The CACNA1C risk allele rs1006737 is associated with age-related prefrontal cortical thinning in bipolar I disorder

Author(s)

Soeiro-de-Souza, M. G. ; Lafer, B. ; Moreno, R. A. ; Nery, F. G. ; Chile, T. ; Chaim, K. ; da Costa Leite, C. ; Machado-Vieira, R. ; Otaduy, M. C. G. ; Vallada, H.

• Document type: Journal article
• Source: TRANSLATIONAL PSYCHIATRY; v. 7, APR 11 2017.
• Web of Science Citations: 2

Abstract

Calcium channels control the inflow of calcium ions into cells and are involved in diverse cellular functions. The CACNA1C gene polymorphism rs1006737 A allele has been strongly associated with increased risk for bipolar disorder (BD) and with modulation of brain morphology. The medial prefrontal cortex (mPFC) has been widely associated with mood regulation in BD, but the role of this CACNA1C polymorphism in mPFC morphology and brain aging has yet to be elucidated. One hundred seventeen euthymic BD type I subjects were genotyped for CACNA1C rs1006737 and underwent 3 T three-dimensional structural magnetic resonance imaging scans to determine cortical thickness of mPFC components (superior frontal cortex (sFC), medial orbitofrontal cortex (mOFC), caudal anterior cingulate cortex (cACC) and rostral anterior cingulate cortex (rACC)). Carriers of the CACNA1C allele A exhibited greater left mOFC thickness compared to non-carriers. Moreover, CACNA1C A carriers showed age-related cortical thinning of the left cACC, whereas among A non-carriers there was not an effect of age on left cACC cortical thinning. In the sFC, mOFC and rACC (left or right), a negative correlation was observed between age and cortical thickness, regardless of CACNA1C rs1006737 A status. Further studies investigating the direct link between cortical thickness, calcium channel function, apoptosis mechanism and their underlying relationship with aging-associated cognitive decline in BD are warranted. (AU)

• FAPESP's process: 10/18672-7 - SPECGENE: genetic association study between single nucleotide polymorphisms of GAD1 and reelin and magnetic ressonance spectroscopy in bipolar I
• Grantee: Ricardo Alberto Moreno
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/23796-2 - "Genetic association study between cognitive performance, polymorphisms of GAD1/Reelin and 3T magnetic ressonance spectroscopy of GABA/glutamate in bipolar I disorder and healthy controls"
• Grantee: Márcio Gerhardt Soeiro-de-Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral