Human Genetics

The search for susceptibility genes for anxiety is a major priority. However, several caveats are noteworthy in attempting to interpret the data generated to date. While many investigators define patient populations based on DSM-IV-TR criteria, controversy exists over whether anxiety phenotypes should be defined more broadly or more narrowly. Thus, discrepancies among similar studies may be due to diagnosis selection criteria. In addition, factors such as comorbidity and heterogeneity within specific anxiety disorder populations must be taken into consideration. Molecular genetic strategies themselves provide differing levels of reproducibility. Linkage studies involve genotyping unknown DNA markers across the genome in large pedigrees or affected relative pairs to determine the approximate chromosomal location of susceptibility genes. In these studies the gene locus does not need to be known, however genes involved in small effects remain undetected. Genetic association studies involve the selection of candidate genes based on location determined from linkage studies or on disease pathology. However, due to both population variability and the choice of polymorphisms, they also show the greatest susceptibility for discrepancies.

Association studies in PTSD have implicated the DRD2 dopamine receptor and the DAT gene as susceptibility gene candidates. Studies in SAD have provided a potential linkage to chromosome 16, a region containing the gene for NET, SLC6A2. Studies in OCD have linked the disorder to 9p24, an area where the glutamate transporter gene, SLC1A1, is located, although no evidence for biased transmission of this transporter was obtained. Association studies have shown varying results but strong susceptibility gene candidates include genes for: 5HT1B, 5HT2A receptors, 5HTTLPR (SERT), and the DRD4 dopamine receptor. Novel candidates awaiting further analysis in OCD include genes for: BDNF (brainderived neurotrophic factor), the GRIN2B (glutamate receptor, ionotropic N-methyl-D-aspartate subunit 2B), and MOG (myelin oligodendrocyte glycoprotein). Association studies in GAD have demonstrated a positive association with the MAO-A gene (catecholamine degradation enzyme). For a review of the genetics of anxiety disorders, see 36.

Conquering Fear In The 21th Century

Conquering Fear In The 21th Century

The Ultimate Guide To Overcoming Fear And Getting Breakthroughs. Fear is without doubt among the strongest and most influential emotional responses we have, and it may act as both a protective and destructive force depending upon the situation.

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