Advanced Glycation End Product (AGE) Accumulation in the Skin is Associated with Depression: The Maastricht Study.
Depression is a highly prevalent disease with a high morbidity and mortality risk. Its pathophysiology is not entirely clear. However, type 2 diabetes is an important risk factor for depression. One mechanism that may explain this association may include the formation of advanced glycation end products (AGEs). We therefore investigated the association of AGEs with depressive symptoms and depressive disorder. In addition, we examined whether the potential association was present for somatic and/or cognitive symptoms of depression.



Cross-sectional data were used from the Maastricht Study (N = 862, mean age 59.8 ± 8.5 years, 55% men). AGE accumulation was measured with skin autofluorescence (SAF) by use of the AGE Reader. Plasma levels of protein-bound pentosidine were measured with high-performance liquid chromatography and fluorescence detection. Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL) were measured with ultraperformance liquid chromatography and tandem mass spectrometry. Depressive symptoms and depressive disorder were assessed by the nine-item Patient Health Questionnaire and the Mini-International Neuropsychiatric Interview.



Higher SAF was associated with depressive symptoms (β = 0.42, 95% CI 0.12-0.73, P = .007) and depressive disorder (OR = 1.42, 95% CI 1.04-1.95, P = .028) after adjustment for age, sex, type 2 diabetes, smoking, BMI, and kidney function. Plasma pentosidine, CML, and CEL were not independently associated with depressive symptoms and depressive disorder.



This study shows that AGE accumulation in the skin is independently associated with higher levels of depressive symptoms and depressive disorder. This association is present for both somatic and cognitive symptoms of depression. This might suggest that AGEs are involved in the development of depression.
Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.|CoRPS-Center of Research on Psychology in Somatic diseases, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands.|MHeNS-Alzheimer Centre Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
Fleur E P
FE
van Dooren
CoRPS-Center of Research on Psychology in Somatic diseases, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands.
Frans
F
Pouwer
Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.|CARIM-Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
Casper G
CG
Schalkwijk
Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.|CARIM-Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
Simone J S
SJ
Sep
Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.|CARIM-Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
Coen D A
CD
Stehouwer
Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.|CARIM-Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
Ronald M A
RM
Henry
CARIM-Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.|CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands.|Department of Epidemiology, Maastricht University, Maastricht, the Netherlands.
Pieter C
PC
Dagnelie
Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.|CARIM-Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.|CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands.
Nicolaas C
NC
Schaper
Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.|CARIM-Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
Carla J H
CJ
van der Kallen
CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands.|Department of Social Medicine, Maastricht University, Maastricht, the Netherlands.
Annemarie
A
Koster
CoRPS-Center of Research on Psychology in Somatic diseases, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands.
Johan
J
Denollet
MHeNS-Alzheimer Centre Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
Frans R J
FR
Verhey
Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands.|CARIM-Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
Miranda T
MT
Schram
D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D003863:Depression / Q000097:blood / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D003866:Depressive Disorder / Q000097:blood / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D012867:Skin / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D001120:Arginine; C062187:pentosidine; D008239:Lysine
advanced glycation end products; cohort; depression; diabetes