Abstract
The pathophysiology of negative affect states in older adults is complex, and a host of central nervous system and peripheral systemic mechanisms may play primary or contributing roles. We conducted an unbiased analysis of 146 plasma analytes in a multiplex biochemical biomarker study in relation to number of depressive symptoms endorsed by 566 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) at their baseline and 1-year assessments. Analytes that were most highly associated with depressive symptoms included hepatocyte growth factor, insulin polypeptides, pregnancy-associated plasma protein-A and vascular endothelial growth factor. Separate regression models assessed contributions of past history of psychiatric illness, antidepressant or other psychotropic medicine, apolipoprotein E genotype, body mass index, serum glucose and cerebrospinal fluid (CSF) τ and amyloid levels, and none of these values significantly attenuated the main effects of the candidate analyte levels for depressive symptoms score. Ensemble machine learning with Random Forests found good accuracy (∼80%) in classifying groups with and without depressive symptoms. These data begin to identify biochemical biomarkers of depressive symptoms in older adults that may be useful in investigations of pathophysiological mechanisms of depression in aging and neurodegenerative dementias and as targets of novel treatment approaches.
Highlights
The prevalence and incidence of clinically significant depressive symptoms increase with advancing age, especially among those with physical illness, cognitive decline and functional disability.[1,2,3] In community-dwelling seniors, the prevalence of major depression is B10%, whereas the rate for ‘minor’, ‘subsyndromal’ or ‘subthreshold’ depression is B30%, but may be as high as 48% among those 475 years
We found no associations between baseline Geriatric Depression Scale (GDS) scores and cerebrospinal fluid (CSF) total t (F 1⁄4 2.06, d.f. 1⁄4 5, 351, P 1⁄4 0.15), p-t181 (F 1⁄4 2.03, d.f. 1⁄4 5, 351, P 1⁄4 0.15), or Ab (F 1⁄4 0.89, d.f. 1⁄4 5, 351, P 1⁄4 0.35), and no modifying effects
Our data identified candidate plasma biomarkers of depressive symptoms in older adults, which may prove useful in investigations into the pathophysiology of negative affect across the lifespan
Summary
The prevalence and incidence of clinically significant depressive symptoms increase with advancing age, especially among those with physical illness, cognitive decline and functional disability.[1,2,3] In community-dwelling seniors, the prevalence of major depression is B10%, whereas the rate for ‘minor’, ‘subsyndromal’ or ‘subthreshold’ depression is B30%, but may be as high as 48% among those 475 years. Age-associated neurological illnesses such as Alzheimer’s disease (AD), stroke and Parkinson’s disease are well-known risk factors and may be associated with depression due to disruption of neural circuitries that mediate the experience and expression of negative emotions and behaviors by their defined neuropathological lesions and neurochemical changes.[5,6,7] Cardiovascular disease, inflammatory conditions, cancer, metabolic and endocrine dysfunction increase with age and are highly associated with depression They are commonly thought to exert their effect via circulating factors such as inflammatory markers produced in the course of these chronic disease processes, evidence to support this is still controversial.[8,9,10,11] Numerous hypothesisbased studies of depression in adulthood and late life have identified associations with glucocorticoids and other stress hormones,[12] insulin resistance,[13] inflammatory cytokines and chemokines[14] and trophic factors[15,16,17] that may be activated with normal and abnormal aging processes and/or in response to illness, injury and other stressors, the data in older adults for all of these are relatively scarce. Whether alterations in these various age- and depressionassociated factors are causative of depression or consequences thereof and how they interact are not established
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
