To date, the evidence to support the functional medicine model of care has been anecdotal, primarily published as case reports. Peer-reviewed evidence for functional medicine is based on specific interventions used by the model, including nutrition, lifestyle, or medications and dietary supplements (monotherapy or polytherapy). To our knowledge, this study is also the first systematic attempt to collect data from patients using validated measures to understand the association of HRQoL with the functional medicine model of care.

In this study, the functional medicine model of care was significantly associated with improved longitudinal PROMIS GPH scores in patients at 6 months, and these improvements remained significant for up to 12 months. Patients seen at the Center for Functional Medicine were more likely to experience a clinically meaningful change (change of ≥5 points) in their PROMIS GPH scores at 6 months, which were less likely to decrease over time. Comparing PROMIS GPH scores with those from the Family Health Center, patients seen at the Center for Functional Medicine experienced a significant longitudinal benefit for up to 12 months. However, a more robust sample size and consistent longitudinal tracking of patients are warranted to confirm this finding. The functional medicine model of care also significantly improved short-term PROMIS GMH scores in patients and demonstrated a larger association than care received in a primary care setting; however, long-term improvements were not statistically significant.

Several factors may have contributed to improvements in HRQoL associated with the functional medicine model of care. First, improvements in HRQoL associated with the functional medicine model of care may be due to the model itself. Functional medicine addresses chronic disease by delivering precision medicine. The ability to deliver precision medicine relies on one’s capability to not only collect data, but also organize it in a way that extracts an understanding of a patient’s biological processes and then maps these processes to human disease. The delivery of precision medicine also requires the ability to focus treatment around specific factors associated with a patient’s symptoms. The formal definition of functional medicine was first introduced in 1991 and tracks with the more recent precision medicine initiative.

Chronic disease is challenging health in the United States with nearly 100 million people having 1 or more chronic conditions in 2014. These individuals contribute to 90% of the nation’s annual health care expenditure. Chronic disease is a major contributor to health care costs owing to the need for disease management and care for elderly individuals. Without new approaches that focus on reversing chronic disease, our current health care model will become economically unsustainable.

Nutrition and lifestyle choices can be used to manage chronic disease; however, their use as a first-line therapy has historically been challenging for primary care physicians because most feel underequipped to deliver lifestyle recommendations despite the fact that nutrition and lifestyle are a foundation for most guidelines. There are various reasons for this feeling of inadequate preparation, including nutrition education level, confidence in the available nutrition evidence, and time with the patient.

Moreover, many chronic diseases are not diseases per se, but rather descriptions of symptoms or laboratory abnormalities. Conventional care is focused on managing symptoms of disease (eg, hypertension, abnormal blood glucose level), but underlying causes are rarely identified.

The functional medicine model of care provides an operating system that works to reverse illness, promote health, and optimize function by addressing underlying causes, symptoms, and functional imbalances in interconnected biological networks. These imbalances may impair principal biological functions (assimilation, defense and repair, energy production, biotransformation, communication, transport, and structural integrity) that result from gene-environment interactions, including lifestyle, environmental toxins, and the microbiome. Functional medicine removes triggers for illness and provides inputs to restore and optimize health. Functional medicine also addresses social determinants, including the psychological, emotional, and spiritual aspects of health and disease. A foundation of functional medicine is the use of food as medicine to prevent, treat, and reverse chronic disease. The functional medicine model of care may have the ability to improve patient’s health-related quality of life (HRQoL), including physical function and well-being. Therefore, the purpose of the present study was to investigate the association between the functional medicine model of care and HRQoL by comparing functional medicine with care received in a family medicine setting.

Importance 
The incidence of chronic disease is increasing along with health care–related costs. The functional medicine model of care provides a unique operating system to reverse illness, promote health, and optimize function. The association between this model of care and patient’s health-related quality of life (HRQoL) is unknown.
Objective 
To assess the association between functional medicine and patient-reported HRQoL using Patient-Reported Outcome Measurement Information System (PROMIS) global health measures.
Design, Setting, and Participants 
A retrospective cohort study was performed to compare 7252 patients aged 18 years or older treated in a functional medicine setting with propensity score (PS)–matched patients in a primary care setting. Sensitivity analyses assessed improvement limited to patients seen at both 6 and 12 months. The study included patients who visited the Cleveland Clinic Center for Functional Medicine or a Cleveland Clinic family health center between April 1, 2015, and March 1, 2017.
Main Outcomes and Measures 
The primary outcome was change in PROMIS Global Physical Health (GPH) at 6 months. Secondary outcomes included PROMIS Global Mental Health (GMH) at 6 months and PROMIS GPH and GMH at 12 months. The PROMIS GPH and GMH scores were transformed to a T-score from 0 to 100 with a mean of 50. Higher scores indicate a better health-related quality of life.
Results 
Of the 7252 patients (functional medicine center: 1595; family health center: 5657), 4780 (65.9%) were women; mean (SD) age was 54.1 (16.0) years. At 6 months, functional medicine patients exhibited significantly larger improvements in PROMIS GPH T-score points than were seen in patients treated at a family health center (mean [SD] change, functional medicine center: 1.59 [6.29] vs family health center: 0.33 [6.09], P = .004 in 398 PS-matched pairs). At 12 months, functional medicine patients showed improvement similar to that observed at 6 months; however, comparisons with patients seen at the family health center were not significant. Patients in the functional medicine center with data at both 6 and 12 months demonstrated improvements in PROMIS GPH (mean [SD], 2.61 [6.53]) that were significantly larger compared with patients seen at a family health center (mean [SD], 0.25 [6.54]) (P = .02 in 91 PS-matched pairs).
Conclusions and Relevance 
In this study, the functional medicine model of care demonstrated beneficial and sustainable associations with patient-reported HRQoL. Prospective studies are warranted to confirm these findings.

Importance The incidence of chronic disease is increasing along with health care–related costs. The functional medicine model of care provides a unique operating system to reverse illness, promote health, and optimize function. The association between this model of care and patient’s health-related quality of life (HRQoL) is unknown.

Objective To assess the association between functional medicine and patient-reported HRQoL using Patient-Reported Outcome Measurement Information System (PROMIS) global health measures.

Design, Setting, and Participants A retrospective cohort study was performed to compare 7252 patients aged 18 years or older treated in a functional medicine setting with propensity score (PS)–matched patients in a primary care setting. Sensitivity analyses assessed improvement limited to patients seen at both 6 and 12 months. The study included patients who visited the Cleveland Clinic Center for Functional Medicine or a Cleveland Clinic family health center between April 1, 2015, and March 1, 2017.

Main Outcomes and Measures The primary outcome was change in PROMIS Global Physical Health (GPH) at 6 months. Secondary outcomes included PROMIS Global Mental Health (GMH) at 6 months and PROMIS GPH and GMH at 12 months. The PROMIS GPH and GMH scores were transformed to a T -score from 0 to 100 with a mean of 50. Higher scores indicate a better health-related quality of life.

Results Of the 7252 patients (functional medicine center: 1595; family health center: 5657), 4780 (65.9%) were women; mean (SD) age was 54.1 (16.0) years. At 6 months, functional medicine patients exhibited significantly larger improvements in PROMIS GPH T -score points than were seen in patients treated at a family health center (mean [SD] change, functional medicine center: 1.59 [6.29] vs family health center: 0.33 [6.09], P = .004 in 398 PS-matched pairs). At 12 months, functional medicine patients showed improvement similar to that observed at 6 months; however, comparisons with patients seen at the family health center were not significant.

Background: Despite treatment advances for inflammatory arthritis, a significant amount of patients fail to achieve remission. Other modifiable factors such as diet, physical activity and environmental exposures may be an important area of focus to help patients achieve disease remission and greater overall health. Functional medicine focuses on these lifestyle factors and may be an important adjunctive therapy. In this study, we examined the impact of functional medicine on patient-reported outcomes in patients with inflammatory arthritis.

Materials And Methods: In this 12-week, retrospective study, patients with confirmed diagnoses of rheumatoid arthritis (RA) or psoriatic arthritis (PsA) were treated according to guidelines from the American College of Rheumatology for RA or PSA respectively. Those in the functional medicine group underwent a functional medicine program adjunctive to the standard of care. Patient reported outcomes, such as PROMIS (Patient Reported Outcomes Measurement Information System) global physical health, mental health and pain scores were collected at baseline and 12 weeks. Multivariable statistical modeling was used to identify the impact of functional medicine on patient-reported outcomes.

Results: 318 patients were screened and 54 patients (mean age 52.9±11.3 years, females 74(67.9%)), were included. Baseline characteristics were similar in both patient groups with the exception of PROMIS global physical health and pain (PROMIS global physical health score 43·2 ± 6·6 and 39·7 ± 8·7 and pain scores of 3·5 ± 1·9 and 5·2 ± 2·7 in the functional medicine group vs. standard of care group respectively). Using multivariable model to account for these differences, patients in the functional medicine group had a statistically significant reduction in pain (0.92, p-value = 0.007) and change in PROMIS physical health score (2·84, p-value = 0.001) as compared to the standard of care. Changes in PROMIS global mental health scores were also significant and were dependent on age and were greatest in those older than 55.

Limitations: Retrospective design, baseline difference in patient reported outcomes.

Conclusions: Functional medicine may have an important role as adjunctive therapy to improve patients' pain, physical and mental health in those who do not see improvement with conventional therapy alone.

The functional medicine model of care is focused on patient-centered rather than disease-centered care. Patient-centered care incorporates the patient's voice or experience of their condition alongside conventional biological factors to provide a "more complete" account of health. PROMIS Global, an NIH-validated patient-reported outcome (PRO) measure that evaluates the health-related quality of life, can be incorporated within the functional medicine model of care to evaluate self-reported physical, mental and social well-being across various conditions and guide personalized management strategies. Proper incorporation of PROMIS Global into clinical care and research is warranted to expand the available evidence base.

Objective: To compare outcomes and costs associated with functional medicine-based care delivered in a shared medical appointment (SMA) to those delivered through individual appointments.

Design: A retrospective cohort study was performed to assess outcomes and cost to deliver care to patients in SMAs and compared with Propensity Score (PS)-matched patients in individual appointments.

Setting: A single-centre study performed at Cleveland Clinic Center for Functional Medicine.

Participants: A total of 9778 patients were assessed for eligibility and 7323 excluded. The sample included 2455 patients (226 SMAs and 2229 individual appointments) aged ≥18 years who participated in in-person SMAs or individual appointments between 1 March 2017 and 31 December 2019. Patients had a baseline Patient-Reported Outcome Measurement Information System (PROMIS) Global Physical Health (GPH) score and follow-up score at 3 months. Patients were PS-matched 1:1 with 213 per group based on age, sex, race, marital status, income, weight, body mass index, blood pressure (BP), PROMIS score and functional medicine diagnostic category.

Primary And Secondary Outcome Measures: The primary outcome was change in PROMIS GPH at 3 months. Secondary outcomes included change in PROMIS Global Mental Health (GMH), biometrics, and cost.

Results: Among 213 PS-matched pairs, patients in SMAs exhibited greater improvements at 3 months in PROMIS GPH T-scores (mean difference 1.18 (95% CI 0.14 to 2.22), p=0.03) and PROMIS GMH T-scores (mean difference 1.78 (95% CI 0.66 to 2.89), p=0.002) than patients in individual appointments. SMA patients also experienced greater weight loss (kg) than patients in individual appointments (mean difference -1.4 (95% CI -2.15 to -0.64), p<0.001). Both groups experienced a 5.5 mm Hg improvement in systolic BP. SMAs were also less costly to deliver than individual appointments.

Conclusion: SMAs deliver functional medicine-based care that improves outcomes more than care delivered in individual appointments and is less costly to deliver.

Functional medicine is essentially patient centered, rather than disease centered. A structure is presented for uniting a patient-centered approach to diagnosis and treatment with the fruits of modern clinical science (which evolved primarily to serve the prevailing model of disease-centered care). The core scientific concepts of disease pathogenesis are antecedents, triggers, and mediators. Antecedents are factors, genetic or acquired, that predispose to illness; triggers are factors that provoke the symptoms and signs of illness; and mediators are factors, biochemical or psychosocial, that contribute to pathological changes and dysfunctional responses. Understanding the antecedents, triggers, and mediators that underlie illness or dysfunction in each patient permits therapy to be targeted to the needs of the individual. The conventional diagnosis assigned to the patient may be of value in identifying plausible antecedents, triggers or mediators for each patient, but is not adequate by itself for the designing of patient-centered care. Applying the model of person-centered diagnosis to patients facilitates the recognition of disturbances that are common in people with chronic illness. Diet, nutrition, and exposure to environmental toxins play central roles in functional medicine because they may predispose to illness, provoke symptoms, and modulate the activity of biochemical mediators through a complex and diverse set of mechanisms. Explaining those mechanisms is a key objective of the Textbook of Functional Medicine (from which this article is excerpted). A patient's beliefs about health and illness are critically important for self-care and may influence both behavioral and physiological responses to illness. Perceived self-efficacy is an important mediator of health and healing. Enhancement of patients' self-efficacy through information, education, and the development of a collaborative relationship between patient and healer is a cardinal goal in all clinical encounters.

Using the functional medicine rubric in physical medicine and rehabilitation (PM&R), a physiatrist can capitalize on addressing the root causes and downstream effects in patients with chronic diseases. Similar to the International Classification of Function model in rehabilitation, the functional medicine model uses biopsychosocial understanding with a systems biology approach to find fulcrum points to create the biggest impact on health care. Given the position of rehabilitation medicine with the type and location of patients, both functional medicine and PM&R would benefit from a mutual partnership.

Mental illness, including depression, anxiety and bipolar disorder, accounts for a significant proportion of global disability and poses a substantial social, economic and heath burden. Treatment is presently dominated by pharmacotherapy, such as antidepressants, and psychotherapy, such as cognitive behavioural therapy; however, such treatments avert less than half of the disease burden, suggesting that additional strategies are needed to prevent and treat mental disorders. There are now consistent mechanistic, observational and interventional data to suggest diet quality may be a modifiable risk factor for mental illness. This review provides an overview of the nutritional psychiatry field. It includes a discussion of the neurobiological mechanisms likely modulated by diet, the use of dietary and nutraceutical interventions in mental disorders, and recommendations for further research. Potential biological pathways related to mental disorders include inflammation, oxidative stress, the gut microbiome, epigenetic modifications and neuroplasticity. Consistent epidemiological evidence, particularly for depression, suggests an association between measures of diet quality and mental health, across multiple populations and age groups; these do not appear to be explained by other demographic, lifestyle factors or reverse causality. Our recently published intervention trial provides preliminary clinical evidence that dietary interventions in clinically diagnosed populations are feasible and can provide significant clinical benefit. Furthermore, nutraceuticals including n-3 fatty acids, folate, S-adenosylmethionine, N-acetyl cysteine and probiotics, among others, are promising avenues for future research. Continued research is now required to investigate the efficacy of intervention studies in large cohorts and within clinically relevant populations, particularly in patients with schizophrenia, bipolar and anxiety disorders.

Psychiatry is at an important juncture, with the current pharmacologically focused model having achieved modest benefits in addressing the burden of poor mental health worldwide. Although the determinants of mental health are complex, the emerging and compelling evidence for nutrition as a crucial factor in the high prevalence and incidence of mental disorders suggests that diet is as important to psychiatry as it is to cardiology, endocrinology, and gastroenterology. Evidence is steadily growing for the relation between dietary quality (and potential nutritional deficiencies) and mental health, and for the select use of nutrient-based supplements to address deficiencies, or as monotherapies or augmentation therapies. We present a viewpoint from an international collaboration of academics (members of the International Society for Nutritional Psychiatry Research), in which we provide a context and overview of the current evidence in this emerging field of research, and discuss the future direction. We advocate recognition of diet and nutrition as central determinants of both physical and mental health.

The nascent field of 'Nutritional Psychiatry' offers much promise for addressing the large disease burden associated with mental disorders. A consistent evidence base from the observational literature confirms that the quality of individuals' diets is related to their risk for common mental disorders, such as depression. This is the case across countries and age groups. Moreover, new intervention studies implementing dietary changes suggest promise for the prevention and treatment of depression. Concurrently, data point to the utility of selected nutraceuticals as adjunctive treatments for mental disorders and as monotherapies for conditions such as ADHD. Finally, new studies focused on understanding the biological pathways that mediate the observed relationships between diet, nutrition and mental health are pointing to the immune system, oxidative biology, brain plasticity and the microbiome-gut-brain axis as key targets for nutritional interventions. On the other hand, the field is currently limited by a lack of data and methodological issues such as heterogeneity, residual confounding, measurement error, and challenges in measuring and ensuring dietary adherence in intervention studies. Key challenges for the field are to now: replicate, refine and scale up promising clinical and population level dietary strategies; identify a clear set of biological pathways and targets that mediate the identified associations; conduct scientifically rigorous nutraceutical and 'psychobiotic' interventions that also examine predictors of treatment response; conduct observational and experimental studies in psychosis focused on dietary and related risk factors and treatments; and continue to advocate for policy change to improve the food environment at the population level.

There is increasing academic and clinical interest in how "lifestyle factors" traditionally associated with physical health may also relate to mental health and psychological well-being. In response, international and national health bodies are producing guidelines to address health behaviors in the prevention and treatment of mental illness. However, the current evidence for the causal role of lifestyle factors in the onset and prognosis of mental disorders is unclear. We performed a systematic meta-review of the top-tier evidence examining how physical activity, sleep, dietary patterns and tobacco smoking impact on the risk and treatment outcomes across a range of mental disorders. Results from 29 meta-analyses of prospective/cohort studies, 12 Mendelian randomization studies, two meta-reviews, and two meta-analyses of randomized controlled trials were synthesized to generate overviews of the evidence for targeting each of the specific lifestyle factors in the prevention and treatment of depression, anxiety and stress-related disorders, schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. Standout findings include: a) convergent evidence indicating the use of physical activity in primary prevention and clinical treatment across a spectrum of mental disorders; b) emerging evidence implicating tobacco smoking as a causal factor in onset of both common and severe mental illness; c) the need to clearly establish causal relations between dietary patterns and risk of mental illness, and how diet should be best addressed within mental health care; and d) poor sleep as a risk factor for mental illness, although with further research required to understand the complex, bidirectional relations and the benefits of non-pharmacological sleep-focused interventions. The potentially shared neurobiological pathways between multiple lifestyle factors and mental health are discussed, along with directions for future research, and recommendations for the implementation of these findings at public health and clinical service levels.

Substance use disorders are a growing concern for all ages, including adolescents. Even though there is an increase in recreational substance use and a wider variety of drugs is available to this young population, treatment options remain scarce. Most medications have limited evidence in this population. Few specialists treat individuals struggling with addiction along with mental health disorders. As the evidence grows, these treatments are usually included in complementary and integrative medicine. This article discusses available evidence for many complementary and integrative treatment approaches while briefly describing existing psychotherapeutic and psychotropic medications.

There is a strong relationship between a healthy diet and mental well-being. Several foods and food compounds are known to modulate biomarkers and molecular mechanisms involved in the aetiogenesis of several mental disorders, and this can be useful in containing the disease progression, including its prophylaxis. This is an updated systematic review of the literature to justify the inclusion and recognition of nutrition in the management of psychiatric illnesses. Such foods and their compounds include dietary flavanols from fruits and vegetables, notable antioxidant and anti-inflammatory agents, probiotics (fermented foods) known to protect good gut bacteria, foods rich in polyunsaturated fatty acids (e.g., Omega-3), and avoiding diets high in saturated fats and refined sugars among others. While the exact mechanism(s) of mitigation of many nutritional interventions are yet to be fully understood, the evidence-based approach warrants the inclusion and co-recognition of nutrition in the management of psychiatric illnesses. For the greater public health benefit, there is a need for policy advocacy aimed at bridging the knowledge gap and encouraging the integration of nutritional intervention with contemporary therapies in clinical settings, as deficiencies of certain nutrients make therapy difficult even with appropriate medication.

Despite evidence that probiotic formulations can improve mental health dating back to the early 20th century, it was only following advances in DNA/RNA sequencing technologies that the involvement of the gut microbiota in the pathophysiology of psychiatric disorders was recognized. Preclinical studies have consistently demonstrated that fecal microbiota transplants from patients with a wide range of psychiatric conditions result in the development of the behavioral and physiological profile of the condition in germ-free mice. This suggests that psychiatric disorders may be associated with a distinct pattern of microbial perturbations, which may serve as a biomarker.

Attempts to characterize the composition of the microbiota in psychiatric populations have yielded plentiful yet contradictory results. Nevertheless, systematic reviews in individual disorders have been able to identify patterns that may be promising biomarker targets. Indeed, the addition of such biomarkers can improve diagnostic accuracy, guide treatment, and assist the monitoring of treatment response. For the definition of a biomarker to be met, ie, “substance, structure or process that can be measured in the body and influence or predict the incidence of outcome or disease,” the specificity and reproducibility of the alteration needs to be demonstrated. Therefore, it is crucial to compare microbial perturbations across the wider range of psychiatric conditions.

We performed an umbrella and updated review and meta-analysis of gut microbiota studies in adults with major depressive disorder (MDD), bipolar disorder, psychosis and schizophrenia, anxiety disorders, obsessive compulsive disorder (OCD), eating disorders (anorexia nervosa and bulimia nervosa), autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), and posttraumatic stress disorder (PTSD) to evaluate the specificity and reproducibility of gut microbiota alterations and delineate those with potential to become biomarkers.

Schizophrenia is a chronic and progressive disorder characterized by cognitive, emotional, and behavioral abnormalities associated with neuronal development and synaptic plasticity alterations. Genetic and epigenetic abnormalities in cortical parvalbumin-positive GABAergic interneurons and consequent alterations in glutamate-mediated excitatory neurotransmission during early neurodevelopment underlie schizophrenia manifestation and progression. Also, epigenetic alterations during pregnancy or early phases of postnatal life are associated with schizophrenia vulnerability and inflammatory processes, which are at the basis of brain pathology and a higher risk of comorbidities, including cardiovascular diseases and metabolic syndrome. In addition, schizophrenia patients adopt an unhealthy lifestyle and poor nutrition, leading to premature death. Here, I explored the role of functional nutrition as an integrated intervention for the long-term management of patients with schizophrenia. Several natural bioactive compounds in plant-based whole foods, including flavonoids, phytonutrients, vitamins, fatty acids, and minerals, modulate brain functioning by targeting neuroinflammation and improving cognitive decline. Although further clinical studies are needed, a functional diet rich in natural bioactive compounds might be effective in synergism with standard treatments to improve schizophrenia symptoms and reduce the risk of comorbidities.

Background: Psychonutrition, i.e. the impact of diet on mental health, is an emerging field of psychiatry.

Objective: The purpose of the present letter was to highlight recent findings in the field to guide nutritional interventions in psychiatry.

Method: An overview of the most recent meta-analyses in the field of psychonutrition in severe mental disorders has been carried out.

Results: The Mediterranean diet showed the best evidence for effectiveness in diminishing the incidence of depressive symptomatology Complementary agents were found to be associated with lower depression levels (even in psychiatric populations): omegas 3 fatty acids, vitamin D, methylfolate and S-adenosylmethionine, all being found in high rates in the Mediterranean diet. The Healthy Eating Index (HEI) has also been found to be associated with lower depression. Moreover, major depression has been associated with inflammatory disturbances and a diet with a low Dietary Inflammatory Index has also been shown to be associated with lower depression. These effects may be mediated by microbiota modifications and probiotic supplementation has been recently shown to be effective in the treatment of depression. A high protein diet may also be particularly useful in psychiatry. The high protein diet has shown effectiveness in weight loss and increasing satiety with no evidence for deleterious effects in subjects without chronic conditions like renal failure, diabetes or cardiovascular disease. A reduction of 20% of calorific intake +/- intermittent fasting (i.e. fasting for 12 to 16 h per day) may also improve microbiota and therefore psychiatric conditions.

Conclusion: In light of these findings, diet modifications appear to be an underutilized tool with which to improve the mental and physical health of psychiatric patients.

Mental illness, including depression, anxiety and bipolar disorder, accounts for a significant proportion of global disability and poses a substantial social, economic and heath burden. Treatment is presently dominated by pharmacotherapy, such as antidepressants, and psychotherapy, such as cognitive behavioural therapy; however, such treatments avert less than half of the disease burden, suggesting that additional strategies are needed to prevent and treat mental disorders. There are now consistent mechanistic, observational and interventional data to suggest diet quality may be a modifiable risk factor for mental illness. This review provides an overview of the nutritional psychiatry field. It includes a discussion of the neurobiological mechanisms likely modulated by diet, the use of dietary and nutraceutical interventions in mental disorders, and recommendations for further research. Potential biological pathways related to mental disorders include inflammation, oxidative stress, the gut microbiome, epigenetic modifications and neuroplasticity. Consistent epidemiological evidence, particularly for depression, suggests an association between measures of diet quality and mental health, across multiple populations and age groups; these do not appear to be explained by other demographic, lifestyle factors or reverse causality. Our recently published intervention trial provides preliminary clinical evidence that dietary interventions in clinically diagnosed populations are feasible and can provide significant clinical benefit. Furthermore, nutraceuticals including n-3 fatty acids, folate, S-adenosylmethionine, N-acetyl cysteine and probiotics, among others, are promising avenues for future research. Continued research is now required to investigate the efficacy of intervention studies in large cohorts and within clinically relevant populations, particularly in patients with schizophrenia, bipolar and anxiety disorders.

The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from "nutrient supplements", such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta-analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta-review of this top-tier evidence, we identified, synthesized and appraised all meta-analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 meta-analyses of placebo-controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention-deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia. Folate-based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high-dose methylfolate in major depressive disorder. There was emergent evidence for N-acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications. In conclusion, clinicians should be informed of the nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence-based supplements, to further elucidate the underlying mechanisms.

Major Depressive Disorder (MDD) is a growing disabling condition affecting around 280 million people worldwide. This complex entity is the result of the interplay between biological, psychological, and sociocultural factors, and compelling evidence suggests that MDD can be considered a disease that occurs as a consequence of an evolutionary mismatch and unhealthy lifestyle habits. In this context, diet is one of the core pillars of health, influencing multiple biological processes in the brain and the entire body. It seems that there is a bidirectional relationship between MDD and malnutrition, and depressed individuals often lack certain critical nutrients along with an aberrant dietary pattern. Thus, dietary interventions are one of the most promising tools to explore in the field of MDD, as there are a specific group of nutrients (i.e., omega 3, vitamins, polyphenols, and caffeine), foods (fish, nuts, seeds fruits, vegetables, coffee/tea, and fermented products) or dietary supplements (such as S-adenosylmethionine, acetyl carnitine, creatine, amino acids, etc.), which are being currently studied. Likewise, the entire nutritional context and the dietary pattern seem to be another potential area of study, and some strategies such as the Mediterranean diet have demonstrated some relevant benefits in patients with MDD; although, further efforts are still needed. In the present work, we will explore the state-of-the-art diet in the prevention and clinical support of MDD, focusing on the biological properties of its main nutrients, foods, and dietary patterns and their possible implications for these patients.

This narrative review was conducted using searches of the PubMed/Medline and Google Scholar databases from inception to November 2019. Clinical trials and relevant articles were identified by cross-referencing major depressive disorder (and/or variants) with the following terms: folate, homocysteine, S-adenosylmethionine (SAMe), L-acetylcarnitine, alpha-lipoic acid, N-acetylcysteine, L-tryptophan, zinc, magnesium, vitamin D, omega-3 fatty acids, coenzyme Q10, and inositol. Manual reviews of references were also performed using article reference lists. Abnormal levels of folate, homocysteine, and SAMe have been shown to be associated with a higher risk of depression. Numerous studies have demonstrated antidepressant activity with L-methylfolate and SAMe supplementation in individuals with depression. Additionally, the amino acids L-acetylcarnitine, alpha-lipoic acid, N-acetylcysteine, and L-tryptophan have been implicated in the development of depression and shown to exert antidepressant effects. Other agents with evidence for improving depressive symptoms include zinc, magnesium, omega-3 fatty acids, and coenzyme Q10. Potential biases and differences in study designs within and amongst the studies and reviews selected may confound results. Augmentation of antidepressant medications with various supplements targeting nutritional and physiological factors can potentiate antidepressant effects. Medical foods, particularly L-methylfolate, and other supplements may play a role in managing depression in patients with inadequate response to antidepressant therapies.

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.

Substance use disorders are a growing concern for all ages, including adolescents. Even though there is an increase in recreational substance use and a wider variety of drugs is available to this young population, treatment options remain scarce. Most medications have limited evidence in this population. Few specialists treat individuals struggling with addiction along with mental health disorders. As the evidence grows, these treatments are usually included in complementary and integrative medicine. This article discusses available evidence for many complementary and integrative treatment approaches while briefly describing existing psychotherapeutic and psychotropic medications.

Issues: Substance use disorders are chronic relapsing disorders, leading to significant impairment in psychosocial functioning. Conventional therapies have not been able to alter the outcome of these disorders significantly and frequent relapses continue to occur, despite the development of newer medications, like baclofen, ondansetron, etc. Hence, there is a need to look at complementary and alternate systems of medicine.

Approach: This article is a review of the evidence for complementary and alternate systems of medicine in substance use disorders. Articles were searched using the Medical Subject Headings (MeSH) database of the PubMed search engine and further non-indexed information was obtained from the Google search engine. The article is organised in parts, each reviewing a different system of medicine in the following order--alternate medical systems, biologically based therapies, energy-based interventions and mind-body interventions; as classified by the National Center for Complementary and Alternative Medicine, National Institutes of Health, USA.

Key Findings: The currently available evidence is limited and not very encouraging. At present only acupuncture, herbal therapies and mind-body interventions have shown some positive results in human trials and hold promise for the future.

Implications: This review emphasises the paucity of research into this important field especially the lack of rigorous human trials.

Conclusion: More systematic studies are required before these systems of medicine can be widely recommended in the treatment of substance use disorders.

Substance use disorders (SUDs) represent a major challenge in psychiatric treatment, with significant relapse rates despite various psychotherapeutic interventions. This systematic review explores the neurobiological underpinnings of addiction and examines the efficacy of psychotherapies, such as Cognitive Behavioral Therapy (CBT), Eye Movement Desensitization and Reprocessing (EMDR), Mindfulness-Based Relapse Prevention (MBRP), and emerging therapies in treating SUDs. Additionally, the study assesses how emerging biomarkers and neuroimaging data could enhance therapeutic outcomes by guiding personalized treatments. Neurobiological markers, such as prefrontal-limbic connectivity, mesolimbic dopaminergic dysregulation, and glutamate transmission deficits, are shown to significantly influence treatment efficacy. For example, prefrontal cortex hypoactivity and amygdala hyperactivity correlate with poor impulse control and emotional regulation, making these individuals more responsive to CBT and EMDR. Similarly, dopaminergic dysfunction in the mesolimbic pathway is closely tied to reward-seeking behavior where Transcranial Magnetic Stimulation (TMS) may offer therapeutic benefits. Epigenetic modifications, primarily those affecting the glucocorticoid receptor (GR), highlight the role of stress in relapse suggesting that trauma-focused therapies can be effective for individuals with high stress vulnerability. This review finds that integrating neurobiological insights with clinically validated psychometric assessments could significantly improve treatment stratification. Future research should focus on aligning diagnostic systems, such as the DSM-5, with neurobiological markers and psychological tells to facilitate more precise and personalized interventions, potentially transforming addiction treatment outcomes.

Mindfulness involves attending to experiences on a moment-to-moment basis with intention to cultivate nonjudgmental, nonreactive states of awareness. Mindfulness-based treatments teach patients to remain in contact with and relate differently to challenging affective or physical states, use alternatives to avoidant-based coping, recognize underlying reasons for maladaptive behaviors, and identify and increase contact with natural contingencies.

Mindfulness training has been associated with reductions in anxiety, disordered eating, and depressive relapse, and a growing body of literature supports its efficacy for SUD treatment. Complementing previous theory, integrating mindfulness practices into treatment may not only provide an alternative to standard RP, it may also enhance its efficacy. Mindfulness-based practices offer incremental training in awareness of environmental cues and internal phenomena, including cognitive and affective states that have previously triggered relapse, interrupting the habitual response of substance use. These practices may also function as exposure to internal experiences that often precipitate relapse, such as negative affect and craving. The resultant habituation may generalize to discomfort associated with a broader class of triggers. In contrast, RP practices often identify specific situations to avoid or present alternative coping strategies. Focus on internal experience vs external cues, however, may increase acceptance and tolerance of substance use cues and associated internal distress, decrease subjective urgency to alleviate discomfort via substance use, and decouple negative affect and substance use.

Background: Emotion (dys)regulation as well as the interventions for improving these difficulties are receiving a growing attention in the literature. The aim of the present paper was to conduct a systematic review about the efficacy of mindfulness-based interventions (MBIs) in both substance and behavioral addictions (BAs).

Method: A literature search was conducted using Cochrane, PubMed, and Web of Science. Fifty-four randomized controlled trials published in English since 2009 to April 2017 were included into a narrative synthesis.

Results: Mindfulness-based interventions were applied in a wide range of addictions, including substance use disorders (from smoking to alcohol, among others) and BAs (namely, gambling disorder). These treatments were successful for reducing dependence, craving, and other addiction-related symptoms by also improving mood state and emotion dysregulation. The most commonly used MBI approaches were as follows: Mindfulness-Based Relapse Prevention, Mindfulness Training for Smokers, or Mindfulness-Oriented Recovery Enhancement, and the most frequent control group in the included studies was Treatment as Usual (TAU). The most effective approach was the combination of MBIs with TAU or other active treatments. However, there is a lack of studies showing the maintenance of the effect over time. Therefore, studies with longer follow-ups are needed.

Conclusion: The revised literature shows support for the effectiveness of the MBIs. Future research should focus on longer follow-up assessments as well as on adolescence and young population, as they are a vulnerable population for developing problems associated with alcohol, drugs, or other addictions.

Mindfulness-based interventions (MBIs) are increasingly suggested as therapeutic approaches for effecting substance use and misuse (SUM). The aim of this article is to review current evidence on the therapeutic efficacy of MBIs for SUM. A literature search was undertaken using four electronic databases and references of retrieved articles. The search included articles written in English published up to December 2011. Quality of included trials was assessed. In total, 24 studies were included, three of which were based on secondary analyses of previously investigated samples. Current evidence suggests that MBIs can reduce the consumption of several substances including alcohol, cocaine, amphetamines, marijuana, cigarettes, and opiates to a significantly greater extent than waitlist controls, non-specific educational support groups, and some specific control groups. Some preliminary evidence also suggests that MBIs are associated with a reduction in craving as well as increased mindfulness. The limited generalizability of the reviewed findings is noted (i.e., small sample size, lack of methodological details, and the lack of consistently replicated findings). More rigorous and larger randomized controlled studies are warranted.

Opioid use is a major public health crisis in the US, with approximately more than 80 000 opioid overdose deaths in 2023. Buprenorphine treatment reduces illicit opioid use and overdose risk; however, studies report that most patients discontinue buprenorphine medical management within 6 months. Several factors that may serve as treatment targets can increase the likelihood of poor outcomes. Comorbid substance use (eg, cocaine, methamphetamine) increases treatment dropout. Psychiatric symptoms (eg, anxiety), benzodiazepine misuse, and opioid craving increase relapse risk. Opioid craving is associated with subsequent use during buprenorphine treatment, is often preceded by negative affect or withdrawal states, and intensifies during exposure to drug cues or stressful life events. Behavioral interventions targeting these factors may improve outcomes, but, aside from contingency management, a systematic review identified no clear benefits to adjunctive individual counseling or cognitive-behavioral therapy. Unlike individual treatment, group treatment attendance has been associated with increased opioid treatment completion, and group-based opioid treatment appears feasible, acceptable, and may improve treatment outcomes.

Mindfulness-based interventions are an increasingly popular evidence-based group treatment for substance use disorders. A recent fully powered randomized clinical trial found that a mindfulness program reduced opioid use and craving among people with both chronic pain and OUD during methadone maintenance. Mindfulness training appears to increase individuals’ capacities for self-regulation through enhanced attentional control, cognitive control, emotion regulation, and self-related processes. Mindful behavior change, a curriculum created to leverage those mechanisms, was shown to reduce anxiety symptoms, increase self-regulation, and catalyze health behavior change in trials of the Mindfulness Training for Primary Care program. The established Mindfulness Training for Primary Care curriculum was adapted for patients with OUD and a 24-week trauma-informed Mindful Recovery Opioid Use Disorder Care Continuum (M-ROCC) was created. A single-arm multisite pilot trial found M-ROCC feasible and acceptable during buprenorphine treatment. Additionally, participants experienced significant reductions in anxiety and decreased benzodiazepine and cocaine use but not opioid use.

Mindfulness-based interventions (MBI) are increasingly used in the treatment of patients with mental disorders, in particular in individuals presenting with affective disorders or in patients exhibiting abnormal levels of impulsive behavior. MBI have been also offered to patients with substance use disorders, where such treatment options may yield considerable clinical effects. Neural effects associated with MBI have been increasingly acknowledged, but is unknown whether MBI exert specific effects on brain structure in patients with substance use disorders. In this study, we investigated 19 inpatients with opioid dependence receiving treatment-as-usual (TAU, n = 9) or additional MBI (n = 10). Structural magnetic resonance imaging data were acquired before and after four weeks of treatment. Source-based morphometry was used to investigate modulation of structural networks after treatment. Both treatment modalities led to significant clinical improvement. Patients receiving MBI showed a significant change in distress tolerance levels. An increase in bilateral striatal/insular and prefrontal/cingulate network strength was found in patients receiving MBI compared to individuals receiving TAU. Prefrontal/cingulate cortical network strength was associated with impulsivity levels. These findings suggest that MBI can have a recognizable role in treatment of substance use disorders and that neural effects of MBI may be captured in terms of frontostriatal structural network change.

Background: Substance use disorders (SUDs) affect ~ 35 million people globally and are associated with strong cravings, stress, and brain alterations. Mindfulness-based interventions (MBIs) can mitigate the adverse psychosocial outcomes of SUDs, but the underlying neurobiology is unclear. Emerging findings were systematically synthesised from fMRI studies about MBI-associated changes in brain function in SUDs and their associations with mindfulness, drug quantity, and craving.

Methods: PsycINFO, Medline, CINAHL, PubMed, Scopus, and Web of Science were searched. Seven studies met inclusion criteria.

Results: Group by time effects indicated that MBIs in SUDs (6 tobacco and 1 opioid) were associated with changes in the function of brain pathways implicated in mindfulness and addiction (e.g., anterior cingulate cortex and striatum), which correlated with greater mindfulness, lower craving and drug quantity.

Conclusions: The evidence for fMRI-related changes with MBI in SUD is currently limited. More fMRI studies are required to identify how MBIs mitigate and facilitate recovery from aberrant brain functioning in SUDs.

Neurofeedback (NF), a form of biofeedback, is used to enhance the self-regulation of brain functions by assessing brain activity and delivering feedback signals to ameliorate emotional attributes, cognitive functions, and behaviors. Despite the potential role of NF in substance use disorder (SUD) treatment, a number of gaps such as variations in NF methods persist. This study aims to address such gaps and present comprehensive insights into EEG and fMRI-NF applications in SUD management. This study has been conducted according to the PRISMA guidelines. The search spanned four major databases: Web of Science, Scopus, PubMed, and Embase. The search terms encompassed "Neurofeedback" OR "EEG biofeedback" OR "neurotherapy" OR "Functional near-infrared spectroscopy Neurofeedback" OR "fNIRS-Neurofeedback" AND addiction OR Drug OR "substance dependence" OR "substance abuse" OR Heroin OR Opioid OR Cannabis OR Marihuana OR Cocaine OR Crack OR Amphetamine OR Methamphetamine OR Hallucinogen. Our systematic review yielded 32 articles, including 18 EEG-, 11 fMRI-neurofeedback, and 3 fNIRS-neurofeedback studies. The primary outcome was reduced drug craving and some aspects of mental health and EEG-NF studies consistently indicated a preference for the alpha-theta protocol, whereas the high heterogeneity among fMRI-NF protocols limited direct comparisons. In conclusion, the results of this systematic review indicate that NF shows promise as an adjunctive intervention for treating SUD.

Introduction: The United States has been battling an opioid epidemic for decades. As substance use disorders have grown, so too has investigation into treatment options, including integrative medicine approaches, for managing opioid withdrawal symptoms (OWS).

Objectives: This systematic review sought to assess the use of integrative medicine approaches for the alleviation of OWS in patients dependent on opioids and to summarize the available data.

Methods: The authors searched using synonyms for opioids, substance use disorder, and integrative medicine and standardized searches in Embase, PubMed, and Cochrane Library. We also hand searched references for systematic reviews. This review did not include articles that could not be obtained as full-text publications via interlibrary loan. The review also excluded studies with interventions involving acupuncture because multiple systematic reviews on this approach already exist. In addition, we also excluded studies of therapy for opioid maintenance. We evaluated studies for inclusion based on the Jadad criteria. We compared opioid withdrawal outcomes of the studies to determine the efficacy of integrative medicine approaches.

Results: The authors identified a total of 382 unique publications initially for possible inclusion through systematic searches. After applying inclusion and exclusion criteria, five studies met Jadad criteria. The authors identified an additional two studies for inclusion via hand searching. A total of seven studies included interventions consisting of passionflower, weinicom, fu-yuan pellet, jinniu capsules, tai-kang-ning, dynorphin, and l-tetrahydropalmatine. Analyzing the articles was difficult given the varied scoring methods they used to quantify opioid withdrawal symptoms and the small sample sizes in the trials. Most showed evidence that supported integrative medicine approaches for OWS, although the strength of evidence was limited because of sample sizes.

Conclusions: This review found evidence of multiple integrative medicine approaches for opioid withdrawal symptoms. Well-designed randomized controlled trials should assess the efficacy of integrative medicine for improvement in OWS.

Mental illness, including depression, anxiety and bipolar disorder, accounts for a significant proportion of global disability and poses a substantial social, economic and heath burden. Treatment is presently dominated by pharmacotherapy, such as antidepressants, and psychotherapy, such as cognitive behavioural therapy; however, such treatments avert less than half of the disease burden, suggesting that additional strategies are needed to prevent and treat mental disorders. There are now consistent mechanistic, observational and interventional data to suggest diet quality may be a modifiable risk factor for mental illness. This review provides an overview of the nutritional psychiatry field. It includes a discussion of the neurobiological mechanisms likely modulated by diet, the use of dietary and nutraceutical interventions in mental disorders, and recommendations for further research. Potential biological pathways related to mental disorders include inflammation, oxidative stress, the gut microbiome, epigenetic modifications and neuroplasticity. Consistent epidemiological evidence, particularly for depression, suggests an association between measures of diet quality and mental health, across multiple populations and age groups; these do not appear to be explained by other demographic, lifestyle factors or reverse causality. Our recently published intervention trial provides preliminary clinical evidence that dietary interventions in clinically diagnosed populations are feasible and can provide significant clinical benefit. Furthermore, nutraceuticals including n-3 fatty acids, folate, S-adenosylmethionine, N-acetyl cysteine and probiotics, among others, are promising avenues for future research. Continued research is now required to investigate the efficacy of intervention studies in large cohorts and within clinically relevant populations, particularly in patients with schizophrenia, bipolar and anxiety disorders.

Psychological and pharmacological interventions are the most common treatments for adult depression. While these interventions have robust evidence supporting their efficacy, there remain up to 60 percent of individuals who do not respond to treatment, or only partially respond. Unfortunately, efforts at improving outcome rates from new or modified versions of psychological or pharmacological interventions have been disappointing. It is argued that increased treatment efficacy for depression may be achieved by utilising integrative or adjunctive treatments. As depression is influenced by an array of psychological, biological, social, environmental, dietary, and lifestyle factors, it is hypothesised that treatment outcomes will only be improved when integrative interventions are utilised. The research supporting the potential of several of these factors are reviewed in this article including those associated with diet, exercise, sleep, sunshine/light, nature, herbs and nutraceuticals, social connections, meditation, religion/spirituality, and alcohol and nicotine use. It is argued that increased efforts should be directed at investigating integrative or adjunctive interventions, rather than stand-alone treatments, to enhance outcomes for depression.

Substance use disorders are a growing concern for all ages, including adolescents. Even though there is an increase in recreational substance use and a wider variety of drugs is available to this young population, treatment options remain scarce. Most medications have limited evidence in this population. Few specialists treat individuals struggling with addiction along with mental health disorders. As the evidence grows, these treatments are usually included in complementary and integrative medicine. This article discusses available evidence for many complementary and integrative treatment approaches while briefly describing existing psychotherapeutic and psychotropic medications.

Psychiatry is at an important juncture, with the current pharmacologically focused model having achieved modest benefits in addressing the burden of poor mental health worldwide. Although the determinants of mental health are complex, the emerging and compelling evidence for nutrition as a crucial factor in the high prevalence and incidence of mental disorders suggests that diet is as important to psychiatry as it is to cardiology, endocrinology, and gastroenterology. Evidence is steadily growing for the relation between dietary quality (and potential nutritional deficiencies) and mental health, and for the select use of nutrient-based supplements to address deficiencies, or as monotherapies or augmentation therapies. We present a viewpoint from an international collaboration of academics (members of the International Society for Nutritional Psychiatry Research), in which we provide a context and overview of the current evidence in this emerging field of research, and discuss the future direction. We advocate recognition of diet and nutrition as central determinants of both physical and mental health.

The nascent field of 'Nutritional Psychiatry' offers much promise for addressing the large disease burden associated with mental disorders. A consistent evidence base from the observational literature confirms that the quality of individuals' diets is related to their risk for common mental disorders, such as depression. This is the case across countries and age groups. Moreover, new intervention studies implementing dietary changes suggest promise for the prevention and treatment of depression. Concurrently, data point to the utility of selected nutraceuticals as adjunctive treatments for mental disorders and as monotherapies for conditions such as ADHD. Finally, new studies focused on understanding the biological pathways that mediate the observed relationships between diet, nutrition and mental health are pointing to the immune system, oxidative biology, brain plasticity and the microbiome-gut-brain axis as key targets for nutritional interventions. On the other hand, the field is currently limited by a lack of data and methodological issues such as heterogeneity, residual confounding, measurement error, and challenges in measuring and ensuring dietary adherence in intervention studies. Key challenges for the field are to now: replicate, refine and scale up promising clinical and population level dietary strategies; identify a clear set of biological pathways and targets that mediate the identified associations; conduct scientifically rigorous nutraceutical and 'psychobiotic' interventions that also examine predictors of treatment response; conduct observational and experimental studies in psychosis focused on dietary and related risk factors and treatments; and continue to advocate for policy change to improve the food environment at the population level.

The field of 'nutritional psychiatry' has evolved with rapidity over the past several years, with an increasing amount of dietary or nutrient-based (nutraceutical) intervention studies being initiated, and more preclinical and epidemiological data being available. This emergent paradigm involves the clinical consideration (where appropriate) of prescriptive dietary modification/improvement, and/or the select judicious use of nutrient-based supplementation to prevent or manage psychiatric disorders. In the last several years, significant links have increasingly been established between dietary quality and mental health (although not all data are supportive). Maternal and early-life nutrition may also affect the mental health outcomes in offspring. In respect to nutraceutical research, like with many recent conventional drug studies, results are fairly mixed across the board, and in many cases there is not emphatic evidence to support the use of nutraceuticals in various psychiatric disorders. This may in part be due to a preponderance of recent studies within the field revealing marked placebo effects. Due to current indicators pointing towards mental disorders having an increasing burden of disease, bold and innovative approaches on a societal level are now required. In light of the widespread use of nutrient supplements by those with and without mental disorders, it is also critical that scientifically rigorous methodologies be brought to bear on the assessment of the efficacy of these supplements, and to determine if, or what dose of, a nutrient supplement is required, for whom, and when, and under what circumstances. More simple studies of additional isolated nutrients are not of great benefit to the field (unless studied in supra-dosage in an individualised, biomarker-guided manner), nor, based on recent data, is the research of 'shotgun' formulations of nutraceuticals. The next critical step for the field is to design psychiatric interventional studies for both dietary modification and nutraceuticals, based on more of a personalised medicine approach, using biomarkers (e.g. nutrient deficiencies, inflammatory cytokine levels, genomic assessment, microbiome analysis) and a person's dietary patterns and individual macro/micronutrient requirements.

To date, the evidence to support the functional medicine model of care has been anecdotal, primarily published as case reports. Peer-reviewed evidence for functional medicine is based on specific interventions used by the model, including nutrition, lifestyle, or medications and dietary supplements (monotherapy or polytherapy). To our knowledge, this study is also the first systematic attempt to collect data from patients using validated measures to understand the association of HRQoL with the functional medicine model of care.

In this study, the functional medicine model of care was significantly associated with improved longitudinal PROMIS GPH scores in patients at 6 months, and these improvements remained significant for up to 12 months. Patients seen at the Center for Functional Medicine were more likely to experience a clinically meaningful change (change of ≥5 points) in their PROMIS GPH scores at 6 months, which were less likely to decrease over time. Comparing PROMIS GPH scores with those from the Family Health Center, patients seen at the Center for Functional Medicine experienced a significant longitudinal benefit for up to 12 months. However, a more robust sample size and consistent longitudinal tracking of patients are warranted to confirm this finding. The functional medicine model of care also significantly improved short-term PROMIS GMH scores in patients and demonstrated a larger association than care received in a primary care setting; however, long-term improvements were not statistically significant.

Several factors may have contributed to improvements in HRQoL associated with the functional medicine model of care. First, improvements in HRQoL associated with the functional medicine model of care may be due to the model itself. Functional medicine addresses chronic disease by delivering precision medicine. The ability to deliver precision medicine relies on one’s capability to not only collect data, but also organize it in a way that extracts an understanding of a patient’s biological processes and then maps these processes to human disease. The delivery of precision medicine also requires the ability to focus treatment around specific factors associated with a patient’s symptoms. The formal definition of functional medicine was first introduced in 1991 and tracks with the more recent precision medicine initiative.

Background: Psychonutrition, i.e. the impact of diet on mental health, is an emerging field of psychiatry.

Objective: The purpose of the present letter was to highlight recent findings in the field to guide nutritional interventions in psychiatry.

Method: An overview of the most recent meta-analyses in the field of psychonutrition in severe mental disorders has been carried out.

Results: The Mediterranean diet showed the best evidence for effectiveness in diminishing the incidence of depressive symptomatology Complementary agents were found to be associated with lower depression levels (even in psychiatric populations): omegas 3 fatty acids, vitamin D, methylfolate and S-adenosylmethionine, all being found in high rates in the Mediterranean diet. The Healthy Eating Index (HEI) has also been found to be associated with lower depression. Moreover, major depression has been associated with inflammatory disturbances and a diet with a low Dietary Inflammatory Index has also been shown to be associated with lower depression. These effects may be mediated by microbiota modifications and probiotic supplementation has been recently shown to be effective in the treatment of depression. A high protein diet may also be particularly useful in psychiatry. The high protein diet has shown effectiveness in weight loss and increasing satiety with no evidence for deleterious effects in subjects without chronic conditions like renal failure, diabetes or cardiovascular disease. A reduction of 20% of calorific intake +/- intermittent fasting (i.e. fasting for 12 to 16 h per day) may also improve microbiota and therefore psychiatric conditions.

Conclusion: In light of these findings, diet modifications appear to be an underutilized tool with which to improve the mental and physical health of psychiatric patients.

The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from "nutrient supplements", such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta-analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta-review of this top-tier evidence, we identified, synthesized and appraised all meta-analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 meta-analyses of placebo-controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention-deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia. Folate-based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high-dose methylfolate in major depressive disorder. There was emergent evidence for N-acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications. In conclusion, clinicians should be informed of the nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence-based supplements, to further elucidate the underlying mechanisms.

There is a strong relationship between a healthy diet and mental well-being. Several foods and food compounds are known to modulate biomarkers and molecular mechanisms involved in the aetiogenesis of several mental disorders, and this can be useful in containing the disease progression, including its prophylaxis. This is an updated systematic review of the literature to justify the inclusion and recognition of nutrition in the management of psychiatric illnesses. Such foods and their compounds include dietary flavanols from fruits and vegetables, notable antioxidant and anti-inflammatory agents, probiotics (fermented foods) known to protect good gut bacteria, foods rich in polyunsaturated fatty acids (e.g., Omega-3), and avoiding diets high in saturated fats and refined sugars among others. While the exact mechanism(s) of mitigation of many nutritional interventions are yet to be fully understood, the evidence-based approach warrants the inclusion and co-recognition of nutrition in the management of psychiatric illnesses. For the greater public health benefit, there is a need for policy advocacy aimed at bridging the knowledge gap and encouraging the integration of nutritional intervention with contemporary therapies in clinical settings, as deficiencies of certain nutrients make therapy difficult even with appropriate medication.

Mental illness, including depression, anxiety and bipolar disorder, accounts for a significant proportion of global disability and poses a substantial social, economic and heath burden. Treatment is presently dominated by pharmacotherapy, such as antidepressants, and psychotherapy, such as cognitive behavioural therapy; however, such treatments avert less than half of the disease burden, suggesting that additional strategies are needed to prevent and treat mental disorders. There are now consistent mechanistic, observational and interventional data to suggest diet quality may be a modifiable risk factor for mental illness. This review provides an overview of the nutritional psychiatry field. It includes a discussion of the neurobiological mechanisms likely modulated by diet, the use of dietary and nutraceutical interventions in mental disorders, and recommendations for further research. Potential biological pathways related to mental disorders include inflammation, oxidative stress, the gut microbiome, epigenetic modifications and neuroplasticity. Consistent epidemiological evidence, particularly for depression, suggests an association between measures of diet quality and mental health, across multiple populations and age groups; these do not appear to be explained by other demographic, lifestyle factors or reverse causality. Our recently published intervention trial provides preliminary clinical evidence that dietary interventions in clinically diagnosed populations are feasible and can provide significant clinical benefit. Furthermore, nutraceuticals including n-3 fatty acids, folate, S-adenosylmethionine, N-acetyl cysteine and probiotics, among others, are promising avenues for future research. Continued research is now required to investigate the efficacy of intervention studies in large cohorts and within clinically relevant populations, particularly in patients with schizophrenia, bipolar and anxiety disorders.

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.

There is increasing academic and clinical interest in how "lifestyle factors" traditionally associated with physical health may also relate to mental health and psychological well-being. In response, international and national health bodies are producing guidelines to address health behaviors in the prevention and treatment of mental illness. However, the current evidence for the causal role of lifestyle factors in the onset and prognosis of mental disorders is unclear. We performed a systematic meta-review of the top-tier evidence examining how physical activity, sleep, dietary patterns and tobacco smoking impact on the risk and treatment outcomes across a range of mental disorders. Results from 29 meta-analyses of prospective/cohort studies, 12 Mendelian randomization studies, two meta-reviews, and two meta-analyses of randomized controlled trials were synthesized to generate overviews of the evidence for targeting each of the specific lifestyle factors in the prevention and treatment of depression, anxiety and stress-related disorders, schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. Standout findings include: a) convergent evidence indicating the use of physical activity in primary prevention and clinical treatment across a spectrum of mental disorders; b) emerging evidence implicating tobacco smoking as a causal factor in onset of both common and severe mental illness; c) the need to clearly establish causal relations between dietary patterns and risk of mental illness, and how diet should be best addressed within mental health care; and d) poor sleep as a risk factor for mental illness, although with further research required to understand the complex, bidirectional relations and the benefits of non-pharmacological sleep-focused interventions. The potentially shared neurobiological pathways between multiple lifestyle factors and mental health are discussed, along with directions for future research, and recommendations for the implementation of these findings at public health and clinical service levels.

This narrative review was conducted using searches of the PubMed/Medline and Google Scholar databases from inception to November 2019. Clinical trials and relevant articles were identified by cross-referencing major depressive disorder (and/or variants) with the following terms: folate, homocysteine, S-adenosylmethionine (SAMe), L-acetylcarnitine, alpha-lipoic acid, N-acetylcysteine, L-tryptophan, zinc, magnesium, vitamin D, omega-3 fatty acids, coenzyme Q10, and inositol. Manual reviews of references were also performed using article reference lists. Abnormal levels of folate, homocysteine, and SAMe have been shown to be associated with a higher risk of depression. Numerous studies have demonstrated antidepressant activity with L-methylfolate and SAMe supplementation in individuals with depression. Additionally, the amino acids L-acetylcarnitine, alpha-lipoic acid, N-acetylcysteine, and L-tryptophan have been implicated in the development of depression and shown to exert antidepressant effects. Other agents with evidence for improving depressive symptoms include zinc, magnesium, omega-3 fatty acids, and coenzyme Q10. Potential biases and differences in study designs within and amongst the studies and reviews selected may confound results. Augmentation of antidepressant medications with various supplements targeting nutritional and physiological factors can potentiate antidepressant effects. Medical foods, particularly L-methylfolate, and other supplements may play a role in managing depression in patients with inadequate response to antidepressant therapies.

Nutrition is a modifiable factor for intervention in mental disorders. This scoping review characterized nutrition intervention research in mental disorders. A 3-category framework characterized nutrition interventions: Guide (e.g., counselling), Provide (e.g., food provisions), and Add (e.g., supplementation). Nutrition interventions were classified as single-component (e.g., Guide) or complex (e.g., Guide-Provide). Sixty-nine trials met inclusion criteria, 96% were randomized controlled trials. Most commonly diagnosed mental disorders were depressive disorder (i.e., persistent) or major depressive disorder (n = 39), schizophrenia (n = 17), and other psychotic disorders (n = 13). Few trials included patients with anxiety disorders (n = 2) or bipolar disorders (n = 3). Several trials (n = 15, 22%) assessed and implemented nutrition interventions to improve dietary patterns, of which 11 (73%) reported statistically significant and clinically important positive effects of nutrition interventions on mental disorders. The majority of the trials (n = 61, 90%) investigated supplementation, most commonly adding essential fatty acids, vitamins, or minerals. The majority (n = 48, 70%) reported either statistically significant or clinically important effect and 31 (51%) reported both. Though most interventions led to statistically significant improvements, trials were heterogeneous for targeted mental disorders, nutrition interventions, and outcomes assessed. Given considerable heterogeneity, further research from robust and clinically relevant trials is required to support high-quality health care with effective nutrition interventions. Novelty Future research on whole-diet interventions powered to detect changes in mental health outcomes as primary objectives is needed. Dietitians may be an opportunity to improve feasibility and efficacy of nutrition interventions for mental disorder patients. Dietitians may be of value to educate mental health practitioners on the importance of nutrition.

Substance use disorders are a growing concern for all ages, including adolescents. Even though there is an increase in recreational substance use and a wider variety of drugs is available to this young population, treatment options remain scarce. Most medications have limited evidence in this population. Few specialists treat individuals struggling with addiction along with mental health disorders. As the evidence grows, these treatments are usually included in complementary and integrative medicine. This article discusses available evidence for many complementary and integrative treatment approaches while briefly describing existing psychotherapeutic and psychotropic medications.

The field of 'nutritional psychiatry' has evolved with rapidity over the past several years, with an increasing amount of dietary or nutrient-based (nutraceutical) intervention studies being initiated, and more preclinical and epidemiological data being available. This emergent paradigm involves the clinical consideration (where appropriate) of prescriptive dietary modification/improvement, and/or the select judicious use of nutrient-based supplementation to prevent or manage psychiatric disorders. In the last several years, significant links have increasingly been established between dietary quality and mental health (although not all data are supportive). Maternal and early-life nutrition may also affect the mental health outcomes in offspring. In respect to nutraceutical research, like with many recent conventional drug studies, results are fairly mixed across the board, and in many cases there is not emphatic evidence to support the use of nutraceuticals in various psychiatric disorders. This may in part be due to a preponderance of recent studies within the field revealing marked placebo effects. Due to current indicators pointing towards mental disorders having an increasing burden of disease, bold and innovative approaches on a societal level are now required. In light of the widespread use of nutrient supplements by those with and without mental disorders, it is also critical that scientifically rigorous methodologies be brought to bear on the assessment of the efficacy of these supplements, and to determine if, or what dose of, a nutrient supplement is required, for whom, and when, and under what circumstances. More simple studies of additional isolated nutrients are not of great benefit to the field (unless studied in supra-dosage in an individualised, biomarker-guided manner), nor, based on recent data, is the research of 'shotgun' formulations of nutraceuticals. The next critical step for the field is to design psychiatric interventional studies for both dietary modification and nutraceuticals, based on more of a personalised medicine approach, using biomarkers (e.g. nutrient deficiencies, inflammatory cytokine levels, genomic assessment, microbiome analysis) and a person's dietary patterns and individual macro/micronutrient requirements.

The need to find new therapeutic interventions in patients diagnosed with psychiatric disorders is supported by the data suggesting high rates of relapse, chronic evolution, therapeutic resistance, or lack of adherence and disability. The use of pre-, pro-, or synbiotics as add-ons in the therapeutic management of psychiatric disorders has been explored as a new way to augment the efficacy of psychotropics and to improve the chances for these patients to reach response or remission. This systematic literature review focused on the efficacy and tolerability of psychobiotics in the main categories of psychiatric disorders and it has been conducted through the most important electronic databases and clinical trial registers, using the PRISMA 2020 guidelines. The quality of primary and secondary reports was assessed using the criteria identified by the Academy of Nutrition and Diabetics. Forty-three sources, mostly of moderate and high quality, were reviewed in detail, and data regarding the efficacy and tolerability of psychobiotics was assessed. Studies exploring the effects of psychobiotics in mood disorders, anxiety disorders, schizophrenia spectrum disorders, substance use disorders, eating disorders, attention deficit hyperactivity disorder (ADHD), neurocognitive disorders, and autism spectrum disorders (ASD) were included. The overall tolerability of the interventions assessed was good, but the evidence to support their efficacy in specific psychiatric disorders was mixed. There have been identified data in favor of probiotics for patients with mood disorders, ADHD, and ASD, and also for the association of probiotics and selenium or synbiotics in patients with neurocognitive disorders. In several domains, the research is still in an early phase of development, e.g., in substance use disorders (only three preclinical studies being found) or eating disorders (one review was identified). Although no well-defined clinical recommendation could yet be formulated for a specific product in patients with psychiatric disorders, there is encouraging evidence to support further research, especially if focused on the identification of specific sub-populations that may benefit from this intervention. Several limitations regarding the research in this field should be addressed, i.e., the majority of the finalized trials are of short duration, there is an inherent heterogeneity of the psychiatric disorders, and the diversity of the explored Philae prevents the generalizability of the results from clinical studies.

Background: Psychiatry is a branch of medicine that focuses on mental, behavioral and emotional well-being. Complementary, alternative, and integrative medicine has been an increasingly popular choice for patients with psychiatric disorders, therefore our study aimed to explore the perceptions of psychiatry researchers and clinicians on the use of CAIM. Methods: We conducted an online, anonymous, cross-sectional survey for researchers and clinicians who have published their work in psychiatry medical journals that are indexed in MEDLINE. 42,667 researchers and clinicians were sent the link to the survey after extraction of their email addresses from their respective publications. Respondents were asked numerous multiple-choice questions regarding their perceptions on various CAIM therapies, followed by an open-ended question where they could include any additional thoughts. Results: The survey was completed by 987 respondents, with a majority identifying as a researcher (n=447, 46.51%), or as both a researcher and a clinician (n=368, 38.29%) within the field of psychiatry. Most respondents (n=629, 78.04%) perceived mind-body therapies such as meditation, biofeedback, hypnosis, and yoga to be the most promising CAIM therapy for the prevention, treatment, and management of psychiatric diseases. Many participants said that they agree (n=285, 38.14%) that most CAIM therapies in general are safe, however, many disagree that CAIM therapies are effective (n=245, 32.93%). Respondents indicated that there is value to conducting research on CAIM therapies (n=356, 47.91%), and that there should be more funding allocated to researching these therapies (n=265, 35.71%). Respondents were also in agreement that clinicians should receive training on CAIM therapies through formal education (n=295, 39.76%) or supplementary education (n=380, 51.28%). Conclusion: The findings from this study showed that there is great interest and potential in researching CAIM within the field of psychiatry. This information can be used as a basis for further research and to develop tailored educational resources for researchers and clinicians in psychiatry.

Complementary and alternative medicine (CAM) is used as a complementary intervention in psychiatric healthcare. The reasons for using or not using CAM in psychiatric care in Sweden, and how such decisions are taken, are largely unknown. The aim was to investigate arguments for and against the use of CAM in Swedish psychiatric care, and how decisions are made. Interviews with 10 persons in decision-making positions in psychiatric health care were analysed thematically. The result shows diverging understandings of the evidence base for CAM. Arguments against CAM referred to scepticism, the importance of evidence-based practice and the obligation to follow national guidelines. Arguments in favour of CAM were that CAM was person-centred, safe, cost-effective, nursing interventions with positive effects, appreciated and demanded by patients, providing space for non-verbal communication and reflection, supporting the therapeutic alliance. Decision paths were described as top-down through a hierarchical structure, or bottom-up, driven by committed staff members. We discuss how detailed national guidelines should be to achieve equal and evidence-based care, while still allowing clinics to make local exceptions, adjusting the care according to clinical expertise and patients' preferences. Conclusion: Evidence-based, safe and cost-effective CAM methods may be relevant complementary interventions in psychiatric care, or as self-care, not to cure the psychiatric disease, but to reduce symptoms and promote sleep. With better knowledge of CAM, health professionals could guide patients through the jungle of CAM methods. Due to research problems on complex multicomponent interventions, high-quality pragmatic trials, including biomarkers, and qualitative studies are recommended.

Increasing use of complementary and alternative medical (CAM) therapies by patients, health care providers, and institutions has made it imperative that physicians consider their ethical obligations when recommending, tolerating, or proscribing these therapies. The authors present a risk-benefit framework that can be applied to determine the appropriateness of using CAM therapies in various clinical scenarios. The major relevant issues are the severity and acuteness of illness; the curability of the illness by conventional forms of treatment; the degree of invasiveness, associated toxicities, and side effects of the conventional treatment; the availability and quality of evidence of utility and safety of the desired CAM treatment; the level of understanding of risks and benefits of the CAM treatment combined with the patient's knowing and voluntary acceptance of those risks; and the patient's persistence of intention to use CAM therapies. Even in the absence of scientific evidence for CAM therapies, by considering these relevant issues, providers can formulate a plan that is clinically sound, ethically appropriate, and targeted to the unique circumstances of individual patients. Physicians are encouraged to remain engaged in problem-solving with their patients and to attempt to elucidate and clarify the patient's core values and beliefs when counseling about CAM therapies.

Psychological and pharmacological interventions are the most common treatments for adult depression. While these interventions have robust evidence supporting their efficacy, there remain up to 60 percent of individuals who do not respond to treatment, or only partially respond. Unfortunately, efforts at improving outcome rates from new or modified versions of psychological or pharmacological interventions have been disappointing. It is argued that increased treatment efficacy for depression may be achieved by utilising integrative or adjunctive treatments. As depression is influenced by an array of psychological, biological, social, environmental, dietary, and lifestyle factors, it is hypothesised that treatment outcomes will only be improved when integrative interventions are utilised. The research supporting the potential of several of these factors are reviewed in this article including those associated with diet, exercise, sleep, sunshine/light, nature, herbs and nutraceuticals, social connections, meditation, religion/spirituality, and alcohol and nicotine use. It is argued that increased efforts should be directed at investigating integrative or adjunctive interventions, rather than stand-alone treatments, to enhance outcomes for depression.

Background: Psychonutrition, i.e. the impact of diet on mental health, is an emerging field of psychiatry.

Objective: The purpose of the present letter was to highlight recent findings in the field to guide nutritional interventions in psychiatry.

Method: An overview of the most recent meta-analyses in the field of psychonutrition in severe mental disorders has been carried out.

Results: The Mediterranean diet showed the best evidence for effectiveness in diminishing the incidence of depressive symptomatology Complementary agents were found to be associated with lower depression levels (even in psychiatric populations): omegas 3 fatty acids, vitamin D, methylfolate and S-adenosylmethionine, all being found in high rates in the Mediterranean diet. The Healthy Eating Index (HEI) has also been found to be associated with lower depression. Moreover, major depression has been associated with inflammatory disturbances and a diet with a low Dietary Inflammatory Index has also been shown to be associated with lower depression. These effects may be mediated by microbiota modifications and probiotic supplementation has been recently shown to be effective in the treatment of depression. A high protein diet may also be particularly useful in psychiatry. The high protein diet has shown effectiveness in weight loss and increasing satiety with no evidence for deleterious effects in subjects without chronic conditions like renal failure, diabetes or cardiovascular disease. A reduction of 20% of calorific intake +/- intermittent fasting (i.e. fasting for 12 to 16 h per day) may also improve microbiota and therefore psychiatric conditions.

Conclusion: In light of these findings, diet modifications appear to be an underutilized tool with which to improve the mental and physical health of psychiatric patients.

Mental illness, including depression, anxiety and bipolar disorder, accounts for a significant proportion of global disability and poses a substantial social, economic and heath burden. Treatment is presently dominated by pharmacotherapy, such as antidepressants, and psychotherapy, such as cognitive behavioural therapy; however, such treatments avert less than half of the disease burden, suggesting that additional strategies are needed to prevent and treat mental disorders. There are now consistent mechanistic, observational and interventional data to suggest diet quality may be a modifiable risk factor for mental illness. This review provides an overview of the nutritional psychiatry field. It includes a discussion of the neurobiological mechanisms likely modulated by diet, the use of dietary and nutraceutical interventions in mental disorders, and recommendations for further research. Potential biological pathways related to mental disorders include inflammation, oxidative stress, the gut microbiome, epigenetic modifications and neuroplasticity. Consistent epidemiological evidence, particularly for depression, suggests an association between measures of diet quality and mental health, across multiple populations and age groups; these do not appear to be explained by other demographic, lifestyle factors or reverse causality. Our recently published intervention trial provides preliminary clinical evidence that dietary interventions in clinically diagnosed populations are feasible and can provide significant clinical benefit. Furthermore, nutraceuticals including n-3 fatty acids, folate, S-adenosylmethionine, N-acetyl cysteine and probiotics, among others, are promising avenues for future research. Continued research is now required to investigate the efficacy of intervention studies in large cohorts and within clinically relevant populations, particularly in patients with schizophrenia, bipolar and anxiety disorders.

The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from "nutrient supplements", such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta-analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta-review of this top-tier evidence, we identified, synthesized and appraised all meta-analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 meta-analyses of placebo-controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention-deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia. Folate-based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high-dose methylfolate in major depressive disorder. There was emergent evidence for N-acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications. In conclusion, clinicians should be informed of the nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence-based supplements, to further elucidate the underlying mechanisms.

There is a strong relationship between a healthy diet and mental well-being. Several foods and food compounds are known to modulate biomarkers and molecular mechanisms involved in the aetiogenesis of several mental disorders, and this can be useful in containing the disease progression, including its prophylaxis. This is an updated systematic review of the literature to justify the inclusion and recognition of nutrition in the management of psychiatric illnesses. Such foods and their compounds include dietary flavanols from fruits and vegetables, notable antioxidant and anti-inflammatory agents, probiotics (fermented foods) known to protect good gut bacteria, foods rich in polyunsaturated fatty acids (e.g., Omega-3), and avoiding diets high in saturated fats and refined sugars among others. While the exact mechanism(s) of mitigation of many nutritional interventions are yet to be fully understood, the evidence-based approach warrants the inclusion and co-recognition of nutrition in the management of psychiatric illnesses. For the greater public health benefit, there is a need for policy advocacy aimed at bridging the knowledge gap and encouraging the integration of nutritional intervention with contemporary therapies in clinical settings, as deficiencies of certain nutrients make therapy difficult even with appropriate medication.

There is increasing academic and clinical interest in how "lifestyle factors" traditionally associated with physical health may also relate to mental health and psychological well-being. In response, international and national health bodies are producing guidelines to address health behaviors in the prevention and treatment of mental illness. However, the current evidence for the causal role of lifestyle factors in the onset and prognosis of mental disorders is unclear. We performed a systematic meta-review of the top-tier evidence examining how physical activity, sleep, dietary patterns and tobacco smoking impact on the risk and treatment outcomes across a range of mental disorders. Results from 29 meta-analyses of prospective/cohort studies, 12 Mendelian randomization studies, two meta-reviews, and two meta-analyses of randomized controlled trials were synthesized to generate overviews of the evidence for targeting each of the specific lifestyle factors in the prevention and treatment of depression, anxiety and stress-related disorders, schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. Standout findings include: a) convergent evidence indicating the use of physical activity in primary prevention and clinical treatment across a spectrum of mental disorders; b) emerging evidence implicating tobacco smoking as a causal factor in onset of both common and severe mental illness; c) the need to clearly establish causal relations between dietary patterns and risk of mental illness, and how diet should be best addressed within mental health care; and d) poor sleep as a risk factor for mental illness, although with further research required to understand the complex, bidirectional relations and the benefits of non-pharmacological sleep-focused interventions. The potentially shared neurobiological pathways between multiple lifestyle factors and mental health are discussed, along with directions for future research, and recommendations for the implementation of these findings at public health and clinical service levels.

Nutrition is a modifiable factor for intervention in mental disorders. This scoping review characterized nutrition intervention research in mental disorders. A 3-category framework characterized nutrition interventions: Guide (e.g., counselling), Provide (e.g., food provisions), and Add (e.g., supplementation). Nutrition interventions were classified as single-component (e.g., Guide) or complex (e.g., Guide-Provide). Sixty-nine trials met inclusion criteria, 96% were randomized controlled trials. Most commonly diagnosed mental disorders were depressive disorder (i.e., persistent) or major depressive disorder (n = 39), schizophrenia (n = 17), and other psychotic disorders (n = 13). Few trials included patients with anxiety disorders (n = 2) or bipolar disorders (n = 3). Several trials (n = 15, 22%) assessed and implemented nutrition interventions to improve dietary patterns, of which 11 (73%) reported statistically significant and clinically important positive effects of nutrition interventions on mental disorders. The majority of the trials (n = 61, 90%) investigated supplementation, most commonly adding essential fatty acids, vitamins, or minerals. The majority (n = 48, 70%) reported either statistically significant or clinically important effect and 31 (51%) reported both. Though most interventions led to statistically significant improvements, trials were heterogeneous for targeted mental disorders, nutrition interventions, and outcomes assessed. Given considerable heterogeneity, further research from robust and clinically relevant trials is required to support high-quality health care with effective nutrition interventions. Novelty Future research on whole-diet interventions powered to detect changes in mental health outcomes as primary objectives is needed. Dietitians may be an opportunity to improve feasibility and efficacy of nutrition interventions for mental disorder patients. Dietitians may be of value to educate mental health practitioners on the importance of nutrition.

The field of 'nutritional psychiatry' has evolved with rapidity over the past several years, with an increasing amount of dietary or nutrient-based (nutraceutical) intervention studies being initiated, and more preclinical and epidemiological data being available. This emergent paradigm involves the clinical consideration (where appropriate) of prescriptive dietary modification/improvement, and/or the select judicious use of nutrient-based supplementation to prevent or manage psychiatric disorders. In the last several years, significant links have increasingly been established between dietary quality and mental health (although not all data are supportive). Maternal and early-life nutrition may also affect the mental health outcomes in offspring. In respect to nutraceutical research, like with many recent conventional drug studies, results are fairly mixed across the board, and in many cases there is not emphatic evidence to support the use of nutraceuticals in various psychiatric disorders. This may in part be due to a preponderance of recent studies within the field revealing marked placebo effects. Due to current indicators pointing towards mental disorders having an increasing burden of disease, bold and innovative approaches on a societal level are now required. In light of the widespread use of nutrient supplements by those with and without mental disorders, it is also critical that scientifically rigorous methodologies be brought to bear on the assessment of the efficacy of these supplements, and to determine if, or what dose of, a nutrient supplement is required, for whom, and when, and under what circumstances. More simple studies of additional isolated nutrients are not of great benefit to the field (unless studied in supra-dosage in an individualised, biomarker-guided manner), nor, based on recent data, is the research of 'shotgun' formulations of nutraceuticals. The next critical step for the field is to design psychiatric interventional studies for both dietary modification and nutraceuticals, based on more of a personalised medicine approach, using biomarkers (e.g. nutrient deficiencies, inflammatory cytokine levels, genomic assessment, microbiome analysis) and a person's dietary patterns and individual macro/micronutrient requirements.

The 'monoamine hypothesis' is insufficient in approaching the aetiology of psychiatric disorders or in developing novel therapies. Accumulating evidence suggests that inflammatory regulation plays an important role in pathophysiology and therapeutic mechanism across the major psychiatric disorders. "Inflammation theory" might not be the full answer for the big picture of mental disorders, but it might explain high occurrence of somatic symptoms and comorbidity of physical illness in certain subtypes of the heterogeneous groups. Due to the complexity of clinical manifestations and bio-psycho-social etiology, each single treatment shows only small effectiveness with limited effect sizes when compared with placebo. Unfortunately, clinicians are still struggling with trial-and-error practice without any reliable clinical or biological markers to predict therapeutic responses. Therefore, it is important to open up our minds to integrative approaches such dietary modification and nutraceutical prescription. In this special issue, we included 15 papers discussing the role of nutrition (blueberries, omega-3 polyunsaturated fatty acids, melatonergic agonist, S-Adenosyl-L-Methionine, Cannabidiol and Kratom) in the context of immunoregulation across different psychiatric disorders from depression, bipolar disorders, and schizophrenia to alcohol-induced dementia and anorexia nervosa. Moreover, we also included research in perinatal depression that highlight the role of estradiol and the component of breast milk and the association with the neurodevelopment of the offspring. In addition, several articles focused on the role of microbiota in mental health and pain as recent research has pointed to the gut-brain axis as a main regulator of brain, behaviour and immunity. Lastly, inflammatory mechanisms underlying psychiatric disorders including alcohol induced dementia and anorexia nervosa are also highlighted in the special issue.