What Causes Anxiety Disorders

Genes passed down through a family may put some people at higher risk for anxiety, but that's not the whole picture. Scientists think that a mix of DNA, environment, and psychological factors are to blame. Researchers are looking at brain chemicals called neurotransmitters, as well as a pair of structures inside the brain called the amygdalae.

• The high genetic correlation (.83) between Panic Disorder and Agoraphobia and the increased odds ratio for Panic Disorder and Agoraphobia in siblings of those with Agoraphobia without Panic Disorder supports the theory of a common genetic etiology for Panic Disorder and Agoraphobia

Anxiety Disorders Study examined Impact of Neuroticism

Webb et al (2012) identified that genetic factors underlying trait neuroticism, reflecting a tendency towards negative affective states, may overlap genetic susceptibility for anxiety disorders and help explain the extensive comorbidity amongst internalizing disorders

11 Genome-wide linkage (GWL) studies of either neuroticism (n=8) or anxiety disorders (n=3) were collected, which comprised of 5341 families with 15 529 individuals.

The rank-based genome scan meta-analysis (GSMA) approach was used to analyze each trait separately and combined, and global correlations between results were examined

Using 10 cM intervals, bins nominally significant for both GSMA statistics, PSR and POR, were found on chromosomes 9, 11, 12, and 14 for neuroticism and on chromosomes 1, 5, 15, and 16 for anxiety disorders

Genome-wide, the results for the two phenotypes were significantly correlated, and a combined analysis identified additional nominally significant bins

Although none reached genome-wide significance, an excess of significant PSRP-values were observed, with 12 bins falling under a FDR threshold of 0.50

As demonstrated by the identification of multiple, consistent signals across the genome, meta-analytically combining existing GWL data is a valuable approach to narrowing down regions relevant for anxiety-related phenotypes. This may prove useful for prioritizing emerging genome-wide association data for anxiety disorders

Webb, B., Guo, A., Maher, B., Zhao, Z., van den Oord, E., Kendler, K., & ... Heath, A. (2012). Meta-analyses of genome-wide linkage scans of anxiety-related phenotypes. European Journal Of Human Genetics, 20(10), 1078-1084. doi:10.1038/ejhg.2012.47

Anxiety Disorders Study examined SLC6A4, BDNF & GABRAa6

Arias et al (2012) aim of their study was to test the individual association of the serotonin transporter gene (SLC6A4), the brain-derived neurotrophic factor gene (BDNF) and the GABAAα6 receptor subunit gene (GABRA6) with anxiety-related traits and to explore putative gene-gene interactions in a Spanish healthy sample

A sample of 937 individuals from the general population completed the Temperament and Character Inventory questionnaire to explore Harm Avoidance (HA) dimension; a subsample of 553 individuals also filled in the Big Five Questionnaire to explore the Neuroticism dimension. The whole sample was genotyped for the 5-HTTLPR polymorphism (SLC6A4 gene), the Val66Met polymorphism (BDNF gene) and the T1521C polymorphism (GABRA6 gene).

Homozygous individuals for the T allele of the T1512C polymorphism presented slightly higher scores for HA than C allele carriers ( F = 2.96, P = 0.019).

There was a significant gene-gene interaction on HA between the 5-HTTLPR and Val66Met polymorphisms ( F = 3.4, P = 0.009)

Conclusion: GABRA6 emerges as a candidate gene involved in the variability of HA. The effect of a significant gene-gene interaction between the SLC6A4 and BDNF genes on HA could explain part of the genetic basis underlying anxiety-related traits

Arias, B. B., Aguilera, M. M., Moya, J. J., Sáiz, P. A., Villa, H. H., Ibáñez, M. I., & ... Fañanás, L. L. (2012). The role of genetic variability in the SLC6A4, BDNF and GABRA6 genes in anxiety-related traits. Acta Psychiatrica Scandinavica, 125(3), 194-202. doi:10.1111/j.1600-0447.2011.01764.x

Anxiety Disorders Study examined Anxiety Sensitivity 

Zavos et al (2012) looked into how anxiety sensitivity is associated with both anxiety and depression and has been shown to be heritable

They explored role of genetic influence on continuity and change of symptoms over time

Their aim was to examine the stability of anxiety sensitivity during adolescence

They used a genetically sensitive design and were also able to investigate the extent to which genetic and environmental factors influence anxiety sensitivity over time

Self-reports of anxiety sensitivity were obtained for over 1,300 twin and sibling pairs at 3 time points

Data were analyzed using multivariate genetic models

Anxiety sensitivity was moderately heritable at all time points with substantial nonshared environmental contributions

Time 1 genetic factors accounted for continuity of symptoms at Times 2 and 3

New genetic factors at Time 2 also influenced Time 3 symptoms

New nonshared environmental influences emerged at each time point

Analysis of a latent factor of trait anxiety sensitivity revealed some stable nonshared environmental influences

Genetic effects were generally stable over time, with new genetic influences emerging in late adolescence

Environmental influences on anxiety sensitivity were, on the whole, more time specific; however, some stable environmental influences were also found

Zavos, H. S., Eley, T. C., & Gregory, A. M. (2012). Longitudinal genetic analysis of anxiety sensitivity. Developmental Psychology, 48(1), 204-212. doi:10.1037/00024996

Anxiety Disorders Study examined Genome Wide Association Study

Trzaskowski et al (2013) used together Genome Wide Association Studies (GWAS) and Genome-wide Complex Trait Analysis (GCTA) and their results suggest that anxiety – similar to height, weight and intelligence − is affected by many genetic variants of small effect, but unlike these other prototypical polygenic traits, genetic influence on anxiety is not well tagged by common SNPs

Trzaskowski, M., Eley, T. C., Davis, O. P., Doherty, S. J., Hanscombe, K. B., Meaburn, E. L., & ... Plomin, R. (2013). First genome-wide association study on anxiety-related Behaviours in childhood. Plos ONE, 8(4), 1-7. doi:10.1371/journal.pone.0058676

ANXIETY DISORDERS GENETIC STUDY REFERENCES

Arias, B. B., Aguilera, M. M., Moya, J. J., Sáiz, P. A., Villa, H. H., Ibáñez, M. I., & ...

Fañanás, L. L. (2012). The role of genetic variability in the SLC6A4, BDNF and GABRA6 genes in anxiety-related traits. Acta Psychiatrica Scandinavica, 125(3), 194-202. doi:10.1111/j.1600-0447.2011.01764.x

Minelli, A., Maffioletti, E., Cloninger, C., Magri, C., Sartori, R., Bortolomasi, M., & ...

Gennarelli, M. (2013). Role of allelic variants of FK506-binding protein 51 (FKBP5) in the development of anxiety disorders. Depression & Anxiety (1091-4269), 30(12), 1170-1176. doi:10.1002/da.22158

Mosing, M. A., Gordon, S. D., Medland, S. E., Statham, D. J., Nelson, E. C., Heath, A.

C., & ... Wray, N. R. (2009). Genetic and environmental influences on the co-morbidity between depression, panic disorder, agoraphobia, and social phobia: a twin study. Depression & Anxiety (1091-4269), 26(11), 1004-1011. doi:10.1002/da.20611

Trzaskowski, M., Eley, T. C., Davis, O. P., Doherty, S. J., Hanscombe, K. B., Meaburn,

E. L., & ... Plomin, R. (2013). First genome-wide association study on anxiety-related Behaviours in childhood. Plos ONE, 8(4), 1-7. doi:10.1371/journal.pone.0058676

Webb, B., Guo, A., Maher, B., Zhao, Z., van den Oord, E., Kendler, K., & ... Heath, A.

(2012). Meta-analyses of genome-wide linkage scans of anxiety-related phenotypes. European Journal Of Human Genetics, 20(10), 1078-1084. doi:10.1038/ejhg.2012.47

Zavos, H. S., Eley, T. C., & Gregory, A. M. (2012). Longitudinal genetic analysis of

anxiety sensitivity. Developmental Psychology, 48(1), 204-212. doi:10.1037/00024996