These results identify a previously undescribed KCNH2 channel isoform involved in cortical physiology, cognition and psychosis, providing a potential new therapeutic drug target.
It is possible that genetic variants of the NPY1R gene affect the NPY-NPY receptor type Y1 signaling system in the brain, which may result in susceptibility to methamphetamine dependence or the development of methamphetamine psychosis, but the present findings need to be confirmed on replication.
DISC1, a promising candidate susceptibility gene, encodes a protein which interacts with many other proteins, including CIT, NDEL1, NDE1, FEZ1 and PAFAH1B1, some of which also have been associated with psychosis.
DISC1, a promising candidate susceptibility gene, encodes a protein which interacts with many other proteins, including CIT, NDEL1, NDE1, FEZ1 and PAFAH1B1, some of which also have been associated with psychosis.
In the unaffected individuals (patients' relatives and healthy controls) we observed an association of KIBRA with immediate and delayed logical memory (p=0.020 and 0.025, respectively), while in patients with psychosis with delayed visual memory (p=0.05).
Our identification of potentially defective NPAS3 variants supports recent studies that implicate perturbations in NPAS3 pathways in impaired neurogenesis and psychosis.
We hypothesize that CRE, Mef2, and GR signaling form a transcription regulating network, which underlies differential amphetamine sensitivity, and therefore, may play an important role in susceptibility to psychosis.
The top psychosis-associated, differentially methylated region, significantly hypomethylated in affected twins, was located in the promoter of ST6GALNAC1 overlapping a previously reported rare genomic duplication observed in SZ.
Taking into account that another metal ions transporter gene, SLC39A3, is associated to bipolar disorder, our findings reveal a role for brain metal homeostasis in psychosis.
Virally mediated overexpression of HDAC2 in frontal cortex decreased mGlu2 transcription and its electrophysiological properties, thereby increasing psychosis-like behavior.
Increased TET1 and decreased APOBEC3A and APOBEC3C found in this study highlight the possible role of altered DNA demethylation mechanisms in the pathophysiology of psychosis.
Increased TET1 and decreased APOBEC3A and APOBEC3C found in this study highlight the possible role of altered DNA demethylation mechanisms in the pathophysiology of psychosis.