Disentangling the pathology of schizophrenia and paraphrenia

Abstract

With increasing longevity, the number of older schizophrenic patients is growing. Previous criteria used the age of symptom onset to differentiate between the late manifestations of early-onset schizophrenia and late-onset schizophreniform disorders. Current DSM-IV or ICD 10 nomenclatures do not differentiate between early- and late-onset schizophrenia. Many decades of repeated failures to provide for distinguishing neuropathological findings have prompted narrower definition criteria. Since psychotic or schizophreniform symptoms in old age may be a manifestation of Alzheimer's disease, we attempted to base a distinction between both early- and late-onset schizophrenia on the presence of degenerative changes. This study examined the brains of 64 schizophrenic patients and 18 controls immunocytochemically for tau and amyloid staining. We divided patients according to their ages at the onset of symptoms: <40, >40. Using Braak's classification, we assessed the presence of neurofibrillary pathology. Stages III and IV were observed in 11.1% (2/18) of controls, 36.7% (11/30) of early-onset schizophrenics (<40) and 58.8% (20/34) of late-onset (>40) schizophrenics (chi2=11.39, P =0.003). Stages V and VI (definite Alzheimer's disease) did not significantly differ among groups (chi2=3.6, P =0.165). Astrocytes, subependymal and fibroblastic, also exhibited tau-positive tangles. Chi-square analysis of the data revealed a significant association between tau-positive glial tangles and Braak staging ( P =0.002). Amyloid deposits were sparse in comparison to tau-related changes. The restricted limbic tauopathy not only affected a majority of patients with late-onset schizophrenia (19 female: 1 male among positive cases) ( P =0.048) but also appeared in one-third of those elderly schizophrenic patients whose symptom onset occurred before 40 years of age (8 female: 3 male among positive cases) ( P =0.048). The resultant changes define a type of neuronal cytoskeletal disruption that alters the flow of information through the hippocampus and provides a useful clinico-pathological correlate to a group of patients until recently diagnosed as schizophrenic.

The Pathology of Paraphrenia

“…In effect, studies from the Newcastle school were biased in patient selection and used inclusionary criteria that selected for older adult patients (eg, Roth and Morrissey [8] studied only case records [n=150] of patients 60 years of age and older when admitted to Graylingwell Hospital). In contradistinction, studies that have not limited their patient selection suggest that paraphrenia-like symptoms become manifest in most patients before 49 years of age [4,15,16]. According to Ravindran et al [15], "… there is an unwarranted implication that paraphrenia is exclusive to the elderly.…”

“…In analogous fashion to the Bozikas et al [34] study, Casanova et al [16] used Braak's classification to assess the presence of neurofibrillary pathology in 64 patients with the diagnosis of schizophrenia or paraphrenia whose complete brains were available for examination. Patients were divided according to age at onset of symptomatology (ie, < 40 or > 40).…”

Late-Onset Psychosis; Is It Real?

“…80 In late-onset schizophrenia patients, these neurofibrillary tangles were predominantly distributed in the entorhinal region, transentorhinal cortex and subiculum of the anterior hippocampus. Patients with late-onset psychosis can often display mild to moderate neurofibrillary tangles in the limbic region 80 but there are few pyramidal neurons in the hippocampus. 78,80 Amyloid plaques are sparse, with no significant cell loss compared to controls.…”

“…Patients with late-onset psychosis can often display mild to moderate neurofibrillary tangles in the limbic region 80 but there are few pyramidal neurons in the hippocampus. 78,80 Amyloid plaques are sparse, with no significant cell loss compared to controls. These pathological findings are compatible with neurofibrillary tangle-predominant form of senile dementia, 81 which is associated with slowly progressive cognitive decline resulting in dementia in extreme old age.…”

Elderly patients with very late-onset schizophrenia-like psychosis and early-onset schizophrenia: Cross-sectional and retrospective clinical findings

“…As there were very few studies conducted on a French-speaking population with VLOSLP, the differential clinical and sociodemographic profile of French-speaking patients with VLOSLP versus that of French-speaking patients with EOS shall be further investigated. Indeed, do VLOSLP patients share the same symptomatology/etiology than EOS, or do they have a neurodegenerative and/or neurovascular substrate to their disorder as it has been suggested by some authors [36][37][38]?…”