VARIANTS IN THE ALPHA(2A) ADRENERGIC-RECEPTOR GENE IN PSYCHIATRIC-PATIENTS

In various studies of psychiatric patients, alterations in adrenergic receptor (AR) expression or function have been suggested. Herein, the alpha(2A) AR gene was screened in 206 patients with schizophrenia, att ention deficit hyperactivity disorder (ADHD), autism, alcohol dependen ce, or cocaine dependence. The entire coding region was examined for s ingle base pair changes, using restriction endonuclease fingerprinting (REF), a screening method that can detect virtually 100% of mutations in 2-kb DNA segments. In the approximately 600 kb of screened sequenc e, six novel nucleotide changes were identified. The changes resulted in four missense changes (A25G, N251K, R368L, and K370N), and a sequen ce in the 3' untranslated region. In addition, a silent change (G363G) was found at high frequency in Asians and Native Americans. Of the fo ur missense changes, two found in patients with alcohol/drug dependenc e occur in highly conserved amino acids, suggesting that these are of likely functional significance. As the alpha(2A) ARs are widely distri buted both pre- and postsynaptically, and as many pharmacological agen ts with multiple effects target these receptors, the novel missense ch anges described herein may be candidates for involvement in alcohol/dr ug dependence, in other clinical disorders or traits, or in differenti al response to pharmacotherapy. (C) 1998 Wiley-Liss, Inc.