ABSTRACT
Abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis is an important pathological finding in pregnant women exhibiting major depressive disorder. They show high levels of cortisol pro-inflammatory cytokines, hypothalamic-pituitary peptide hormones and catecholamines, along with low dehydroepiandrosterone levels in plasma. During pregnancy, the TH2 balance together with the immune system and placental factors play crucial roles in the development of the fetal allograft to full term. These factors, when altered, may generate a persistent dysfunction of the HPA axis that may lead to an overt transfer of cortisol and toxicity to the fetus at the expense of reduced activity of placental 11ß-hydroxysteroid dehydrogenase type 2. Epigenetic modifications also may contribute to the dysregulation of the HPA axis. Affective disorders in pregnant women should be taken seriously, and therapies focused on preventing the deleterious effects of stressors should be implemented to promote the welfare of both mother and baby.
Subject(s)
Depressive Disorder, Major/physiopathology , Hypothalamus/metabolism , Pituitary-Adrenal System/metabolism , Pregnancy Complications/physiopathology , Animals , Arginine Vasopressin/metabolism , Corticotropin-Releasing Hormone/metabolism , Depression, Postpartum/metabolism , Depression, Postpartum/physiopathology , Depressive Disorder, Major/metabolism , Female , Glucocorticoids/metabolism , Humans , Pregnancy , Pregnancy Complications/metabolism , Receptors, Corticotropin-Releasing Hormone/metabolism , Receptors, Glucocorticoid/metabolism , Receptors, Vasopressin/metabolism , Stress, Psychological/metabolism , Stress, Psychological/physiopathologyABSTRACT
OBJECTIVE: To identify and characterize high-order gene-to-gene interactions in antisocial personality disorder (ASPD). METHODS: Participants for case-control study were selected from the inmate male population in Bellavista prison from Medellin. The study included 310 individuals with ASPD and 200 with no ASPD. Diagnoses were made according to a best-estimate procedure based on a semistructured interview (diagnostic interview for genetic studies 3.0). We genotyped some single-nucleotide polymorphisms in candidate genes with main serotonin pathway effects. The gene-gene interaction was examined using the multifactor dimensionality reduction method version 2.0.α. We assessed model sizes of 2 and 3 loci and counted the number of replicates that contained the causal loci in the final best model that was identified using 10-fold cross validation. RESULTS: We find epistatic interaction with catechol-O-methyl transferase (COMT), tryptophan hydroxylase, and 5-HTR2A (serotonin receptor) with ASPD. This data supports an important role of polymorphism in serotonin receptors and low enzyme activity of COMT for susceptibility to ASPD. CONCLUSION: This study suggests that gene interactions between genetic variants in COMT, 5-HTR2A and tryptophan hydroxylase gene would be associated with ASPD and influence the dopamine rewards pathways and modulate serotonin levels in ASPD.
