Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety
- 20 January 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular Psychiatry
- Vol. 14 (7), 681-695
- https://doi.org/10.1038/mp.2008.143
Abstract
Individual risk markers for depression and anxiety disorders have been identified but the explicit pathways that link genes and environment to these markers remain unknown. Here we examined the explicit interactions between the brain-derived neurotrophic factor (BDNF) Val66Met gene and early life stress (ELS) exposure in brain (amygdala–hippocampal–prefrontal gray matter volume), body (heart rate), temperament and cognition in 374 healthy European volunteers assessed for depression and anxiety symptoms. Brain imaging data were based on a subset of 89 participants. Multiple regression analysis revealed main effects of ELS for body arousal (resting heart rate, P=0.005) and symptoms (depression and anxiety, PP=0.013), heart rate elevations (P=0.0002) and a decline in working memory (P=0.022). Structural equation path modeling was used to determine if this interaction predicts anxiety and depression by mediating effects on the brain, body and cognitive measures. The combination of Met carrier status and exposure to ELS predicted reduced gray matter in hippocampus (PPP=0.005). Higher depression was associated with poorer working memory (P=0.005), and slowed response speed. The BDNF Met–ELS interaction also predicted elevated neuroticism and higher depression and anxiety by elevations in body arousal (PBDNF V/V genotype and ELS predicted increases in gray matter of the amygdala (P=0.003) and associated medial prefrontal cortex (PP=0.026) and higher anxiety (P=0.026). Higher anxiety was linked to verbal memory, and to impulsivity. These effects were specific to the BDNF gene and were not evident for the related 5HTT-LPR polymorphism. Overall, these findings are consistent with the correlation of depression and anxiety, yet suggest that partially differentiated gene–brain cognition pathways to these syndromes can be identified, even in a nonclinical sample. Such findings may aid establishing an evidence base for more tailored intervention strategies.Keywords
This publication has 91 references indexed in Scilit:
- Testing the tripartite model in young adolescents: Is hyperarousal specific for anxiety and not depression?Journal of Affective Disorders, 2007
- Genetic Variant BDNF (Val66Met) Polymorphism Alters Anxiety-Related BehaviorScience, 2006
- Standardized assessment of cognitive functioning during development and aging using an automated touchscreen batteryArchives of Clinical Neuropsychology, 2006
- BDNF in schizophrenia, depression and corresponding animal modelsMolecular Psychiatry, 2005
- Is Psychopharmacologic "Inoculation" Effective in Preventing Posttraumatic Stress Disorder?The Journal of Clinical Psychiatry, 2005
- PRELIMINARY VALIDITY OF “INTEGNEUROTM”: A NEW COMPUTERIZED BATTERY OF NEUROCOGNITIVE TESTSInternational Journal of Neuroscience, 2005
- THE EFFECTS OF STRESSFUL LIFE EVENTS ON DEPRESSIONAnnual Review of Psychology, 1997
- Association of depression witk reduced heart rate variability in coronary artery diseaseThe American Journal of Cardiology, 1995
- The Fagerström Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance QuestionnaireBritish Journal of Addiction, 1991
- Tripartite model of anxiety and depression: Psychometric evidence and taxonomic implications.Journal of Abnormal Psychology, 1991