TY - JOUR
T1 - Fibroblast growth factor 21 (FGF21) is increased in MDD and interacts with body mass index (BMI) to affect depression trajectory
AU - Mason, Brittany L
AU - Minhajuddin, Abu
AU - Czysz, Andrew
AU - Jha, Manish K.
AU - Gadad, Bharathi
AU - Mayes, Taryn
AU - Trivedi, Madhukar H.
N1 - Funding Information:
BLM has no conflict of interest to declare. AHC has received contracted research support from Janssen Research & Development, LLC. MHT has received funding from Agency for Healthcare Research and Quality (AHRQ), Cyberonics, Inc., National Alliance for Research in Schizophrenia and Depression, National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and Johnson & Johnson. He has also served as an advisor or consultant for Abbott Laboratories, Inc., Akzo (Organon Pharmaceuticals, Inc.), Allergan Sales LLC, Alkermes, Arcadia Pharmaceuticals, Inc., AstraZeneca, Axon Advisors, Brintellix, Bristol-Myers Squibb Company, Cephalon, Inc., Cerecor, Eli Lilly & Company, Evotec, Fabre Kramer Pharmaceuticals, Inc., Forest Pharmaceuticals, GlaxoSmithKline, Global Medical Education, Inc., Health Research Associates, Johnson & Johnson, Lundbeck, MedAvante, Medscape, Medtronic, Merck, Mitsubishi Tanabe Pharma Development America, Inc., MSI Methylation Sciences, Inc., Nestle Health Science-PamLab, Inc., Naurex, Neuronetics, One Carbon Therapeutics, Ltd, Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals, Inc., Pfizer, Inc., PgxHealth, Phoenix Marketing Solutions, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche Products, Ltd, Sepracor, SHIRE Development, Sierra, SK Life and Science, Sunovion, Takeda, Tal Medical/Puretech Venture, Targacept, Transcept, VantagePoint, Vivus, and Wyeth-Ayerst Laboratories.
Funding Information:
The EMBARC study was supported by the National Institute of Mental Health of the National Institutes of Health under award numbers U01MH092221 (MHT) and U01MH092250 (McGrath, PJ, Parsey, RV, Weissman, MM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The work was further supported by the EMBARC National Coordinating Center at UT Southwestern Medical Center, MHT, MD, Coordinating PI, and the Data Center at Columbia and Stony Brook Universities. Additional funds for this report were generously provided by The Hersh Foundation and Evelyn Rose.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Fibroblast growth factor 21 (FGF21) is a key regulator of metabolic function and nutrient preference. It also affects biological pathways associated with major depressive disorder (MDD), including corticotrophin-releasing hormone (CRH), leptin, and sympathetic activity. Lower levels of cerebrospinal fluid FGF21 have been associated with higher Beck Depression Inventory scores. FGF21 was examined as a metabolic marker that could be associated with MDD and evaluated as a biomarker of antidepressant treatment response in a large, randomized placebo-controlled trial in chronic, early-onset MDD participants. FGF21 levels at baseline and during treatment were determined for participants in the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) study. FGF21 was analyzed by ELISA in individuals with chronic, early-onset MDD (first major depressive episode before 30 years) compared to healthy control participants. Participants with MDD had higher levels of FGF21 compared to healthy controls (HCs), even after controlling for baseline age, sex, race, Hispanic ethnicity, BMI, and site (β-coefficient = 1.20, p < 0.0001, Cohen’s d = 0.60). FGF21 did not change over time nor differ between treatment groups. Interestingly though, those with normal BMI and lower FGF21 levels showed a reduction in depression severity over time compared to all other groups. In conclusion, depression is associated with higher levels of FGF21 compared to healthy controls and those with lower levels of FGF21 (25th percentile of the sample) in the context of normal-weight BMI seem to have improved depression severity over time.
AB - Fibroblast growth factor 21 (FGF21) is a key regulator of metabolic function and nutrient preference. It also affects biological pathways associated with major depressive disorder (MDD), including corticotrophin-releasing hormone (CRH), leptin, and sympathetic activity. Lower levels of cerebrospinal fluid FGF21 have been associated with higher Beck Depression Inventory scores. FGF21 was examined as a metabolic marker that could be associated with MDD and evaluated as a biomarker of antidepressant treatment response in a large, randomized placebo-controlled trial in chronic, early-onset MDD participants. FGF21 levels at baseline and during treatment were determined for participants in the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) study. FGF21 was analyzed by ELISA in individuals with chronic, early-onset MDD (first major depressive episode before 30 years) compared to healthy control participants. Participants with MDD had higher levels of FGF21 compared to healthy controls (HCs), even after controlling for baseline age, sex, race, Hispanic ethnicity, BMI, and site (β-coefficient = 1.20, p < 0.0001, Cohen’s d = 0.60). FGF21 did not change over time nor differ between treatment groups. Interestingly though, those with normal BMI and lower FGF21 levels showed a reduction in depression severity over time compared to all other groups. In conclusion, depression is associated with higher levels of FGF21 compared to healthy controls and those with lower levels of FGF21 (25th percentile of the sample) in the context of normal-weight BMI seem to have improved depression severity over time.
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U2 - 10.1038/s41398-021-01679-y
DO - 10.1038/s41398-021-01679-y
M3 - Article
C2 - 35017468
AN - SCOPUS:85122817669
VL - 12
JO - Translational Psychiatry
JF - Translational Psychiatry
SN - 2158-3188
IS - 1
M1 - 16
ER -