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. 2022 Feb 28;10(3):561. doi: 10.3390/biomedicines10030561

Table 3.

Summary of major points for the gene TDO2.

Important environmental cue
reviewed 		Stress
Direction of
effect 		Stress is predicted to increase expression of gene via the established effect of glucocorticoids to stimulate TDO2 mRNA expression
Risk of schizophrenia (scz) consistent with known gene function? Yes:
  • (1)

    periods of acute stress are often the trigger for psychotic breaks

  • (2)

    upregulation of TDO2 metabolic product seen in several other disorders associated with psychosis
Strength of
genetic
association 		Weak as a single locus: one study showing association only as part of complex genotype; however, contributes to PRS
Epigenetic data
of relevance? 		Yes:
  • (1)

    hypomethylation of site in alt-exon-1 associated with childhood adversity; net effect cannot be predicted

  • (2)

    hypermethylation of a site in intron 3 found in pregnant women engaged in night-shift work; function unclear

  • (3)

    chronic mild stress in rats decreases methylation in promoter region

  • (4)

    two GRE sites have CpG sites; methylation at these sites would incr. cortisol binding

  • (5)

    hypermethylation of a CpG site in 5′UTR by maternal smoking; expected to downregulate expression; consistent with TDO2 expression results reported for smokers
Consistency of
gene expression data 		Consistent:
  • (1)

    mRNA upregulated in scz (4 studies) and bipolar disorder with psychosis (2 studies)

  • (2)

    expression found to be decreased in smokers, consistent with epigenetic data for smokers and with two expression studies of smokers in controls, scz and BPD wi psychosis; but not enough of an effect to overpower upregulation by the disorders