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


METHODS
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.


CONCLUSIONS
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.
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA. mromanow@stanford.edu
Magdalena
M
Romanowicz
Shawna
S
Ehlers
Denise
D
Walker
Paul
P
Decker
James
J
Rundell
Gen
G
Shinozaki
Mark
M
Litzow
William
W
Hogan
David
D
Mrazek
John L
JL
Black
D000275:Adjustment Disorders / Q000235:genetics; D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D015331:Cohort Studies; D003863:Depression / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation / Q000523:psychology*; D006801:Humans; D007938:Leukemia / Q000523:psychology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics; D012189:Retrospective Studies; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D013315:Stress, Psychological / Q000235:genetics*; D022021:Tacrolimus Binding Proteins / Q000235:genetics; D000099052:CRF Receptor, Type 1; D000099159:Tacrolimus Binding Protein 5
D019208:Brain-Derived Neurotrophic Factor; D018019:Receptors, Corticotropin-Releasing Hormone; D050486:Serotonin Plasma Membrane Transport Proteins; D022021:Tacrolimus Binding Proteins; D000099052:CRF Receptor, Type 1; D000099159:Tacrolimus Binding Protein 5; C493230:SLC6A4 protein, human