Reduced plasma Fetuin-A is a promising biomarker of depression in the elderly
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ORIGINAL PAPER
Reduced plasma Fetuin‑A is a promising biomarker of depression in the elderly Giuseppe Fanelli1 · Francesco Benedetti2 · Sheng‑Min Wang3 · Soo‑Jung Lee3 · Tae‑Youn Jun3 · Prakash S. Masand4 · Ashwin A. Patkar5 · Changsu Han6 · Alessandro Serretti1 · Chi‑Un Pae3,5,7,8 · Chiara Fabbri9 Received: 1 April 2019 / Accepted: 11 December 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019
Abstract Depression affects 7% of the elderly population, and it often remains misdiagnosed or untreated. Peripheral biomarkers might aid clinicians by allowing more accurate and well-timed recognition of the disease. We sought to determine if plasma protein levels predict the severity of depressive symptomatology or distinguish patients from healthy individuals. The severity of depressive symptoms and global cognitive functioning were assessed by the Geriatric Depression Scale (GDS) and Mini-Mental State Examination (MMSE) in 152 elderly subjects, 76 of which with major depressive disorder (MDD). Plasma levels of 24 proteins were measured by multiplexing and analyzed as continuous predictors or dichotomized using the median value. The association between individual plasma proteins and MDD risk or depressive symptoms severity was investigated using multiple logistic and linear regressions including relevant covariates. Sensitivity analyses were performed excluding cognitively impaired individuals or non-acute patients with MDD. After adjusting for possible confounders and false discovery rate (FDR) correction, we found lower Fetuin-A levels in MDD patients vs. controls (p FDR = 1.95 × 10–6). This result was confirmed by the sensitivity and dichotomized analyses. Lower prolactin (PRL) levels predicted more severe depressive symptoms in acute MDD patients (pFDR = 0.024). Fetuin-A is a promising biomarker of MDD in the elderly as this protein was negatively associated with the disorder in our sample, regardless of the global cognitive functioning. Lower PRL levels may be a peripheral signature of impaired neuroprotective processes and serotoninergic neurotransmission in more severely depressed patients. Keywords Major depression · Biomarkers · Neuroinflammation · Elderly · Fetuin-A · Prolactin
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00406-019-01090-1) contains supplementary material, which is available to authorized users. * Chi‑Un Pae [email protected] 1
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
2
Psychiatry and Clinical Psychobiology Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
3
Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
4
Global Medical Education, New York, NY, USA
5
Department of Psychiatry and Behavioural Sciences, Duke University Medical Center, Durham, NC, USA
The world population aged over 60 is rapidly growing, and it is expected to more than double within the next
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