The Role of Humanization and Robustness of Large Language Models in Conversational Artificial Intelligence for Individuals With Depression: A Critical Analysis.

Unlabelled: Large language model (LLM)-powered services are gaining popularity in various applications due to their exceptional performance in many tasks, such as sentiment analysis and answering questions. Recently, research has been exploring their potential use in digital health contexts, particularly in the mental health domain. However, implementing LLM-enhanced conversational artificial intelligence (CAI) presents significant ethical, technical, and clinical challenges. In this viewpoint paper, we discuss 2 challenges that affect the use of LLM-enhanced CAI for individuals with mental health issues, focusing on the use case of patients with depression: the tendency to humanize LLM-enhanced CAI and their lack of contextualized robustness. Our approach is interdisciplinary, relying on considerations from philosophy, psychology, and computer science. We argue that the humanization of LLM-enhanced CAI hinges on the reflection of what it means to simulate "human-like" features with LLMs and what role these systems should play in interactions with humans. Further, ensuring the contextualization of the robustness of LLMs requires considering the specificities of language production in individuals with depression, as well as its evolution over time. Finally, we provide a series of recommendations to foster the responsible design and deployment of LLM-enhanced CAI for the therapeutic support of individuals with depression.

Considering the Role of Human Empathy in AI-Driven Therapy.

Recent breakthroughs in artificial intelligence (AI) language models have elevated the vision of using conversational AI support for mental health, with a growing body of literature indicating varying degrees of efficacy. In this paper, we ask when, in therapy, it will be easier to replace humans and, conversely, in what instances, human connection will still be more valued. We suggest that empathy lies at the heart of the answer to this question. First, we define different aspects of empathy and outline the potential empathic capabilities of humans versus AI. Next, we consider what determines when these aspects are needed most in therapy, both from the perspective of therapeutic methodology and from the perspective of patient objectives. Ultimately, our goal is to prompt further investigation and dialogue, urging both practitioners and scholars engaged in AI-mediated therapy to keep these questions and considerations in mind when investigating AI implementation in mental health.

Social Media Use and Serious Psychological Distress Among Adolescents.

Unlabelled: This Research Letter describes the increasing trend of almost-constant social media use among California adolescents and the association with serious psychological distress, focusing on the influence of familial and experiential factors.

Exploration beyond osteoarthritis: the association and mechanism of its related comorbidities.

Osteoarthritis is the most prevalent age-related degenerative joint disease and a leading cause of pain and disability in aged people. Its etiology is multifaceted, involving factors such as biomechanics, pro-inflammatory mediators, genetics, and metabolism. Beyond its evident impact on joint functionality and the erosion of patients' quality of life, OA exhibits symbiotic relationships with various systemic diseases, giving rise to various complications. This review reveals OA's extensive impact, encompassing osteoporosis, sarcopenia, cardiovascular diseases, diabetes mellitus, neurological disorders, mental health, and even cancer. Shared inflammatory processes, genetic factors, and lifestyle elements link OA to these systemic conditions. Consequently, recognizing these connections and addressing them offers opportunities to enhance patient care and reduce the burden of associated diseases, emphasizing the need for a holistic approach to managing OA and its complications.

Dilemmas concerning the course of pregnancy in patients with anorexia nervosa considering hormonal and somatic parameters.

Mental anorexia nervosa is a rare, potentially severe, chronic, and recurrent mental disorder that occurs more often in women than in men, especially during the childbearing years. The disorder is associated with an increased risk of mortality, mainly related to the physical consequences of severe malnutrition and suicide. Malnutrition of the body can cause serious hormonal and somatic problems. Despite significant hormonal disturbances that reduce fertility, a woman with anorexia can become pregnant. A new phenomenon now seen with increasing frequency is pregorexia, an eating disorder associated with pregnancy. It involves the use of dietary restrictions to avoid excessive weight gain during pregnancy. Pregnancy changes the hormonal economy mainly due to the development of the placenta, which secretes many hormones, not just sex hormones. Mental anorexia poses a significant risk to both mother and child if not diagnosed and treated properly. Treatment of anorexia involves simultaneous somatic and psychological treatment. During pregnancy, additional care should be taken to create an optimal environment for the developing foetus. Unfortunately, there is still a lack of research providing guidance in this area. Available studies are mainly case reports or reports focusing on specific clinical situations. It is worth noting that no study to date has attempted a comprehensive assessment of endocrine disruption in pregnant women with anorexia. Recognising the existing knowledge gap on endocrine disorders in pregnant women with anorexia nervosa, a systematic review of the literature was conducted.

The impact of nutrition on psycho-affective status in an older Cretan population: a cross-sectional study.

BACKGROUND: Cognitive and mood status influence both personal and social daily activities, with great impact on life quality, particularly among the elderly population. AIM: This cross-sectional study aimed to investigate the psycho-affective status concerning eating habits within an elderly population of the Chania area in Crete, Greece. METHODS: Cognitive status was assessed in 101 elderly subjects through the Mini-Mental State Examination (MMSE), and mood was evaluated using the Hospital Anxiety and Depression Scale (HADS). Nutritional status was assessed using a validated food frequency questionnaire. RESULTS: Multivariable statistical analysis, after adjustment for age, marital status, education, and comorbidity, highlighted among males a positive association of the MMSE score with vegetable consumption (RR 1.18; 95%CI 1.03‒1.34) and a negative association with potato consumption (RR 0.83; 95%CI 0.72‒0.95). Conversely, among females, no statistically significant association was observed for any food. Further, among males, a protective effect on affective status was identified for chicken meat (RR 0.45; 95%CI 0.27‒0.77), fish (RR 0.41; 95%CI 0.21‒0.82), fruit (RR 0.70; 95%CI 0.52‒0.94), cereals (RR 0.67; 95%CI 0.53‒0.87), and cheese (RR 0.78; 95%CI 0.63‒0.97) consumption. Among females, the adjusted model showed a significant detrimental effect of vegetable consumption (RR 1.33; 95%CI 1.02‒1.73). CONCLUSION: A predominantly vegetable-based diet-with the notable exception of fruits and legumes-was associated with better cognitive status in males, albeit not in females. A higher intake of fruit, as well as fish, chicken meat, and cheese among males was associated with a better affective status, indicating that adequate protein supply may play a role in maintaining emotional balance.

Assessing the Alignment of Large Language Models With Human Values for Mental Health Integration: Cross-Sectional Study Using Schwartz's Theory of Basic Values.

BACKGROUND: Large language models (LLMs) hold potential for mental health applications. However, their opaque alignment processes may embed biases that shape problematic perspectives. Evaluating the values embedded within LLMs that guide their decision-making have ethical importance. Schwartz's theory of basic values (STBV) provides a framework for quantifying cultural value orientations and has shown utility for examining values in mental health contexts, including cultural, diagnostic, and therapist-client dynamics. OBJECTIVE: This study aimed to (1) evaluate whether the STBV can measure value-like constructs within leading LLMs and (2) determine whether LLMs exhibit distinct value-like patterns from humans and each other. METHODS: In total, 4 LLMs (Bard, Claude 2, Generative Pretrained Transformer [GPT]-3.5, GPT-4) were anthropomorphized and instructed to complete the Portrait Values Questionnaire-Revised (PVQ-RR) to assess value-like constructs. Their responses over 10 trials were analyzed for reliability and validity. To benchmark the LLMs' value profiles, their results were compared to published data from a diverse sample of 53,472 individuals across 49 nations who had completed the PVQ-RR. This allowed us to assess whether the LLMs diverged from established human value patterns across cultural groups. Value profiles were also compared between models via statistical tests. RESULTS: The PVQ-RR showed good reliability and validity for quantifying value-like infrastructure within the LLMs. However, substantial divergence emerged between the LLMs' value profiles and population data. The models lacked consensus and exhibited distinct motivational biases, reflecting opaque alignment processes. For example, all models prioritized universalism and self-direction, while de-emphasizing achievement, power, and security relative to humans. Successful discriminant analysis differentiated the 4 LLMs' distinct value profiles. Further examination found the biased value profiles strongly predicted the LLMs' responses when presented with mental health dilemmas requiring choosing between opposing values. This provided further validation for the models embedding distinct motivational value-like constructs that shape their decision-making. CONCLUSIONS: This study leveraged the STBV to map the motivational value-like infrastructure underpinning leading LLMs. Although the study demonstrated the STBV can effectively characterize value-like infrastructure within LLMs, substantial divergence from human values raises ethical concerns about aligning these models with mental health applications. The biases toward certain cultural value sets pose risks if integrated without proper safeguards. For example, prioritizing universalism could promote unconditional acceptance even when clinically unwise. Furthermore, the differences between the LLMs underscore the need to standardize alignment processes to capture true cultural diversity. Thus, any responsible integration of LLMs into mental health care must account for their embedded biases and motivation mismatches to ensure equitable delivery across diverse populations. Achieving this will require transparency and refinement of alignment techniques to instill comprehensive human values.

Usability Comparison Among Healthy Participants of an Anthropomorphic Digital Human and a Text-Based Chatbot as a Responder to Questions on Mental Health: Randomized Controlled Trial.

BACKGROUND: The use of chatbots in mental health support has increased exponentially in recent years, with studies showing that they may be effective in treating mental health problems. More recently, the use of visual avatars called digital humans has been introduced. Digital humans have the capability to use facial expressions as another dimension in human-computer interactions. It is important to study the difference in emotional response and usability preferences between text-based chatbots and digital humans for interacting with mental health services. OBJECTIVE: This study aims to explore to what extent a digital human interface and a text-only chatbot interface differed in usability when tested by healthy participants, using BETSY (Behavior, Emotion, Therapy System, and You) which uses 2 distinct interfaces: a digital human with anthropomorphic features and a text-only user interface. We also set out to explore how chatbot-generated conversations on mental health (specific to each interface) affected self-reported feelings and biometrics. METHODS: We explored to what extent a digital human with anthropomorphic features differed from a traditional text-only chatbot regarding perception of usability through the System Usability Scale, emotional reactions through electroencephalography, and feelings of closeness. Healthy participants (n=45) were randomized to 2 groups that used a digital human with anthropomorphic features (n=25) or a text-only chatbot with no such features (n=20). The groups were compared by linear regression analysis and t tests. RESULTS: No differences were observed between the text-only and digital human groups regarding demographic features. The mean System Usability Scale score was 75.34 (SD 10.01; range 57-90) for the text-only chatbot versus 64.80 (SD 14.14; range 40-90) for the digital human interface. Both groups scored their respective chatbot interfaces as average or above average in usability. Women were more likely to report feeling annoyed by BETSY. CONCLUSIONS: The text-only chatbot was perceived as significantly more user-friendly than the digital human, although there were no significant differences in electroencephalography measurements. Male participants exhibited lower levels of annoyance with both interfaces, contrary to previously reported findings.

Capacity of Generative AI to Interpret Human Emotions From Visual and Textual Data: Pilot Evaluation Study.

BACKGROUND: Mentalization, which is integral to human cognitive processes, pertains to the interpretation of one's own and others' mental states, including emotions, beliefs, and intentions. With the advent of artificial intelligence (AI) and the prominence of large language models in mental health applications, questions persist about their aptitude in emotional comprehension. The prior iteration of the large language model from OpenAI, ChatGPT-3.5, demonstrated an advanced capacity to interpret emotions from textual data, surpassing human benchmarks. Given the introduction of ChatGPT-4, with its enhanced visual processing capabilities, and considering Google Bard's existing visual functionalities, a rigorous assessment of their proficiency in visual mentalizing is warranted. OBJECTIVE: The aim of the research was to critically evaluate the capabilities of ChatGPT-4 and Google Bard with regard to their competence in discerning visual mentalizing indicators as contrasted with their textual-based mentalizing abilities. METHODS: The Reading the Mind in the Eyes Test developed by Baron-Cohen and colleagues was used to assess the models' proficiency in interpreting visual emotional indicators. Simultaneously, the Levels of Emotional Awareness Scale was used to evaluate the large language models' aptitude in textual mentalizing. Collating data from both tests provided a holistic view of the mentalizing capabilities of ChatGPT-4 and Bard. RESULTS: ChatGPT-4, displaying a pronounced ability in emotion recognition, secured scores of 26 and 27 in 2 distinct evaluations, significantly deviating from a random response paradigm (P<.001). These scores align with established benchmarks from the broader human demographic. Notably, ChatGPT-4 exhibited consistent responses, with no discernible biases pertaining to the sex of the model or the nature of the emotion. In contrast, Google Bard's performance aligned with random response patterns, securing scores of 10 and 12 and rendering further detailed analysis redundant. In the domain of textual analysis, both ChatGPT and Bard surpassed established benchmarks from the general population, with their performances being remarkably congruent. CONCLUSIONS: ChatGPT-4 proved its efficacy in the domain of visual mentalizing, aligning closely with human performance standards. Although both models displayed commendable acumen in textual emotion interpretation, Bard's capabilities in visual emotion interpretation necessitate further scrutiny and potential refinement. This study stresses the criticality of ethical AI development for emotional recognition, highlighting the need for inclusive data, collaboration with patients and mental health experts, and stringent governmental oversight to ensure transparency and protect patient privacy.

Changes in institution for mental diseases (IMD) ownership status and insurance acceptance over time.

State Medicaid programs are prohibited from using federal dollars to pay institutions for mental diseases (IMDs)-freestanding psychiatric facilities with more than 16 beds. Increasingly, regulatory mechanisms have made payment of treatment in these settings substantially more feasible. This study evaluates if changing financial incentives are associated with increases in for-profit ownership among IMD facilities relative to non-IMD facilities, as well as greater increases in Medicaid acceptance among for-profit IMD facilities relative to for-profit non-IMD facilities. We used data from the 2014-2020 National Mental Health Services Surveys and examined 11 945 facility-years. Relative to non-IMDs, the increase in for-profit ownership among IMDs was 6.6 percentage points greater. The largest proportional change in Medicaid acceptance occurred among for-profit IMD facilities relative to for-profit non-IMDs (18.5 percentage points). Existing research is mixed on the quality of inpatient and residential psychiatric care provided in for-profit vs nonprofit and public facilities, as well as in IMD relative to non-IMD facilities. As payment policy increasingly incentivizes for-profit facilities to enter the psychiatric care space, we should be mindful of the impact of these decisions on patient safety.

Utilization of Medications for Opioid Use Disorder Among West Virginia Medicaid Enrollees Following Medicaid Coverage of Methadone.

BACKGROUND: West Virginia entered an institution for mental disease Section 1115 waiver with the Centers for Medicare & Medicaid Services in 2018, which allowed Medicaid to cover methadone at West Virginia's nine opioid treatment programs (OTPs) for the first time. METHODS: We conducted time trend and geospatial analyses of Medicaid enrollees between 2016 and 2019 to examine medications for opioid use disorder utilization patterns following Medicaid coverage of methadone, focusing on distance to an OTP as a predictor of initiating methadone and conditional on receiving any, longer treatment duration. RESULTS: Following Medicaid coverage of methadone in 2018, patients receiving methadone comprised 9.5% of all Medicaid enrollees with an opioid use disorder (OUD) diagnosis and 10.6% in 2019 (P < 0.01). In 2018, two-thirds of methadone patients either had no prior OUD diagnosis or were not previously enrolled in Medicaid in our observation period. Patients residing within 20 miles of an OTP were more likely to receive methadone (marginal effect [ME]: -0.041, P < 0.001). Similarly, patients residing in metropolitan areas were more likely to receive treatment than those residing in nonmetropolitan areas (ME: -0.019, P < 0.05). Metropolitan patients traveled an average of 15 miles to an OTP; nonmetropolitan patients traveled more than twice as far (P < 0.001). We found no significant association between distance and treatment duration. CONCLUSIONS: West Virginia Medicaid's new methadone coverage was associated with an influx of new enrollees with OUD, many of whom had no previous OUD diagnosis or prior Medicaid enrollment. Methadone patients frequently traveled far distances for treatment, suggesting that the state needs additional OTPs and innovative methadone delivery models to improve availability.

The Frequency of Design Studies Targeting People With Psychotic Symptoms and Features in Mental Health Care Innovation: Secondary Analysis of a Systematic Review.

This study examined and reflected on the frequency of people with psychotic symptoms and features as the target population in design studies for mental health care innovation.

Repurposing of pexidartinib for microglia depletion and renewal.

Pexidartinib (PLX3397) is a small molecule receptor tyrosine kinase inhibitor of colony stimulating factor 1 receptor (CSF1R) with moderate selectivity over other members of the platelet derived growth factor receptor family. It is approved for treatment of tenosynovial giant cell tumors (TGCT). CSF1R is highly expressed by microglia, which are macrophages of the central nervous system (CNS) that defend the CNS against injury and pathogens and contribute to synapse development and plasticity. Challenged by pathogens, apoptotic cells, debris, or inflammatory molecules they adopt a responsive state to propagate the inflammation and eventually return to a homeostatic state. The phenotypic switch may fail, and disease-associated microglia contribute to the pathophysiology in neurodegenerative or neuropsychiatric diseases or long-lasting detrimental brain inflammation after brain, spinal cord or nerve injury or ischemia/hemorrhage. Microglia also contribute to the growth permissive tumor microenvironment of glioblastoma (GBM). In rodents, continuous treatment for 1-2 weeks via pexidartinib food pellets leads to a depletion of microglia and subsequent repopulation from the remaining fraction, which is aided by peripheral monocytes that search empty niches for engraftment. The putative therapeutic benefit of such microglia depletion or forced renewal has been assessed in almost any rodent model of CNS disease or injury or GBM with heterogeneous outcomes, but a tendency of partial beneficial effects. So far, microglia monitoring e.g. via positron emission imaging is not standard of care for patients receiving Pexidartinib (e.g. for TGCT), so that the depletion and repopulation efficiency in humans is still largely unknown. Considering the virtuous functions of microglia, continuous depletion is likely no therapeutic option but short-lasting transient partial depletion to stimulate microglia renewal or replace microglia in genetic disease in combination with e.g. stem cell transplantation or as part of a multimodal concept in treatment of glioblastoma appears feasible. The present review provides an overview of the preclinical evidence pro and contra microglia depletion as a therapeutic approach.

Principais Dificuldades dos Cuidadores Informais da Pessoa com Doença Mental Grave / Main Difficulties of Informal Caregivers of People with Severe Mental Illness / Principales Dificultades de los Cuidadores Informales de la Persona con Enfermedad Mental Grave

Resumo Contexto: O processo de desinstitucionalização da pessoa com doença mental grave, trouxe uma nova realidade ao exigir uma adaptação das famílias, perante a necessidade dos seus membros assumirem o papel de cuidadores informais. Objetivo: Identificar as dificuldades dos cuidadores informais da pessoa com doença mental grave. Metodologia: Realizou-se um estudo descritivo transversal de base quantitativa. Foi constituída uma amostra probabilística aleatória simples de 27 cuidadores informais da pessoa adulta com doença mental grave, acompanhada na consulta externa de psiquiatria dum hospital da região Sul de Portugal. Como instrumento de colheita de dados foi aplicado o Índice de Avaliação das Dificuldades do Cuidador (CADI) e um questionário de caraterização sociodemográfica do cuidador informal. Resultados: Relativamente às características sociodemográficas dos participantes apurou-se que estas estão de acordo com o perfil que caracteriza os cuidadores informais em Portugal. Da aplicação do CADI, resulta que os fatores em que se verificaram mais dificuldades relacionadas com o cuidar foram os fatores relacionados com a falta de apoio familiar, com problemas financeiros, seguindo-se as reações à prestação de cuidados e a falta de apoio profissional. Conclusões: A função de cuidar causa dificuldades ao cuidador, que se vê perante um contexto diferente do habitual e a ter de desempenhar um novo papel. Assim, constatamos que os cuidadores familiares constituem um grupo com necessidades e dificuldades especificas, perante as quais o Enfermeiro Especialista Enfermagem Saúde Mental e Psiquiátrica tem um papel fundamental em termos de intervenção, na capacitação e empoderamento de quem cuida.

Abstract Context: The process of deinstitutionalization of the person with serious mental illness brought a new reality by requiring an adaptation of families, given the need for their members to assume the role of informal caregivers. Objective: To identify the difficulties of informal caregivers of people with severe mental illness. Methodology: A descriptive cross-sectional quantitative study was carried out. A simple random probabilistic sample of 27 informal caregivers of an adult person with severe mental illness was constituted, accompanied in the outpatient psychiatric clinic of a hospital in the south of Portugal. As a data collection instrument, the Caregiver's Difficulties Assessment Index (CADI) and a sociodemographic characterization questionnaire of the informal caregiver, were applied. Results: Regarding the sociodemographic characteristics of the participants, it was found that these are in line with the profile that characterizes informal caregivers in Portugal. From the application of the CADI, it appears that the factors in which there were more difficulties related to care were factors related to the lack of family support, financial problems, followed by reactions to the provision of care and the lack of professional support. Conclusions: The role of caring causes difficulties for the caregiver, who is faced with a different context than usual and having to play a new role. Thus, we found that family caregivers constitute a group with specific needs and difficulties, in view of which the Specialist Nurse Mental Health and Psychiatric Nursing has a fundamental role in terms of intervention, in the training and empowerment of those who care.

Resumen Contexto: El proceso de desinstitucionalización de la persona con enfermedad mental grave trajo una nueva realidad al exigir una adaptación de las familias, ante la necesidad de que sus miembros asuman el rol de cuidadores informales. Objetivo: Identificar las dificultades de los cuidadores informales de personas con enfermedad mental grave. Metodología: Se realizó un estudio cuantitativo descriptivo de corte transversal. Se constituyó una muestra probabilística aleatoria simple de 27 cuidadores informales de una persona adulta con enfermedad mental grave, acompañados en la consulta externa de psiquiatría de un hospital del sur de Portugal. Como instrumento de recolección de datos, se aplicó el Índice de Evaluación de Dificultades del Cuidador (CADI) y un cuestionario de caracterización sociodemográfica del cuidador informal. Resultados: En cuanto a las características sociodemográficas de los participantes, se constató que estas están en consonancia con el perfil que caracteriza a los cuidadores informales en Portugal. De la aplicación del CADI se desprende que los factores en los que hubo más dificultades relacionadas con el cuidado fueron los relacionados con la falta de apoyo familiar, los problemas económicos, seguidos de las reacciones a la prestación del cuidado y la falta de apoyo profesional. Conclusiones: El rol de cuidar genera dificultades para el cuidador, que se enfrenta a un contexto diferente al habitual y al tener que desempeñar un nuevo rol. Así, encontramos que los cuidadores familiares constituyen un grupo con necesidades y dificultades específicas, por lo que la Enfermera Especialista en Salud Mental y Enfermería Psiquiátrica tiene un papel fundamental en términos de intervención, en la formación y empoderamiento de quienes cuidan.

Effect of collaborative care intervention on productivity losses among people with comorbid common mental disorders and cardiovascular disease in rural Karnataka.

Introduction: Common mental disorders (CMD) and cardiovascular diseases (CVD), common health problems among patients seeking primary healthcare, contribute to high economic productivity losses. Collaborative care programs for CMDs and CVDs have shown improvement in clinical outcomes for both conditions; however, data on productivity outcomes are scarce. Objective: Effect of integrated collaborative care on productivity among people with comorbid CMD and CVD in rural Karnataka primary health clinics. Methods: Participants were recruited within a randomized trial in rural South India, where patients received either collaborative or enhanced standard care. In this substudy, 303 participants were followed for 3 months and assessed with the iMTA Productivity Cost Questionnaire (iPCQ). Results: We found a reduction in the proportion of individuals reporting productivity loss at 3 months (66%) compared to baseline (76%; P = 0.002). Productivity losses decreased from INR 30.3 per person per day at baseline to 17.7 at 3 months. Reductions were similar in the two treatment conditions. Conclusion: Medical intervention may foster reduced productivity losses among patients with CMD and CVD. Collaborative care did not translate into higher reductions in productivity losses than "enhanced standard care."

MMiKG: a knowledge graph-based platform for path mining of microbiota-mental diseases interactions.

The microbiota-gut-brain axis denotes a two-way system of interactions between the gut and the brain, comprising three key components: (1) gut microbiota, (2) intermediates and (3) mental ailments. These constituents communicate with one another to induce changes in the host's mood, cognition and demeanor. Knowledge concerning the regulation of the host central nervous system by gut microbiota is fragmented and mostly confined to disorganized or semi-structured unrestricted texts. Such a format hinders the exploration and comprehension of unknown territories or the further advancement of artificial intelligence systems. Hence, we collated crucial information by scrutinizing an extensive body of literature, amalgamated the extant knowledge of the microbiota-gut-brain axis and depicted it in the form of a knowledge graph named MMiKG, which can be visualized on the GraphXR platform and the Neo4j database, correspondingly. By merging various associated resources and deducing prospective connections between gut microbiota and the central nervous system through MMiKG, users can acquire a more comprehensive perception of the pathogenesis of mental disorders and generate novel insights for advancing therapeutic measures. As a free and open-source platform, MMiKG can be accessed at http://yangbiolab.cn:8501/ with no login requirement.

Epigenetic Aberrations in Major Psychiatric Diseases Related to Diet and Gut Microbiome Alterations.

Nutrition and metabolism modify epigenetic signatures like histone acetylation and DNA methylation. Histone acetylation and DNA methylation in the central nervous system (CNS) can be altered by bioactive nutrients and gut microbiome via the gut-brain axis, which in turn modulate neuronal activity and behavior. Notably, the gut microbiome, with more than 1000 bacterial species, collectively contains almost three million functional genes whose products interact with millions of human epigenetic marks and 30,000 genes in a dynamic manner. However, genetic makeup shapes gut microbiome composition, food/nutrient metabolism, and epigenetic landscape, as well. Here, we first discuss the effect of changes in the microbial structure and composition in shaping specific epigenetic alterations in the brain and their role in the onset and progression of major mental disorders. Afterward, potential interactions among maternal diet/environmental factors, nutrition, and gastrointestinal microbiome, and their roles in accelerating or delaying the onset of severe mental illnesses via epigenetic changes will be discussed. We also provide an overview of the association between the gut microbiome, oxidative stress, and inflammation through epigenetic mechanisms. Finally, we present some underlying mechanisms involved in mediating the influence of the gut microbiome and probiotics on mental health via epigenetic modifications.

Global Impacts of Western Diet and Its Effects on Metabolism and Health: A Narrative Review.

The Western diet is a modern dietary pattern characterized by high intakes of pre-packaged foods, refined grains, red meat, processed meat, high-sugar drinks, candy, sweets, fried foods, conventionally raised animal products, high-fat dairy products, and high-fructose products. The present review aims to describe the effect of the Western pattern diet on the metabolism, inflammation, and antioxidant status; the impact on gut microbiota and mitochondrial fitness; the effect of on cardiovascular health, mental health, and cancer; and the sanitary cost of the Western diet. To achieve this goal, a consensus critical review was conducted using primary sources, such as scientific articles, and secondary sources, including bibliographic indexes, databases, and web pages. Scopus, Embase, Science Direct, Sports Discuss, ResearchGate, and the Web of Science were used to complete the assignment. MeSH-compliant keywords such "Western diet", "inflammation", "metabolic health", "metabolic fitness", "heart disease", "cancer", "oxidative stress", "mental health", and "metabolism" were used. The following exclusion criteria were applied: (i) studies with inappropriate or irrelevant topics, not germane to the review's primary focus; (ii) Ph.D. dissertations, proceedings of conferences, and unpublished studies. This information will allow for a better comprehension of this nutritional behavior and its effect on an individual's metabolism and health, as well as the impact on national sanitary systems. Finally, practical applications derived from this information are made.