Title | L-type Ca(2+) channels in mood, cognition and addiction: integrating human and rodent studies with a focus on behavioural endophenotypes. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Kabir ZD, Lee AS, Rajadhyaksha AM |
Journal | J Physiol |
Volume | 594 |
Issue | 20 |
Pagination | 5823-5837 |
Date Published | 2016 Oct 15 |
ISSN | 1469-7793 |
Abstract | Brain Cav 1.2 and Cav 1.3 L-type Ca(2+) channels play key physiological roles in various neuronal processes that contribute to brain function. Genetic studies have recently identified CACNA1C as a candidate risk gene for bipolar disorder (BD), schizophrenia (SCZ), major depressive disorder (MDD) and autism spectrum disorder (ASD), and CACNA1D for BD and ASD, suggesting a contribution of Cav 1.2 and Cav 1.3 Ca(2+) signalling to the pathophysiology of neuropsychiatric disorders. Once considered sole clinical entities, it is now clear that BD, SCZ, MDD and ASD share common phenotypic features, most likely due to overlapping neurocircuitry and common molecular mechanisms. A major future challenge lies in translating the human genetic findings to pathological mechanisms that are translatable back to the patient. One approach for tackling such a daunting scientific endeavour for complex behaviour-based neuropsychiatric disorders is to examine intermediate biological phenotypes in the context of endophenotypes within distinct behavioural domains. This will better allow us to integrate findings from genes to behaviour across species, and improve the chances of translating preclinical findings to clinical practice. |
DOI | 10.1113/JP270673 |
Alternate Journal | J. Physiol. (Lond.) |
PubMed ID | 26913808 |
PubMed Central ID | PMC5063939 |
Grant List | F31 DA032169 / DA / NIDA NIH HHS / United States R01 DA029122 / DA / NIDA NIH HHS / United States |