Testing a diathesis-stress model: potential genetic risk factors for development of distress in context of acute leukemia diagnosis and transplant.

Abstract

OBJECTIVE:

Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has antidepressant-like effects in animals and may be implicated in the etiology of mood-related phenotypes, specifically in the context of stressful life events. We hypothesized that this single-nucleotide polymorphism will predict the development of psychological distress among patients diagnosed with acute leukemia and preparing for hematopoietic stem cell transplant (HSCT). We also explored the relationship of other genetic factors to psychological distress, including 5HTTLPR and STin2, FKBP5, and the CRHR1 TAT haplotype.

METHOD:

In a retrospective cohort design, 107 adult acute leukemia survivors preparing for HSCT at a major medical center completed a pre-HSCT psychological evaluation and volunteered to donate blood to the HSCT Cell and Serum Research Repository for future research studies.

RESULTS:

There was evidence of a potential association between BDNF (Val66Met) and psychological distress. More specifically, rs6265 was related to both personal mental health history (P = 0.09, 0.06 adjusted) and diagnosis of depression/adjustment disorder at time of pre-transplant evaluation (P = 0.11, 0.09 adjusted). Other genetic factors were unrelated to distress.

CONCLUSION:

The BDNF Val66Met polymorphism may contribute to development of depressive symptomatology in patients undergoing stressful life events, such as diagnosis of acute leukemia and preparation for HSCT. The SNPs in BDNF might be applicable in identifying patients at risk for developing psychological distress and depression in the context of coping with stressful medical conditions. Polymorphism in other genes (FKBP5, CRHR1, and 5HTT) did not show any significant relationships. Replication studies are needed with larger samples of people undergoing similar significant life stressors.

• Authors: Magdalena Romanowicz, Shawna Ehlers, Denise Walker, Paul Decker, James Rundell, Gen Shinozaki, Mark Litzow, William Hogan, David Mrazek, John L Black
• Journal: Psychosomatics (Psychosomatics) 2012 Sep-Oct Vol. 53 Issue 5 Pg. 456-62 ISSN: 1545-7206 [Electronic] England
• PMID: 22652301 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Chemical References

• Brain-Derived Neurotrophic Factor
• Receptors, Corticotropin-Releasing Hormone
• SLC6A4 protein, human
• Serotonin Plasma Membrane Transport Proteins
• CRF receptor type 1
• Tacrolimus Binding Proteins
• tacrolimus binding protein 5

Topics

• Adjustment Disorders (genetics)
• Adult
• Brain-Derived Neurotrophic Factor (genetics)
• Cohort Studies
• Depression (genetics)
• Female
• Gene Frequency
• Genetic Predisposition to Disease
• Genotype
• Hematopoietic Stem Cell Transplantation (psychology)
• Humans
• Leukemia (psychology)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Receptors, Corticotropin-Releasing Hormone (genetics)
• Retrospective Studies
• Serotonin Plasma Membrane Transport Proteins (genetics)
• Stress, Psychological (genetics)
• Tacrolimus Binding Proteins (genetics)