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Correlates of Social Position in Brain Serotonergic Function

Correlates of Social Position in Brain Serotonergic Function. NIA & IPSR May 2009. Atherosclerotic Cardiovascular Disease: Aging’s Fellow Traveler. Components of Heart Disease Risk. HABIT & LIFESTYLE. PSYCHOSOCIAL. Disorders and traits of mood & affect Hopelessness

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Correlates of Social Position in Brain Serotonergic Function

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  1. Correlates of Social Position in Brain Serotonergic Function NIA & IPSR May 2009

  2. Atherosclerotic Cardiovascular Disease: Aging’s Fellow Traveler

  3. Components of Heart Disease Risk HABIT & LIFESTYLE PSYCHOSOCIAL Disorders and traits of mood & affect Hopelessness Anger/Hostility Social Isolation Smoking Physical Inactivity Diet Immoderate Alcohol Use BIOLOGICAL Blood Pressure Dyslipidemia Obesity Insulin Resistance Inflammation Autonomic Dysregulation CV Reactivity

  4. Web of Heart Disease Risk HABIT & LIFESTYLE PSYCHOSOCIAL BIOLOGICAL

  5. Variation In Central Serotonergic Responsivity Assessed By Neuropharmacologic Challenge Fenfluramine- Stimulated Prolactin Rises In High, Intermediate and Low Responsive Subjects

  6. Correlates of Brain 5-HT Responsivity HABIT & LIFESTYLE PSYCHOSOCIAL Depression Low Daily Positive Affect Aggression/Hostility Impulsivity Smoking Physical Inactivity BIOLOGICAL Blood Pressure Dyslipidemia Obesity Insulin Resistance Inflammation Autonomic Dysregulation CV Reactivity Atherosclerosis

  7. Individual and Area-Level Socioeconomic Indicators Predict: HABIT & LIFESTYLE PSYCHOSOCIAL Disorders of mood & affect Aggressive Conduct Social Isolation Smoking Physical Inactivity Diet Alcohol Abuse BIOLOGICAL Blood Pressure Dyslipidemia Obesity Insulin Resistance Inflammation Autonomic Dysregulation Atherosclerosis

  8. Chronic Social Stress Lowers 5-HT Activity in Prefrontal Cortex of Male Cynomolgus Monkeys

  9. Peer Rearing Lowers 5-HT Turnover in Rhesus Monkeys, at Both Juvenile and Adult Ages Peer-Reared Mother-Reared

  10. Personal Socioeconomic Indicators Covary with Central Serotonergic Responsivity (CSR) CSR [log PRL (fen)] 1 2 3 4 Individual SES (quartiles)

  11. Interactive Effects of rh5-HTTLPR Genotype and Early Rearing Environment on CSF 5-HIAA Concentrations of Rhesus Monkeys Bennett et al., Mol Psychiatry (2002)

  12. Serotonin (5-HT) Transporter Gene-Linked Polymorphic Region [5-HTTLPR] A 44-bp insertion/deletion polymorphism located in the 5' regulatory region of the 5-HT transporter gene, on chromosome 17. Allele Frequency Long (l) 60% Short (s) 40%

  13. Interaction of SES and 5-HTTLPR Genotype on Central 5-HT Responsivity

  14. Census Variables Median Household Income % Households on Public Assistance % Households in Poverty % Workforce Unemployed Median Value of Owner-Occupied Housing Median Rent, as % of Income % Adults (>25 yr) Without HS Degree

  15. Area-Level Socioeconomic Indicators Covary with Central Serotonergic Responsivity (CSR) CSR [log PRL (fen)] 1 2 3 4 Community SES (quartiles)

  16. Age <45 >45 r2 = 0.01, n.s. r2 = 0.10, p = 0.0084 CSR [log PRL (fen)] Community SES (Males)

  17. CSR [log PRL (fen)] Age <45 >45 r2 = 0.17, p = 0.0012 r2 = 0.00, n.s. Community SES (Females)

  18. Conclusions • Individual differences in brain 5-HT activity comprise a neural mechanism of potential relevance to heart disease and to the covariation of both behavioral and biological components of cardiovascular risk

  19. Conclusions • The origin of these individual differences may entail diverse sources of environmental adversity (including social inequalities at both the individual and community levels), functional variation in serotonin regulating genes, and interactions among genetic, environmental, and demographic factors (e.g., age, sex)

  20. Parental Social Position Covaries With Threat-related Amygdala Reactivity Gianaros et al., SCAN 2008

  21. Parental Social Position Covaries With Threat-related Amygdala Reactivity Gianaros et al., SCAN 2008

  22. Lo CNS 5HT Gradient Hi Hostility Depression Smoking Alcohol Carbohydrates/Calories Physical Activity Blood Pressure SNS Reactivity Body mass/Obesity Dyslipidemia Insulin Resistance

  23. 5HT Gene Polymorphisms Social/Environmental Experiences Lo CNS 5HT Gradient Hi Hostility Depression Smoking Alcohol Carbohydrates/Calories Physical Activity Blood Pressure SNS Reactivity Body mass/Obesity Dyslipidemia Insulin Resistance

  24. Area-Level Income, Social Fragmentation, and CSR

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