Beneficial effects of omega-3 fatty acid supplementation in schizophrenia: possible mechanisms.

BACKGROUND: Schizophrenia is a serious long-term psychotic disorder marked by positive and negative symptoms, severe behavioral problems and cognitive function deficits. The cause of this disorder is not completely clear, but is suggested to be multifactorial, involving both inherited and environmental factors. Since human brain regulates all behaviour, studies have focused on identifying changes in neurobiology and biochemistry of brain in schizophrenia. Brain is the most lipid rich organ (approximately 50% of brain dry weight). Total brain lipids is constituted of more than 60% of phospholipids, in which docosahexaenoic acid (DHA, 22:6n-3) is the most abundant (more than 40%) polyunsaturated fatty acid (PUFA) in brain membrane phospholipids. Results from numerous studies have shown significant decreases of PUFAs, in particular, DHA in peripheral blood (plasma and erythrocyte membranes) as well as brain of schizophrenia patients at different developmental phases of the disorder. PUFA deficiency has been associated to psychotic symptoms and cognitive deficits in schizophrenia. These findings have led to a number of clinical trials examining whether dietary omega-3 fatty acid supplementation could improve the course of illness in patients with schizophrenia. Results are inconsistent. Some report beneficial whereas others show not effective. The discrepancy can be attributed to the heterogeneity of patient population. METHODS: In this review, results from recent experimental and clinical studies, which focus on illustrating the role of PUFAs in the development of schizophrenia were examined. The rationale why omega-3 supplementation was beneficial on symptoms (presented by subscales of the positive and negative symptom scale (PANSS), and cognitive functions in certain patients but not others was reviewed. The potential mechanisms underlying the beneficial effects were discussed. RESULTS: Omega-3 fatty acid supplementation reduced the conversion rate to psychosis and improved both positive and negative symptoms and global functions in adolescents at ultra-high risk for psychosis. Omega-3 fatty acid supplementation could also improve negative symptoms and global functions in the first-episode patients with schizophrenia, but improve mainly total or general PANSS subscales in chronic patients. Patients with low PUFA (particularly DHA) baseline in blood were more responsive to the omega-3 fatty acid intervention. CONCLUSION: Omega-3 supplementation is more effective in reducing psychotic symptom severity in young adults or adolescents in the prodromal phase of schizophrenia who have low omega-3 baseline. Omega-3 supplementation was more effective in patients with low PUFA baseline. It suggests that patients with predefined lipid levels might benefit from lipid treatments, but more controlled clinical trials are warranted.

Nonmedical Interventions for Schizophrenia: A Review of Diet, Exercise, and Social Roles.

Schizophrenia is a major mental illness with a disease course that is influenced by lifestyle. The risk-benefit ratio for alternative interventions is more favorable than for antipsychotics in long-term treatment. Dietary interventions may target autoimmune features, vitamin or mineral deficiencies, abnormal lipid metabolism, gluten sensitivity, or others. Examples of interventions involving diet, physical activity, or physical processes or social interventions including talk therapy exist in the literature. Notwithstanding, the general utility of these types of interventions remains inconclusive, awaiting long-term randomized trials. A perspective that separates the cause of the disease from its symptoms may be helpful in treatment planning and is warranted to distinguish between short-term and long-term recovery goals.

Diet and Psychosis: A Scoping Review.

INTRODUCTION: Schizophrenia spectrum disorders (SSD) represent a cluster of severe mental illnesses. Diet has been identified as a modifiable risk factor and opportunity for intervention in many physical illnesses and more recently in mental illnesses such as unipolar depression; however, no dietary guidelines exist for patients with SSD. OBJECTIVE: This review sought to systematically scope the existing literature in order to identify nutritional interventions for the prevention or treatment of mental health symptoms in SSD as well as gaps and opportunities for further research. METHODS: This review followed established methodological approaches for scoping reviews including an extensive a priori search strategy and duplicate screening. Because of the large volume of results, an online program (Abstrackr) was used for screening and tagging. Data were extracted based on the dietary constituents and analyzed. RESULTS: Of 55,330 results identified by the search, 822 studies met the criteria for inclusion. Observational evidence shows a connection between the presence of psychotic disorders and poorer quality dietary patterns, higher intake of refined carbohydrates and total fat, and lower intake or levels of fibre, ω-3 and ω-6 fatty acids, vegetables, fruit, and certain vitamins and minerals (vitamin B12 and B6, folate, vitamin C, zinc, and selenium). Evidence illustrates a role of food allergy and sensitivity as well as microbiome composition and specific phytonutrients (such as L-theanine, sulforaphane, and resveratrol). Experimental studies have demonstrated benefit using healthy diet patterns and specific vitamins and minerals (vitamin B12 and B6, folate, and zinc) and amino acids (serine, lysine, glycine, and tryptophan). DISCUSSION: Overall, these findings were consistent with many other bodies of knowledge about healthy dietary patterns. Many limitations exist related to the design of the individual studies and the ability to extrapolate the results of studies using dietary supplements to dietary interventions (food). Dietary recommendations are presented as well as recommendations for further research including more prospective observational studies and intervention studies that modify diet constituents or entire dietary patterns with statistical power to detect mental health outcomes.

Use of a Gluten-Free Diet in Schizophrenia: A Systematic Review.

We performed a systematic review of the literature to determine whether adherence to a gluten-free diet (GFD) leads to improved outcomes for patients with schizophrenia. We searched the AMED (Allied and Complementary Medicine; 1985-June 2016), MEDLINE (1946-June 2016), and Embase (1980-2016 week 24) databases using the terms "wheat" or "glutenin" or "gliadin" or "gluten" AND "schizophrenia." A total of 9 studies met the inclusion criteria for this review: 1 randomized controlled trial, 7 crossover studies, and 1 open-label pilot study. Six of the included studies demonstrated beneficial effects including improved functioning and decreased symptom severity after the course of a GFD, whereas 3 studies found no benefits. All of the included studies found that a GFD is well tolerated and can be adhered to by patients with schizophrenia. The findings of this systematic review should be interpreted with caution due to limitations inherent to nonrandomized trials, as well as the heterogeneity in the study design and the length of the GFD applied in each study. Publication bias is another potential limitation. Further research is required to examine the biomarkers of gluten sensitivity and inflammation to effectively target those patients with schizophrenia who will benefit most from this dietary intervention.

Ketogenic diet for schizophrenia: Nutritional approach to antipsychotic treatment.

Schizophrenia is a mental disorder that mostly appears in the second or third decade of life with no consistent appearance. The first-line pharmacological treatment are antipsychotic drugs, which mainly act by suppressing the activity of dopamine. Unfortunately many of schizophrenic patients suffer from persistent positive or negative symptoms that cannot be fully treated with available medication. With exploration on the possible causes of the disease there is evidence on dopaminergic transmission defects, there is a need to find more holistic way in treating the disease and a diet regimen could be one of them. Ketogenic diet, which is a popular diet regimen that consists in low-carbohydrate (about 30-50 g/day), medium-protein (up to 1 g/kg daily) and high-fat intake (around 80% of daily calories) mainly known for its helpful role in weight-loss. The key mechanism is to generate ketosis. A state in which ketones bodies in the blood provides energy part of the body's energy comes from ketone bodies in the blood. Possible hypothesis can be that ketogenic diet changes the ratio of GABA:glutamate in favor of GABA, by suppressing the catabolism and increasing the synthesis of GABA as well as glutamate metabolism, which could help to compensate the disrupted GABA levels in schizophrenic brain, leading to possible better outcome of the disease regarding symptomatology and preventing the weight-gain regarding some medications used and the correlating diseases responsible for weight gain.

The Evaluation of Folic Acid-Deficient or Folic Acid-Supplemented Diet in the Gestational Phase of Female Rats and in Their Adult Offspring Subjected to an Animal Model of Schizophrenia.

Although folic acid (FA) supplementation is known to influence numerous physiological functions, especially during pregnancy, little is known about its direct effects on the mothers' health. However, this vitamin is essential for the health of the mother and for the normal growth and development of the fetus. Thus, the aim of this study was (1) to evaluate the cognitive effects and biochemical markers produced by the AIN-93 diet (control), the AIN-93 diet supplemented with different doses of FA (5, 10, and 50 mg/kg), and a FA-deficient diet during pregnancy and lactation in female mother rats (dams) and (2) to evaluate the effect of maternal diets on inflammatory parameters in the adult offspring which were subjected to an animal model of schizophrenia (SZ) induced by ketamine (Ket). Our study demonstrated through the Y-maze test that rats subjected to the FA-deficient diet showed significant deficits in spatial memory, while animals supplemented with FA (5 and 10 mg/kg) showed no deficit in spatial memory. Our results also suggest that the rats subjected to the FA-deficient diet had increased levels of carbonylated proteins in the frontal cortex and hippocampus and also increased plasma levels of homocysteine (Hcy). Folate was able to prevent cognitive impairments in the rats supplemented with FA (5 and 10 mg/kg), data which may be attributed to the antioxidant effect of the vitamin. Moreover, FA prevented protein damage and elevations in Hcy levels in the rats subjected to different doses of this vitamin (5, 10, and 50 mg/kg). We verified a significant increase of the anti-inflammatory cytokine (interleukin-4 (IL-4)) and a reduction in the plasma levels of proinflammatory cytokines (interleukin-6 (IL-6)) and TNF-α) in the dams that were subjected to the diets supplemented with FA (5, 10, and 50 mg/kg), showing the possible anti-inflammatory effects of FA during pregnancy and lactation. In general, we also found that in the adult offspring that were subjected to an animal model of SZ, FA had a protective effect in relation to the levels of IL-4, IL-6, and TNF-α, which indicates that the action of FA persisted in the adult offspring, since FA showed a lasting effect on the inflammatory response, which was similar in both the dams and their offspring. In conclusion, the importance of supplementation with FA during pregnancy and lactation should be emphasized, not only for the benefit of the offspring but also for the health of the mother. All this is due to the considerable protective effect of this vitamin against oxidative damage, cognitive impairment, hyperhomocysteinemia, immune function, and also its ability in preventing common processes in post-pregnancy stages, as well as in reducing the risks of neurodevelopmental disorders and enhancing fetal immune development.

Effects of Omega-3 in the treatment of violent schizophrenia patients.

OBJECTIVE: This study was designed to explore the relationship in between the daily consumption of fish oil (360mg DHA+540mg EPA), and reduction of symptoms and violent behavior among patients with schizophrenia. METHOD: Fifty inpatients meeting ICD-10 criteria for schizophrenia and scoring more than four of Modified Overt Aggression Scale (MOAS) with antipsychotics treatment were randomly assigned to receive either fish oil (N=28) or a placebo (N=22) in a twelve week, double-blind supplementation trial. Assessments were performed at baseline and at weeks 4, 8 and 12. RESULTS: The PANSS and CGI scores decreased at the week of 4, 8 and 12, but no differences were found between the two groups. MOAS scores declined significantly at weeks 4, 8 and 12. At week 12, MOAS scores of the fish oil group declined significantly than the placebo group (t=-2.40, P<0.05). CONCLUSIONS: violent schizophrenia patients treated with fish oil (360mg DHA+540mg EPA) demonstrated a decrease in violence, but improvement in positive and negative symptoms was no greater than patients treated with the placebo after twelve weeks.

Vitamin D Supplementation in Chronic Schizophrenia Patients Treated with Clozapine: A Randomized, Double-Blind, Placebo-controlled Clinical Trial.

BACKGROUND: While accumulating evidence suggests that vitamin D deficiency may be involved in the risk to develop schizophrenia and its outcome, there are no studies on vitamin D supplementation in this context. We sought to assess the effect of vitamin D supplementation on psychiatric, cognitive and metabolic parameters in chronic clozapine-treated schizophrenia patients. METHODS: This eight-week, randomized, double-blind, placebo-controlled clinical trial, recruited schizophrenia patients who had been maintained on clozapine treatment for at least 18weeks and had low levels of vitamin D (<75nmol/l) and total PANSS scores >70 (to ascertain the presence of residual symptoms). Patients were randomly allocated to either weekly oral drops of vitamin D (14,000IU) or placebo and subsequently assessed at two-week intervals for psychosis severity, mood, cognition and metabolic profile. RESULTS: Twenty four patients were randomly assigned to vitamin D (aged 39.4±9.6years, 75% males) and the other 23 patients to the placebo arm (aged 42.5±11.2years, 60.9% males). After eight weeks, the vitamin D group exhibited a significant increase in vitamin D levels (31.4 vs -0.4nmol/l, p<0.0001). There was no significant effect of vitamin D on psychotic, depressive or metabolic parameters. However, in the vitamin D group, there was a trend towards improved cognition (effect size=0.17, significance lost following Bonferroni correction). CONCLUSIONS: Vitamin D supplementation was associated with a trend towards improved cognition, but did not affect psychosis, mood or metabolic status. It is possible that the robust decrease in the PANSS scores in both groups may have obscured an effect of vitamin D supplementation.

Nutritional supplements in psychotic disorders.

There is growing interest about the potential of diet and nutrients to improve the mental health of the population and for the treatment of psychiatric disorders. In the case of schizophrenia, the limitations of antipsychotic drugs to achieve adequate rates of clinical remission and functional recovery have promoted the search for complementary approaches. This narrative review approaches the dietary patterns and interventions in schizophrenia, efficacy of specific nutrients and therapeutic modulation of the gut microflora by probiotics. As a whole, schizophrenia patients follow a low-quality diet and are exposed to deficiencies in various nutrients that are essential for brain functioning. Although clinical trials with nutritional supplements are still limited and have inconsistent results, specific nutrients, as Omega-3, vitamin D and Group B vitamins can be useful as complementary strategies in the treatment of schizophrenia. It is hoped that the initiation of personalized medicine strategies, such as stratification and using a clinical staging approach, will make it possible to identify the subgroups of patients who can obtain maximum benefit from dietary and nutritional interventions.

Low dietary intake of n-3 fatty acids, niacin, folate, and vitamin C in Korean patients with schizophrenia and the development of dietary guidelines for schizophrenia.

Inappropriate dietary intake and poor nutritional status are reported to be associated with metabolic syndrome and psychopathology in patients with schizophrenia. We hypothesized that inappropriate dietary habits and insufficient dietary intake of specific nutrients are associated with schizophrenia. To test the hypothesis, we assessed the dietary habits and nutritional intake of patients with schizophrenia and then developed suitable dietary guidelines. In total, 140 subjects (73 controls and 67 patients with schizophrenia from community mental health centers) were included, and dietary intakes were analyzed using a semi-quantitative food frequency questionnaire. As a result, the proportion of overweight or obese patients was significantly higher in schizophrenia subjects (64.2%) compared with control subjects (39.7%) (P=.004). The male schizophrenia patients had significantly lower dietary intakes of protein, polyunsaturated fatty acids (PUFAs), vitamin K, niacin, folate, and vitamin C than the male control subjects. In all multiple logistic regression models, subjects with the "low" dietary intake of protein, n-3 PUFAs, niacin, folate, and vitamin C had a significantly higher odds ratios for schizophrenia compared with those with the "high" dietary intake category of each nutrient. Therefore, maintenance of a healthy body weight and sufficient dietary intake of protein, PUFAs, niacin, folate, and vitamin C are recommended for Korean patients with schizophrenia.

Cysteine-rich whey protein isolate (Immunocal®) ameliorates deficits in the GFAP.HMOX1 mouse model of schizophrenia.

Schizophrenia is a neuropsychiatric disorder that features neural oxidative stress and glutathione (GSH) deficits. Oxidative stress is augmented in brain tissue of GFAP.HMOX1 transgenic mice which exhibit schizophrenia-relevant characteristics. The whey protein isolate, Immunocal® serves as a GSH precursor upon oral administration. In this study, we treated GFAP.HMOX1 transgenic mice daily with either Immunocal (33mg/ml drinking water) or equivalent concentrations of casein (control) between the ages of 5 and 6.5 months. Immunocal attenuated many of the behavioral, neurochemical and redox abnormalities observed in GFAP.HMOX1 mice. In addition to restoring GSH homeostasis in the CNS of the transgenic mice, the whey protein isolate augmented GSH reserves in the brains of wild-type animals. These results demonstrate that consumption of whey protein isolate augments GSH stores and antioxidant defenses in the healthy and diseased mammalian brain. Whey protein isolate supplementation (Immunocal) may constitute a safe and effective modality for the management of schizophrenia, an unmet clinical imperative.

Antioxidant and anti-inflammatory nutrient status, supplementation, and mechanisms in patients with schizophrenia.

Over 50 million people around the world suffer from schizophrenia, a severe mental illness characterized by misinterpretation of reality. Although the exact causes of schizophrenia are still unknown, studies have indicated that inflammation and oxidative stress may play an important role in the etiology of the disease. Pro-inflammatory cytokines are crucial for normal central nervous development and proper functioning of neural networks and neurotransmitters. Patients with schizophrenia tend to have abnormal immune activation resulting in elevated pro-inflammatory cytokine levels, ultimately leading to functional brain impairments. Patients with schizophrenia have also been found to suffer from oxidative stress, a result of an imbalance between the production of free radicals and the ability to detoxify their harmful effects. Furthermore, inflammation and oxidative stress are implicated to be related to the severity of psychotic symptoms. Several nutrients are known to have anti-inflammatory and antioxidant functions through various mechanisms in our body. The present review evaluates studies and literature that address the status and supplementation of omega-3 polyunsaturated fatty acids, vitamin D, B vitamins (B6, folate, B12), vitamin E, and carotenoids in different stages of schizophrenia. The possible anti-inflammatory and antioxidant mechanisms of action of each nutrient are discussed.

Suplementos nutricionales en los trastornos psicóticos / Nutritional supplements in psychotic disorders

Existe un interés creciente en el potencial de la dieta y los nutrientes para mejorar la salud mental de la población y para el tratamiento de los trastornos psiquiátricos. En el caso de la esquizofrenia, las limitaciones de los fármacos antipsicóticos para lograr tasas adecuadas de remisión clínica y recuperación funcional han impulsado la búsqueda de abordajes complementarios. En esta revisión narrativa se abordan los patrones dietéticos y las intervenciones dietéticas en esquizofrenia, la eficacia de nutrientes específicos y la modulación terapéutica de la microflora intestinal mediante probióticos. En conjunto, los pacientes con esquizofrenia siguen dietas de pobre calidad y están expuestos a deficiencias en varios nutrientes esenciales para el funcionamiento cerebral. Aunque los ensayos clínicos con suplementos nutricionales son aún escasos y con resultados inconsistentes, nutrientes específicos, como los Omega-3, la vitamina D y las vitaminas del grupo B, pueden ser útiles como estrategias complementarias en el tratamiento de la esquizofrenia. Se espera que la puesta en marcha de estrategias de medicina personalizada, como la estratificación y una perspectiva de estadiaje clínico, posibilite identificar a los subgupos de pacientes que puedan obtener el máximo beneficio de las intervenciones diéteticas y nutricionales (AU)

There is growing interest about the potential of diet and nutrients to improve the mental health of the population and for the treatment of psychiatric disorders. In the case of schizophrenia, the limitations of antipsychotic drugs to achieve adequate rates of clinical remission and functional recovery have promoted the search for complementary approaches. This narrative review approaches the dietary patterns and interventions in schizophrenia, efficacy of specific nutrients and therapeutic modulation of the gut microflora by probiotics. As a whole, schizophrenia patients follow a low-quality diet and are exposed to deficiencies in various nutrients that are essential for brain functioning. Although clinical trials with nutritional supplements are still limited and have inconsistent results, specific nutrients, as Omega-3, vitamin D and Group B vitamins can be useful as complementary strategies in the treatment of schizophrenia. It is hoped that the initiation of personalized medicine strategies, such as stratification and using a clinical staging approach, will make it possible to identify the subgroups of patients who can obtain maximum benefit from dietary and nutritional interventions (AU)

Vitamin E and essential polyunsaturated fatty acids supplementation in schizophrenia patients treated with haloperidol.

OBJECTIVES: Previously, oxidative damage has been associated with severity of clinical symptoms and supplementation with antioxidants and essential polyunsaturated fatty acids (EPUFAs) was proposed to have beneficial effects in schizophrenia. We evaluated the effects of supplementation with EPUFAs and vitamin E in patients treated with haloperidol depot injection. DESIGN: This was a double-blind randomized placebo-controlled study with four arms (Placebo, vitamin E, EPUFAs, and vitamin E + EPUFAs). Biomarkers of oxidative stress, neurochemistry, psychopathology, and extrapyramidal symptoms were assessed at baseline and after 4 months. RESULTS: In EPUFAs group of patients, reduced glutathione concentration was increased compared to placebo. Concentration of oxidized glutathione was decreased in patients receiving vitamin E. In addition, compared to placebo a non-significant trend of increased activity of catalase and superoxide dismutase was observed in all three treatment groups. Patients receiving vitamin E experienced less motor retardation. No difference in extrapyramidal symptoms was found. DISCUSSION: Our study indicates that supplementation with vitamin E and EPUFAs may improve the antioxidative defense, especially glutathione system, while there is no major effect on symptoms severity. Supplemental treatment with EPUFAs and vitamin E in schizophrenia patients treated with haloperidol is potentially beneficial and a larger independent study appears warranted.

A randomized controlled study of the efficacy of six-month supplementation with concentrated fish oil rich in omega-3 polyunsaturated fatty acids in first episode schizophrenia.

Short-term clinical trials of omega-3 polyunsaturated fatty acids (n-3 PUFA) as add-on therapy in patients with schizophrenia revealed mixed results. The majority of these studies used an 8- to 12-week intervention based on ethyl-eicosapentaenoic acid. A randomized placebo-controlled trial was designed to compare the efficacy of 26-week intervention, composed of either 2.2 g/day of n-3 PUFA, or olive oil placebo, with regard to symptom severity in first-episode schizophrenia patients. Seventy-one patients (aged 16-35) were enrolled in the study and randomly assigned to the study arms. The primary outcome measure of the clinical evaluation was schizophrenia symptom severity change measured by the Positive and Negative Syndrome Scale (PANSS). Mixed models repeated measures analysis revealed significant differences between the study arms regarding total PANSS score change favouring n-3 PUFA (p = 0.016; effect size (ES) = 0.29). A fifty-percent improvement in symptom severity was achieved significantly more frequently in the n-3 PUFA group than in the placebo group (69.4 vs 40.0%; p = 0.017). N-3 PUFA intervention was also associated with an improvement in general psychopathology, measured by means of PANSS (p = 0.009; ES = 0.32), depressive symptoms (p = 0.006; ES = 0.34), the level of functioning (p = 0.01; ES = 0.31) and clinical global impression (p = 0.046; ES = 0.29). The findings suggest that 6-month intervention with n-3 PUFA may be a valuable add-on therapy able to decrease the intensity of symptoms and improve the level of functioning in first-episode schizophrenia patients.

Improvement of Psychotic Symptoms and the Role of Tissue Plasminogen Activator.

Tissue plasminogen activator (tPA) mediates a number of processes that are pivotal for synaptogenesis and remodeling of synapses, including proteolysis of the brain extracellular matrix, degradation of adhesion molecules, activation of neurotrophins, and activation of the N-methyl-d-aspartate receptor. Abnormalities in these processes have been consistently described in psychotic disorders. In this paper, we review the physiological roles of tPA, focusing on conditions characterized by low tPA activity, which are prevalent in schizophrenia. We then describe how tPA activity is influenced by lifestyle interventions and nutritional supplements that may ameliorate psychotic symptoms. Next, we analyze the role of tPA in the mechanism of action of hormones and medications effective in mitigating psychotic symptoms, such as pregnenolone, estrogen, oxytocin, dopamine D3 receptor antagonists, retinoic acid, valproic acid, cannabidiol, sodium nitroprusside, N-acetyl cysteine, and warfarin. We also review evidence that tPA participates in the mechanism by which electroconvulsive therapy and cigarette smoking may reduce psychotic symptoms.

Fatty acid and vitamin interventions in adults with schizophrenia: a systematic review of the current evidence.

Current psychopharmacological approaches to reduce psychotic phenomenology in schizophrenia are associated with adverse effects including extrapyramidal and metabolic side effects. In view of the emerging data on nutritional supplementation interventions in schizophrenia which are not entirely consistent, we aimed to review existent studies focusing on fatty acid and vitamin interventions and summarise current evidence on such nutritional supplementations in schizophrenia. We searched the digital databases (ScienceDirect, Scopus, SpringerLINK, PubMed/Medline) for relevant studies pertaining to fatty acid and vitamin supplementation interventions in the management of psychotic symptoms in schizophrenia up to February 2015. Overall, there were more studies conducted on fatty acid over vitamin supplementations in patients with schizophrenia. There were more positive findings in support of fatty acid supplementation compared with vitamin supplementation in the context of specific intervention features (dose of nutrient supplementation, single versus combination nutritional interventions, specific antipsychotic), subject features (older age, long duration of illness, baseline polyunsaturated fatty acid levels) and clinical outcomes (improvements of psychotic symptoms and/or extrapyramidal side effects from antipsychotics). However, investigations of both supplementation modalities were limited by relatively small study sample sizes, short study duration, which precluded further segmentation of impact on more diverse patient subtypes and symptom profiles. Future studies may consider examining larger samples over a longer time period, recruiting younger subjects with shorter duration of illness, examination of different clinical features including specific cognitive domains, and use of single versus combination nutritional interventions.

Dietary Intake of Sulforaphane-Rich Broccoli Sprout Extracts during Juvenile and Adolescence Can Prevent Phencyclidine-Induced Cognitive Deficits at Adulthood.

Oxidative stress and inflammation play a role in cognitive impairment, which is a core symptom of schizophrenia. Furthermore, a hallmark of the pathophysiology of this disease is the dysfunction of cortical inhibitory γ-aminobutyric acid (GABA) neurons expressing parvalbumin (PV), which is also involved in cognitive impairment. Sulforaphane (SFN), an isothiocyanate derived from broccoli, is a potent activator of the transcription factor Nrf2, which plays a central role in the inducible expressions of many cytoprotective genes in response to oxidative stress. Keap1 is a cytoplasmic protein that is essential for the regulation of Nrf2 activity. Here, we found that pretreatment with SFN attenuated cognitive deficits, the increase in 8-oxo-dG-positive cells, and the decrease in PV-positive cells in the medial prefrontal cortex and hippocampus after repeated administration of phencyclidine (PCP). Furthermore, PCP-induced cognitive deficits were improved by the subsequent subchronic administration of SFN. Interestingly, the dietary intake of glucoraphanin (a glucosinolate precursor of SFN) during the juvenile and adolescence prevented the onset of PCP-induced cognitive deficits as well as the increase in 8-oxo-dG-positive cells and the decrease in PV-positive cells in the brain at adulthood. Moreover, the NRF2 gene and the KEAP1 gene had an epistatic effect on cognitive impairment (e.g., working memory and processing speed) in patients with schizophrenia. These findings suggest that SFN may have prophylactic and therapeutic effects on cognitive impairment in schizophrenia. Therefore, the dietary intake of SFN-rich broccoli sprouts during the juvenile and adolescence may prevent the onset of psychosis at adulthood.

Nutritional interventions for the adjunctive treatment of schizophrenia: a brief review.

Schizophrenia is a chronic condition that impacts significantly not only on the individual and family, but the disorder also has wider consequences for society in terms of significant costs to the economy. This highly prevalent condition affects approximately 1% of the worldwide population, yet there are few therapeutic options. The predominant treatment strategy for schizophrenia is anti-psychotic medication (with or without additional talking therapy) even though this approach lacks efficacy in managing the negative symptoms of the condition, is not effective in one-third of the patient group and the side effects of the medication can be severe and debilitating. In recent years, a number of pathophysiological processes have been identified in groups of people with schizophrenia including oxidative stress, one-carbon metabolism and immune-mediated responses. A number of studies have shown that these altered physiological mechanisms can be ameliorated by nutritional interventions in some individuals with schizophrenia. This review briefly describes the aforementioned processes and outlines research that has investigated the utility of nutritional approaches as an adjunct to anti-psychotic medication including antioxidant and vitamin B supplementation, neuroprotective and anti-inflammatory nutrients and exclusion diets. Whilst none of these interventions provides a 'one-size-fits-all' therapeutic solution, we suggest that a personalised approach warrants research attention as there is growing agreement that schizophrenia is a spectrum disorder that develops from the interplay between environmental and genetic factors.