An Integrative Perspective on the Role of Dopamine in Schizophrenia Supplemental Information PREDICTIONS AND FURTHER TESTS OF THE HYPOTHESES THAT SCHIZOPHRENIA INVOLVES INCREASED SPONTANEOUS AND DECREASED ADAPTIVE TRANSIENTS

The main strength of the hypotheses, advanced in this article, that schizophrenia involves (a) increased spontaneous transients, which relate to positive symptoms, and (b) decreased adaptive transients, which relate to negative symptoms, is the extensive set of findings that they explain (see Figs. 4–5 in the article). Directly and more definitively testing these hypotheses would ideally involve measuring dopamine transients in the striatum of patients with schizophrenia (vs. healthy controls), both at rest, to measure spontaneous transients, and during reward-related learning, to measure adaptive transients. Unfortunately, limitations in current imaging technology mean that noninvasively measuring dopamine transients in vivo in the striatum in humans is not possible: molecular-imaging techniques, such as PET and SPECT, are too slow to capture these transients, and faster techniques, such as fMRI, do not measure neurochemistry. Nonetheless, these hypotheses lead to several, less direct, predictions that can be tested experimentally (some of which are listed below). Given that such tests are indirect, none of them individually, nor, indeed, all of them together, will be sufficient to definitively prove or disprove these hypotheses. Nonetheless, they would add to the existing body of circumstantial evidence, on a par with the evidence already reviewed in this article, thereby helping to strengthen further or instead weaken confidence in these hypotheses. The following provides a list of possible indirect tests of these hypotheses: