People with anxiety disorders such as panic attacks and agoraphobia may have a genetic mutation that makes them susceptible to these conditions, a Spanish study has found (Cell 2001;106:367-79).
The research, led by geneticist Xavier Estivill of the Medical and Molecular Genetic Center and psychiatrist Antoni Bulbena of the Hospital del Mar, both in Barcelona, was based on an earlier observation of a clinical association between anxiety disorders and laxity of the joints, which involved 178 members of seven families from the same village near Barcelona.
The scientists studied the genome of 93 individuals who had anxiety (panic/phobic) disorders, hyperlaxity, or both these disorders. They found a region of chromosome 15 (15q24-26) that was duplicated (named DUP25) and contained high numbers of repetitive sequences known as "duplicons."
The DUP25 abnormality, harbouring about 10 million nucleotides, was detected in 67 (72%) of the 93 subjects. The mutation was observed in 90% of patients with anxiety disorders and 87% with joint laxity. All those who had panic attacks carried DUP25.
The researchers replicated these findings in a further sample of 70 unrelated outpatients aged 18 and over with panic disorder, with or without agoraphobia. The DUP25 mutation was detected in 68 of these patients. The duplication was found in only 14 of 189 control samples. Chromosomal studies were performed mainly by fluorescence in situ hybridisation (FISH) on peripheral blood lymphocytes.
"The mechanism by which this duplication leads to panic and phobic disorders and joint laxity is probably through a dosage effect, with overexpression of one or several genes of DUP25," the scientists commented.
In particular, the neurotrophin 3 receptor (NTRK3) gene contained within DUP25 was found to be overexpressed in the study. This gene has a fundamental role in behavioural arousal in response to stimuli, and an overexpression could reduce emotional arousal thresholds and trigger panic attacks.
Dr Estivill said that the results provided the first clear evidence that genetic factors are involved in the susceptibility to common psychiatric disorders. He said that, in addition to providing a biological basis for the development of psychiatric diseases, "the identification of DUP25 opens a new era for the understanding of psychiatric disorders, which should lead to new definitions of the biological, genetic and clinical basis of anxiety disorders."
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