The Interplay of Genetics, Behavior, and Pain with Depressive Symptoms in the Elderly.

PURPOSE OF STUDY About 25% of older adults suffer from depressive symptoms. Commonly studied candidate genes associated with depression include those that influence serotonin (SLC6A4), dopamine (COMT), or neuroplasticity (BDNF, NTRK3). However, the majority of candidate gene studies do not consider the interplay of genetics, demographic, clinical, and behavioral factors and how they jointly contribute to depressive symptoms among older adults. The purpose of this study was to gain a more comprehensive understanding of depressive symptoms among older adults. DESIGN AND METHODS In this descriptive study, demographic, behavioral, and clinical characteristics (age, gender, comorbidities, volunteering, physical activity, pain, and fear of falling) were obtained via interview of 114 residents in a continuing care retirement community. Peripheral whole blood was collected for DNA extraction. We examined common single nucleotide polymorphisms (SNPs) in the aforementioned genes using path analyses. RESULTS SNPs in the NTRK3 gene, pain, physical activity, and fear of falling were directly associated with depressive symptoms in older adults. Those who had polymorphisms in the NTRK3 gene, pain, fear of falling, and were less physically active were more likely to exhibit depressive symptoms. None of the SNPs in SLC6A4, COMT, or BDNF genes were significantly associated with depressive symptoms. IMPLICATIONS Our use of a path analysis to examine a biopsychosocial model of depressive symptoms provided the opportunity to describe a comprehensive clinical picture of older adults at risk for depressive symptoms. Thus, interventions could be implemented to identify older adults at risk for depressive symptoms.

[1]  B. Resnick,et al.  The Useful Depression Screening Tool for Older Adults: Psychometric Properties and Clinical Applicability. , 2015, Journal of nursing measurement.

[2]  Y. Omidi,et al.  Asymmetrical expression of BDNF and NTRK3 genes in frontoparietal cortex of stress‐resilient rats in an animal model of depression , 2014, Synapse.

[3]  M. Hagger,et al.  What keeps a body moving? The brain-derived neurotrophic factor val66met polymorphism and intrinsic motivation to exercise in humans , 2014, Journal of Behavioral Medicine.

[4]  H. Anisman,et al.  Catechol-O-methyltransferase Val158Met polymorphism and altered COMT gene expression in the prefrontal cortex of suicide brains , 2014, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[5]  M. Menchetti,et al.  Prevalence and gender differences in late-life depression: a population-based study. , 2014, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[6]  K. Tansey,et al.  Interaction between stress and the BDNF Val66Met polymorphism in depression: a systematic review and meta-analysis , 2014, BMC Medicine.

[7]  B. Resnick,et al.  Volunteering and Depressive Symptoms Among Residents in a Continuing Care Retirement Community , 2014, Journal of gerontological social work.

[8]  A. Serretti,et al.  The role of COMT gene variants in depression: Bridging neuropsychological, behavioral and clinical phenotypes , 2013, Neuroscience & Biobehavioral Reviews.

[9]  B. Resnick,et al.  Volunteer Behavior and Factors that Influence Volunteering Among Residents in Continuing Care Retirement Communities , 2013 .

[10]  K. Bhui,et al.  The reciprocal relationship between physical activity and depression in older European adults , 2012, Evidence Based Nursing.

[11]  Kevin M. Beaver,et al.  An interaction between perceived stress and 5HTTLPR genotype in the prediction of stable depressive symptomatology. , 2012, The American journal of orthopsychiatry.

[12]  W. Taylor,et al.  Stressful life events, perceived stress, and 12-month course of geriatric depression: Direct effects and moderation by the 5-HTTLPR and COMT Val158Met polymorphisms , 2012, Stress.

[13]  I. Belfer,et al.  Genetic basis of pain variability: recent advances , 2011, Journal of Medical Genetics.

[14]  Ipsit V Vahia,et al.  A tune in "a minor" can "b major": a review of epidemiology, illness course, and public health implications of subthreshold depression in older adults. , 2011, Journal of affective disorders.

[15]  T. Garland,et al.  The biological control of voluntary exercise, spontaneous physical activity and daily energy expenditure in relation to obesity: human and rodent perspectives , 2011, Journal of Experimental Biology.

[16]  H. Hermens,et al.  The Genetic Influence on the Cortical Processing of Experimental Pain and the Moderating Effect of Pain Status , 2010, PloS one.

[17]  E. Castrén,et al.  The role of BDNF and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticity , 2010, Developmental neurobiology.

[18]  T. Lehtimäki,et al.  Catechol-O-methyltransferase val108/158met genotype, major depressive disorder and response to selective serotonin reuptake inhibitors in major depressive disorder , 2010, Psychiatry Research.

[19]  Joongbaeck Kim,et al.  Volunteering and Trajectories of Depression , 2010, Journal of aging and health.

[20]  N. Risch,et al.  Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. , 2009, JAMA.

[21]  P. Duberstein,et al.  One-year outcomes of minor and subsyndromal depression in older primary care patients , 2009, International Psychogeriatrics.

[22]  N. Wray,et al.  Association study of candidate variants of COMT with neuroticism, anxiety and depression , 2008, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[23]  D. Lawlor,et al.  Genetic association study of BDNF in depression: Finding from two cohort studies and a meta‐analysis , 2008, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[24]  N. Yanay,et al.  The decline of motivation?: From commitment to dropping out of volunteering , 2008 .

[25]  E. Stordal,et al.  Depression and anxiety in relation to catechol-O-methyltransferase Val158Met genotype in the general population: The Nord-Trøndelag Health Study (HUNT) , 2008, BMC psychiatry.

[26]  J. Potash,et al.  Linkage Disequilibrium Mapping of a Chromosome 15q25-26 Major Depression Linkage Region and Sequencing of NTRK3 , 2008, Biological Psychiatry.

[27]  J. Gádoros,et al.  Association of the neurotrophic tyrosine kinase receptor 3 (NTRK3) gene and childhood-onset mood disorders. , 2008, The American journal of psychiatry.

[28]  J. González,et al.  Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disorders. , 2008, Human molecular genetics.

[29]  E. van Rossum,et al.  Feelings of anxiety and symptoms of depression in community-living older persons who avoid activity for fear of falling. , 2008, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[30]  Burton H Singer,et al.  Feelings of Usefulness to Others, Disability, and Mortality in Older Adults: the MacArthur Study of Successful Aging. , 2007, The journals of gerontology. Series B, Psychological sciences and social sciences.

[31]  D. Murphy,et al.  A novel, putative gain-of-function haplotype at SLC6A4 associates with obsessive-compulsive disorder. , 2007, Human molecular genetics.

[32]  K. Chou.  Reciprocal relationship between pain and depression in older adults: evidence from the English Longitudinal Study of Ageing. , 2007, Journal of affective disorders.

[33]  Y. Conwell,et al.  The clinical significance of subsyndromal depression in older primary care patients. , 2007, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[34]  S. Kivelä,et al.  The effects of physical exercise on depressive symptoms among the aged: a systematic review , 2006, International journal of geriatric psychiatry.

[35]  James A. Blumenthal,et al.  Exercise training and depression in older adults , 2005, Neurobiology of Aging.

[36]  M. Rizzo,et al.  The effects of physical activity and sedentary behavior on cognitive health in older adults. , 2005, Journal of aging and physical activity.

[37]  K. Spratt,et al.  Pain Intensity Assessment in Older Adults: Use of Experimental Pain to Compare Psychometric Properties and Usability of Selected Pain Scales With Younger Adults , 2004, The Clinical journal of pain.

[38]  R. Spitzer,et al.  The Patient Health Questionnaire-2: Validity of a Two-Item Depression Screener , 2003, Medical care.

[39]  A. Caspi,et al.  Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene , 2003, Science.

[40]  F. Porreca,et al.  Neurotrophic factors as novel therapeutics for neuropathic pain , 2003, Nature Reviews Drug Discovery.

[41]  Claudia Sommer,et al.  Absence of Thermal Hyperalgesia in Serotonin Transporter-Deficient Mice , 2003, The Journal of Neuroscience.

[42]  S. Borson,et al.  The Mini‐Cog: a cognitive ‘vital signs’ measure for dementia screening in multi‐lingual elderly , 2000, International journal of geriatric psychiatry.

[43]  P. Sullivan,et al.  Genetic epidemiology of major depression: review and meta-analysis. , 2000, The American journal of psychiatry.

[44]  B. Resnick.  Functional Performance of Older Adults in a Long-Term Care Setting , 1998, Clinical nursing research.

[45]  Harold I. Kaplan,et al.  Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences Clinical Psychiatry , 1994 .

[46]  C. Caspersen,et al.  A survey for assessing physical activity among older adults. , 1993, Medicine and science in sports and exercise.

[47]  K. Herr,et al.  Comparison of selected pain assessment tools for use with the elderly. , 1993, Applied nursing research : ANR.

[48]  K. Herr,et al.  Complexities of pain assessment in the elderly. Clinical considerations. , 1991, Journal of gerontological nursing.

[49]  G. Yancopoulos,et al.  BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra , 1991, Nature.

[50]  R. P. McDonald,et al.  Structural Equations with Latent Variables , 1989 .

[51]  J. Ballenger.  The Serotonin Transporter Promoter Variant (5-HTTLPR), Stress, and Depression Meta-analysis Revisited: Evidence of Genetic Moderation , 2012 .

[52]  L. Taylor,et al.  Factors associated with physical activity among older people--a population-based study. , 2005, Preventive medicine.

[53]  J. Twisk,et al.  Longitudinal relationship between pain and depression in older adults: sex, age and physical disability , 2002, Social Psychiatry and Psychiatric Epidemiology.

[54]  L. DiPietro,et al.  The Impact of Physical Activity and Physical Fitness on Health Indicators among Older Adults , 1994 .

[55]  Giuseppe De Arcangelis,et al.  Structural equations with latent variables, kenneth a. bollen. john wiley & sons, inc., new york, chichester, brisbane, toronto, singapore, 1989, isbn 0-471-01171-1, £39.90 hardbound, pp. xiv + 514 , 1993 .

[56]  J. Loehlin.  Latent variable models , 1987 .

[57]  G. L. Engel,et al.  The clinical application of the biopsychosocial model. , 1980, The American journal of psychiatry.