Heterogeneity of the Psychoses: Is There a Neurodegenerative Psychosis?

Abstract

Whereas etiological heterogeneity of the various types of schizophrenia has been repeatedly proposed, relatively few attempts have been made to separate the component diseases. Using a strategy focusing on bimodal distributions within several relevant domains of schizophrenia, we demonstrate that currently available data on schizophrenia patients are consistent with the hypothesis that some of these patients have an ongoing neurodegenerative disease, whereas others do not. We review studies (longitudinal and cross-sectional) documenting progressive increases in ventricular size, accelerated loss of brain tissues, progressive delays in treatment response, and neurochemical (magnetic resonance spectroscopy) and neurophysiological (P300) indices, all of which are consistent with ongoing cerebral degeneration in a significant subgroup of schizophrenia patients. These lines of evidence converge on a conceptualization of schizophrenia as being composed of several etiologically distinct processes, with one subset of psychotic patients evidencing progressive brain degeneration. We conclude with a discussion of possible etiologies for this condition.

Schizophrenia and viral infection during neurodevelopment: a focus on mechanisms

“…These paradigms should be designed with the recognition that schizophrenia is a heterogeneous disease, and clinical subtypes of the disease may be reflections of sub-mechanisms of pathogenesis. [49][50][51][52] The first step in refining these paradigms of pathogenesis is to ask what type of data can be reasonably expected if viruses are involved in the etiology of schizophrenia. The human host is constantly confronted with emerging and undefined viral pathogens.…”

Atrophic and Static (Neurodevelopmental) Schizophrenic Psychoses Premorbid Functioning, Symptoms and Neuroleptic Response

“…It is likely that the putative expanding ventricle endophenotype is associated with a degenerative process (Knoll et al 1998), although the evidence at this point is circumstantial. Another putative endophenotype of psychosis appears to occur without such ventricular expansion, and may be indicative of anatomical anomalies arising in the remote past, probably during neurodevelopment.…”

“…A meta-analysis of such data however, reveals that the rate of VBR increase (not the VBR itself) does not fit a normal distribution pattern, but resembles a bimodal pattern, with one group of patients showing a rate of change within the error of the method, and another group of patients showing a excessive rate of increase substantially outside of the method's error. Thus, there appears to be a bimodality of the rate of change of VBR (Knoll et al 1998).…”

“…A series of investigations are presently underway to determine the etiology(ies) of the atrophic process, including studies of lipid peroxidation, of neurotrophic deficiencies, and of autoimmune phenomenon (Knoll et al 1998). It remains possible that there is simply a progressive packing of neuropile associated with progressive volumetric reduction of brain and with ventricular expansion.…”

“…The clinical characterization is based on 17 of the initially reported patients with serial ventricular studies (Nair et al 1997), plus six additional patients who have since completed serial scans. The a priori hypotheses were: (1) there would be two groups of patients with respect to rate of ventricular change (Nair et al 1997;Knoll et al 1998); (2) changing ventricle patients would have a "delayed" response to neuroleptics (Kaplan et al 1990); (3) there would be a strong relationship between total ventricular volume and age in patients with rapidly expanding ventricles (evidence for a continuous process of expansion); and (4) alcohol and drug use between ventricular volume assessments would be associated with more rapid ventricular expansion. An exploratory analyses was designed to assess interactions of conventional antipsychotics and symptoms, including differential symptom change in the two putative psychotic illnesses delineated by the two ventricular expansion rates.…”