Genetic Associations between Voltage-Gated Calcium Channels and Psychiatric Disorders

Abstract

Psychiatric disorders are mental, behavioral or emotional disorders. These conditions are prevalent, one in four adults suffer from any type of psychiatric disorders world-wide. It has always been observed that psychiatric disorders have a genetic component, however new methods to sequence full genomes of large cohorts have identified with high precision genetic risk loci for these conditions. Psychiatric disorders include, but are not limited to, bipolar disorder, schizophrenia, autism spectrum disorder, anxiety disorders, major depressive disorder, and attention-deficit and hyperactivity disorder. Several risk loci for psychiatric disorders fall within genes that encode for voltage-gated calcium channels (CaVs). Calcium entering through CaVs is key for multiple neuronal processes. In this review, we will summarize recent findings that link CaVs and their auxiliary subunits to psychiatric disorders. First, we will provide a general overview of CaVs structure, classification, function, expression and pharmacology. Next, we will summarize tools and databases to study risk loci associated with psychiatric disorders. We will examine functional studies of risk variations in CaV genes when available. We will review pharmacological evidence of the use of CaV modulators to treat psychiatric disorders. Our review will be of interest for those studying pathophysiological aspects of CaVs.

Unusual Molecular Regulation of Dorsolateral Prefrontal Cortex Layer III Synapses Increases Vulnerability to Genetic and Environmental Insults in Schizophrenia

“…Thus, microduplications that increase VIPR2-cAMP signaling would weaken layer III dlPFC connectivity. Genetic alterations in voltage-gated Ca 2+ channels are also a replicated risk factor for schizophrenia (98). In particular, a gain-of-function mutation (99) in CACNA1C, which encodes for the alpha subunit of the L-type Ca 2+ channel, Cav1.2, is consistently linked to increased risk of schizophrenia and bipolar disorder (69,81,(100)(101)(102).…”

FLASH Syndrome: Tapping into the Root of Chronic Illness

“…An important clue to what that abnormality might be comes from gene association studies for common psychiatric, neurologic, and general medical conditions. The most robust and consistent outcome of these studies has been the identification of gene variants whose protein products fail to adequately regulate the excitability of neurons [71, [77][78][79][80][81][82][83][84][85][86][87][88][89]. Consistent with the wide distribution of neurons (and other excitable cells) throughout the body, ion channelopathies have been linked to a plethora of illnesses including anxiety [74,83,87], depression [74,79,80,87], bipolar disorder [74,[77][78][79][80][81]87], schizophrenia [74,79,[84][85][86][87], autism [74], epilepsy [78,88,89], migraine headache [88], irritable bowel syndrome [88], diabetes mellitus [88], high blood pressure [88], cardiac conduction abnormalities [88,89], renal abnormalities [88], asthma ...…”

COVID-19, Cation Dysmetabolism, Sialic Acid, CD147, ACE2, Viroporins, Hepcidin and Ferroptosis: A Possible Unifying Hypothesis

“…The movement of this mineral across cellular membranes is highly regulated through the VGCC, which have an important role also in multiple pathological clinical conditions involving muscular, neural, cardiac and endothelial cells, just to name a few. [43][44][45][46][47][48] Interestingly, patients with later stages of COVID-19 often show altered serum concentration of other cations, such as sodium, potassium and magnesium. [49][50][51][52] Pathophysiology of this disease and, more specifically, cation dysmetabolism is linked to a series of viral interactions with human cell membrane receptors.…”