title: The CACNA1C risk allele rs1006737 is associated with age-related prefrontal cortical thinning in bipolar I disorder.
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.
authors.affiliation: Mood Disorders Unit (GRUDA), Department of Psychiatry, Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), São Paulo, Brazil.|Genetics and Pharmacogenetics Unit (PROGENE), Department of Psychiatry, Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), São Paulo, Brazil.
authors.forename: M G
authors.identifier: 0000-0002-9293-3128
authors.initials: MG
authors.lastname: Soeiro-de-Souza
authors.affiliation: Bipolar Disorder Program (PROMAN), Department of Psychiatry, Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), São Paulo, Brazil.
authors.forename: B
authors.initials: B
authors.lastname: Lafer
authors.affiliation: Mood Disorders Unit (GRUDA), Department of Psychiatry, Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), São Paulo, Brazil.
authors.forename: R A
authors.initials: RA
authors.lastname: Moreno
authors.affiliation: Bipolar Disorder Program (PROMAN), Department of Psychiatry, Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), São Paulo, Brazil.
authors.forename: F G
authors.initials: FG
authors.lastname: Nery
authors.affiliation: Genetics and Pharmacogenetics Unit (PROGENE), Department of Psychiatry, Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), São Paulo, Brazil.
authors.forename: T
authors.initials: T
authors.lastname: Chile
authors.affiliation: Laboratory of Magnetic Resonance LIM44, Department and Institute of Radiology, University of São Paulo (InRad-FMUSP), São Paulo, Brazil.
authors.forename: K
authors.initials: K
authors.lastname: Chaim
authors.affiliation: Laboratory of Magnetic Resonance LIM44, Department and Institute of Radiology, University of São Paulo (InRad-FMUSP), São Paulo, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: da Costa Leite
authors.affiliation: Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Machado-Vieira
authors.affiliation: Laboratory of Magnetic Resonance LIM44, Department and Institute of Radiology, University of São Paulo (InRad-FMUSP), São Paulo, Brazil.
authors.forename: M C G
authors.initials: MC
authors.lastname: Otaduy
authors.affiliation: Genetics and Pharmacogenetics Unit (PROGENE), Department of Psychiatry, Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), São Paulo, Brazil.
authors.forename: H
authors.initials: H
authors.lastname: Vallada
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000483:Alleles; D001714:Bipolar Disorder / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D020746:Calcium Channels, L-Type / Q000235:genetics*; D004292:Dominance, Cerebral / Q000235:genetics / Q000502:physiology; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type