AKT Serine/Threonine Kinase 1
AKT Serine/Threonine Kinase 1 (AKT1) is an enzyme which responds to key growth factors promoting neuronal survival, and is encoded for by the AKT1 gene 1. Due to its role in promoting cell survival AKT1 was first described as a cancer modulating gene, it was only through later study that its true role was described.
Impact of AKT1 mutations
The SNP G49A located within AKT1 which is responsible for the severe Proteus syndrome which is associated with widespread overgrowth of tissues such as skin and bone 2. As the disorder is so severe and requires intensive therapy we do not discuss it here. There is an additional SNP, rs2494732 or A1172+23G which is associated with poor health outcomes.
|rsID Number||Major Allele||Minor Allele||Minor Allele Frequency (%)|
The risk ‘C’ allele of G1172+23A is associated with several neurological conditions including schizophrenia 3 and cannabis related psychosis 4,5.
The association between the risk ‘C’ allele of G1172+23A and schizophrenia risk is descriptive only and the authors do not describe a mechanism.
In those who regularly smoke cannabis there was a significant increase in the risk of developing psychosis, especially in those carrying two copies of the risk ‘C’ allele where a seven fold increase in risk was reported. AKT1 is known to respond to dopamine 6, and tetrahydrocannabinol (THC) the active component of cannabis has been shown to induce dopamine release 7. The authors hypothesise that the ‘C’ allele of of AKT1 leads a reduced responsiveness to dopamine. Therefore when cannabis is used, THC stimulates dopamine release. This dopamine remains active for longer periods in those carrying the risk ‘C’ allele, as it is not processed as efficiently. Importantly, dopamine remaining active for long periods without processing has been associated with the development of psychotic symptoms 8.
The risk allele ‘C’ of G1172+23A is associated with an increased risk of developing psychosis in those regularly consuming cannabis 5.
Therefore carriers, especially those carrying two copies of the ‘C’ allele should consider avoiding any intake of cannabis.
Discuss this information with your doctor before taking any course of action.