Sleep and Health

AGING: SLEEP AND INFLAMMATORY MECHANISMS IN DEPRESSION PREVENTION
PI: Michael R. Irwin
NIA
Depression in the elderly is a major public health concern. Indeed, as the population ages in high-income countries, depression is projected to increase by 2030 to a position of the greatest contributor to illness burden. Moreover, because elderly persons with depression often do not receive diagnosis and treatment, and only about one-third of depressed older adults achieve remission using current treatment approaches, over two-thirds of the disease burden remains intact leading to staggering costs in the health care sector. The objective of this study is to evaluate the ability of a behavioral intervention, cognitive behavioral therapy for sleep quality (CBT-SQ) to reduce sleep complaints, depression recurrence, and cellular and genomic markers of inflammation in older adults with sleep complaints who have a prior history of depression. We aim to: 1) evaluate the effects of CBT-SQ vs. Sleep Seminar (SS) on objective (actigraphy) and subjective (sleep diary; questionnaire) measures of sleep symptoms over a two-year follow-up; 2) determine the effects of CBT-SQ vs. SS on recurrence of depressive symptoms and depression episode(s) over a two-year follow-up. We will also secondarily examine the effects of CBT-SQ vs. SS on cellular and genomic markers of inflammation over a two-year follow-up, and explore whether markers of inflammation and cytokine genes can explain variability in the risk of depression recurrence in those older adults receiving CBT-SQ vs. SS. The present study is highly significant by being the first study, to our knowledge, to focus on the prevention of depression in community dwelling older adults who have a history of depression, and by targeting sleep disturbance, a modifiable risk factor to prevent depression recurrence.

SUBJECTIVE SOCIAL ISOLATION AND SLEEP DISTURBANCES: INFLAMMATORY MECHANISM IN AGING
PI: Michael R. Irwin, MD
NIA
Social isolation has significant health consequences in older adults, but it is not known how feelings of loneliness and loss of emotional connections lead to increases in disease risk. Given our evidence that social isolation is associated with sleep disturbance, and such sleep difficulties increase inflammation with consequences for a number of medical disorders including cardiovascular disorder, diabetes mellitus, and cancer, this study will examine the relationships between social isolation, sleep disturbance and inflammation in socially isolated older adults. This study will inform the development of potential treatments that target disordered sleep with possible prevention of disease outcomes in older adults who are socially isolated.

TAI CHI EFFECTS ON CHRONIC INSOMNIA IN BREAST CANCER SURVIVORS: IMMUNE MECHANISMS
PI: Michael R. Irwin, MD
NCI
Immune Mechanisms Breast cancer is the most common cancer in women. After completion of successful therapy, many behavioral symptoms persist with over 20% of breast cancer survivors reporting chronic insomnia of greater than 6 months duration that fulfils clinical diagnostic criteria with associated functional limitations, decreased quality of life, and possible effects on long-term survival. Behavioral interventions are highly efficacious in the treatment of insomnia and preferred over hypnotic medications when insomnia is chronic. However, insomnia studies conducted in cancer are scarce. The proposed research builds upon a program of study that has examined the efficacy of a mind-body intervention, Tai Chi Chih (TCC), on health outcomes including sleep impairments. Preliminary studies show that TCC, a slow moving meditation, contributes to improvements in subjective sleep quality, sleep amounts and sleep efficiency. We have further found that sleep, fatigue, and proinflammatory cytokine activity are reciprocally related and that TCC decreases proinflammatory cytokine levels. Thus, we further hypothesize that cytokine network is one physiological mechanism through which TCC carries its effects on sleep outcomes. In this randomized, controlled trial, 100 breast cancer survivors will be randomly assigned to TCC or sleep hygiene/education control (EC) over 16 weeks and followed for one year. The aims of this project are to: 1) evaluate the effects of TCC vs. EC on objective and subjective measures of sleep continuity, fatigue, and health functioning in breast cancer survivors with chronic insomnia; 2) determine the effects of TCC vs. EC on measures of proinflammatory cytokine activity; 3) evaluate whether circulating levels of proinflammatory cytokines temporally correlate with measures of sleep continuity in breast cancer survivors with insomnia over the course of the treatment trial. This project will constitute the first, randomized controlled clinical trial of the effects of TCC on sleep outcomes in breast cancer survivors, and will advance psychobiological models of insomnia treatment mechanisms. 

AGING: INSOMNIA TREAMENT AND ENERGY BALANCE
PI: Sarosh Motivala, PhD
NIA
Over 50% of adults older than 65 years report problems sleeping and the prevalence of persistent insomnia is estimated to be over 30% in this population, and steadily increases with age. Behavioral treatments for chronic insomnia have demonstrated consistent improvements in self-reported sleep, but outcome assessment, including polysomnography, behavioral factors such as health functioning and biologic factors impacted by sleep have not been comprehensively examined, especially in older adults. In particular, one promising area of research is the impact of interventions on energy balance. The hormones ghrelin and leptin are thought to convey information about energy balance to the brain, and dysregulation of these hormones lead to increases in appetite and lipid accumulation. Epidemiologic studies have found that poor sleep is associated with elevated ghrelin and decreased leptin, corroborated by experimental sleep restriction studies as well. Elevated ghrelin and decreased leptin levels also correlate with increased sympathetic activity; which is seen in insomnia patients. Taken together, these findings indicate that older insomnia patients may have altered energy balance. Yet few studies have measured objective sleep assessment following insomnia interventions and no study has reported its effects on energy balance. The proposed project is an ancillary study to a newly funded NIA randomized, controlled trial comparing the effects of cognitive-behavioral therapy (CBT), Tai Chi Chih (TCC), and hygiene/education control (EC) on sleep outcomes in older insomnia patients. This K23 project is an opportunity for the PI (a health-clinical psychologist) to utilize expertise in sleep and psychophysiology assessment and previous clinical training while developing expertise in behavioral insomnia treatment research and biological effects of treatment. The unique aims of this K23 project are to: 1) evaluate the effects of CBT vs. TCC vs. EC on ghrelin and leptin levels at baseline, mid- treatment, post-treatment and 3- and 12-month follow-ups; 2) determine the effects of CBT vs. TCC vs. EC on nocturnal autonomic function (power spectral analysis of heart rate variability) during sleep assessments at the UCLA GCRC at baseline and post-treatment; 3) examine whether energy balance and autonomic function are related to improvements in objective and subjective measures of sleep over the course of the treatment trial.

Relevant Publications

Diurnal cortisol in Complicated and Non-Complicated Grief: Slope differences across the day. O'Connor MF, Wellisch DK, Stanton AL, Olmstead R, Irwin MR. Psychoneuroendocrinology. 2011 Sep 16. [Epub ahead of print] PMID: 21925795  

Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward. Eisenberger NI, Berkman ET, Inagaki TK, Rameson LT, Mashal NM, Irwin MR. Biol Psychiatry. 2010 Oct 15;68(8):748-54. Epub 2010 Aug 16. PMID: 20719303  

Inflammation and social experience: an inflammatory challenge induces feelings of social disconnection in addition to depressed mood. Eisenberger NI, Inagaki TK, Mashal NM, Irwin MR. Brain Behav Immun. 2010 May;24(4):558-63. Epub 2010 Jan 4. PMID: 20043983  Free PMC Article  

Social-evaluative threat and proinflammatory cytokine regulation: an experimental laboratory investigation. Dickerson SS, Gable SL, Irwin MR, Aziz N, Kemeny ME. Psychol Sci. 2009 Oct;20(10):1237-44. Epub 2009 Sep 14. PMID: 19754527 Free PMC Article  

Neural sensitivity to social rejection is associated with inflammatory responses to social stress. Slavich GM, Way BM, Eisenberger NI, Taylor SE. Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14817-22. Epub 2010 Aug 2. PMID: 20679216 Free PMC Article  

Black sheep get the blues: a psychobiological model of social rejection and depression. Slavich GM, O'Donovan A, Epel ES, Kemeny ME. Neurosci Biobehav Rev. 2010 Sep;35(1):39-45. Epub 2010 Jan 18. Review. PMID: 20083138 Free PMC Article  

Antagonistic pleiotropy at the human IL6 promoter confers genetic resilience to the pro-inflammatory effects of adverse social conditions in adolescence. Cole SW, Arevalo JM, Manu K, Telzer EH, Kiang L, Bower JE, Irwin MR, Fuligni AJ. Dev Psychol. 2011 Jul;47(4):1173-80. PMID: 21639625  

Transcript origin analysis identifies antigen-presenting cells as primary targets of socially regulated gene expression in leukocytes. Cole SW, Hawkley LC, Arevalo JM, Cacioppo JT. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):3080-5. Epub 2011 Feb 7. PMID: 21300872 Free PMC Article

Sleep depth and fatigue: role of cellular inflammatory activation. Thomas KS, Motivala S, Olmstead R, Irwin MR. Brain Behav Immun. 2011 Jan;25(1):53-8. Epub 2010 Jul 23. PMID: 20656013 

Nocturnal levels of ghrelin and leptin and sleep in chronic insomnia. Motivala SJ, Tomiyama AJ, Ziegler M, Khandrika S, Irwin MR. Psychoneuroendocrinology. 2009 May;34(4):540-5. Epub 2008 Dec 6. PMID:19059729 Free PMC Article 

Improving sleep quality in older adults with moderate sleep complaints: A randomized controlled trial of Tai Chi Chih. Irwin MR, Olmstead R, Motivala SJ. Sleep. 2008 Jul;31(7):1001-8. PMID: 18652095 Free PMC Article