CACNA1C polymorphism and altered phosphorylation of tau in bipolar disorder

Joel Jakobsson; Erik Pålsson; Carl Sellgren; Frida Rydberg; Agneta Ekman; Henrik Zetterberg; Kaj Blennow; Mikael Landén

doi:10.1192/bjp.bp.114.159806

CACNA1C polymorphism and altered phosphorylation of tau in bipolar disorder

Br J Psychiatry. 2016 Feb;208(2):195-6. doi: 10.1192/bjp.bp.114.159806. Epub 2015 Nov 5.

Authors

Joel Jakobsson¹, Erik Pålsson², Carl Sellgren², Frida Rydberg², Agneta Ekman², Henrik Zetterberg², Kaj Blennow², Mikael Landén²

Affiliations

¹ Joel Jakobsson, PhD, Erik Pålsson, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Carl Sellgren, PhD, MD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Frida Rydberg, MD, Agneta Ekman, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Henrik Zetterberg, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden and UCL Institute of Neurology, London, UK; Kaj Blennow, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Mikael Landén, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Department of Medical Epidemiology and Biostatistics, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden joel.jakobsson@neuro.gu.se.
² Joel Jakobsson, PhD, Erik Pålsson, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Carl Sellgren, PhD, MD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Frida Rydberg, MD, Agneta Ekman, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Henrik Zetterberg, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden and UCL Institute of Neurology, London, UK; Kaj Blennow, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Mikael Landén, PhD, MD, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Department of Medical Epidemiology and Biostatistics, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

PMID: 26541689
DOI: 10.1192/bjp.bp.114.159806

Abstract

Several genome-wide association studies and case-control studies have associated the single nucleotide polymorphism (SNP) rs1006737, situated in CACNA1C encoding the alpha 1C subunit of the L-type voltage-gated calcium channel, with bipolar disorder and other psychiatric disorders. However, the causal pathway linking genetic variants in CACNA1C with increased risk for developing brain disorders remains unclear. Here, we explored the association between the rs1006737 SNP and cerebrospinal fluid (CSF) markers. We found a significant association between the risk allele in rs1006737 and a decreased CSF hyperphosphorylated tau/total tau ratio in patients with bipolar disorder, thus linking variation in the CACNA1C gene to a neurochemical marker of neuroaxonal plasticity in those with this disorder.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Alleles
Biomarkers / cerebrospinal fluid
Bipolar Disorder / genetics*
Calcium Channels, L-Type / genetics*
Case-Control Studies
Female
Genetic Predisposition to Disease
Genetic Variation
Humans
Male
Middle Aged
Phosphorylation
Polymorphism, Single Nucleotide*
tau Proteins / cerebrospinal fluid*

Substances

Biomarkers
CACNA1C protein, human
Calcium Channels, L-Type
tau Proteins