Decreased cerebrospinal fluid secretogranin II concentrations in severe forms of bipolar disorder

Decreased cerebrospinal fluid secretogranin II concentrations in severe forms of bipolar disorder

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J Psychiatry Neurosci 2013; 38(4): E21-E26

Joel Jakobsson, PhD; Mats Stridsberg, MD, PhD; Henrik Zetterberg, MD, PhD; Kaj Blennow, MD, PhD; Carl- Johan Ekman, MD, PhD (candidate); Anette G.M. Johansson, MD, PhD; Carl Sellgren, MD, PhD (candidate); Mikael Landén, MD, PhD

Jakobsson, Zetterberg, Blennow, Landén — Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy, University of Gothenburg, Gothenburg and Mölndal, Sweden; Stridsberg — Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Zetterberg — UCL Institute of Neurology, Queen Square, London, England; Ekman, Johansson, Landén — Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Sellgren, Landén — Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

Abstract

Background: Bipolar disorder is a common psychiatric mood disorder that is defined by recurrent episodes of abnormally elevated mood and depression. Progressive structural brain changes in individuals with bipolar disorder have been suggested to be associated with defects in the secretion of neurotrophic factors. We sought to assess how the regulated secretory pathway in the brain is affected in patients with bipolar disorder by measuring chromogranin B and secretogranin II, which are 2 cerebrospinal fluid (CSF) biological markers for this process.

Methods: We measured the concentrations of chromogranin B (peptide 439–451) and secretogranin II (peptide 154–165) in the CSF of patients with well-defined bipolar disorder and healthy controls. The lifetime severity of bipolar disorder was rated using the Clinical Global Impression (CGI) scale.

Results: We included 126 patients with bipolar disorder and 71 healthy controls in our analysis. Concentrations of secretogranin II were significantly lower in patients with bipolar disorder type I than in healthy controls. The reduction was most pronounced in patients with high CGI scores (i.e., severe disease).

Limitations: The cross-sectional design of the current study limits the ability to pinpoint the causalities behind the observed associations.

Conclusion: This study shows that the CSF marker secretogranin II has the potential to act as a biological marker for severe forms of bipolar disorder. Our findings indicate that patients with bipolar disorder possess defects in the regulatory secretory pathway, which may be of relevance to the progressive structural brain changes seen in those with severe forms of the disease.


Submitted Aug. 27, 2012; Revised Nov. 20, Dec. 6, 2012; Accepted Dec. 10, 2012.

Acknowledgements: We thank the staff at the St. Göran Bipolar Affective Disorder Unit, including coordinator Martina Wennberg, study nurse Agneta Carlswärd-Kjellin, and data manager Haydeh Olofsson for the diagnostic assessments and enrolling patients for this study. Yngve Hallström is acknowledged for performing lumbar punctures on patients and controls. We also thank the patients and controls participating in this study. This research was supported as part of the St. Göran bipolar project. This work was supported by grants from the Swedish Foundation for Strategic Research, the Swedish Medical Research Council (K2011-61X -14647-09-3, K2010- 61X-21569-01-1 and K2010-61P-21568-01-4), the Swedish Brain Foundation, and the regional agreement on medical training and clinical research between Stockholm County Council and the Karolinska Institutet (ALF 20100305; C.-J. Ekman, M. Landén).

Competing interests: None declared for J. Jakobsson, M. Stridsberg, A.G.M. Johansson and C. Sellgren. H. Zetterberg has received grant support through his institution from the Swedish Research Council, Swedish state support for clinical research and the Alzheimer’s Association. K. Blennow declares advisory board membership with Innogenetics, Lilly and Roche. C.-J. Ekman and M. Landén declare having received research support through their institution as listed in the acknowledgement above.

Contributors: J. Jakobsson, H. Zetterberg, K. Blennow, C. Sellgren and M. Landén designed the study. J. Jakobsson, H. Zetterberg, C.-J. Ekman, A.G.M. Johansson and M. Landén acquired the data. J. Jakobsson, M. Stridsberg, H. Zetterberg, K. Blennow and M. Landén analyzed the data. J. Jakobsson wrote the article. All authors reviewed the article and approved its publication.

DOI: 10.1503/jpn.120170

Correspondence to: J. Jakobsson, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy, Sahlgrenska University Hospital, Blå Stråket 15, floor 3, SE-413 45 Gothenburg, Sweden; joel.jakobsson@neuro.gu.se