The biological correlates of childhood trauma in first episode psychosis

Objective To overview biological mechanisms connecting childhood trauma to the development of psychosis. Methods We reviewed the evidence regarding biological correlates associated with childhood trauma in individuals affected by first episode psychosis (FEP) in terms of: 1) Hypothalamic-pituitary- adrenal (HPA) axis & cytokines levels; 2) gene × environment interaction, epigenetic and gene expression modifications and 3) metabolic biomarkers. Results Childhood trauma and early psychosis even when explored separately were found associated with several biological correlates. Regarding the immune system activity, in terms of both HPA axis functioning and cytokines levels, FEP patients exposed to childhood trauma showed 1) a less reactive HPA axis, characterized by a blunted cortisol awakening response, and higher serum levels of Tumor necrosis Factor-α (TNF-α) and C-reactive protein (CRP) in comparison with patients without childhood trauma. Genetics and epigenetics were also proven significantly different in traumatized FEP in comparison with non-exposed individuals. Specifically, first 2) the Val/Val genotype at the Val158Met polymorphism in the COMT gene, the A allele at rs4713916 and rs9296158 single nucleotide polymorphisms (SNPs) and the TT homozygosis at rs1360780 SNP in the FKBP5 gene were demonstrated to be risk factors for psychosis in traumatized individuals. Second, childhood trauma in FEP was proven significantly associated with global DNA hypo-methylation and lower BDNF gene expression. Finally, regarding metabolic changes associated with childhood trauma in FEP 3) higher levels of glycated hemoglobin and higher c-peptide and insulin levels were proven in patients exposed to childhood trauma in comparison with those without childhood trauma. Conclusions This review has given evidence regarding associations between childhood trauma and its biological correlates in first episode psychosis. Nonetheless, future studies are warranted to investigate putative biological mediators and their temporal sequence in order to elucidate developmental trajectories.