Exploring the sortilin related receptor, SorLA, in depression

Henriette N Buttenschøn; Betina Elfving; Marit Nielsen; Sune Skeldal; Mathias Kaas; Ole Mors; Simon Glerup

doi:10.1016/j.jad.2018.02.050

Exploring the sortilin related receptor, SorLA, in depression

Henriette N Buttenschøn, Betina Elfving, Marit Nielsen, Sune Skeldal, Mathias Kaas, Ole Mors, Simon Glerup

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Abstract

BACKGROUND: Studies of individual biomarkers for depression have shown insufficient sensitivity and specificity for clinical use, and most likely combinations of biomarkers may provide a better signature. The sorting-related receptor with A-type repeats (SorLA) is a well-studied pathogenic factor for Alzheimer's. SorLA belongs to the Vps10p domain receptor family, which also encompasses sortilin and SorCS1-3. All family members have been implicated in neurological and mental disorders. Notably, the SORCS3 gene is genome-wide significantly associated with depression and serum protein levels of sortilin are reduced in depressed individuals. SorLA regulates the activity of neurotrophic factors and cytokines and we hence speculated that SorLA might be implicated in depression.

METHODS: Serum SorLA levels were measured in two well-defined clinical samples using ELISA. Generalized linear models were used in the statistical analyses.

RESULTS: We identified a multivariate model to discriminate depressed individuals from healthy controls. Interestingly, the model consisted of serum SorLA levels and additional four predictors: previous depressive episode, stressful life events, serum levels of sortilin and VEGF. However, as an isolated factor, we observed no significant difference in SorLA levels between 140 depressed individuals and 140 healthy controls. Nevertheless, we observed a significant increase in SorLA levels following 12 weeks of treatment with nortriptyline, but not escitalopram.

LIMITATIONS: The number of biomarkers included in the multivariate model for depression and lack of replication limit our study.

CONCLUSIONS: Our results suggest SorLA as one of five factors that in combination may support the depression diagnosis, but not as an individual biomarker for depression or treatment response.

Originalsprog	Engelsk
Tidsskrift	Journal of Affective Disorders
Vol/bind	232
Sider (fra-til)	260-267
Antal sider	8
ISSN	0165-0327
DOI	https://doi.org/10.1016/j.jad.2018.02.050
Status	Udgivet - maj 2018

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10.1016/j.jad.2018.02.050

Citationsformater

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title = "Exploring the sortilin related receptor, SorLA, in depression",

abstract = "BACKGROUND: Studies of individual biomarkers for depression have shown insufficient sensitivity and specificity for clinical use, and most likely combinations of biomarkers may provide a better signature. The sorting-related receptor with A-type repeats (SorLA) is a well-studied pathogenic factor for Alzheimer's. SorLA belongs to the Vps10p domain receptor family, which also encompasses sortilin and SorCS1-3. All family members have been implicated in neurological and mental disorders. Notably, the SORCS3 gene is genome-wide significantly associated with depression and serum protein levels of sortilin are reduced in depressed individuals. SorLA regulates the activity of neurotrophic factors and cytokines and we hence speculated that SorLA might be implicated in depression.METHODS: Serum SorLA levels were measured in two well-defined clinical samples using ELISA. Generalized linear models were used in the statistical analyses.RESULTS: We identified a multivariate model to discriminate depressed individuals from healthy controls. Interestingly, the model consisted of serum SorLA levels and additional four predictors: previous depressive episode, stressful life events, serum levels of sortilin and VEGF. However, as an isolated factor, we observed no significant difference in SorLA levels between 140 depressed individuals and 140 healthy controls. Nevertheless, we observed a significant increase in SorLA levels following 12 weeks of treatment with nortriptyline, but not escitalopram.LIMITATIONS: The number of biomarkers included in the multivariate model for depression and lack of replication limit our study.CONCLUSIONS: Our results suggest SorLA as one of five factors that in combination may support the depression diagnosis, but not as an individual biomarker for depression or treatment response.",

keywords = "Biomarker, Depression, Neurotrophic factor, SorLA, Sortilin, VSP10 domain receptors",

author = "Buttensch{\o}n, {Henriette N} and Betina Elfving and Marit Nielsen and Sune Skeldal and Mathias Kaas and Ole Mors and Simon Glerup",

year = "2018",

month = may,

doi = "10.1016/j.jad.2018.02.050",

language = "English",

volume = "232",

pages = "260--267",

journal = "Journal of Affective Disorders",

issn = "0165-0327",

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TY - JOUR

T1 - Exploring the sortilin related receptor, SorLA, in depression

AU - Buttenschøn, Henriette N

AU - Elfving, Betina

AU - Nielsen, Marit

AU - Skeldal, Sune

AU - Kaas, Mathias

AU - Mors, Ole

AU - Glerup, Simon

PY - 2018/5

Y1 - 2018/5

N2 - BACKGROUND: Studies of individual biomarkers for depression have shown insufficient sensitivity and specificity for clinical use, and most likely combinations of biomarkers may provide a better signature. The sorting-related receptor with A-type repeats (SorLA) is a well-studied pathogenic factor for Alzheimer's. SorLA belongs to the Vps10p domain receptor family, which also encompasses sortilin and SorCS1-3. All family members have been implicated in neurological and mental disorders. Notably, the SORCS3 gene is genome-wide significantly associated with depression and serum protein levels of sortilin are reduced in depressed individuals. SorLA regulates the activity of neurotrophic factors and cytokines and we hence speculated that SorLA might be implicated in depression.METHODS: Serum SorLA levels were measured in two well-defined clinical samples using ELISA. Generalized linear models were used in the statistical analyses.RESULTS: We identified a multivariate model to discriminate depressed individuals from healthy controls. Interestingly, the model consisted of serum SorLA levels and additional four predictors: previous depressive episode, stressful life events, serum levels of sortilin and VEGF. However, as an isolated factor, we observed no significant difference in SorLA levels between 140 depressed individuals and 140 healthy controls. Nevertheless, we observed a significant increase in SorLA levels following 12 weeks of treatment with nortriptyline, but not escitalopram.LIMITATIONS: The number of biomarkers included in the multivariate model for depression and lack of replication limit our study.CONCLUSIONS: Our results suggest SorLA as one of five factors that in combination may support the depression diagnosis, but not as an individual biomarker for depression or treatment response.

AB - BACKGROUND: Studies of individual biomarkers for depression have shown insufficient sensitivity and specificity for clinical use, and most likely combinations of biomarkers may provide a better signature. The sorting-related receptor with A-type repeats (SorLA) is a well-studied pathogenic factor for Alzheimer's. SorLA belongs to the Vps10p domain receptor family, which also encompasses sortilin and SorCS1-3. All family members have been implicated in neurological and mental disorders. Notably, the SORCS3 gene is genome-wide significantly associated with depression and serum protein levels of sortilin are reduced in depressed individuals. SorLA regulates the activity of neurotrophic factors and cytokines and we hence speculated that SorLA might be implicated in depression.METHODS: Serum SorLA levels were measured in two well-defined clinical samples using ELISA. Generalized linear models were used in the statistical analyses.RESULTS: We identified a multivariate model to discriminate depressed individuals from healthy controls. Interestingly, the model consisted of serum SorLA levels and additional four predictors: previous depressive episode, stressful life events, serum levels of sortilin and VEGF. However, as an isolated factor, we observed no significant difference in SorLA levels between 140 depressed individuals and 140 healthy controls. Nevertheless, we observed a significant increase in SorLA levels following 12 weeks of treatment with nortriptyline, but not escitalopram.LIMITATIONS: The number of biomarkers included in the multivariate model for depression and lack of replication limit our study.CONCLUSIONS: Our results suggest SorLA as one of five factors that in combination may support the depression diagnosis, but not as an individual biomarker for depression or treatment response.

KW - Biomarker

KW - Depression

KW - Neurotrophic factor

KW - SorLA

KW - Sortilin

KW - VSP10 domain receptors

U2 - 10.1016/j.jad.2018.02.050

DO - 10.1016/j.jad.2018.02.050

M3 - Journal article

C2 - 29499509

SN - 0165-0327

VL - 232

SP - 260

EP - 267

JO - Journal of Affective Disorders

JF - Journal of Affective Disorders

ER -

Exploring the sortilin related receptor, SorLA, in depression

Abstract

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