Long-term effects of schizophrenic disease on brain structure and function have been extensively documented. These include decreased gray matter volume (Glahn et al., 2008), ventricular enlargement (Vita et al., 2006), focal alteration of white matter tracts (Ellison-Wright and Bullmore, 2009) and reduced obligatory auditory cortical responses (Todd et al., 2008). Cognitive abilities as well as affective domains are also affected by disease duration (Fujino et al., 2014). The duration of the schizophrenic illness is strongly associated with long-term treatment with antipsychotic drugs. Recent evidence has shown that exposure to antipsychotic treatment is associated with loss of cortical gray matter (Vita et al., 2012, 2015) and this has generated a debate as to whether the effect of “disease duration” on brain structures and functions in schizophrenia is an expression of a “natural” progression of the illness or a result of a neuro-degenerative effect of antipsychotics. Moreover, early stages of the schizophrenic disease have different clinical and pathophysiological features from those seen in patients with long disease duration (van Os and Kapur, 2009). Furthermore, positive and negative symptoms associated with acute Ketamine
