AGING and WELLNESS
AGING: SLEEP AND INFLAMMATORY MECHANISMS IN DEPRESSION PREVENTION
PI: Michael R. Irwin
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.
CHRONIC MODERATE SLEEP RESTRICTION IN OLDER LONG SLEEPERS AND OLDER AVERAGE SLEEPERS
PI: Youngsteadt, Univ. of South Carolina, Michael R. Irwin, UCLA PI
People who sleep little (less than 7 hours) and people who sleep a lot (8 hours or more) tend to die sooner and have other health problems compared with people who sleep 7-8 hours. There are many studies that show that experimental sleep deprivation has a lot of negative effects. However, these studies have mostly been short (5 days or less) and have involved extreme levels of sleep deprivation. There is little information about what happens following more prolonged (weeks) and modest reduction in sleep (1 hour), which is much more common. Long sleepers could even benefit from modest restriction of sleep. It is especially important to examine whether long-term modest sleep restriction has benefits or negative effects in older adults. A modest amount of sleep restriction might reduce the number of interruption of sleep and help older adults sleep better. This experiment will examine 100 older long sleepers and 100 older average-duration sleepers over 5 years in 4 difference sites: Columbia, SC, Brooklyn, NY, Tucson, AZ, and Los Angeles. Subjects will spend 1 hour less in bed for 12 weeks and we will examine many potential negative and positive effects, including depression, sleepiness, and blood sugar levels.
SUBJECTIVE SOCIAL ISOLATION AND SLEEP DISTURBANCES: INFLAMMATORY MECHANISM IN AGING
PI: Michael R. Irwin, MD
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.
UCLA OLDER AMERICANS INDEPENDENCE CENTER (Pepper Center)
PI: David Reuben, MD; Michael R. Irwin, MD, Co-I
The UCLA Claude Pepper Older Americans Independence Center (OAIC) is designed to promote research aimed at maintaining and restoring the independence of older persons. Through its theme of Translational Research to Maintain Independence, the UCLA OAlC's research extends across the full spectrum from T1 to T2 translational research. Within this theme, an important focus of the UCLA OAIC is on developing and understanding interventions that reduce inflammation. To accomplish its goals, the UCLA OAIC has established 4 Research Cores (Recruitment and Retention, Research Operations, Analysis and Cost Effectiveness, and Inflammatory Biology) and a new Information Dissemination Core that will facilitate OAlC-related research at every step (recruitment, measurement, data management, analysis, interpretation, and adoption of findings). Research cores provide support at 4 levels: Consultation (e.g., providing up to several hours of advice, reading a paper or a proposal) Short-term (e.g., up to a couple days of consultation, performing assays) Ongoing or long-term support (e.g., ongoing, part of the project team) Partnership on new proposals In addition, the UCLA OAIC Pilot and Exploratory Studies Core and Research Career Development Core stimulate new research via a pipeline of junior investigators and pilot awards and recruit successful investigators into OAlC-related research. A specific goal of the Center is to create teams of translational researchers and to train junior faculty in the principles of conducting research that bridges basic, clinical, and health services/dissemination research. The Leadership/Administrative Core ensures that these specific activities are accomplished and the goals of the UCLA OAIC are optimally achieved. By focusing efforts and resources through the OAIC, the timeline for research to develop, test, and disseminate promising innovations to maintain independence can be accelerated. At the end ofthe 5-year cycle, the UCLA OAIC will be a model program for translational research extending from basic science to clinical practice and policy and will have created a generation of new researchers who can begin to assume leadership in this theme.
RESILENCE & HEALTH WITHIN PERONS & ACROSS COMMUNITIES
PI: Michael R. Irwin, UCLA PI
The fundamental question asked in this investigation is whether measures of resilience capacity, identified from recent theoretical advances and empirical study, will predict physical and emotional functioning beyond that provided from well-established risk factors for disease and psychological ill-health for community residents from a wide range of backgrounds. A community sample of men and women aged 40 to 65 (total N = 800) will be drawn from 40 census neighborhoods that vary in average income, age, and ethnic composition. Using multi-level methods, participants and their neighborhoods will be evaluated on global indices of risk and resilience. Deeper probing of the underlying bio-behavioral mechanisms of risk and resilience will be conducted through laboratory testing and electronic diary assessments with a sub-sample (N = 200) drawn from the larger pool of participants. Current functioning and precursors of future health status of the mid-aged adults will be taken as outcomes. For those mid-aged adults with children, the outcome measures will also be assessed in one their children approaching adult life (aged 16 to 24 years; N = 160) to probe the transmission of resilience across generations.
Complementary use of tai chi chih augments escitalopram treatment of geriatric depression: a randomized controlled trial.  Lavretsky H, Alstein LL, Olmstead RE, Ercoli LM, Riparetti-Brown M, Cyr NS, Irwin MR. Am J Geriatr Psychiatry. 2011 Oct;19(10):839-50. doi: 10.1097/JGP.0b013e31820ee9ef. PMID: 21358389
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
An evaluation of a biopsychosocial framework for health-related quality of life and disability in rheumatoid arthritis.  Nicassio PM, Kay MA, Custodio MK, Irwin MR, Olmstead R, Weisman MH. J Psychosom Res. 2011 Aug;71(2):79-85. Epub 2011 May 14. PMID: 21767687
When grief heats up: pro-inflammatory cytokines predict regional brain activation.  O'Connor MF, Irwin MR, Wellisch DK. Neuroimage. 2009 Sep;47(3):891-6. Epub 2009 May 27. PMID: 19481155 Free PMC Article 
Mitigating Cellular Inflammation in Older Adults: A Randomized Controlled Trial of Tai Chi Chih.  Irwin MR, Olmstead R. Am J Geriatr Psychiatry. 2011 Sep 19. [Epub ahead of print] PMID: 21934474
Reciprocal regulation of the neural and innate immune systems.  Irwin MR, Cole SW. Nat Rev Immunol. 2011 Aug 5;11(9):625-32. doi: 10.1038/nri3042. PMID: 21818124
Major depressive disorder and immunity to varicella-zoster virus in the elderly.  Irwin MR, Levin MJ, Carrillo C, Olmstead R, Lucko A, Lang N, Caulfield MJ, Weinberg A, Chan IS, Clair J, Smith JG, Marchese RD, Williams HM, Beck DJ, McCook PT, Johnson G, Oxman MN. Brain Behav Immun. 2011 May;25(4):759-66. Epub 2011 Feb 15. PMID: 21329753
Prior depression history and deterioration of physical health in community-dwelling older adults--a prospective cohort study.  Cho HJ, Lavretsky H, Olmstead R, Levin M, Oxman MN, Irwin MR. Am J Geriatr Psychiatry. 2010 May;18(5):442-51. PMID: 20220581 Free PMC Article 
Improving depression and enhancing resilience in family dementia caregivers: a pilot randomized placebo-controlled trial of escitalopram.  Lavretsky H, Siddarth P, Irwin MR. Am J Geriatr Psychiatry. 2010 Feb;18(2):154-62. PMID: 20104071 Free PMC Article