Accepted Manuscript Title: Elevated levels of plasma brain derived neurotrophic factor in rapid cycling bipolar disorder patients Author: Klaus Munkholm Bente Klarlund Pedersen Lars Vedel Kessing Maj Vinberg PII: DOI: Reference:
S0306-4530(14)00183-8 http://dx.doi.org/doi:10.1016/j.psyneuen.2014.05.011 PNEC 2701
To appear in: Received date: Revised date: Accepted date:
7-1-2014 5-5-2014 5-5-2014
Please cite this article as: Munkholm, K., Pedersen, B.K., Kessing, L.V., Vinberg, M.,Elevated levels of plasma brain derived neurotrophic factor in rapid cycling bipolar disorder patients, Psychoneuroendocrinology (2014), http://dx.doi.org/10.1016/j.psyneuen.2014.05.011 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Title Elevated levels of plasma brain derived neurotrophic factor in rapid cycling bipolar disorder patients
ip t
Authors
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Klaus Munkholm, M.D. a, * Bente Klarlund Pedersen, M.D., DMSc b
us
Lars Vedel Kessing, professor, M.D., DMSc a
an
Maj Vinberg, M.D., Ph.d. a
Psychiatric Center Copenhagen, Rigshospitalet, University of Copenhagen, Denmark
b
The Centre of Inflammation and Metabolism and the Centre for Physical Activity
M
a
*
Ac ce pt e
Denmark
d
Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen,
Corresponding author contact information:
Psychiatric Center Copenhagen Rigshospitalet
Blegdamsvej 9
DK-2100 Copenhagen Copenhagen Denmark
Telephone: +45 38 64 70 75 Fax: +45 38 64 70 77
1 Page 1 of 50
E-Mail: [email protected]
Running Title
Ac ce pt e
d
M
an
us
cr
ip t
Elevated plasma brain derived neurotrophic factor in bipolar disorder
2 Page 2 of 50
Abstract Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder,
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involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is
cr
based primarily on case-control designs.
The aim of this study was to investigate whether BDNF and NT-3 levels differ between
us
patients with rapid cycling bipolar disorder and healthy control subjects and whether BDNF
an
and NT-3 levels alter with affective states in rapid cycling bipolar disorder patients.
M
Plasma levels of BDNF and NT-3 were measured in 37 rapid cycling bipolar disorder patients and in 40 age- and gender matched healthy control subjects using enzyme-linked
d
immunosorbent assay (ELISA). In a longitudinal design, repeated measurements of BDNF
Ac ce pt e
and NT-3 were evaluated in various affective states in bipolar disorder patients during a 612 months period and compared with repeated measurements in healthy control subjects. Careful attention was given to standardization of all procedures and adjustment for potential confounders of BDNF and NT-3.
In linear mixed models, adjusting for demographical and lifestyle factors, levels of BDNF were significantly elevated in bipolar disorder patients in euthymic- (p
S0306-4530(14)00183-8 http://dx.doi.org/doi:10.1016/j.psyneuen.2014.05.011 PNEC 2701
To appear in: Received date: Revised date: Accepted date:
7-1-2014 5-5-2014 5-5-2014
Please cite this article as: Munkholm, K., Pedersen, B.K., Kessing, L.V., Vinberg, M.,Elevated levels of plasma brain derived neurotrophic factor in rapid cycling bipolar disorder patients, Psychoneuroendocrinology (2014), http://dx.doi.org/10.1016/j.psyneuen.2014.05.011 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Title Elevated levels of plasma brain derived neurotrophic factor in rapid cycling bipolar disorder patients
ip t
Authors
cr
Klaus Munkholm, M.D. a, * Bente Klarlund Pedersen, M.D., DMSc b
us
Lars Vedel Kessing, professor, M.D., DMSc a
an
Maj Vinberg, M.D., Ph.d. a
Psychiatric Center Copenhagen, Rigshospitalet, University of Copenhagen, Denmark
b
The Centre of Inflammation and Metabolism and the Centre for Physical Activity
M
a
*
Ac ce pt e
Denmark
d
Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen,
Corresponding author contact information:
Psychiatric Center Copenhagen Rigshospitalet
Blegdamsvej 9
DK-2100 Copenhagen Copenhagen Denmark
Telephone: +45 38 64 70 75 Fax: +45 38 64 70 77
1 Page 1 of 50
E-Mail: [email protected]
Running Title
Ac ce pt e
d
M
an
us
cr
ip t
Elevated plasma brain derived neurotrophic factor in bipolar disorder
2 Page 2 of 50
Abstract Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder,
ip t
involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is
cr
based primarily on case-control designs.
The aim of this study was to investigate whether BDNF and NT-3 levels differ between
us
patients with rapid cycling bipolar disorder and healthy control subjects and whether BDNF
an
and NT-3 levels alter with affective states in rapid cycling bipolar disorder patients.
M
Plasma levels of BDNF and NT-3 were measured in 37 rapid cycling bipolar disorder patients and in 40 age- and gender matched healthy control subjects using enzyme-linked
d
immunosorbent assay (ELISA). In a longitudinal design, repeated measurements of BDNF
Ac ce pt e
and NT-3 were evaluated in various affective states in bipolar disorder patients during a 612 months period and compared with repeated measurements in healthy control subjects. Careful attention was given to standardization of all procedures and adjustment for potential confounders of BDNF and NT-3.
In linear mixed models, adjusting for demographical and lifestyle factors, levels of BDNF were significantly elevated in bipolar disorder patients in euthymic- (p
