When does structural brain change appear in schizophrenia and is it clinically relevant?

Abstract

Despite Kraepelin’s descriptions in the early 1900’s of structural brain pathology at the cellular level in patients with dementia praecox (Kraepelin 1919), little acceptance of this notion was present among 20^thcentury psychiatrists who were focused on perfecting psychoanalytic techniques even for schizophrenia (Fromm-Reichmann 1943). Great care was taken to separate psychoses into those that were “organic” (i.e. a brain disease) and those that were functional (i.e. due to psychological factors; Davison 1987). Although early pneumoencephalographic studies clearly showed evidence that brain ventricular enlargement was present in patients with chronic schizophrenia (Haug et al. 1963, 1982; Huber 1957, 1979; Jacobi and Winkler 1927), it was not until Johnstone et al. (1976) and then Weinberger et al. (1979) demonstrated with CT that this finding was widely present in populations of patients with schizophrenia, that researchers began to accept its presence and attempt to uncover its relevance. When magnetic resonance imaging was available for human medical imaging, numerous brain scans of subjects with schizophrenia were examined further for both cortical and subcortical structural changes, and a large array of findings about brain structure, other than ventricular enlargement, emerged (reviewed in Shenton et al. 2001). Without any clear indication that duration of illness or any treatments had an effect on these findings, various brain developmental hypotheses about schizophrenia were proposed (Weinberger 1987; Murray et al. 1991; Feinberg 1982/83) and consideration was also given to a lifetime trajectory of deviant brain change that is likely to be genetically controlled (DeLisi 1997), or at least have both a developmental and degenerative component (Woods 1998; Waddington et al. 1997). In addition, what has emerged relatively consistently across studies is that some changes are asymmetrical and sometimes only relate to differences in asymmetry rather than absolute differences in one side of the brain, leading Crow and colleagues (1989) to propose that the primary defect in schizophrenia relates to the anomalous development of normal cerebral asymmetries.