The by AKT1 signaling pathway. They used several variations

The AKT1
genotype could be a potential schizophrenia susceptibility gene.

 

Emamian,
Hall, Birnbaum, Karayiorgou and Gogos (2004) showed that the pathogenesis of
schizophrenia were provided by AKT1 signaling pathway. They used several
variations of kinases that were implicated in synaptic plasticity that are
expressed in various cell types such as peripheral blood lymphoctes. Their
first results showed that individuals with schizophrenia had 68% lower levels
of AKT1 kinases than controls, in contrast with the other protein kinases. They
found reduced AKT1 levels in the frontal cortex and lymphocytes in
schizophrenia patients. Second, they found 5 SNPs of the AKT1 locus in 268
families (a total of 335 schizophrenia patients) that were associated with
schizophrenia. These 5 SNPs markers were also associated with frontostriatal
dopaminergic system in healthy individuals by Tan et al. (2008). They showed that
genetic variation of AKT1 is linked to PFC function by dopamine. They found the
strongest association with frontal lobe function with the A allele of the AKT1
SNP rs1130233. To measure the cortical structural and functional changes in DA
signaling, the subjects had to perform a task (which is linked to cortical DA function)
while undergoing functional magnetic resonance imaging scanner (fMRI). They
found that carriers of the A allele had reduced information processing in the
PFC. On top of that, carriers had also reduced gray-matter volume in the right
PFC and the caudate nucleus.  Besides the
AKT1 gene that has been associated with schizophrenia there are more genes,
like the dystrobrevin-binding protein 1 (DTNBP1). Dysbindin is believed to play
a role in synaptic plasticity and signal transduction. Numakawa et al. (2004) showed
that the phosphorylation levels of AKT were suppressed by the downregulation of
dysbindin expression. They examined the neurotrophic effect through AKT
signaling pathway as a function of dysbindin. They showed that overexpression
of dysbindin resulted in activation of AKT. A PI3 kinase inhibitor, LY294002, inhibited
the activation of AKT by the overexpression of dysbindin. Their data implicates
that AKT signaling in schizophrenia patients might be caused by reduced
expression of dysbindin.