mRNA levels of HPA axis mediators in drug-naïve, first episode psychosis patients before and after antipsychotic treatment.

Objective: In this study we assessed if the genetic variation and gene expression of stress-associated mediators contribute to First Episode in Psychosis (FEP) and explored how mRNA levels of Hypothalamus-Pituitary-Adrenal (HPA) axis mediators change after treatment with antipsychotics.

Methods: We genotyped FKBP5 and SLC6A4 variants and associated them with Positive and Negative Syndrome Scale (PANSS). We assessed the mRNA levels of HPA axis mediators in FEPs before and after treatment with antipsychotics, while comparing them to matched controls.

Results: FKPB5 rs1360780 T allele was associated with higher and lower scores in the PANSS-Negative and PANSS-General scales. FKPB5 rs3800373 C allele carriers had lower risk to suffer from FEP. FEP individuals had decreased NR3C2 and increased FKBP5 and GILZ/TSC22D3 mRNA levels. After treatment, the mRNA levels of GILZ/TSC22D3 were comparable to those of the control group. Higher FKBP5 and GILZ expression levels were associated with higher risk for FEP occurrence and the difference in FKBP5 and GILZ expression levels before and after treatment with antipsychotics was associated with the difference in PANSS-T scores.

Conclusion: The data above, pinpoint towards a dysregulated HPA axis, that putatively affects the outcome and symptomatology of a First Episode in Psychosis.