The Health Thread

Introduction:

Metabolic psychiatry is an emerging field that investigates the bidirectional relationship between metabolic dysregulation and psychiatric disorders. Increasing evidence suggests that disturbances in metabolism, including alterations in glucose metabolism, lipid metabolism, and hormonal imbalances, may contribute to the pathophysiology of various mental health conditions. This research article aims to explore the latest findings and concepts in metabolic psychiatry, highlighting the potential implications for understanding and managing psychiatric disorders.

Metabolism and Mental Health:

Traditionally, mental health disorders have been primarily viewed as disorders of the brain, focusing on neurotransmitter imbalances and neuronal dysfunction. However, emerging research indicates that disturbances in metabolism can impact brain function and significantly contribute to psychiatric symptoms. Metabolic abnormalities, such as insulin resistance, inflammation, oxidative stress, and mitochondrial dysfunction, have been observed in individuals with depression, anxiety, bipolar disorder, schizophrenia, and other mental health conditions.

Insulin Resistance and Depression:

Insulin resistance, a condition characterized by impaired cellular response to insulin, has been associated with an increased risk of depression. Studies have demonstrated that insulin resistance disrupts neuronal signaling pathways, affects neurotransmitter metabolism, and promotes neuroinflammation, all of which may contribute to the development and persistence of depressive symptoms. A longitudinal study by Timonen et al. (2005) found that insulin resistance predicted the onset of depressive symptoms in middle-aged individuals.

The global prevalence of type 2 diabetes is on the rise. Within the diabetic population, approximately 30% experience comorbid mental health issues, such as depression, schizophrenia, delirium, and substance misuse, including tobacco smoking. Interestingly, there is evidence suggesting a bidirectional relationship between these mental disorders and diabetes. Moreover, the prevalence of depression and anxiety among individuals with diabetes exceeds that of the general population, with a striking 50-100% heightened risk of depression in diabetic patients. Presently, psychiatrists recognize the interplay between psychiatric disorders and medical conditions, acknowledging that they often influence each other (Al-Atram AA. ,2018).

Dyslipidemia and Bipolar Disorder:

Dyslipidemia, characterized by abnormal levels of lipids (e.g., cholesterol and triglycerides) in the bloodstream, has been implicated in bipolar disorder. Altered lipid metabolism can influence membrane composition and fluidity, affecting neuronal signaling and synaptic function. Several studies have reported associations between dyslipidemia and bipolar disorder, including altered lipid profiles in individuals with the disorder Fagiolini et al. (2014) found that patients with bipolar disorder had significantly higher levels of triglycerides and lower levels of high-density lipoprotein (HDL) cholesterol compared to healthy controls.

Depression stands as one of the most prevalent psychiatric disorders among adults, posing a significant public health concern in the United States. Mounting evidence suggests a correlation between depression and heightened risks of diabetes and cardiovascular diseases (CVD).

Metabolic syndrome (MetS), comprising various CVD risk factors like central obesity, hyperglycemia, elevated blood pressure, hypertriglyceridemia, and reduced HDL cholesterol, is widespread in the general populace and is linked to increased susceptibility to diabetes and CVD. Given the substantial public health burdens posed by both depression and MetS, recent focus has been directed towards understanding the relationship between these two conditions (Pan et.al,2012)

Hormonal Imbalances and Schizophrenia:

Hormonal imbalances, particularly involving the hypothalamic-pituitary-adrenal (HPA) axis and sex hormones, have been implicated in the pathophysiology of schizophrenia. Dysregulation of the HPA axis, characterized by abnormal cortisol levels and stress response, is frequently observed in individuals with schizophrenia. Moreover, alterations in sex hormone levels, such as estrogen and testosterone, have been associated with symptom severity and cognitive impairments in schizophrenia. A study by Riecher-Rössler et al. (2018) demonstrated that estrogen treatment improved symptoms and cognition in postmenopausal women with schizophrenia.

Conclusion:

Metabolic psychiatry offers a novel perspective on the etiology and treatment of psychiatric disorders by exploring the interplay between metabolic dysregulation and mental health conditions. The emerging evidence supports the concept that disturbances in metabolism can contribute to the pathophysiology of depression, bipolar disorder, schizophrenia, and other psychiatric disorders. Understanding the role of metabolic factors in mental health opens new avenues for developing targeted interventions, such as lifestyle modifications, dietary interventions, and pharmacological approaches that address metabolic dysfunctions alongside traditional psychiatric treatments.

Further research is needed to elucidate the complex mechanisms underlying the relationship between metabolism and mental health and to identify potential therapeutic targets. Integrating metabolic assessments and interventions into psychiatric practice holds promise for personalized approaches and improved outcomes in the management of mental health disorders.

Background

Non-Communicable diseases (NCDs) are the leading causes of death globally with cardiovascular diseases (CVDs) accounting for the highest number of deaths followed by cancer, respiratory diseases and diabetes. The impact of NCDs in health has been varied with reduction of the disability adjusted life years due to various comorbidities. Additionally, it affects the families, health system and national economies of the country. Community based screening for NCDs is the most effective means for detection of undiagnosed NCD cases and early treatment initiation. Prevention strategies are not only effective for populations against developing an NCD, but also for mitigating and reducing the burden of various NCDs. Hence, NCD and Mental Health Campaign was started in one of the urbanized settings (A place called Saraswatinagar) in Central Nepal as part of the healthy city initiative envisioned by World Health Organization (WHO). The major objective of starting this campaign is to educate the Sarswatinagar Community regarding NCDs and Mental Health and its major risk factors. Furthermore, we aim to screen the population of Sarswatinagar for NCDs biomarkers and apply appropriate dietary and behavioral modification interventions to stop the further progression of diseases.

Site Selection

NCDs has boomed in the urbanized community in last decades or so. The major causes are urbanization, consumption of junk foods, inactive lifestyles and careless attitude of people towards their health. In rural terai region, hilly mountains people do physical activity by doing various sorts of physical activity. Additionally, they consume healthy food grown up in their own backyards. However, in the urbanized community this is seen less with people travelling in vehicles and consume various sorts of junk foods without adequate healthy lifestyles. Sarswatinagar community located in Kathmandu Nepal is an urbanized community and we anticipate similar behaviors of people as in other urbanized community. This initiative will give model health city initiative concept which could be replicated further.

Local Collaboration Concept

This activity has been collaborated with Local Fitness Club, 738 Fitness, Leo Club Parikalpana and Local Subunit, Sarswatinagar Sudhar Sang with Nepalese Society of Community Medicine (NESCOM) being the primary body leading the campaign. The concept behind collaboration with local fitness club is that there are only limited people who work on their physique as a means of staying disease-free and healthy. As per the literature, physical activity is one of the strongest means of reducing the burden of NCDs and Mental Health. Gym club trainers and the members do these activities regularly and could be advocate for change for NCDs and Mental Health Prevention in the community. They could be developed as “NCDs Champions. Leo Club Parikalpana is the youth wing of Lions international. Their role basically is in data collection. Sarswatinagar Sudhar Sang on the other hand is one of the active subunits in Kathmandu metropolitan city. They conduct their own election and nominate the team to work for the development of the Sarswatinagar locality. The local subunit was chosen because they could facilitate the NCD and Mental Health Campaign in the areas through various means. NESCOM furthermore is the primary body leading the campaign. It is a “not for profit” professional society of graduates in Community Medicine established in 2015 with the vision to ensure highest attainable health of people of Nepal. It is a network of over 200 residents and graduates who are actively engaged in academics, research, and development projects in Nepal and abroad. Nescom has been primarily chosen as they being varied expertise and can be a huge workforce leading the campaign.

Schedule of the Program

This awareness campaign is being conducted on 1^st week of every Saturday of Nepali Calendar month from 7 a.m. to 12 p.m. in the morning in the summer and 8 a.m. to 1 p.m. in the winter. In this program there is 1 hour of walking in the morning followed by 1 hour of lecture, discussion and interaction on varied topics related to NCD and Mental Health. Additionally, blood pressure and blood sugar are measured and appropriate advice given to the participants. Recently we have started collecting data for evidence generation through Kobo collect application.

Future plans

We plan to empower community of Sarswatinagar about the importance of early identification of prediabetes and prehypertension status and importance of lifestyle modification to slow the progression of diabetes and hypertension and various other NCDs. Construct a workout plan in coherence with standard physical activity suited for the local context. Screen Community Members of 30 -65 years of age in their locality. If found pre-diabetic (HbA1c of 5.7% to 6.4%) and prehypertensive (B.P = 120-139mmHg / 80-89mmHg) put them on workout plan, dietary modification and behavioral change modification. Assess the blood pressure and blood sugar and compare the changes before and after the workout plan. We also envision to scale up this campaign in all the 32 wards of Kathmandu Metropolitan city if the current model gets successful.

Short Term Impact of the Program

The program will help to create community awareness about NCDs and Mental Health. Additionally, this will also help in for community engagement and partnership with the local people, groups for the awareness and prevention in the matter of health and other areas.

Long Term Impact of the Program

The campaign will screen the population and identify the risk group for timely prevention through various intervention measures. This in turn will reduce premature deaths from NCDs, reduce out of pocket expenditures and long-term complications due to the effects of NCDs. This will further leverage the concept of Healthy city initiative envisioned by WHO

Current progress

Till date (as of December 2023) we have educated and screened around 1500 to 2000 participants in last 1.5 years. 

Photographs

Dr. Prajjwal Pyakurel, MD

Cardiovascular Epidemiologist and Community Physician

General Secretary, Nepalese Society of Community Medicine (NESCOM)

Introduction:

Tumor growth is a complex process influenced by various genetic and environmental factors. Epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNA molecules, play a crucial role in the regulation of gene expression and can contribute to abnormal cell growth and the development of tumors. The ketogenic diet, a high-fat, low-carbohydrate eating plan, has been studied for its potential impact on gene regulation and its influence on tumor growth. This article aims to provide an overview of the factors inducing tumor growth, the role of epigenetics in abnormal growth, and the emerging research on the ketogenic diet’s effects on gene regulation and cell growth.

Factors Inducing Tumor Growth:

Tumor growth is influenced by a combination of genetic and environmental factors. Genetic mutations can lead to the activation of oncogenes and the inactivation of tumor suppressor genes, disrupting normal cellular processes and promoting uncontrolled cell growth. Environmental factors, such as exposure to carcinogens, chronic inflammation, hormonal imbalances, and metabolic dysregulation, can also contribute to tumor initiation and progression.

Epigenetics and Abnormal Growth:

Epigenetic modifications can have a profound impact on gene expression and contribute to abnormal cell growth and tumor development. Altered DNA methylation patterns, histone modifications, and dysregulated non-coding RNA molecules can lead to the activation or silencing of genes involved in cell proliferation, differentiation, and apoptosis. Aberrant epigenetic marks can promote oncogenic pathways and inhibit tumor-suppressive mechanisms, thereby driving tumor growth.

The Role of Epigenetics in Tumor Growth:

DNA Methylation: Hypermethylation of CpG islands within promoter regions of tumor suppressor genes can lead to their silencing, allowing uncontrolled cell growth. Hypomethylation in other regions of the genome can activate oncogenes, promoting cell proliferation. A study by Li et al. (2020) demonstrated global DNA hypomethylation in tumor tissues compared to adjacent normal tissues in colorectal cancer patients.

Histone Modifications: Abnormal histone modifications can alter chromatin structure and gene accessibility, impacting gene expression. Histone acetylation, methylation, and phosphorylation patterns can regulate oncogenic signaling pathways. Research by Rasmussen and Helin (2016) highlighted the dysregulation of histone-modifying enzymes in cancer and their potential as therapeutic targets.

Non-coding RNA: Non-coding RNAs, such as microRNAs and long non-coding RNAs, can modulate gene expression by binding to messenger RNA molecules. Dysregulated expression of these non-coding RNAs has been associated with tumor growth and metastasis. A study by Wu et al. (2021) identified specific microRNAs involved in promoting glioblastoma cell growth and invasion.

The Impact of the Ketogenic Diet on Gene Regulation and Tumor Growth:

The ketogenic diet has gained attention for its potential impact on gene regulation and its effects on tumor growth. The diet’s ability to alter cellular metabolism and induce a state of ketosis may influence gene expression patterns and cellular processes relevant to tumor growth.

Metabolic Effects: The ketogenic diet alters cellular metabolism by promoting the production of ketone bodies as an alternative energy source. Ketone bodies can affect signaling pathways involved in cell growth and survival. A study by Elgendy et al. (2021) demonstrated that ketone bodies derived from a ketogenic diet inhibited the growth of lung cancer cells in vitro.

Epigenetic Modifications: Recent research has suggested that the ketogenic diet may induce epigenetic modifications that impact gene expression. For instance, a study by Tan-Shalaby et al. (2016) showed that a ketogenic diet altered the expression of genes involved in metabolism and inflammation in a mouse model of glioblastoma, potentially impacting tumor progression.

Conclusion:

Tumor growth is a multifactorial process influenced by genetic and environmental factors. Epigenetic modifications play a critical role in the regulation of gene expression and can contribute to abnormal cell growth and tumor development. The ketogenic diet shows promise in altering gene regulation and metabolic processes relevant to tumor growth. However, further research is needed to elucidate the underlying mechanisms and assess the clinical implications of the ketogenic diet in cancer treatment.

Understanding the interplay between epigenetics, nutrition, and tumor growth opens up new avenues for targeted therapies and personalized approaches in cancer management.

Introduction:

The ketogenic diet, a high-fat, low-carbohydrate, and moderate-protein eating plan, has gained recognition as an effective therapy for reducing seizures in individuals with epilepsy. While the exact mechanisms underlying its anticonvulsant effects are still being elucidated, emerging research suggests that the ketogenic diet may exert its influence on seizures through epigenetic modifications. Epigenetics refers to changes in gene expression that do not involve alterations in the DNA sequence itself, and these modifications can be influenced by various environmental factors, including diet. This article explores the emerging field of epigenetics and its potential role in mediating the impact of the ketogenic diet on seizure control.

Epigenetics and Seizure Control:

Epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNA molecules, play critical roles in regulating gene expression and determining cellular function. Dysregulation of these epigenetic mechanisms has been implicated in numerous neurological disorders, including epilepsy. Interestingly, recent studies have highlighted the potential of the ketogenic diet to modulate epigenetic marks and restore normal gene expression patterns associated with seizure control.

DNA Methylation:

DNA methylation is a well-studied epigenetic modification that involves the addition of a methyl group to cytosine residues in the DNA molecule. Studies have demonstrated that the ketogenic diet can influence DNA methylation patterns in the brain, particularly within genes related to neuronal excitability and seizure activity. For example, a study by Liu et al. (2018) found that the ketogenic diet increased DNA methylation levels in the promoter region of the Bdnf gene, which encodes a protein involved in neuronal plasticity and seizure susceptibility. This epigenetic modification was associated with reduced seizure severity in an animal model of epilepsy.

Histone Modifications:

Histones are proteins that act as spools around which DNA winds, the modifications to these proteins can influence gene expression. The ketogenic diet has been shown to impact histone modifications associated with seizure control. For instance, McEvoy et al. (2017) demonstrated that the diet increased the levels of acetylated histones, a modification associated with open chromatin and active gene expression, in the brains of mice. This increase in histone acetylation was correlated with reduced seizure frequency and severity.

Non-coding RNA Molecules:

Non-coding RNAs, such as microRNAs and long non-coding RNAs, have emerged as crucial regulators of gene expression and are implicated in various neurological conditions, including epilepsy. Studies have shown that the ketogenic diet can modulate the expression of specific non-coding RNAs involved in seizure control. For example, Sada et al. (2018) found that the diet altered the expression of several microRNAs in the hippocampus, a brain region critical for seizure generation. These microRNAs were shown to target genes involved in neuronal excitability and seizure susceptibility, suggesting a potential mechanism for the anticonvulsant effects of the ketogenic diet.

Conclusion:

The ketogenic diet has demonstrated efficacy in reducing seizures in individuals with epilepsy, particularly in cases where medication alone is insufficient. Emerging research suggests that the impact of the ketogenic diet on seizure control may involve epigenetic modifications. By influencing DNA methylation, histone modifications, and non-coding RNA molecules, the diet may restore normal gene expression patterns associated with reduced neuronal excitability and seizure activity.

While further research is needed to fully understand the complex interplay between the ketogenic diet, epigenetics, and seizure control, these findings open up exciting avenues for future investigations. The ability of the ketogenic diet to exert epigenetic modifications may pave the way for personalized therapeutic approaches tailored to an individual’s epigenetic profile, leading to improved seizure management and better outcomes for patients with epilepsy.