Diminished GABA_A Receptor-Binding Capacity and a DNa Base Substitution in a Patient with Treatment-Resistant Depression and Anxiety

In this report, we describe the case of a caucasion male patient, aged 42 years, suffering from severe treatment-resistant generalized anxiety disorder with panic attacks and from major depression for which he was treated with a course of electroconvulsive therapy. During electroconvulsive treatment, anesthesia was difficult to induce with etomidate and, once, propofol. Bispectral indices recordings (assessing the depth of anesthesia) revealed a much shorter duration of loss of responsiveness compared to a control patient receiving also a course of electroconvulsive therapy. Since GABA_A receptors with ¹²³I-iomazenil SPECT and found a clearly diminished binding of the radiotracer in the right frontal and orbitotemporal regions compared to the recordings in a 38-year-old healthy male control. Genetic analysis of the exons 7 and 8 of the GABRBI-3 genes coding for the 1-3-subunits of the GABA_A receptors revealed a silent G to A substitution in the third position of amino acid 257 of the b1-subunit. To our knowledge, this is the first report of a link between insensivity to anesthetic agents and altered GABA_A receptor function in a clinical case. Whereas reduced GABA _A receptor-binding capacity has been investigated in anxiety disorders, this has not been the case in depressive disorders. This case illustrates how clinical observations in psychiatry can prompt investigations by modern techniques and potentially link clinics and basic sciences. No conclusion can, however, be made about casual links in this single case.