BDNF Val 66 Met and 5-HTTLPR genotype moderate the impact of early psychosocial adversity on plasma brain-derived neurotrophic factor and depressive symptoms: a prospective study.
Recent studies have emphasized an important role for neurotrophins, such as brain-derived neurotrophic factor (BDNF), in regulating the plasticity of neural circuits involved in the pathophysiology of stress-related diseases. The aim of the present study was to examine the interplay of the BDNF Val⁶⁶Met and the serotonin transporter promoter (5-HTTLPR) polymorphisms in moderating the impact of early-life adversity on BDNF plasma concentration and depressive symptoms. Participants were taken from an epidemiological cohort study following the long-term outcome of early risk factors from birth into young adulthood. In 259 individuals (119 males, 140 females), genotyped for the BDNF Val⁶⁶Met and the 5-HTTLPR polymorphisms, plasma BDNF was assessed at the age of 19 years. In addition, participants completed the Beck Depression Inventory (BDI). Early adversity was determined according to a family adversity index assessed at 3 months of age. Results indicated that individuals homozygous for both the BDNF Val and the 5-HTTLPR L allele showed significantly reduced BDNF levels following exposure to high adversity. In contrast, BDNF levels appeared to be unaffected by early psychosocial adversity in carriers of the BDNF Met or the 5-HTTLPR S allele. While the former group appeared to be most susceptible to depressive symptoms, the impact of early adversity was less pronounced in the latter group. This is the first preliminary evidence indicating that early-life adverse experiences may have lasting sequelae for plasma BDNF levels in humans, highlighting that the susceptibility to this effect is moderated by BDNF Val⁶⁶Met and 5-HTTLPR genotype.
Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.
Arlette F
AF
Buchmann
Rainer
R
Hellweg
Marcella
M
Rietschel
Jens
J
Treutlein
Stephanie H
SH
Witt
Ulrich S
US
Zimmermann
Martin H
MH
Schmidt
Günter
G
Esser
Tobias
T
Banaschewski
Manfred
M
Laucht
Michael
M
Deuschle
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D003863:Depression / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism / Q000523:psychology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009473:Neuronal Plasticity / Q000235:genetics; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D002666:Psychology, Child; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D013315:Stress, Psychological; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C579455:BDNF protein, human