Invention:
Diagnostic test to guide administration of aversion therapy to patients with anxiety disorders like post-traumatic stress disorder (PTSD) and phobias. Patients who have a certain mutation in the BDNF gene (the val66met SNP) will be less responsive, and will need adjuvant therapy. The molecular diagnostic test may be supplemented with a behavioral test as well

The Val66Met SNP occurs in a region of BDNF where crucial chaperone proteins bind to BDNF; these chaperones guide the regulated secretion of BDNF, which in turn promotes development of the brain and helps synapses to function normally. In a sense, the SNP "breaks the handle" of BDNF, preventing normal secretion. Humans with this SNP tend to have smaller hippocampi, and tend to be more anxious and aggressive.

Cornell investigators ran parallel experiments on mice and humans with this mutation. Both mice and humans (with the SNP and without) were given a conditioned fear response in a simple experiment that involved playing a loud noise while showing the subject a symbol. Both mice and humans with the SNP had difficulty "extinguishing" the association between the symbol and the expectation of the loud noise, while wild type mice and humans quickly learned to dissociate them. Humans with the SNP also displayed atypical frontoamygdala activity under functional MR imaging (fMRI), providing yet another validation of the molecular test.

The invention may be useful to guide treatment of paitents with anxiety disorders, as patients with the val66met SNP may require longer aversion therapy or may be helped by drugs that enhance learning. Further, the test provides a test to identify people likely to develop PTSD, which may be useful to screen members of the military or others who may be exposed to trauma.

File Number: 5006