Diet and Psychiatric Disorders

Schizophrenia is a mental health disorder that is prevalent across the world regardless of culture, socioeconomic conditions, or geography. Understanding the neurochemical baseline of schizophrenia, disease contributors, and potential treatments are avenues of current research. However, it has become increasingly apparent that utilizing the neurochemical discrepancies demonstrated in individuals suffering from schizophrenia has not yielded entirely satisfactory outcomes. Therefore, the potential of utilizing non-pharmacological interventions in the management of schizophrenia presents a worthwhile novel approach. Recently, nutrition has been shown to play a significant part in schizophrenia, with influence on disease onset, course and treatment. In this review, Onaolapo and Onaolapo (2021) investigated existing scientific literature looking at potential links between nutrition and schizophrenia to, firstly, understand the influence of diet and nutritional discrepancies on the etiology, course, treatment and sequelae of schizophrenia, and secondly, to study the impact nutritional supplements may have on the prevention of schizophrenia, as a solitary intervention or as therapeutic aids. The authors conclude that in spite of what we know and what we can assume on the relationship between nutrition and schizophrenia, the bigger obstacles remain in fashioning precise nutrition interventions as a trusted modality for prevention of schizophrenia and as a daily management strategy. [NPID: Brain, diet, mental health, nutritional psychiatry, psychosis, schizophrenia spectrum disorders]

This 2021 animal study was designed to test the effects of high-sucrose diets on mice lacking an enzyme called glyoxalase-1 (GLO1). The results demonstrated that a high-sucrose diet during adolescence induced psychosis-related behavioral factors such as hyperactivity and poor working memory. Following the intake of the high-sucrose diet, the researchers observed impairments in microcapillaries and reduced brain glucose uptake in the brains of the mice. Aspirin provided the rats with protection from angiopathy (this disease of the blood vessels). Brain glucose uptake was enhanced, and abnormal behavioral phenotypes were prevented. Similar vascular damage was seen in the brains of randomly collected schizophrenia and bipolar disorder patients, suggesting that psychiatric disorders are associated with angiopathy in the brain caused by various environmental stresses, including metabolic stress. [NPID: brain angiopathy, glucose uptake, psychosis, high sugar diets, sucrose, memory, hyperactivity]

This 1968 article presents the idea that the preferred treatment for many mentally ill patients may be the provision of the optimum concentrations of important brain constituents. It seems likely that the brain is more sensitive to changes in concentration of vital substances than are other organs and tissues. The mental symptoms of vitamin deficiency sometimes appear long before any physical symptoms. In some cases it is possible that cerebrospinal concentration of a vital substance is extremely low, while the concentration in the blood and lymph is essentially normal. Decreased integrity of the blood-brain barrier or increased metabolism of the substance in the brain may result in cerebral shortages and ultimately a mental disease. Diseases of this sort may be called localized cerebral deficiency diseases. It has been suggested that the genes responsible for deficiencies in the concentration of vital substances in the brain may also be behind increased expression of the gene for schizophrenia. Additionally, this gene for schizophrenia may itself induce a localized cerebral deficiency in one or more vital substances. [NPID: orthomolecular psychiatry, brain, vitamins, schizophrenia, mental disease, gene expression]

For this 2020 article, Johnstone et al. found randomized controlled trials where people with psychiatric symptoms took part in multinutrient interventions. A systematic search identified 16 trials with participants suffering from depression, post-disaster stress, antisocial behavior, behavioral deficits in dementia, attention-deficit/hyperactivity disorder, or autism. Only the studies using subjects with Attention-Deficit/Hyperactivity Disorder (ADHD) were selected to be included in the meta-analysis due to the variations found across studies such as participants, multinutrient formulas, outcome measures, and absence of complete data. In these individuals with ADHD, the multinutrient interventions significantly improved global functioning and measures of ADHD inattentive symptoms. The interventions also had positive influences on post-natural disaster anxiety and the number of violent incidents in prison. Formulas with greater variations of vitamins and minerals demonstrated more robust effects than formulas with fewer ingredients. This review emphasizes the need for randomized controlled trials to report full data for all outcomes, to uncover the true impact of micronutrients on psychiatric symptoms. [NPID: psychiatric disorder, depression, post-disaster stress, autism, ADHD, review, meta-analysis, diet, multinutrients, intervention, dietary intervention]

This 2020 review discusses the roles of dietary factors in the risk and symptomatology of major depressive disorder (MDD). Despite being somewhat overlooked, dietary factors represent a highly promising approach towards finding new antidepressant pathways. Patients with mental disorders are deficient in various groups of nutrients such as vitamins. Also, people with major depressive disorder seem to show an imbalance of fatty acids and insufficient levels of some minerals such as magnesium and zinc. Some of these factors are relevant to the synthesis of monoamines (a type of neurotransmitter), while others are important in relation to inflammation, neuroprotection, and the production of growth factors. Mood and behavior can change in some cases when nutrient levels return to normal. Furthermore, it is possible that the consumption of supplements (or nutraceuticals) can improve major depressive disorder symptoms even if the affected person is not deficient. Whatsmore, caffeine is believed to increase behavioral and molecular markers of major depressive disorder. The authors state that the molecular structures of most dietary factors are not known, but the study of these relatively unknown factors can potentially help develop strategies for treating the symptoms of major depressive disorder. [NPID: dietary factors, major depressive disorder, depression, psychiatric disorder, vitamins, diet, minerals, fatty acids, nutrients]

This 2021 review examined studies looking at the cost effectiveness of dietary interventions in people with mental disorders. Firstly, the reviewers searched five different databases for cost-analysis studies that implemented interventions to enhance dietary consumption in people with mental disorders. A total of 13 articles reporting on 8 studies were included in this review. Seven of these studies were in community settings, while the other study was set in community housing. Both male and female adults took part in 7 out of the 8 studies, while one study only recruited female subjects. There were people defined to have serious or severe mental disorders in 3 of the studies, while others included patients with major depression, schizophrenia, bulimia nervosa, schizoaffective disorder or first episode psychosis. The interventions also varied in that some (5) interventions took multiple behaviors into account, while others implemented diet-only interventions or used eating disorders treatments. The intervention was said to show cost-effectiveness in 25% of the studies (2). But in the other 4 studies, there was a mix of positive and neutral results. In conclusion, there was limited evidence evaluating the cost effectiveness of dietary interventions in people with mental disorders. [NPID: cost effectiveness, dietary interventions, depression, schizophrenia, bulimia, schizoaffective disorder, psychosis]

Since severe mental illness is believed to relate to lower diet quality and negative eating behaviors, Teasdale et al. (2019) decided to conduct a rigorous review of studies looking at dietary intake in psychotic disorders and bipolar disorder. Fifty-eight eligible articles were identified by searching on six electronic databases. This review planned to examine dietary assessment methods and dietary intakes. Data was pooled into a meta-analysis if possible and compared with healthy controls. The data revealed that people with severe mental illness consumed higher levels of energy and salt than healthy controls. It was suggested that higher intakes of energy and salt were linked with poorer diet quality and eating patterns. The authors conclude that interventions designed to improve weight and other physical health outcomes in people with severe mental illness should consider energy and salt as key targets to tackle. [NPID: severe mental illness, meta-analysis, systematic review, diet quality, eating behavior, psychotic disorders, bipolar disorder]

In this 2004 study, Peet sought to establish dietary factors that can predict the outcome of schizophrenia as well as the prevalence of depression. Variations in diet had already been known to predict the incidence of diabetes and heart disease, but its influence on mental health had not been evaluated yet. Peet performed an ecological analysis (a method of investigating the effects of time-specific interventions on population health at a large scale). National dietary patterns were analyzed against international variations in the outcome of schizophrenia and prevalence of depression. The results showed that a higher national consumption of refined sugar and dairy products predict a worse 2-year outcome of schizophrenia. Moreover, low dietary intake of fish and seafood could predict a high national incidence of depression. Therefore, Peet concluded that the dietary factors that predict schizophrenia outcome and occurrence of depression are similar to the predictors of coronary heart disease and diabetes, in which nutritional approaches are recommended. [NPID: depression, psychiatric disorders, schizophrenia, fish, seafood, refined sugar, dairy products]

In this review, Fond et al. (2020) discuss the most recent meta-analyses carried out in the field of psychonutrition in severe mental disorders. Their aim was to showcase recent findings in order to inform nutritional interventions in psychiatry. The Mediterranean diet has demonstrated the strongest evidence for effectiveness in reducing incidence of depressive symptomatology. Some of its main constituents — such as omegas 3 fatty acids, vitamin D, methylfolate and S-adenosylmethionine — have also individually been associated with a lower prevalence of depression. Secondly, the Healthy Eating Index (HEI) has been correlated with a lower incidence of depression. In other studies, major depression has been linked with inflammatory interference, while lower levels of depression have been seen in people who consume diets with low Dietary Inflammatory Index. Inflammation may be mediated by altered microbiota in the gut. Reducing caloric intake by 20% and/or intermittent fasting (fasting for 12 to 16 hours per day) has shown to enhance the microbiota and improve psychiatric outcomes. Supplementation with probiotics has also demonstrated effectiveness in treating depression. Finally, diets high in protein have shown promise. To conclude, the authors state that modifying the diets of psychiatric patients may be an underused tool that could improve mental and physical health. [NPID: depression, psychiatric disorders, zinc, major depressive disorder, MDD, inflammation, gut microbiota, intermittent fasting, probiotics, protein]

In this 2017 clinical study, 69 patients with current depressive episode, 45 patients in remission, and 50 healthy control participants were assessed (using electrothermal atomic absorption spectrometry [ET AAS]) to compare their levels of zinc and to discuss the potential in monitoring zinc concentrations as a biomarker of depression. The severity of depression was assessed by using the Hamilton Rating Scale for Depression (HDRS) and the Montgomery-Asberg Depression Rating Scale (MADRS). It was discovered that patients suffering from depression had significantly lower levels of zinc compared with the controls, while there was no significant difference between those in remission and those in the control group. However, a variation in zinc readings was found within the remission group between individuals who had experienced drug resistance in their previous episode and those who had not. Within the remission group, there was also an association between their zinc levels and the average number of depressive episodes the person had gone through in the last year. Finally, serum zinc levels did not show dependence on age, presence of psychotic symptoms or melancholic syndrome, or depression-related factors such as severity, atypical features, age of onset or duration of disease, number of episodes in the lifetime, or the duration of the episode/remission. These findings support the previously reported link between zinc deficiency and depressive episodes, and indicate that there is potential in the use of blood zinc concentration as a biological biomarker of MDD. [NPID: depression, psychiatric disorders, zinc, major depressive disorder, MDD]

In this article, Morris et al. (2020) explain the mechanisms by which induced ketosis might reduce mitochondrial dysfunction, inflammation, and oxidative stress in neuropsychiatric disorders, and may be able to ameliorate abnormal levels of molecules and signaling pathways that appear to contribute to the pathophysiology of disorders such as schizophrenia, bipolar disorder, and major depressive disorder. In addition, the authors examine the safety data relating to induced ketosis over the long term and discuss future study design. [NPID: mood disorders, psychiatric disorders, ketosis, ketones, ketogenic diet, keto, mitochondrial dysfunction, inflammation, oxidative stress, major depressive disorder, MDD, bipolar disorder, BD]

In this double-blind, placebo-controlled trial, Qiao et al. (2020) investigated the impact of administering fish oil (omega-3 fatty acids) supplements on the hostility and psychopathology among patients with acute violent schizophrenia. The participants were acute hospitalized patients showing violent behavior attributed to their schizophrenia, and who were being treated with antipsychotics. Thirty-two patients were given the fish oil supplement while 35 were treated with placebo as a result of random allocation. Assessments were conducted at baseline, week 4 and week 8. Reductions in symptoms and hostility were reported after treatment at the 4-week and 8-week marks for both groups, with no variation between the fish oil intervention and placebo. This data implies that omega-3 fatty acids do not reduce psychopathology nor hostility in acute patients with schizophrenia. [NPID: mood disorders, psychiatric disorders, fish oil, omega-3 fatty acids, schizophrenia]

This 2019 study examined patients with bipolar disorder (BD): their dietary habits, fatty acid desaturase (FADS) genotype, and their proinflammatory cytokine levels. Both inflammation and irregular polyunsaturated fatty acid (PUFA) levels have been implicated in the development of BD, while the FADS genotype is relevant since a locus was found in this FADS gene cluster that conferred vulnerability to develop BD. Here, Koga et al. (2019) measured the PUFA levels of 83 patients with BD and 217 healthy controls. The researchers also genotyped three FADS single nucleotide polymorphisms (SNPs) and took plasma interleukin (IL)-6 and tumor necrosis factor alpha (TNFα) readings of a subsample of 65 BD sufferers and of 90 controls. Participants then completed diet history questionnaires to determine their consumption of fish. There were significant differences between the patients and the controls in all 7 PUFAs tested here — in particular, n-3 eicosapentaenoic acid (EPA) levels were lower and n-6 arachidonic acid concentrations were much higher in patients than in healthy controls (p < 0.0001 for both). The levels of EPA were found to be negatively correlated with IL-6 and TNFα levels in patients with BD, in whom these inflammatory markers were significantly higher compared with the control individuals. The FADS genotype, which was linked with increased n-6 PUFA levels, was also linked with elevated levels of TNFα, while a decreased frequency of fish consumption was connected with low EPA and high IL-6 readings. These findings not only strengthen the link between plasma PUFA modification and abnormal proinflammatory cytokine levels with bipolar disorder, but suggest that FADS genotype and fish consumption may contribute to the alterations in PUFA levels and to the inflammation in BD. [NPID: mood disorders, psychiatric disorders, gut microbiota, microbiome, inflammation, bipolar disorder, BD, PUFA, cytokine levels, EPA, fish]

In this review, Gondalia et al. (2019) discuss various comorbid conditions linked with bipolar disorder — such as inflammation, irritable bowel disease, and antibiotic induced mania — which indicate possible involvement of the gut microbiota. Although there is a clear interaction between psychiatry and gastrointestinal health, it has not been well researched thus far. The authors explore the relationships between bipolar disorder, inflammation, and the gut microbiome while discussing the potential of dietary, probiotic, and prebiotic interventions as adjuvant therapies for managing mood disorders. [NPID: mood disorders, psychiatric disorders, gut microbiota, microbiome, inflammation, bipolar disorder, irritable bowel disease, antibiotic induced mania, probiotic, prebiotic]

In this 2018 paper, Cuomo et al. reviewed research on the relationship between microbiome, schizophrenia, and treatment resistance, as well as the link between schizophrenia and the immune inflammatory response. Cuomo et al. present studies on probiotic and prebiotic use in schizophrenia. The publications on microbiome, immune-mediated pathology, schizophrenia, and neurodevelopmental disorders were retrieved from the Cochrane Library and PubMed databases, and additional papers were selected from these publications’ references. Given the close relationship between the gastrointestinal tract and central nervous system, the authors conclude that a relationship between schizophrenia and microbiota is likely. The key studies identified on this topic are summarized in the full paper. The authors also state that the role of the microbiome and immune-mediated pathology in schizophrenia should be explored further, even in clinical trials, and especially when investigating gut microbiota-altering agents and those that may be capable of influencing gastrointestinal inflammation and its mechanism. The authors found a lack of treatments targeting the microbiome being used in patients with mental illness, particularly in those with schizophrenia. [NPID: mood disorders, psychiatric disorders, gut microbiota, microbiome, schizophrenia, inflammation, probiotics, prebiotics, neurodevelopmental disorders]

In this article, Akhondzadeh (2019) briefly reviews data that suggest that the microbiome may improve our understanding of schizophrenia. While antipsychotic treatments exist, they have effectiveness and safety limitations, and lack the capacity to treat the negative symptoms of schizophrenia as effectively as antipsychotics used for positive symptoms. Researchers have identified a subset of bacteria in schizophrenia patients that differ from that in individuals without this disorder. When samples of this bacteria were taken from patients and administered to healthy mice, behavioral changes occurred. This evidence suggests that the gut biomes of individuals with schizophrenia are different from neurotypical people and implies that certain bacteria may be associated with schizophrenia-related symptoms. These bacteria are thought to interact with microbiota gut-brain amino acids and play a role in lipid metabolic pathways. Overall, this research has led to revelations that the bacteria in the human gut may be linked with our moods, feelings, and even our thoughts. [NPID: mood disorders, psychiatric disorders, gut microbiota, microbiome, schizophrenia]

The ‘leaky gut hypothesis’ proposes that increasing intestinal permeability may contribute to the association between inflammation with major depressive disorder (MDD) and suicidal behavior. This 2019 study thus evaluated patients with a recent suicide attempt (rSA), MDD subjects with no history of a suicide attempt (nsMDD), and healthy controls (HC) on their plasma gut permeability marker levels, and explored the markers’ relationship with symptom severity and inflammation. This study recruited 54 rSAs, 13 nsMDDs, and 17 HCs, who were psychologically assessed using Montgomery–Åsberg Depression Rating Scale (MADRS) and Suicide Assessment Scale (SUAS). The markers determined in the participants were zonulin, intestinal fatty acid binding protein (I‐FABP), soluble CD14, and interleukin‐6 (IL‐6). The results showed that the rSA group exhibited higher I‐FABP and lower zonulin levels compared with the other two groups, while I‐FABP levels were positively associated with MADRS among all subjects. IL‐6 readings in the sample correlated positively with I-FABP and negatively with zonulin. Furthermore, higher I-FABP levels were linked with greater SUAS scores, showing statistical significance in the nsMDD group. The ‘leaky gut hypothesis’ may indeed help understand the relationship between inflammation and suicidal behavior. [NPID: mood disorders, psychiatric disorders, leaky gut, inflammation, major depressive disorder, MDD, suicide]

Based on several studies suggesting that taking ketone supplements, such as ketone salts or ketone esters, can generate rapid and sustained nutritional ketosis and metabolic changes (which may evoke potential therapeutic effects in psychiatric diseases), Kovács et al. (2019) summarized the current literature on ketone supplementation as a potential therapeutic tool for psychiatric disorders. Ketone supplementation elevates the levels of ketone bodies in the blood such as D-β-hydroxybutyrate (βHB), acetoacetate (AcAc), and acetone. It is said that these compounds exert positive effects on the mitochondria, glycolysis, neurotransmitter levels, and the activity of free fatty acid receptor 3 (FFAR3), hydroxycarboxylic acid receptor 2 (HCAR2), and histone deacetylase, as well as the functioning of NOD-like receptor pyrin domain 3 (NLRP3) inflammasome and mitochondrial uncoupling protein (UCP) expression. Kovács et al. also state that the result is reduction in the pathophysiology associated with various psychiatric disorders. The conclusion is that supplement-induced nutritional ketosis leads to metabolic changes and improvements, and that there is a strong case for the development of specific adjunctive ketogenic protocols for psychiatric diseases. [NPID: psychiatric disorders, keto, ketogenic diet, psychosis, ketones, ketone supplements]

This 2020 article provides us with a brief overview of preclinical and clinical evidence supporting the progress of ketogenic therapies in a variety of psychiatric disorders, especially in psychosis. This comes after Morris et al. (2020) published a review recognizing the exciting potential of the ketogenic diet and other ketogenic therapies in the treatment of serious mental disorders. This present article aims to further strengthen the case for induced ketosis in psychiatry. [NPID: psychiatric disorders, keto, ketogenic diet, psychosis]

Zhu et al. (2019) studied the total intracranial volume (TIV) of 50 patients with major depressive disorder (MDD). They used high-resolution structural magnetic resonance imaging to explore the neural substrate that underlies the link between depression and vitamin D deficiency. As well as collecting peripheral venous blood samples (to measure serum vitamin D concentrations), the researchers employed the Hamilton Rating Scale for Depression (HAMD) to assess depression symptom severity. In patients with MDD, HAMD score was negatively correlated with TIV and serum vitamin D concentration, and TIV was positively correlated with serum vitamin D concentration. TIV and serum vitamin D levels were observed to significantly predict HAMD score in the linear regression analyses, while mediation analysis showed that TIV significantly mediated the relationship between serum vitamin D concentration and HAMD scores. The researchers conclude that TIV may serve as a neural biomarker for monitoring responses to adjuvant therapy of vitamin D in patients with MDD. [NPID: psychiatric disorders, major depressive disorder, MDD, vitamin D]

This 2019 review by Westfall and Pasinetti explored several potential therapeutic mechanisms in which dietary polyphenols are able to establish cognitive resilience in neuropsychiatric disorders. It also looked at how synbiotics (combination of probiotics and dietary polyphenols) may provide a novel therapeutic strategy for depression. The authors state that the multifactorial pathophysiology of depression requires a broad acting strategy, as gut-brain-axis signaling may play a crucial role in promoting resilience to several stress-induced changes. Furthermore, the interaction of the gut microbiota with dietary polyphenols can synergistically alleviate the biological signatures of depression. The phenolic metabolites of dietary polyphenols are known to have multiple beneficial properties and therapeutic efficacy against depression, while symbiotics have the potential to lessen neuroinflammation by modulating a number of factors — such as oxidative stress and serotonin metabolism. Effectively, they are capable of simultaneously targeting several major pathological risk factors of depression. Overall, synbiotics may act as a novel therapeutic paradigm for neuropsychiatric disorders. Further understanding of the fundamental mechanisms of gut-brain-axis signaling will allow greater utilization of the gut microbiota as a therapeutic tool. [NPID: psychiatric disorders, polyphenols, probiotics, synbiotics, depression, gut-brain axis, neuroinflammation, inflammation, oxidative stress, serotonin, microbiome, gut microbiota]

Luo et al. (2020) conducted a network meta-analysis comparing the efficacy of different dosages of n-3 polyunsaturated fatty acids (PUFAs) on patients with Major Depressive Disorder (MDD) from an early period. Using the PubMed, Embase, and Cochrane databases, the researchers extracted randomized controlled trials (RCTs) exploring the efficacy of n-3 PUFA supplementation for adult (>18 years old) MDD patients with no comorbidities. A total of 910 MDD patients in 10 trials with three adjuvant therapy strategies (high-dose n-3 PUFAs, low-dose n-3 PUFAs and placebo) were included. Pairwise meta-analysis revealed that n-3 PUFAs were superior to placebos, while network meta-analysis demonstrated that both the high and low doses of n-3 PUFAs were better than placebos, and that the efficacy of high-dose n-3 PUFAs is superior compared to low-dose. Although additional head-to-head clinical trials need to be carried out to support these findings, this meta-analysis showed that high dose n-3 PUFA supplementation may be superior to the low-dose in the early therapy period of MDD patients. [NPID: psychiatric disorders, n-3 polyunsaturated fatty acids, n-3 PUFA, Major Depressive Disorder, MDD]

Briguglio et al. (2020) provide an overview of the current evidence for healthy eating education, physical activity programs, and sleep hygiene promotion (HEPAS) in the prevention and management of neuropsychiatric disorders. They also outline suggestions for clinical practice. There are plenty of determinants that contribute to the worsening of neuropsychiatric disorders, including unhealthy lifestyles — which are a significant contributor in the interplay between genetic, epigenetic (non-genetic influences on gene expression), and environmental factors that ultimately represent the pathophysiological basis of these conditions. HEPAS has the potential to become one of the most suitable interventions to lower the risk of developing neuropsychiatric disorders. However, Briguglio et al. believe that in the overall management of these disorders, it is essential for HEPAS to be paired with pharmacological and psychological therapies with the aim of reducing disability and enhancing quality of life. [NPID: psychiatric disorders, neuropsychiatric disorders, HEPAS, disability, quality of life]

Gill et al. (2021) conducted the first study to investigate self-reported dietary habits of acute psychiatric inpatients. The researchers took the participants’ diet history and compared their food habits to a Mediterranean dietary index. Related variables, such as socio-economic characteristics, physical activity, income, BMI, and educational achievement, were taken into consideration in order to better understand the relationships between these factors and the subjects’ diet and mental well-being. Results showed that the majority (75%) of the psychiatric inpatients had an unhealthy diet, and that patients with schizophrenia consumed greater quantities of sugar. Unhealthy diets correlated with higher body mass index (BMI) and lower education level. In conclusion, enhancing dietary habits (e.g. following a Mediterranean diet) may help short-stay inpatients recover from their symptoms more quickly. [NPID: psychiatric disorders, Mediterranean diet, well-being, schizophrenia, sugar]