The Effects of Childhood Maltreatment and Genomic Variation in the Hypothalamic-Pituitary-Adrenal (HPA) Axis on Neuropsychological Functioning in Offspring of Depressed Parents
Childhood maltreatment has been associated with an increased risk for psychiatric disorders and suicide. The primary role of the hypothalamic-adrenal-pituitary (HPA) axis is to maintain homeostasis when challenged with stress. Genomic variation in genes of the HPA axis may play a role in the effects of maltreatment on neuropsychological functioning. The aims of the dissertation study were: (1) to examine the effect of childhood maltreatment on neuropsychological functioning; (2) to examine the effects polymorphisms in genes of the HPA axis (CRH, CRHBP, CRHR1, CRHR2, and NR3C1) with neuropsychological functioning; and (3) to explore gene environment interactions between genes of the HPA axis and exposure to childhood maltreatment on neuropsychological function. This was a secondary data analysis of neuropsychological testing, psychiatric assessments, and genomic data from the Familial Pathways to Early Onset Suicide Attempt Study. A total of 369 subjects were included in Aim 1 and 145 subjects in Aims 2 and 3. Multiple linear regression was used to analyze the effects of maltreatment, genotype, and their interactions on neuropsychological functioning. Physical abuse was associated with poorer performance in the memory domain (p=.006). While no longer significant after controlling for multiple comparisons, results trended trend toward significance (q=.088). Emotional abuse was associated with better scores on measures of verbal fluency (p=.03), but the results were no longer significant after false discovery rate (FDR) correction. Before FDR testing, significant protective effects were detected for two SNPs in the CRHBP gene and one single nucleotide polymorphisms (SNPs) in the CRHR2 gene; and significant risk effects were detected for two SNPs in the CRHR1 gene and one SNP in the NR3C2 gene. However, after FDR corrections, only one result remained significant, a protective effect for CRHBP rs7704995 on the Impulse Control Domain. No significant gene environment interactions were detected. These findings are consistent with the literature showing that exposure to physical abuse is associated with deficits in memory. Further studies are needed with larger sample sizes and all the relevant genes of the HPA axis to determine whether genomic variation in genes of the HPA axis have a direct effect on neuropsychological functioning
