The influence of genetics on the development of anxiety

Research in the field of genetics has come a long way in recent times.

While our understanding of genetics and how it works can still be greatly improved, the knowledge it brings has enabled great advances. Science has made it possible to advance in the treatment of different diseases and disorders by locating the elements of DNA that cause or facilitate them and allowing the creation of more appropriate medicines and treatments to cure or alleviate their effects, or to avoid transmitting them to offspring.

An example of this is the treatment of various genetic disorders and the prevention of diseases with a high probability of occurrence (such as some cases of breast cancer). However, genetics does not allow an exact prediction of the occurrence of the phenomena, the expression of the genes being affected by the vital history of the people. In the case of some disorders such as the mental ones, the exploration of the genome still has a long way to go, and there is still no knowledge exact information on which genes predispose to suffer them, but it is known that in some cases there is a predisposition due to the influence genetics. It is the case of 

anxiety disorders.

What is anxiety?

The concept of anxiety refers to a diffuse emotional state similar to fear, in which the advent of a future threat is expected. This fear is disproportionate, irrational and induces avoidance or a desire to avoid feared or similar situations.

Various disorders are included within the category of anxiety disorders, such as generalized anxiety disorder, the phobias and panic disorder with or without agoraphobia. Formerly it was also considered obsessive compulsive disorder as part of this category because the subjects with this disorder present a very high level of anxiety and their symptoms being derived from a particular management of this, although its differential characteristics mean that it has been separated from this group in the latest version of the American classification of mental disorders par excellence (DSM-V).

The anxiety disorders They are the most frequent type of mental disorder both in the clinical population and in the non-clinical population. The presence of vital traumas in early childhood is a risk factor for suffering. In addition, a certain genetic predisposition has been found in some subjects to suffer from it, a predisposition that has contributed to promote the investigation of genes that can explain this relationship.

Seven genes recently linked to anxiety

Recent investigations have tried to find a link between some genes and the existence of anxiety disorders or anxiety-related symptoms.

In this sense, it must be taken into account that even when speaking of specific genes, the presence or absence of genetic predisposition does not depend on a single gene, but is considered to be polygenic. That is to say, a gene does not mark a characteristic by itself, but this depends on the joint action of various genes and how they are configured in the set of chromosomes.

1. Mmp9 gene (Matrix metallopeptidase 9)

In this gene, four haplotypes or mutations and different combinations of specific alleles have been analyzed and found to be linked to anxiety. According to previous studies, this gene is involved in coronary disorders and cancer, which correlates positively when it comes to both suffering from anxiety as a predisposing element to suffer it as a result of knowledge of the disease.

2. Gene Bdnf (Brain-derived neurotrophic factor)

Only one haplotype of this gene, AGAT, presents a good high association with the predisposition to anxiety disorders.. This gene contributes to cell maintenance, allowing the modification of the synaptic space between neurons through the secretion of neurotrophins. It has also been associated with brain plasticity. It has been linked to serotonin neurotransmitterIt also affects the proliferation of neurons.

3. Gene Ntf4 (Neurotrophin 4)

This gene is involved in the modulation of the synaptic gap. It is essential for the survival and maintenance of neurons, being essential especially for those of the striatum. More research is needed regarding its involvement in anxiety disorders, but studies seem to indicate that it is involved in vulnerability to these disorders, especially if it occurs in conjunction with the previous

4. Egr2 and Egr4 genes (Early-Growth Response 2 & 4)

These genes are involved in synaptic plasticity, especially in learning and memory.. They are also involved in bone formation of the skull and myelination of the peripheral nervous system.

5. Grm2 gene (Glutamate receptor 2)

This gene participates, as can be imagined by its name, in the reception and metabolism of glutamate, the major exciter of the central nervous system. This link with the glutamate makes this gene an element closely linked to anxiety disorders and even to the schizophrenia. In addition to anxiety disorders, it is linked to learning.

6. Arc gene (Activity-regulated cytoskeleton-associated protein)

This gene is known and studied for its link with neuronal plasticity and the genesis of proteins that allow it.. Participates and acts on NMDA receptors.

Careful! Caution with biological determinism

The discovery of these genes and their relationship with anxiety-related mental disorders represents a milestone of great importance when it comes to contributing to the study and treatment of alterations anxious. However, it must be taken into account that the presence of certain genetic configurations implies only an innate predisposition to express the phenotypes to characteristics to which predispose

Considering that having these genes means suffering from an anxiety disorder would be a fallacy, since it can make us forget the shaping influence of the environment and education, elements that can awaken or ignore the biological predisposition. And it is that anxiety disorders, like the rest of psychological disorders in general, have a plural and biopsychosocial etiology.

Care must be taken not to fall into reductionism and consider the effect of all the variables that may have an implication in disorders, both anxiety and other types.

Bibliographic references:

• American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders. Fifth edition. DSM-V. Massón, Barcelona.

• Ardelt, A.A.; Flaris, N.A. & Roth, K.A. (1994). Neurotrophin-4 Selectively Promotes Survival of Striatal Neurons in Organotypic Slice Culture. Brain Res. 647: 340–344.

• Bayes, M.; deCid, R.; Vallejo, J. & Estivill, X. (2008). Extensive genotyping of the BDNF and NTRK2 genes defines protective haplotypes against obsessive-compulsive disorder. Biol. Psychiatry 63: 619–628

• Levi, G.; Topilko, P.; Schneider-Maunoury, S.; Lasagna, M.; Mantero, S.; Cancedda, R. & Charnay, P. (1996). Defective bone formation in Krox-20 mutant mice. Development122: 113–120

• Milbrandt, J. (1988). Nerve growth factor induces a gene homologous to the glucocorticoid receptor gene. Neuron 1:183–188.

• Park, S.; Park, J.M.; Kim, S.; Kim, J-A.; Shepherd, J.D.; Smith-Hicks, C.L.; Chowdhury, S.; Kaufmann, W.; Kuhl, D.; Ryazanov, A.G.; Huganir, R.L.; Linden, D.J. & Worley, P.F. (2008). Elongation Factor 2 and Fragile X Mental Retardation Protein Control the Dynamic Translation of Arc/Arg3.1 Essential for mGluR-LTD. Neuron 59: 70–83.

• Swanson, C.J.; Bures, M.; Johnson, M.P.; Linden, A-M.; Monn, J.A. & Schoepp, D.D. (2005). Metabotropic glutamate receptors as novel targets for anxiety and stress disorders. Nat. Rev. Drug Discov. 4: 131–144

• Topilko, P.; Schneider-Maunoury, S.; Levi, G.; Baron-Van Evercooren, A.; Chennoufi, A.B.Y.;Seitanidou, T.; Babinet, C. & Charnay, P. (1994). Krox-20 controls myelination in the peripheral nervous system.

• Wade, N. (2014). The identification of novel susceptibility genes involved in anxiety disorders. Stellenbosch University