The BDNF Val66Met polymorphism: relation to familiar risk of affective disorder, BDNF levels and salivary cortisol.
BACKGROUND
Brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis are considered to play an important role in the pathophysiology of affective disorders. The aim of the present study was to investigate whether the BDNF Val66Met polymorphism is associated with a familiar risk of affective disorder and whether these genotypes affect whole blood BDNF level and salivary cortisol.


METHODS
In a high-risk study, healthy monozygotic and dizygotic twins with and without a co-twin (high- and low-risk twins, respectively) history of affective disorder were identified through nationwide registers.


RESULTS
Familiar predisposition to unipolar and bipolar disorder was not associated with any specific genotype pattern of the BDNF Val66Met polymorphism, not in this sample of 124 val/val, 58 val/met and 8 met/met individuals. However, the combination of having a high familiar risk of affective disorder and the met allele was associated with a higher whole blood BDNF (p=0.02) and a higher evening cortisol level (p=0.01), but not with awakening cortisol.


CONCLUSIONS
Individuals at high risk of affective disorders and who are carriers of the met allele of the Val66Met polymorphism may present with an enhanced stress response. The presence of a specific genotype alone may not enhance the risk of developing an affective episode. Rather, the altered stress response may be expressed only in combination with other risk variants through interactions with the environment.
Vinberg
Maj
M
Department of Psychiatry, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. maj.vinberg@rh.regionh.dk
Trajkovska
Viktorija
V
Bennike
Bente
B
Knorr
Ulla
U
Knudsen
Gitte M
GM
Kessing
Lars V
LV
D000328:Adult; D000483:Alleles; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012463:Saliva / Q000378:metabolism; D014429:Twins, Dizygotic / Q000378:metabolism / Q000523:psychology; D014430:Twins, Monozygotic / Q000378:metabolism / Q000523:psychology
D019208:Brain-Derived Neurotrophic Factor; D006854:Hydrocortisone