Toward a Multidimensional Continuum Model of Functional Psychoses for Research Purposes

Abstract

Schizophrenia (SZ), schizoaffective disorder (SA), major depressive disorder (MDD) and bipolar disorder (BPD) are clinically heterogeneous conditions called ``functional psychoses'' (FP). The paradigm, underlying the current model of FP, was based on Kraepelinian dichotomy and was a practical starting point for the categorical classification of FP. Nevertheless, the concept is increasingly challenged by emerging data from modern research in the field of clinical, genetic epidemiology, molecular genetics, neuroscience and neurobiological studies. The literature suggests that, despite intensive efforts and progress towards more reliability in classification, no definite and causally relevant biological abnormalities have been identified to date. Because the underlying disease mechanisms are poorly understood it is difficult to define a biologically plausible classification of functional psychoses. Recent research findings support a multidimensional model for FP. This chapter describes proof-of-concept for the Multidimensional Continuum Model (MDC model) of functional psychoses for research purposes. It is based on multi-dimensional parameterization of the clinical-endophenotype-genetic domains with a three-axis continuum (distribution) of psychopathological and behavior patterns among FP-affected persons, their relatives and the general population, on a hypothesis-free approach, and on an endophenotype strategy. The MDC model provides a framework for research purposes, in particular, for the study of the interactions between clinical, neurocognitive, behavioral, brain imaging and other neurobiological representations of functional psychoses. Postulated common to functional psychoses etiological and pathogenetic mechanisms include at least four interactive hits: a genetic load hit (''genetic vulnerability''), a neurodevelopmental hit (''neuronal vulnerability''), a stress sensitization hit (''life stress vulnerability''), and a neurodegeneration hit. These hits were presented as a Multi-Hits Vulnerability Model of functional psychoses. Implications for future researches in this field are discussed.