Genetic influences on stress reactivity: BDNF Val66Met polymorphism and the limbic-hypothalamic-pituitary-adrenal axis



Grant no. PN-II-RU-PD-2012-3-0501 

Contract no. 62/30.04.2013


Research team:

Adina Chiş, PhD (PI)

Andrei C. Miu, PhD (Supervisor)




Stress is a negative emotional experience accompanied by a cascade of physiological, cognitive, and behavioral changes that are directed either toward altering the stressful event or accommodating to its effects. There is extensive evidence that dysregulation of stress responses, either as critical elevations or reductions from a homeostatic level, plays an important role in the pathogenesis of many psychiatric and psychosomatic disorders such as affective disorders, anxiety disorders, anorexia and chronic inflammatory disorders. Complex autonomic (sympathetic and parasympathetic) and neuroendocrine responses (hypothalamic-pituitary-adrenal axis, HPA) are involved in stress reactivity and resilience.

The integration of human genetics and neuroscience has resulted in major advances in our understanding of the biology of human mental health and disease. For instance, twin studies have revealed that 40-70% of various aspects of emotion, cognition, temperament, and personality are attributable to genetic factors. The estimation of the heritability of emotional traits and states, and the identification of functional genetic polymorphisms that are associated with emotional aspects of behavior hold great promises for understanding the etiology and pathogenesis of mood and anxiety disorders.

One of the functional polymorphisms on which recent gene candidate studies have focused is Val66Met in the brain-derived neurotrophic gene (BDNF). The main purpose of this research project is to uncover the links between BDNF gene variations and biological responses to stress assessed using a variety of psychophysiological, neuroendocrine and psychopharmacological approaches.


Aims (download official document with Aims [in Romanian]):


Aim 1: Documenting the research design and piloting the study on BDNF polymorphisms and individual differences in acute stress response (downloadpresentation of study ) [in Romanian)

• Timeframe: 2013

• Stage: Completed (download Scientific Report [in English]


Aim 2: Investigating the genetic influences of BDNF Val66Met and 5 HTTLPR/rs25531polymorphisms on the acute stress response

• Timeframe: 2013 - 2014

• Stage: Completed (download presentation of results ) [in English]; download Scientific Report [in English])

Aim 3: Investigating the genetic influences of BDNF polymorphisms on stress reactivity in infants
• Timeframe: 2014 - 2016;

• Stage 1: Completed (download Raport Stiintific [in Romanian], Scientific Report [in English]);

• Stage 2: Completed (download Raport Stiintific [in Romanian], Scientific Report [in English]).





 As part of this project, a study on genetic influences on stress reactivity in infants is underway. See the flyer above (in Romanian).


Conferences and publications


Chiș, A., Blaj., B., Crișan, L. G., Vulturar, R., & Miu, A. C. (2014). Brain-derived neurotrophic factor Val66Met polymorphism and cardiac stress reactivity. Psychophysiology, under revision.

Chiș A., Crișan L. G., Blaj B., Vulturar R. & Miu A. C. (2014). Brain-derived neurotrophic factor Val66Met polymorphism and cardiac stress reactivity. 47th Conference of the European Society of Human Genetics (ESHG), Milano, Italy.

Chiș A., Crișan L. G., Blaj B., Vulturar R., & Miu A. C. (2013). Genetic influences on heart rate variability during mental stress: Associations with BDNF val66met and 5-HTTLPR/rs25531. Invited paper in the symposium on “Genes, brain and emotions” at the 4th Conference of the National Neuroscience Society of Romania (SNN), Bucharest, Romania.