 Previous studies of D2 receptors using 11Craclopride, 11CNMSP and 123IIBZM have been limited by the lack of sensitivity of those radioligands to receptors outside the striatum. Striatal D2 receptor binding has been reported to be abnormally increased in psychotic bipolar subjects relative to both controls and non-psychotic bipolar subjects using 11CNMSP Pearlson et al., 1995 and unaltered in subjects with Major Depressive Disorder MDD compared to controls in two studies using 123IIBZM Klimke et al., 1999; Parsey et al., 2001. An increased basal ganglia-to-cerebellum ratio of D2 receptor binding using 123IIBZM has been reported in depressed MDD subjects compared to controls DHanenen and Bossuyt, 1994; Ebert et al., 1996. SPECT imaging studies show that 123IIBZM binding to striatal D23 receptors is abnormally elevated in MDD. Although these studies were confounded by medication effects and small subject samples, because 123IIBZM binding is sensitive to competition from endogenous DA, this abnormality could reflect reduced intrasynaptic DA levels in the striatum of MDD subjects. 