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Middeldorp, C.M.; Slof-Op 't Landt, M.C.T.; Medland, S.E.; Beijsterveldt, C.E.M. van; Bartels, M.; Willemsen, G.; ... ; Boomsma, D.I. (2010)

Anxiety and depression in children and adults: influence of serotonergic and neurotrophic genes?

Article / Letter to editor
There are two major hypotheses regarding the etiology of anxiety and depression: the mono-amine hypothesis and the hypothesis of an abnormal stress response acting partly via reduced neurogenesis. Association studies have focused on genes involved in these processes, but with inconclusive results. This study investigated the effect of 45 single nucleotide polymorphisms (SNPs) in genes encoding for serotonin receptors 1A, 1D, 2A, catechol-O-methyltransferase (COMT), tryptophane hydroxylase type 2 (TPH2), brain derived neurotrophic factor (BDNF), PlexinA2 and regulators of G-protein-coupled signaling (RGS) 2, 4, 16. Anxious depression (A/D) symptoms were assessed five times in 11 years in over 11 000 adults with 1504 subjects genotyped and at age 7, 10, 12 and during adolescence in over 20 000 twins with 1078 subjects genotyped. In both cohorts, a longitudinal model with one latent factor loading on all A/D measures over time was analysed. The genetic association effect modeled at the...Show moreThere are two major hypotheses regarding the etiology of anxiety and depression: the mono-amine hypothesis and the hypothesis of an abnormal stress response acting partly via reduced neurogenesis. Association studies have focused on genes involved in these processes, but with inconclusive results. This study investigated the effect of 45 single nucleotide polymorphisms (SNPs) in genes encoding for serotonin receptors 1A, 1D, 2A, catechol-O-methyltransferase (COMT), tryptophane hydroxylase type 2 (TPH2), brain derived neurotrophic factor (BDNF), PlexinA2 and regulators of G-protein-coupled signaling (RGS) 2, 4, 16. Anxious depression (A/D) symptoms were assessed five times in 11 years in over 11 000 adults with 1504 subjects genotyped and at age 7, 10, 12 and during adolescence in over 20 000 twins with 1078 subjects genotyped. In both cohorts, a longitudinal model with one latent factor loading on all A/D measures over time was analysed. The genetic association effect modeled at the level of this latent factor was 60% and 70% heritable in the children and adults, respectively, and explained around 50% of the total phenotypic variance. Power analyses showed that the samples contained 80% power to detect an effect explaining between 1.4% and 3.6% of the variance. However, no SNP showed a consistent effect on A/D. To conclude, this longitudinal study in children and adults found no association of SNPs in the serotonergic system or core regulators of neurogenesis with A/D. Overall, there has been no convincing evidence, so far, for a role of genetic variation in these pathways in the development of anxiety and depression.Show less
Anxiety cell signaling depression genetics neurogenesis serotonin netherlands twin register bdnf val66met polymorphism genome-wide association environmental-influences combined linkage metaanalysis disorder susceptibility schizophrenia personality
All authors
Middeldorp, C.M.; Slof-Op 't Landt, M.C.T.; Medland, S.E.; Beijsterveldt, C.E.M. van; Bartels, M.; Willemsen, G.; Hottenga, J.J.; Geus, E.J.C. de; Suchiman, H.E.D.; Dolan, C.V.; Neale, M.C.; Slagboom, P.E.; Boomsma, D.I.
Date
2010-10-31
Journal
Genes, Brain and Behavior
Volume
9
Issue
7
Pages
808 - 816