Is there a schizophrenia subtype resembling frontotemporal dementia? Neurocognition and social cognition perspectives

Abstract

More than a century ago, Emil Kraepelin proposed the concept of schizophrenia as dementia praecox, or premature dementia, in order to capture the young age of onset and inevitable decline into a state of dementia which he observed to be characteristic of this population. In the modern age, Kraepelin’s dementia praecox may correspond to a small group of severely-unwell and treatment-resistant patients with chronic schizophrenia. This subtype of schizophrenia has been termed Kraepelinian schizophrenia. Compared to the broader community-dwelling chronic schizophrenia group, this poorly-functioning subpopulation may be subjected to recurrent hospitalisations and dependency on others in daily living. Carer reports of functional and cognitive decline often raise the suspicion of an underlying dementia. In the research literature, parallels have been drawn between the clinical, cognitive, and neuroimaging profiles of patients with schizophrenia and patients with behavioural variant frontotemporal dementia (FTD). However, no study has comprehensively compared neurocognition and social cognition in these two patient populations, particularly between hospitalised patients with schizophrenia who are chronically and severely unwell (i.e., the Kraepelinian schizophrenia subtype) and FTD. The overall aim of this thesis was to compare patients with severe chronic schizophrenia and patients with FTD in a number of neurocognitive and social cognitive domains in a series of three studies. In the first study, retrospective neuropsychological data was compared between 26 inpatients with severe chronic schizophrenia and 34 inpatients with FTD. Out of 16 cognitive domains, group differences were significant only in the executive function subdomain of set-shifting,with a 45% overlap in score distributions between groups. Differences in several domains were associated with small-to-moderate effect sizes and less than 85% overlap. In the second study, 7 inpatients with severe chronic schizophrenia, 13 outpatients with chronic schizophrenia who maintained community-living, 12 patients with FTD, and 18 healthy controls were administered a battery of neuropsychological measures. Across 16 cognitive domains, the inpatient schizophrenia-FTD groups were found to share more similar profiles than the outpatient schizophrenia-FTD groups. Differences between the inpatient schizophrenia and FTD groups were not significant, although medium and large effect sizes were observed in several domains. In the third study, the same groups from the second study were administered a social cognition battery consisting of measures for emotion recognition, theory of mind, and empathy. The FTD group demonstrated pervasive deficits across social cognitive domains, the inpatient schizophrenia group was similarly impaired but to a lesser degree, and the outpatient schizophrenia group showed more circumscribed deficits. The studies here are the only ones to have comprehensively investigated various domains of cognition in the two disorders. There are several important clinical and research implications of the current findings. Taken together, the findings demonstrate that hospitalised chronic schizophrenia patients and patients with FTD share more similarities than differences in their cognitive profiles. The findings support the Kraepelinian-non-Kraepelinian dichotomy and highlight the value of adopting a subtyping approach in schizophrenia research.