title: Increased serum levels of sortilin are associated with depression and correlated with BDNF and VEGF.
abstract: Neurotrophic factors have been investigated in relation to depression. The aim of the present study was to widen this focus to sortilin, a receptor involved in neurotrophic signalling. The serum sortilin level was investigated in 152 individuals with depression and 216 control individuals, and eight genetic markers located within the SORT1 gene were successfully analysed for association with depression. Genotyping was performed using the Sequenom MassARRAY platform. All the individuals returned a questionnaire and participated in a semi-structured diagnostic interview. Sortilin levels were measured by immunoassay, and potential determinants of the serum sortilin level were assessed by generalized linear models. Serum levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were measured in previous studies. We identified a significant increase of serum sortilin levels in depressed individuals compared with controls (P=0.0002) and significant positive correlation between serum sortilin levels and the corresponding levels of BDNF and VEGF. None of the genotyped SNPs were associated with depression. Additional analyses showed that the serum sortilin level was influenced by several other factors. Alcohol intake and body mass index, as well as depression, serum BDNF and serum VEGF were identified as predictors of serum sortilin levels in our final multivariate model. In conclusion, the results suggest a role of circulating sortilin in depression which may relate to altered activity of neurotrophic factors.
authors.affiliation: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.|The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.
authors.forename: H N
authors.initials: HN
authors.lastname: Buttenschøn
authors.affiliation: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.|Department of Biomedicine and Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark.
authors.forename: D
authors.initials: D
authors.lastname: Demontis
authors.affiliation: The Lundbeck Foundation Research Center, MIND, Aarhus University, Aarhus, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Kaas
authors.affiliation: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Elfving
authors.affiliation: The Lundbeck Foundation Research Center, MIND, Aarhus University, Aarhus, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Mølgaard
authors.affiliation: The Lundbeck Foundation Research Center, MIND, Aarhus University, Aarhus, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Gustafsen
authors.affiliation: Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.|Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Kaerlev
authors.affiliation: The Lundbeck Foundation Research Center, MIND, Aarhus University, Aarhus, Denmark.
authors.forename: C M
authors.initials: CM
authors.lastname: Petersen
authors.affiliation: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.|Department of Biomedicine and Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark.
authors.forename: A D
authors.initials: AD
authors.lastname: Børglum
authors.affiliation: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.|Research Department P, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: O
authors.initials: O
authors.lastname: Mors
authors.affiliation: The Lundbeck Foundation Research Center, MIND, Aarhus University, Aarhus, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Glerup
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000097:blood*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D003866:Depressive Disorder / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011795:Surveys and Questionnaires; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*; D000099183:Sortilin
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D019208:Brain-Derived Neurotrophic Factor; D042461:Vascular Endothelial Growth Factor A; D000099183:Sortilin; C579455:BDNF protein, human