Abstract
Background: Abnormalities in the activation of the hypothalamic-pituitary-adrenal (HPA) axis, specifically elevated cortisol levels during the day and a blunted cortisol awakening response (CAR), have been previously shown at the onset of psychosis. Although stressful events and childhood abuse have been suggested to possibly play a role in these abnormalities, the evidence behind this remains inconsistent and it has been suggested that these could be partly due to genetic predisposition. The aim of this study was to test interaction between history of childhood abuse and rs1360780 FKBP5 genotype on cortisol levels during the day and cortisol awakening response.
Methods: We recruited 82 first episode psychosis patients and 53 controls. Saliva samples were collected at multiple time points during the day to measure diurnal cortisol levels and cortisol awakening response (CAR); DNA was extracted from blood or saliva samples and evaluated for a functional polymorphism at the rs1360780 locus in FKBP5. Information about presence of absence childhood physical or sexual abuse was collected using the Childhood Experience of Care and Abuse questionnaire. Univariate analyses were performed to test the effects of the interaction between presence of childhood abuse and FKBP5 genotype on cortisol measurements.
Results: We found a significant interaction between history of childhood abuse and FKBP5 genotype on the CAR in first episode psychosis (F = 1.132, p = 0.01) but not in controls (p = 0.3). In particular patients with T allele (CT or TT) and history of childhood abuse had higher CAR than those with the same allele but without childhood abuse, while patients with CC genotype and history of childhood abuse had lower CAR than those with the same genotype but without childhood abuse. We also found a trend for interaction between history of childhood abuse and FKBP5 genotype on the cortisol levels during the day (F = 3.604, p = 0.06) in first episode psychosis but in controls (p = 0.03). In particular patients with T allele (CT or TT) and history of childhood abuse had higher diurnal cortisol levels than those with the same allele but without childhood abuse, while patients with CC genotype and history of childhood abuse had lower diurnal cortisol levels than those with the same genotype but without childhood abuse.
Conclusions: Our findings suggest a role of interaction between childhood abuse and FKBP5 genotype in determining HPA axis abnormalities observed at the onset of psychosis.
Methods: We recruited 82 first episode psychosis patients and 53 controls. Saliva samples were collected at multiple time points during the day to measure diurnal cortisol levels and cortisol awakening response (CAR); DNA was extracted from blood or saliva samples and evaluated for a functional polymorphism at the rs1360780 locus in FKBP5. Information about presence of absence childhood physical or sexual abuse was collected using the Childhood Experience of Care and Abuse questionnaire. Univariate analyses were performed to test the effects of the interaction between presence of childhood abuse and FKBP5 genotype on cortisol measurements.
Results: We found a significant interaction between history of childhood abuse and FKBP5 genotype on the CAR in first episode psychosis (F = 1.132, p = 0.01) but not in controls (p = 0.3). In particular patients with T allele (CT or TT) and history of childhood abuse had higher CAR than those with the same allele but without childhood abuse, while patients with CC genotype and history of childhood abuse had lower CAR than those with the same genotype but without childhood abuse. We also found a trend for interaction between history of childhood abuse and FKBP5 genotype on the cortisol levels during the day (F = 3.604, p = 0.06) in first episode psychosis but in controls (p = 0.03). In particular patients with T allele (CT or TT) and history of childhood abuse had higher diurnal cortisol levels than those with the same allele but without childhood abuse, while patients with CC genotype and history of childhood abuse had lower diurnal cortisol levels than those with the same genotype but without childhood abuse.
Conclusions: Our findings suggest a role of interaction between childhood abuse and FKBP5 genotype in determining HPA axis abnormalities observed at the onset of psychosis.
| Original language | English |
|---|---|
| Type | Supplement |
| Publisher | Elsevier |
| Number of pages | 2 |
| Place of Publication | Psychoneuroendocrinology |
| Volume | 71 |
| DOIs | |
| Publication status | Published - Sept 2016 |