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The Social Environment: The Impact of Loneliness

The Social Environment: The Impact of Loneliness. Louise C. Hawkley & John T. Cacioppo University of Chicago. Prepared for The New York Academy of Medicine/Royal Society of Medicine New York, NY September 27, 2011. Experimental Effects of Social Isolation in Non-Humans.

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The Social Environment: The Impact of Loneliness

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  1. The Social Environment: The Impact of Loneliness Louise C. Hawkley & John T. Cacioppo University of Chicago Prepared for The New York Academy of Medicine/Royal Society of Medicine New York, NY September 27, 2011

  2. Experimental Effects of Social Isolation in Non-Humans • Decreases lifespan of the fruit fly, Drosophila melanogaster(Ruan & Wu, PNAS, 2008) • Promotes the development of obesity and Type 2 diabetes in mice (Nonogaki, Nozue, & Oka, Endocrinology, 2007) • Delays the positive effects of running on neurogenesis in adult rats (Stranahan, Khalil, & Gould, Nature Neuroscience, 2006) • Increases activation of the sympatho-adrenomedullary response to an acute immobilization or cold stressor in rats (Dronjak, Gavrilović, Filipović, & Radojčić, Physiology & Behavior, 2004) • Decreases the expression of genes regulating glucocorticoid response [glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11b-hydroxysteroid dehydrogenases 1 & 2 (11b-HSD1 & 11b-HSD2)] in the frontal cortex of piglets (Poletto, Steibel, Siegford, & Zanella, Brain Research, 2006) • Decreases open field activity, increases basal cortisol concentrations, and decreases lymphocyte proliferation to mitogens in pigs (Kanitz, Tuchscherer, Puppe, Tuchscherer, & Stabenow, Brain, Behavior, and Immunity, 2004) • Larger morning rises in cortisol in squirrel monkeys (Lyons, Ha, & Levine, Hormones and Behavior, 1995) • Higher 24 hr urinary catecholamines and evidence of oxidative stress in the aortic arch of the Watanabe Heritable Hyperlipidemic rabbit (Nation, et al., Psychosomatic Medicine, 2008)

  3. Level of Social Integration and Age-Adjusted Mortality in Five Prospective Studies House, Landis, & Umberson, 1988

  4. For humans, simply feeling isolated is detrimental to health and well-being. This distressing feeling is called LONELINESS

  5. Defining loneliness • Discrepancy between actual and desired quantity and/or quality of social relationships. • Aversive feeling

  6. Loneliness intensity: Age differences? Many 18-25 year-olds Few Many 50-68 year-olds Few Not lonely Lonely

  7. Perceived Social Isolation in Humans • Diminished immunity (Kiecolt-Glaser et al., Psychosomatic Medicine, 1984; Pressman et al., Health Psychology, 2005) • Less salubrious sleep (Hawkley et al., 2010; Jacobs et al., Journal of the American Geriatric Society, 2006; Pressman et al., Health Psychology, 2005) • Progression of Alzheimer’s Disease (Wilson et al., Archives of General Psychiatry, 2007) • Reduction in independent living (Russell et al., Psychology & Aging, 1997) • Obesity (Lauder et al., Psychology, Health, & Medicine, 2006) • Alcoholism (Akerlind & Hornquist, Social Science & Medicine, 1992) • Reduced physical activity (Hawkley, Thisted, & Cacioppo, 2009)

  8. Perceived Social Isolation in Humans • Altered gene transcription favoring pro-inflammatory status (Cole et al., 2007, 2010). • Increased hypothalamic pituitary adrenocortical activity (Steptoe et al., 2004) • Depression (Heikkinen & Kauppinen, Archives of Gerontology and Geriatrics, 2004; ) and suicidal ideation and behavior (Rudatsikira, Muula, Siziya, & Twa-twa, BMC Psychiatry, 2007) • Poorer health (Caspi et al., Archives of Pediatric Adolescent Medicine, 2006; Seeman , American Journal of Health Promotion, 2000; Thurston & Kubzansky, 2009) • Mortality (Olsen et al., 1991; Patterson & Veenstra, 2010; Penninx et al., 1999; Shiovitz-Ezra & Ayalon, 2009).

  9. Health & Retirement Study (HRS) • Nationally representative, longitudinal study of older Americans (born before 1953) re-interviewed every two years. • Data from 2002, 2004, 2006, 2008 • N = 2,101 in Year 2002 • Effect of loneliness on mortality risk over a six-year period, 2002-2008 • HR = 1.14 (1.06-1.23) • Those with highest loneliness levels were 2.21X as likely to die as those with lowest levels Luo, Hawkley, Waite, & Cacioppo, under review

  10. Hazard ratios of the Weibull models of mortality from 2002 to 2008

  11. Hazard ratios of the Weibull models of mortality from 2002 to 2008 1 2 3

  12. Loneliness: Conceptual Background • Aversive: • Social equivalent to physical pain (Eisenberger & Lieberman, 2004) • Social rejection activates affectiveand sensory components of physical pain (Kross et al., 2011) Cacioppo & Hawkley, TICS, 2009

  13. Pleasant social - Pleasant nonsocial Ventral striatum + Loneliness: Conceptual Background - • Appetitive: • Functions like hunger and thirst to motivate & reward formation and maintenance of social connections crucial for the survival of the genes (Cacioppo & Hawkley, TICS, 2009) Cacioppo et al., 2009

  14. Consequences of Loneliness • Neurobiological • Cardiovascular • Hypothalamic-pituitary-adrenocortical axis • Gene transcription • Behavioral • Physical activity • Functional limitations • Sleep quality

  15. Total Peripheral Resistance in 18-25 yr-olds Altered blood pressure regulation in lonely young adults SBP = TPR * CO • Until about age 55, the primary determinant of increased SBP is TPR (Franklin et al., 1997). Cacioppo, Hawkley, Crawford, et al., 2002; Hawkley, Burleson, Berntson, & Cacioppo, 2003

  16. * Loneliness is associated with elevated SBP in older adults in CHASRS (50-68 years old) Systolic Blood Pressure in 50-68 yr-olds Hawkley, Berry, Masi, & Cacioppo, Psychology & Aging, 2006

  17. Loneliness predicts greater increases in SBP Time-varying covariates: Social network size, Drinking, smoking, BMI, exercise, Chronic conditions, CV & anti-lipid meds …2 …3 …4 …5 .773** .768** .768** .768** L1 L2 L3 L4 L5 Demographic Covariates: Age Gender Race/ethnicity Education -.004 .011 .011 .011 .15* .15* .15* .190* -.053 -.021 -.184* -.078 .152 -.080 -.080 -.080 BP1 BP2 BP3 BP4 BP5 .498** .503** .503** .503** …1 …2 …3 …4 …5 Hawkley, Thisted, Masi, & Cacioppo, Psychology & Aging, 2010

  18. RISK FACTORS Psychosocial Factors: LONELINESS + HPA Pathway Total Peripheral Resistance Oxidative stress Endothelial function Personality CV Risk Demographics SES SNS Pathway Physiological mechanisms • What mechanisms contribute to loneliness differences in TPR in younger adults? • What mechanisms contribute to increased risk for chronic disease and disability?

  19. Loneliness predicts altered HPA regulation Salivary cortisol (ng/ml) In 50-68 year-olds, the cortisol “stress” reaction ramps up more quickly and peaks higher in lonely than in nonlonely adults. Adam, Hawkley, Kudielka, & Cacioppo, PNAS, 2006

  20. Day-Specific Morning Cortisol Parameters Loneliness predicts altered HPA regulation Day Before Reports Same Day Reports .09** Cortisol Awakening Response Day Before Perceived Isolation -.05 Same Day Perceived Isolation n.s. Higher day before loneliness, higher next day awakening response -.07* Day Before Fatigue Morning Cortisol Level Same Day Fatigue -.03 n.s. Higher morning cortisol, less fatigue later that day Adam, Hawkley, Kudielka, & Cacioppo, PNAS, 2006

  21. Lonely Non-lonely Loneliness-related transcripts 25 100 50 125 150 75 0 Down-regulated Difference: p = .0001 Up-regulated Loneliness is associated with altered gene transcription Cole, Hawkley, Arevalo, Sung, Rose, & Cacioppo, 2007

  22. NF-kB Glucocorticoid p = .011 p = .033 .50 .40 .40 .30 .30 promoter sites / gene promoter sites / gene .20 .20 .10 .10 .00 .00 Isolated Isolated Integrated Integrated Gene expression: Pro-inflammatory profile Difference p = .007 • Down-regulated genes • Type 1 interferon; innate antiviral responses; innate antimicrobial responses • Up-regulated genes • leukocyte activation and inflammation; pro-inflammatory cytokines; cellular responses to oxidative stress • Differences in gene expression were replicated in a confirmation sample (N = 93) • Differences in gene expression were linked to perceived social isolation, not objective social isolation, indicating the instrumental role of the CNS Observed ratio = 5.08 (chance: 35/10,000) .12 .10 .8 .6 Cole, Hawkley, Arevalo, Sung, Rose, & Cacioppo, 2007; Cole, Hawkley, Arevalo, & Cacioppo, 2010 .4 .2 0 3 .1 .3 1 10 Genome cis-structural NF-kB / GRE ratio

  23. Physical activity in 50-68 year-old CHASRS participants • 63% reported spending <30 min/day (range = 1 – 107 min/day) • 11% did not report any vigorous activity during the past 2 weeks

  24. Loneliness predicts decreases in physical activity 100% In 50-68 year-olds, loneliness was associated with an increased rate of discontinuation of physical activity over a two-year period. * * * 75% 1 2 3 Year  Hawkley, Thisted, & Cacioppo, Health Psychology, 2009

  25. Loneliness predicts increases in functional limitations L2 L4 L6 * * * * FL2 FL4 FL6 • Estimates hold constant sociodemographic variables plus • social integration • health behaviors Luo, Hawkley, Waite, & Cacioppo, under review

  26. Loneliness & Implicit Vigilance for Social Threat Social Emotional Stroop Green Loved Blue Blue Belong Yellow Red Green Rejected Yellow Red Isolated Negative social Positive social Egidi, Shintel, Nusbaum, & Cacioppo, unpublished

  27. Loneliness, vulnerability and poor sleep quality • Undergraduates at OSU: loneliness was associated with daytime dysfunction (Cacioppo, Hawkley, et al., 2002) • Sleep cap study of undergraduates showed that loneliness was associated with greater sleep disruption (micro-awakenings), but not with less sleep duration (Cacioppo, Berntson, Hawkley, et al., 2002) • Hutterites: lower levels of loneliness than general population, but individual differences were associated with poorer sleep quality as measured by an index of sleep fragmentation (Kurina et al., in press).

  28. Loneliness predicts daytime dysfunction, not sleep duration (50-68 yr-olds) Hawkley, Preacher, & Cacioppo, 2010

  29. Loneliness Interventions • Meta-analytic review • Keywords: loneliness, intervention, treatment, prospective, medication, and/or pharmacology • Published between 1970 and September 2009

  30. Loneliness interventions (1970-2009) meta-analysis 27 50 0 20 Masi, Chen, Hawkley, & Cacioppo, Personality & Social Psychology Review, 2010

  31. Loneliness interventions meta-analysis: Randomized group comparison (N = 20) Mean effect size = -0.198 (95% CI: -0.32, -0.08) • Intervention type • Social cognitive training (4 studies) = -0.598** • Reframing of negative social experiences; modifying attributional styles (e.g., McWhirter & Horan, 1996) • Social support (12 studies) = -0.162* • Group meetings to share stressful experiences and coping strategies (e.g., Samarel et al., 2002) • Social skills training (2 studies) = -0.062 • How to initiate and maintain positive friendships (e.g., Kremers et al., 2006) • Social access (2 studies) = 0.017 • Internet access & training: chat room, email exchange (e.g., White et al., 2002) Masi, Chen, Hawkley, & Cacioppo, Personality & Social Psychology Review, 2010

  32. Age Female Black Hispanic Education Married/live-in partner Psych1 Antidepress1 PhysFx1 Age Female Black Hispanic Education Married/live-in partner Psych2 Antidepress2 PhysFx2 Age Female Black Hispanic Education Married/live-in partner Psych3 Antidepress3 PhysFx3 Age Female Black Hispanic Education Married/live-in partner Psych4 Antidepress4 PhysFx4 Age Female Black Hispanic Education Married/live-in partner Psych5 Antidepress5 PhysFx5 Loneliness predicts increases in depressive symptoms L1 L2 L3 L4 L5 .79** .79** .79** .79** .10 .10 .10 .10 .58** .45** .43* .33* .30* .18* . 18* .18* .18* .57** .57** .57** .57** D1 D2 D3 D4 D5 Age Female Black Hispanic Education Married/live-in partner Psych1 Antidepress1 PhysFx1 Age Female Black Hispanic Education Married/live-in partner Psych2 Antidepress2 PhysFx2 Age Female Black Hispanic Education Married/live-in partner Psych3 Antidepress3 PhysFx3 Age Female Black Hispanic Education Married/live-in partner Psych4 Antidepress4 PhysFx4 Age Female Black Hispanic Education Married/live-in partner Psych5 Antidepress5 PhysFx5 Cacioppo , Hawkley, & Thisted, Psychology & Aging, 2010

  33. Loneliness reduction effects accumulate • If interventions to reduce loneliness by one standard deviation were made one and two years prior to assessing depressive symptoms, both would have an effect and would together result in an average reduction in depressive symptoms of 0.34 standard deviations (95% CI: 0.21, 0.46, P<0.0001). VanderWeele, Hawkley, Thisted, & Cacioppo, JCCP, 2011

  34. Summary • Loneliness is not equivalent to being alone. • Loneliness is not inevitable with age. • Loneliness is painful. • Loneliness feels unsafe and elicits implicitvigilance for threat. Green Blue Loved Blue Yellow Belong Red Green Rejected Yellow Red Isolated Negative social Positive social

  35. Summary • Feeling lonely/isolated has neurobiological and behavioral consequences. • Cardiovascular health: acceleration of age-related increases in SBP • HPA regulation: elevated cortisol • Gene transcription: pro-inflammatory profile • Functional limitations • Impaired sleep quality • Depressive symptoms • Effects are not explained by social support, perceived stress, hostility • Effects are not explained by health behaviors

  36. Summary • Effects of loneliness accumulate (Caspi et al., 2006; Hawkley et al., 2010), and interventions to reduce loneliness may also accumulate to benefit health outcomes (e.g., depressive symptoms). • Optimal age/time of intervention(s) may differ depending on outcome • Loneliness and well-being ? http://dayspringkids.us/learn_2.jpg

  37. With thanks to collaborators and contributors: • John T. Cacioppo, Ph.D., University of Chicago • Steve Cole, Ph.D., UCLA • Emma Adam, Ph.D., Northwestern University • Ron Thisted, Ph.D. University of Chicago • Linda Waite, Ph.D. University of Chicago • Ye Luo, Ph.D., Clemson University Catherine Norris, Ph.D., Dartmouth University Chris Masi, M.D., Ph.D., University of Chicago Kristopher Preacher, Ph.D., University of Kansas And the staff of the University of Chicago Social Neuroscience Laboratory This research was supported by grants from the National Institute on Aging to J. T. Cacioppo (PI), PO1 AG-034052 & RO1 AG-033590, and to L. C. Hawkley (PI), RO1 AG-036433. • Jessica Bell, M. A. • Hsi-Yuan Chen, M.A. • Laura Finch, B.A. • Danielle Lerner, B.A. • Sara Polis, M.A. • Josh Rooks, B.A. • Ashley Smith, M.A.

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