The theoretical perspectives offered by the authors of the articles in this special section of the Schizophrenia Bulletin
focus on the roles of aberrant dopaminergic signaling,3
N-methyl-D-aspartate receptor-mediated dysconnectivity,4
in the etiology and/or pathophysiology of the disorder. All are explicitly multilevel models; each clearly has merit in explaining a range of observations that are considered more or less established facts about the disorder,5
and within each there are clearly identified causal hypotheses. In many ways, the presence of these theories at this stage of knowledge is a reassuring indicator of a maturing branch of science because enough generally established “facts” have been elucidated to support model building of this sort.5
At the same time, it is also clear that these theories are not (and are not intended by their authors to be) mutually exclusive of each other. Rather, they provide explanations that differ in relative emphasis, eg, on distal vs proximal causes and on broad vs narrow behavioral end points. It is therefore possible for all of them to be “right” in at least a general sense. Hypothesizing a causal role of aberrant dopaminergic signaling in schizophrenia does not rule out a causal role of glutamatergic signaling (ie, because the 2 systems interact or are differentially relevant to certain cases or features of the disorder), and both systems can be influenced by disruptions of cellular connectivity that in turn may derive from the influences of multiple risk factors during the course of brain development. Thus, although constructed separately and with some theory-specific features, the 3 theoretical accounts offered in this special issue can nevertheless be pieced together into a whole, as in the different modules of the International Space Station.
Although not the fault of the authors of these theoretical articles, who were not asked to build competing models, this nonexclusivity is problematic and likely to hinder the pace of progress because we cannot make use of the efficiency of deductive logic by focusing our data collection efforts on differential predictions of models. If the extant models do not make differential causal hypotheses, they are not truly competitors as explanatory theories of schizophrenia. The task is then to recognize those aspects of proposed theoretical models that are compatible with each other as reflecting the same fundamental causal hypotheses, but at different levels of analysis, putting empirical evaluation of those aspects aside, and to focus attention on causal hypotheses that are potentially differential between competing theoretical views.
In principle, the contrast points will be found in theoretical constructions that implicitly or explicitly refer to integration of causes across levels of analysis. A causally additive formulation differs in its predictions about the structure of relationships among observed variables than a causally interactive formulation (ie, as in whether a multiplicative term adds to or subsumes the variance accounted for by multiple independent terms in a multiple regression analysis). A causally transductive vs directly causal process can be tested using the principles of mediation analysis, whereby a variable A either influences another variable B directly or through A's effects on a third variable C.8
These points of theoretical contrast find ready application in the statistical models (ANOVA, regression, structural equation modeling) commonly used in correlational science.9