Metabolic Disturbances in Mental Disorders Flashcards
What is the relationship between cardiometabolic disorders and psychiatric disorders, and in which populations is co-morbidity most common?
- There is significant overlap and co-morbidity between cardiometabolic and psychiatric disorders.
- This co-morbidity is common in the elderly population, particularly those over 65 years of age, where it is considered the norm rather than the exception.
- It is increasingly common in younger populations living in areas of socioeconomic deprivation and in low-income countries.
What is metabolic syndrome, and how is it related to mental disorders?
1) Metabolic syndrome includes conditions like heart disease, lipid problems, hypertension, type 2 diabetes, dementia, cancer, polycystic ovarian syndrome, and non-alcoholic fatty liver disease.
2) It is highly prevalent in individuals with mental disorders, such as schizophrenia (19-68%) and depression (~20-45%).
What is co-morbidity, and how does it impact people with mental disorders?
(1) Co-morbidity refers to the coexistence of several chronic disorders in one individual.
(2) It accounts for 60% of the excess mortality in the mentally ill population.
(3) There is an overall increased risk for completed suicide in people with mental disorders.
What is the relationship between long-term physical health problems and mental health?
(1) People with long-term physical health problems are 2-3 times more likely to suffer from mental health problems than the general population.
(2) 30% of individuals with long-term physical conditions also experience mental health problems.
What is mental/metabolic comorbidity, and why is it important?
1) Mental/metabolic comorbidity refers to the coexistence of mental disorders and metabolic disorders in the same individual.
2) This is important because it can worsen health outcomes, leading to an increased risk of cardiovascular diseases, diabetes, and increased mortality.
What are common risk factors for metabolic syndrome in chronic psychiatric illness?
1) Excessive alcohol consumption
2) Food imbalance and poor dietary habits
3) Genetic predisposition
4) Hormonal imbalances (e.g., involving cortisol and leptin)
5) Second-generation antipsychotics and their side effects
6) Sedentary lifestyle
What are the contributors to metabolic disorders in individuals with mental illness?
1) Genetic factors
2) Unhealthy lifestyle (physical inactivity, poor diet, smoking, inappropriate alcohol use)
3) Antipsychotic drugs
4) Oxidative stress
How does an unhealthy lifestyle contribute to metabolic disorders?
1) Physical inactivity
2) Poor diet
3) Smoking
4) Inappropriate alcohol use
–> These behaviors, combined with low socioeconomic status (SES), contribute to metabolic disorders.
How do metabolic disorders affect health, and what conditions do they lead to?
1) Weight gain
2) Hypertension
3) Impaired glucose and lipid metabolism
4) AGEs accumulation (advanced glycation end products)
—> These contribute to the development of cardiovascular diseases.
What are the diagnostic criteria for metabolic syndrome?
(1) WHO: Diabetes + 2 of the following: central obesity, high triglycerides, low HDL, high BP, high glucose.
(2) IDF: Central obesity + 2 of the following: high triglycerides, low HDL, high BP, high glucose.
(3) EGIR: Insulin resistance + 2 of the following: central obesity, high triglycerides, low HDL, high BP, high glucose.
(4) NCEP-ATP III: At least 3 of the following: central obesity, high triglycerides, low HDL, high BP, high glucose.
What are the key aspects of treating metabolic disturbances in mental health?
1) Assessment and personalized therapy based on patient profile.
2) Prevention/control of type 2 diabetes, cardiovascular events, dementia, and some cancers.
3) Drug therapy for central obesity, hypertension, hyperglycemia, dyslipidemia, and future innovative targets.
4) Healthy lifestyle:
–> Diet, physical activity, emotion regulation, self-care.
–> Address economic, behavioral, social factors, knowledge, beliefs, fears, and sedentarism.
What are the mechanisms involved in metabolic disturbances in mental health?
(1) Insulin resistance, inflammation, psychotropics, developmental programming, and gene-environment interactions contribute to metabolic disturbances.
(2) Metabolic syndrome leads to endothelial cell dysfunction and atherosclerosis.
(3) Poor diet and inactivity cause:
–> Neuroinflammation, adipose tissue changes, gut dysbiosis.
–> Increased cortisol, CRP, insulin, and inflammation.
—> Leads to hypertension, insulin resistance, HPA dysfunction, stress, and genetic factors.
What roles does insulin play in the brain, and which regions are involved?
(1) Insulin Receptors: Present throughout the brain (neurons use GLUT transporters for glucose, not insulin).
(2) Key Regions:
(a) Hippocampus: Involved in memory formation.
(b) Ventral Tegmental Area (VTA): Houses dopaminergic neurons; key for reward, learning, and behavior modulation (also has leptin/ghrelin receptors).
(c) Fusiform Gyrus: Processes object recognition (including food) and positive emotions.
(d) Prefrontal Cortex (PFC): Integrates sensory info and exerts inhibitory control over eating.
(e) Hypothalamus: Central regulator of energy homeostasis and food intake.
How does insulin signal in the brain and which intracellular pathways are involved?
- Insulin Binding: Activates its receptor on neurons.
- AKT (PI3K/Akt) Pathway: Linked to metabolic signaling and cognitive functions (e.g., memory).
- MAPK Pathway: Involved in mitogenic signaling and other cellular responses.
How do early life stress and chronic stress influence insulin resistance and metabolic disturbances?
- Early life and chronic stress disrupt the HPA axis, impairing glucose sensitivity and insulin production.
- This dysregulation contributes to insulin resistance, increasing risks for type II diabetes, metabolic disorders, and mood disorders.
- Epigenetic changes from early stress can alter individual stress responses later in life.
What roles do neuroinflammation, mitochondrial function, and lifestyle factors play in brain insulin signaling?
- Unhealthy diet and inactivity lead to neuroinflammation, adipose tissue changes, gut dysbiosis, and increased oxidative stress (ROS).
- Mitochondrial Function: Crucial for maintaining oxidative balance and reducing stress from ROS.
- Regular physical activity boosts neurotrophins, supporting healthy brain insulin signaling and cognitive function.
- Glycemic Dysregulation is directly linked to mood disorders, emphasizing the metabolism-mood connection.
How do chronic glucocorticoids affect insulin signaling and glucose homeostasis in different tissues?
(1) Adipose Tissue:
- Inhibit glucose uptake; stimulate lipolysis and gluconeogenesis, leading to insulin resistance.
(2) Skeletal Muscle:
- Reduce insulin signaling and glycogen storage; increase protein degradation.
(3) Liver:
- Enhance gluconeogenesis and lipogenesis; decrease insulin receptor binding.
(4) Pancreas:
- Lower β-cell sensitivity and insulin secretion; promote β-cell hyperplasia and oxidative stress.
(5) Brain:
- Cause abnormalities in cerebral glucose metabolism; reduce insulin uptake and receptor expression (notably in the hippocampus and hypothalamus), affecting cognition and mood.
How do inflammatory mechanisms link stress to metabolic disturbances in mental disorders?
-An imbalance between pro-inflammatory and anti-inflammatory cytokines plays a key role.
- Increases in pro-inflammatory cytokines, chemokines, adhesion molecules, and acute phase reactants contribute to systemic inflammation.
- Stressors (early adversity, interpersonal conflict, social isolation) activate the CRH system and NF-kB pathway.
- NF-kB, active in macrophages, triggers the immune response leading to increased production of pro-inflammatory mediators.
- The inflammatory cascade decreases trophic factors, increases excitotoxicity, and reduces monoamine levels, negatively affecting mood and cognitive function.
- Endocrine responses (via ACTH and cortisol from the adrenal glands) and neural pathways (like the vagus nerve) further link stress to metabolic dysregulation.
- This integrated process connects stress-induced inflammation to both metabolic disturbances and mental health disorders, explaining how chronic stress contributes to conditions like insulin resistance and mood disorders.
How do psychotropic medications affect cardiovascular and metabolic health?
(1) Atypical Antipsychotics:
- Second-generation drugs (e.g., clozapine and olanzapine) have a high risk for weight gain and obesity.
- Clozapine, olanzapine, and risperidone are associated with a higher risk of developing diabetes.
(2) Antidepressants:
- Tricyclics and SSRIs can lead to weight gain due to increased appetite and sedation.
(3) Mood Stabilizers:
- Sodium valproate and lithium are also linked to weight gain.
How do developmental programming and gene-environment interactions contribute to psychiatric and cardiometabolic disorders?
(1) Early Vulnerabilities:
- Globally, about one-quarter of live births (≈35.3 million babies) are vulnerable (born too soon, too small, or with low birthweight).
- These early vulnerabilities are linked to later risks of mood disorders, addiction, type 2 diabetes, hypertension, and metabolic syndrome.
(2) Gene-Environment Interactions:
- Genetic factors and environmental influences (e.g., low birthweight) interact, shaping long-term outcomes.
- An example is the interaction between low birth weight and striatum-related genes.
(3) Molecular Mechanisms:
- Networks such as the SLC6A3 co-expression gene in the striatum are implicated.
- Key pathways include insulin signaling, dopamine receptor activity, ribosome production, and inflammatory responses.
