransmitters and neurohormones including serotonin, dopamine, adrenaline, acetylcholine, GABA, glutamate, D-serine, glycine, histamine and melatonin. Those vitamins are highly involved in brain energetic metabolism and respiration at the cellular level. They have a broad range of anti-inflammatory, immunomodulatory, antioxidant and neuroprotective properties. Furthermore, some of those vitamins are involved in the regulation of permeability of the intestinal and blood-brain barriers. Despite the fact that a substantial amount of the above vitamins is acquired from various dietary sources, deficiencies are not uncommon, and it is estimated that micronutrient deficiencies affect about two billion people worldwide. The majority of gut-resident microbes and the broad range of bacteria available in fermented food, express genetic machinery enabling the synthesis and metabolism of B-vitamins and, consequently, intestinal microbiota and fermented food rich in probiotic bacteria are essential sources of B-vitamins for humans. All in all, there is growing evidence that intestinal bacteria-derived vitamins play a significant role in physiology and that dysregulation of the "microbiota-vitamins frontier" is related to various disorders. In this review, we will discuss the role of vitamins in mental health and explore the perspectives and potential of how gut microbiota-derived vitamins could contribute to mental health and psychiatric treatment.

Psychological comorbidity in gastrointestinal diseases: Update on the brain-gut-microbiome axis.

The high comorbidity of psychological disorders in both functional and organic gastrointestinal diseases suggests the intimate and complex link between the brain and the gut. Termed the brain-gut axis, this bidirectional communication between the central nervous system and enteric nervous system relies on immune, endocrine, neural, and metabolic pathways. There is increasing evidence that the gut microbiome is a key part of this system, and dysregulation of the brain-gut-microbiome axis (BGMA) has been implicated in disorders of brain-gut interaction, including irritable bowel syndrome, and in neuropsychiatric disorders, including depression, Alzheimer's disease, and autism spectrum disorder. Further, alterations in the gut microbiome have been implicated in the pathogenesis of organic gastrointestinal diseases, including inflammatory bowel disease. The BGMA is an attractive therapeutic target, as using prebiotics, probiotics, or postbiotics to modify the gut microbiome or mimic gut microbial signals could provide novel treatment options to address these debilitating diseases. However, despite significant advancements in our understanding of the BGMA, clinical data is lacking. In this article, we will review current understanding of the comorbidity of gastrointestinal diseases and psychological disorders. We will also review the current evidence supporting the key role of the BGMA in this pathology. Finally, we will discuss the clinical implications of the BGMA in the evaluation and management of psychological and gastrointestinal disorders.

Gut microbiota, kynurenine pathway and mental disorders - Review.

The intestine and the gut-associated limphoid tissue constitute the largest immunity organ of the human body. Among several possible tryptophan metabolism routes, the kynurenine pathway can be influenced by the gut microbiota. Disturbances of gut biodiversity may cause increased gut permeability and cause systemic inflammation, also related to central nervous system. Proinflammatory cytokines induce kynurenine pathway enzymes resulting in formation of neuroactive metabolites, which are being associated with several psychiatric disorders. The kynurenine pathway may also be influenced by certain bacteria species directly. The aim of this review is to highlight the current knowledge on the interaction of gut microbiota and the central nervous system with the kynurenine pathway taken into special account. Up to date study results on specific psychiatric disorders such as schizophrenia, bipolar disorder, Alzheimer's disease, autism spectrum disorders, depression and alcoholism are presented. Available evidence suggests that toxicity of kynurenine metabolites may be reduced by adjunction of probiotics which can affect proinflammatory cytokines. Due to their potential for modulation of the kynurenine pathway, gut microbiota pose an interesting target for future therapies.

A systematic review of microbiome changes and impact of probiotic supplementation in children and adolescents with neuropsychiatric disorders.

OBJECTIVES: In recent decades, the diagnostic and therapeutic implications of the microbiome changes and the impact of probiotic supplementation have increased rapidly. However, the potential for clinical translation of microbiome research for children and adolescents with psychiatric disorders is unclear. This review examined available evidence related to gut microbiota as well as the impact of probiotic supplementation on psychiatric disorders in the pediatric population reported to date. METHODS: We performed a literature search for the gut microbiota in child and adolescent population (0-18 years old) with mental health disorders from July 1999 through July 2019 in several databases: ClinicalTrials.gov, Ovid EBM Reviews, Ovid Embase, Ovid Medline, Ovid PsycINFO, Scopus, and Web of Science. RESULTS: A total of 7 studies met inclusion criteria consisting of randomized controlled trials and cohort studies that examined various associations between psychiatric disorders and gut microbiota in youth. Six studies examined the effects of various treatment interventions such as probiotic supplementation on microbiota composition and behaviors. One study showed an increase in prosocial behavior in children with Autism Spectrum Disorder (ASD) and an increase in the Lachnospiraceae family following prebiotic supplementation. Another study suggested that prebiotic supplementation increased bifidobacterial populations for ASD and healthy controls. A study evaluating infant supplementation of prebiotics showed both a decreased likelihood of developing Attention Deficit Hyperactivity Disorder (ADHD) or ASD and decreased gut Bifidobacterium. One study did not find significant differences in microbiome composition after micronutrient treatment. CONCLUSION: The main goal of this systematic review was to comprehensively examine and summarize the current evidence focused on the potential effect of the relationship between microbiota gut composition as well as the effects of probiotic supplementation on psychiatric disorders in children and adolescents. This is a relatively new area of research and the number of included studies is limited. More studies are needed to determine whether gut dysbiosis leads to the development and/or contributes to the severity of mental disorders or whether gut dysbiosis is a result of other processes that accompany mental disorders. CLINICAL SIGNIFICANCE: A better understanding of the specific bacteria contributions, gut-brain pathways, and role in pathophysiological mechanisms in neuropsychiatric disorders in the child and adolescent populations can possibly provide alternative tools for a clinical psychiatrist. Moreover, it may ultimately aid the clinician with intervention strategies, or detect populations at risk for developing neuropsychiatric disorders.

Evaluation of the Prebiotic Potential of a Commercial Synbiotic Food Ingredient on Gut Microbiota in an Ex Vivo Model of the Human Colon.

Behavior and mood disorders have been linked to gut microbiota dysbiosis through the "microbiota-gut-brain axis". Microbiota-targeting interventions are promising therapeutic modalities to restore or even maintain normal microbiome composition and activity in these disorders. Here, we test the impact of a commercial synbiotic formulation on gut microbiota composition and metabolic activity. We employed an ex-vivo continuous fermentation model that simulates the proximal colon to assess the effect of this formulation on microbiota structure and functionality as compared to no treatment control and microcrystalline cellulose as a dietary fiber control. The test formulation did not alter the diversity of gut microbiota over 48 h of treatment. However, it induced the enrichment of Lactobacillus, Collinsella and Erysipelotrichaceae. The test formulation significantly increased the level of microbiota-generated butyrate within 12 h of treatment as compared to 24 h required by microcrystalline cellulose to boost its production. The test formulation did not lead to a significant change in amino acid profiles. These results provide evidence of potential benefits related to synbiotic effects and general gut health and support the potential of this food formulation as a therapeutic dietary intervention in mood and behavior disorders.

Ketogenic diet as a metabolic treatment for mental illness.

PURPOSE OF REVIEW: Ketogenic diets, which have been used to treat drug-refractory paediatric epilepsy for over 100 years, are becoming increasingly popular for the treatment of other neurological conditions, including mental illnesses. We aim to explain how ketogenic diets can improve mental illness biopathology and review the recent clinical literature. RECENT FINDINGS: Psychiatric conditions, such as schizophrenia, depression, bipolar disorder and binge eating disorder, are neurometabolic diseases that share several common mechanistic biopathologies. These include glucose hypometabolism, neurotransmitter imbalances, oxidative stress and inflammation. There is strong evidence that ketogenic diets can address these four fundamental diseases, and now complementary clinical evidence that ketogenic diets can improve the patients' symptoms. SUMMARY: It is important that researchers and clinicians are made aware of the trajectory of the evidence for the implementation of ketogenic diets in mental illnesses, as such a metabolic intervention provides not only a novel form of symptomatic treatment, but one that may be able to directly address the underlying disease mechanisms and, in so doing, also treat burdensome comorbidities (see Video, Supplementary Digital Content 1, http://links.lww.com/COE/A16, which summarizes the contents of this review).

Effectiveness of mandatory peer review to reduce antipsychotic prescriptions for Medicaid-insured children.

BACKGROUND: Prior authorization of prescription medications is a policy tool that can potentially impact care quality and patient safety. OBJECTIVE: To examine the effectiveness of a mandatory peer-review program in reducing antipsychotic prescriptions among Medicaid-insured children, accounting for secular trends that affected antipsychotic prescribing nationally. DATA SOURCE: Medicaid Analytical eXtracts (MAX) with administrative claims for health services provided between January 2006 and December 2011. STUDY DESIGN: This retrospective, observational study examined prescription claims records from Washington State (Washington) and compared them to a synthetic control drawing from 20 potential donor states that had not implemented any antipsychotic prior authorization program or mandatory peer review for Medicaid-insured children during the study period. This method provided a means to control for secular trends by simulating the antipsychotic use trajectory that the program state would have been expected to experience in the absence of the policy implementation. PRINCIPAL FINDINGS: Before the policy implementation, antipsychotic use prevalence closely tracked those of the synthetic control (6.17 per 1000 in Washington vs. 6.21 in the synthetic control group). Within two years after the policy was implemented, prevalence decreased to 4.04 in Washington and remained stable in the synthetic control group (6.47), corresponding to an approximately 38% decline. CONCLUSION: Prior authorization program designs and implementations vary widely. This mandatory peer-review program, with an authorization window and two-stage rollout, was effective in moving population level statistics toward safe and judicious use of antipsychotic medications in children.

Oat bran in cardiovascular risk control in mental disorder.

OBJECTIVE: To evaluate the effect of oat bran supplementation on cardiovascular risk components of patients with mental disorders. METHOD: A before-and-after study, no control group. Cardiovascular risk indicators were assessed at baseline (M0), 90 (M1), 180 days (M2) and 180 days after supplementation (M3). RESULTS: Of the 45 patients admitted to a psychiatric institution using antipsychotics, more than two thirds had high cardiovascular risk assessed by abdominal obesity. Forty-six point seven percent were overweight and 31.1% metabolic syndrome. Oat bran was effective in reducing serum cholesterol (M0-M1), HDL-cholesterol (M1-M2), triglycerides (M1-M2), (M2-M3) and (M1-M3). In M3, there was a statistical difference for all indicators evaluated. CONCLUSION: Oat bran supplementation was effective in improving triglyceride, total cholesterol and HDL-cholesterol levels, suggesting that it is a therapeutic option for cardiovascular risk control in patients with psychiatric disorders.

Mental, emotional, and behavioral effects of ketogenic diet for non-epileptic neuropsychiatric conditions.

Ketogenic diet (KD) is comprised of a distinct macronutrient combination: i.e. 90% fat, 8% of protein and 2% of carbohydrates, typically characterized as a high-fat low-carbohydrate diet. KD's efficacy was largely established for treatment resistant epilepsy in children, but its mental, emotional and behavioral effects remain largely unknown. Nevertheless, the efficacious effects of KD in childhood epilepsy provide rationale for repurposing this approach for other brain-based disorders. Consequently, clinicians and researchers should be aware of the evidence regarding efficacy, as well as the benefits and risks of adopting this diet. Results from animals and humans studies provide equivocal evidence across multiple domains of psychopathology. Conceptually, KD shows promise to serve as an efficacious treatment for mental disorders.

Portion-control intervention for people with serious mental illness: A feasibility study.

PURPOSE: Portion control can be an effective weight-loss strategy for people with serious mental illnesses (SMI). This study aimed to examine the feasibility of portion-control intervention (PCI) for people with SMI. DESIGN AND METHODS: A randomized experimental design was used. The PCI group received weekly, telephone-delivered behavioral counseling over 12 weeks. Newsletter group received monthly newsletters regarding healthy eating. Descriptive statistics were used to analyze data collected at baseline and at 12 weeks. FINDINGS: The acceptability of the PCI and significant decreases in waist circumference among the participants of the PCI group were reported. PRACTICE IMPLICATIONS: Simple and structured guidelines to manage portion size, akin to those featured in our PCI, can benefit those with SMI.

Ketogenic therapy in neurodegenerative and psychiatric disorders: From mice to men.

Ketogenic diet is a low carbohydrate and high fat diet that has been used for over 100 years in the management of childhood refractory epilepsy. More recently, ketogenic diet has been investigated for a number of metabolic, neurodegenerative and neurodevelopmental disorders. In this comprehensive review, we critically examine the potential therapeutic benefits of ketogenic diet and ketogenic agents on neurodegenerative and psychiatric disorders in humans and translationally valid animal models. The preclinical literature provides strong support for the efficacy of ketogenic diet in a variety of diverse animal models of neuropsychiatric disorders. However, the evidence from clinical studies, while encouraging, particularly in Alzheimer's disease, psychotic and autism spectrum disorders, is limited to case studies and small pilot trials. Firm conclusion on the efficacy of ketogenic diet in psychiatric disorders cannot be drawn due to the lack of randomised, controlled clinical trials. The potential mechanisms of action of ketogenic therapy in these disorders with diverse pathophysiology may include energy metabolism, oxidative stress and immune/inflammatory processes. In conclusion, while ketogenic diet and ketogenic substances hold promise pre-clinically in a variety of neurodegenerative and psychiatric disorders, further studies, particularly randomised controlled clinical trials, are warranted to better understand their clinical efficacy and potential side effects.

Induced Ketosis as a Treatment for Neuroprogressive Disorders: Food for Thought?

Induced ketosis (or ketone body ingestion) can ameliorate several changes associated with neuroprogressive disorders, including schizophrenia, bipolar disorder, and major depressive disorder. Thus, the effects of glucose hypometabolism can be bypassed through the entry of beta-hydroxybutyrate, providing an alternative source of energy to glucose. The weight of evidence suggests that induced ketosis reduces levels of oxidative stress, mitochondrial dysfunction, and inflammation-core features of the above disorders. There are also data to suggest that induced ketosis may be able to target other molecules and signaling pathways whose levels and/or activity are also known to be abnormal in at least some patients suffering from these illnesses such as peroxisome proliferator-activated receptors, increased activity of the Kelch-like ECH-associated protein/nuclear factor erythroid 2-related factor 2, Sirtuin-1 nuclear factor-κB p65, and nicotinamide adenine dinucleotide (NAD). This review explains the mechanisms by which induced ketosis might reduce mitochondrial dysfunction, inflammation, and oxidative stress in neuropsychiatric disorders and ameliorate abnormal levels of molecules and signaling pathways that also appear to contribute to the pathophysiology of these illnesses. This review also examines safety data relating to induced ketosis over the long term and discusses the design of future studies.

Mendelian randomisation for nutritional psychiatry.

Nutritional psychiatry is a growing area of research, with several nutritional factors implicated in the cause of psychiatric ill-health. However, nutritional research is highly complex, with multiple potential factors involved, highly confounded exposures and small effect sizes for individual nutrients. This Personal View considers whether Mendelian randomisation provides a solution to these difficulties, by investigating causality in a low-risk and low-cost way. We reviewed studies using Mendelian randomisation in nutritional psychiatry, along with the potential opportunities and challenges of using this approach for investigating the causal effects of nutritional exposures. Several studies have identified nutritional exposures that are potentially causal by using Mendelian randomisation in psychiatry, offering opportunities for further mechanistic research, intervention development, and replication. The use of Mendelian randomisation as a foundation for intervention development facilitates the best use of resources in an emerging discipline in which opportunities are rich, but resources are often poor.

Probiotics and prebiotics: focus on psychiatric disorders - a systematic review.

CONTEXT: The gut-brain axis and microbial dysbiosis may play a role in psychiatric diseases. In this view, the gut microbiota has been considered a potential therapeutic target using probiotics and prebiotics. OBJECTIVE: This systematic review aims to find the existing clinical evidence that may justify the use of probiotics or prebiotics in psychiatric patients. DATA SOURCES: PRISMA guidelines were followed for a systematic literature review of randomized controlled trials that assessed the effect of prebiotics or probiotics in patients diagnosed with a classified psychiatric disorder. DATA EXTRACTION: From a total of 212 studies screened, 11 were included in the final systematic review. Quality assessment of the included trials was assessed by the Jadad scale. RESULTS: Probiotics seem to offer some benefit in major depressive disorder and Alzheimer's disease. One study showed that probiotics reduced rehospitalization in patients with acute mania. In autism spectrum disorders, the results were controversial; however a single study found that early administration of probiotics showed a preventive role. No benefits were found for patients with schizophrenia. In most studies, no major adverse effects were reported. CONCLUSIONS: Although recent findings in specific psychiatric disorders are encouraging, the use of prebiotics and probiotics in clinical practice stills lacks sufficiently robust evidence.

The impact of neuropsychiatric disease on fetal growth: a case-control study.

PURPOSE: To determine the impact of depression, epilepsy and drug abuse during pregnancy on delivery and fetal outcome. Due to the worldwide increasing prevalence of neurological and psychiatric diseases and drug abuse, the number of affected pregnant women is increasing. METHODS: A large-scale retrospective case-control analysis of pregnancies affected by depression, epilepsy or drug abuse with and without medication was conducted in two German perinatal centres between 2013 and 2017. The case group consisted of 706 pregnant women who had a diagnosis of depression, epilepsy or drug abuse vs. 12,574 pregnant women without neuropsychiatric diagnosis (control group). The analysis included the rate of intrauterine growth restriction, birth weight and length, neonatal head circumference. RESULTS: Significant differences in the subgroups were found in the parameters intrauterine growth restriction, birth weight, length and head circumference. Women with epilepsy were affected less often than women with depression and substance abuse. Major differences were found in the group of women with substance abuse. Negative associations were found within the non-pharmacologically managed disease group itself compared to women exposed to medication. CONCLUSION: The present results demonstrated a negative association between maternal neurological or psychiatric disease and pregnancy outcome in the examined parameters. However, the non-pharmacologically treated maternal disease was identified as a risk factor itself.