Table 2.
Extant Models of schizophrenia. This list is not meant to be exhaustive, but illustrates examples of the main lines of thinking about schizophrenia on the domains of clinical disease expression, pathophysiology, and etiology. The extent to which each of these models explains the known etiologic, pathophysiologic, and/or clinical facts of the entity of schizophrenia are rated in successive columns, and discussed further in the text.
| Model | Main refs | Etiology | Patho-physiology | Clinical features | Treatment | Testability (animal models) |
|---|---|---|---|---|---|---|
| Models of disease expression | ||||||
| Self-monitoring dysfunction | (Frith and Done, 1988, Feinberg, 1978) | NC | + | + | NC | NA |
| Deficit syndrome | (Carpenter et al., 1988) | NC | + | + | ± | NA |
| Impaired Information processing | (Hemsley and Zawada, 1976) | NC | + | + | NC | |
| Aberrant salience | (Kapur, 2003) (Howes and Kapur, 2009) | NC | + | + | + | A |
| Language development and speciation | (Crow, 1995) | ± | + | + | NC | NA |
| Models of pathophysiology | ||||||
| Heteromodal association cortex | (Ross and Pearlson, 1996) | NC | + | + | NC | NA |
| Cortico-cerebellar- thalamic-cortical circuit [CCTCC]). | (Andreasen, 1999) | NC | + | + | NC | NA |
| Aberrant default state networks | (Williamson, 2007) | NC | + | + | NC | NA |
| Disturbances of Inhibitory Neural Circuits and Gamma Oscillations | (Kwon et al., 1999) | NC | + | + | NC | A |
| Dopamine imbalance hypothesis | (Weinberger, 1987); (Grace, 1991) | ± | + | ++ | + | A |
| Amphetamine sensitization | (Lieberman et al., 1990) | NC | + | + | + | A |
| Altered Glutamatergic neurotransmission | (Kim et al., 1980); (Javitt and Zukin, 1991); (Olney and Farber, 1995); (Coyle, 2006) | ± | + | + | + | A |
| Altered GABA neurotransmission | (Lewis and Hashimoto, 2007); (Benes and Berretta, 2001) | ± | + | + | − | A |
| Altered membrane integrity | (Hitzemann et al., 1984, Horrobin et al., 1994) | ± | + | + | + | NA |
| Increased oxidative | (Reddy and stress Yao, 1996) | + | + | + | + | NA |
| Inflammatory response | (Smith, 1991) | + | + | + | + | A |
| Models of pathogenesis | ||||||
| “early” developmental models | (Murray, 2002); (Weinberger, 1987); (Akbarian et al., 1993) | + | + | + | NC | A |
| “Late” developmental models | (Feinberg, 1982); (Hoffman and McGlashan, 1994); (Keshavan et al., 1994, DeLisi, 2008) | ± | + | + | NC | NA |
| Progressive/developmental models (“2-hit” or “3-hit” models | (DeLisi, 1997); (Weinberger, 1987); (Woods et al., 2009) | ± | + | + | NC | NA |
| Models of etiology | ||||||
| Genetic models | (Gottesman and Gould, 2003) | ++ | + | + | NC | A |
| Environmental models: early (intra/perinatal infections, nutrition) and later environmental factors (cannabis exposure, psychosocial stress) | (van Os et al., 2005) | ++ | + | + | NC | A |
| Epigenetic and gene-environmental interaction models | (Petronis et al., 1999); (Costa et al., 2001) | ++ | + | + | NC | A |
NC= not considered in this theory; ++ = most of the facts in this domain are explained by the theory; + some but not all facts are explained or are consistent with this theory; ±= some data but not conclusive; − and no evidence at this time for treatment relevance despite available studies. A= animal models available (briefly mentioned in text); NA= not available.