Catechol-O-methyltransferase (COMT): a gene contributing to sex differences in brain function, and to sexual dimorphism in the predisposition to psychiatric disorders.
The COMT Val<sup>158</sup>Met genotype and PTSD association persists after controlling for race (multivariable OR of 0.29, 95% CI [0.10-0.83]) and pre-existing psychiatric disorders/substance abuse (multivariable OR of 0.32, 95% CI [0.11-0.97]).
Additionally, these findings contribute to the growing literature on sex-specific effects of COMT on the predisposition to psychiatric disorders and personality traits.
But the co-occurrence among outcomes between exposures to chemical stressors, non-chemical stressors, and the low activity MAOA genotype suggest that mental illness in children may be influenced by multiple interacting factors.
COMT is a known neuropsychiatric candidate gene, which contains a genotype variant (Val<sup>108/158</sup>Met) that affects protein function and has been found associated with several psychiatric disorders.
To examine, in a sample of young psychiatric patients, (n = 157, mean age 17.01 years (SD = 3.6)) whether i) age at first cannabis use and age at emergence of psychiatric disorders are related and ii) such a relationship is modulated by the Val158Met polymorphism in the COMT gene.
The rs1006737 (A/G) single nucleotide polymorphism within the gene encoding the Ca<sub>v</sub>1.2 subunit of the L-type voltage-dependent calcium channel (CACNA1C) has been strongly implicated in psychiatric disorders.
Calcium influx through high-voltage-gated Ca2+ channels is central to synaptic plasticity, and altered expression of Cav1.2 channels and the CACNA1C gene have been associated with severe learning deficits and psychiatric disorders.
Genome-wide association studies have identified the CACNA1C single nucleotide polymorphism (SNP) rs1006737 as one of the most consistent genetic findings as susceptibility locus for major psychiatric disorders.
We review the genetic structure and variation of CACNA1C, discussing relevant human genetic and clinical findings, as well as the biological actions of Ca(v)1.2 that are most relevant to psychiatric illness.
Genome-wide association studies have identified allelic variation in CACNA1C as a risk factor for multiple psychiatric disorders associated with limbic system dysfunction, including bipolar disorder, schizophrenia, and depression.
Genetic variation in CACNA1C, which encodes the alpha-1 subunit of Cav1.2 L-type voltage-gated calcium channels (VGCCs), has been strongly linked to risk for psychiatric disorders including schizophrenia and bipolar disorder.
To identify the neural system mechanism that explains the genetic association between the CACNA1C gene and psychiatric illness using neuroimaging and human brain expression.
Here we show that embryonic deletion of Cacna1c in forebrain glutamatergic neurons promotes the manifestation of endophenotypes related to psychiatric disorders including cognitive decline, impaired synaptic plasticity, reduced sociability, hyperactivity and increased anxiety.
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.
Our study is the first to provide evidence for an impairing behavioral effect of the CACNA1C risk variant rs1006737 on facial emotion recognition in healthy individuals and adds to the growing number of studies pointing towards CACNA1C as affecting intermediate phenotypes of psychiatric disorders.
In the current study, we use an imaging genetics approach to examine the impact of CACNA1C, one of the most promising genetic risk factors for psychiatric disorders, on prosody processing on a behavioral, functional and microstructural level.
Our findings implicate abnormal perigenual and hippocampal activation as a promising intermediate phenotype for psychiatric disease and suggest a pathophysiologic mechanism conferred by a CACNA1C variant being implicated in risk for symptom dimensions shared among bipolar disorder, major depression, and schizophrenia.