Drug repositioning opportunities in psychiatry

Since the mid-twentieth century, “single neurotransmitter, single disease” hypotheses have shaped the understanding of the neurobiology of mental illness. Beginning with the catecholamine hypothesis of bipolar disorder (Schildkraut, 1965) and the dopamine hypothesis of schizophrenia (Van Rossum, 1966), causality has been proposed for most neurotransmitter/disorder combinations, with abnormalities in dopaminergic, adrenergic, noradrenergic, serotonergic, glutamatergic, GABAergic, and cholinergic neurotransmission having all at one time or another been posited as the underlying cause of depressive, anxiety, psychotic, manic, and autistic disorders (Schildkraut, 1965; Van Rossum, 1966; Emrich et al., 1980; Charney and Redmond, 1983; Kahn and Van Praag, 1988; Dilsaver and Coffman, 1989; Leiva, 1990; Hussman, 2001; Mahmood and Silverstone, 2001; Battaglia, 2002; Baumeister and Hawkins, 2004; Bergink et al., 2004; Previc, 2007; Yoo et al., 2007; Luscher et al., 2011; Choudhury et al., 2012; Egerton and Stone, 2012; Möhler, 2012; Sanacora et al., 2012; Harrington et al., 2013; Pålsson et al., 2015). As others have noted (Insel and Scolnick, 2006), these hypotheses have resulted in few new treatments over the past 5 decades.