The Relationship Between Schizophrenia and Frontotemporal Dementia

1Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
Journal of Geriatric Psychiatry and Neurology (Impact Factor: 2.24). 06/2013; 26(3). DOI: 10.1177/0891988713490992
Source: PubMed


Schizophrenia is a relatively common disorder diagnosed by the presentation of psychotic symptoms in the absence of identifiable neurologic or other organic cause. Frontotemporal dementia (FTD) is a relatively rare progressive neurodegenerative disorder that can present with a multitude of cognitive and behavioral symptoms including psychosis. At times, this phenotypic overlap can mean that schizophrenia and FTD are 2 possibilities in the differential diagnosis of a psychotic presentation. In this article, we systematically review the literature on the relationship between schizophrenia and FTD including case reports that highlight the potential for diagnostic confusion, clinical studies examining the relationship between the disorders, and the molecular evidence of shared pathophysiologic mechanisms. Although a relationship between the disorders is not definitively supported by the current literature, we identify the characteristics of a psychotic presentation that should alert the clinician to the possibility of FTD and describe the areas where further research is needed to clarify the pathophysiologic relationship.

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Available from: Fred Ovsiew
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    • "Recently, it has been acknowledged that there is an overrepresentation of other psychiatric disorders, such as schizophrenia and bipolar disorder, in close relatives of FTD patients. A possible association between FTD and schizophrenia has also been discussed (Cooper and Ovsiew, 2013; Harciarek et al., 2013). There is no conclusive evidence regarding anatomical correlation of psychotic features in FTD. "
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    ABSTRACT: Background: Frontotemporal dementia (FTD) constitutes a spectrum of neurodegenerative disorders associated with degeneration of, predominantly, the frontal and temporal lobes. The clinical heterogeneity is evident, and early diagnosis is a challenge. The primary objectives were to characterize psychotic symptoms, initial clinical diagnoses and family history in neuropathologically verified FTD-patients and to analyze possible correlations with different neuropathological findings. Methods: The medical records of 97 consecutive patients with a neuropathological diagnosis of frontotemporal lobar degeneration (FTLD) were reevaluated. Psychotic symptoms (hallucinations, delusions, paranoid ideas), initial diagnosis and family history for psychiatric disorders were analyzed. Results: Psychotic symptoms were present in 31 patients (32%). There were no significant differences in age at onset, disease duration or gender between patients with and without psychotic symptoms. Paranoid ideas were seen in 20.6%, and hallucinations and delusions in 17.5% in equal measure. Apart from a strong correlation between psychotic symptoms and predominantly right-sided brain degeneration, the majority of patients (77.4%) were tau-negative. Only 14.4% of the patients were initially diagnosed as FTD, while other types of dementia were seen in 34%, other psychiatric disorders in 42%, and 9.2% with other cognitive/neurological disorders. The patients who were initially diagnosed with a psychiatric disorder were significantly younger than the patients with other initial clinical diagnoses. A positive heredity for dementia or other psychiatric disorder was seen in 42% and 26% of the patients respectively. Conclusions: Psychotic symptoms, not covered by current diagnostic criteria, are common and may lead to clinical misdiagnosis in FTD.
    Full-text · Article · Dec 2014 · International Psychogeriatrics
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    • "Beyond overlaps in clinical features, we have previously reported FTD-like pathological abnormalities in a small subset of patients who presented with schizophrenia aged 50 years or older (Velakoulis et al., 2009b). Two very recent reviews of the overlaps between schizophrenia and FTD did not report any conclusive phenotypic or genotypic relationship, although it was proposed that the same causal mechanisms may be involved early in schizophrenia and late in FTD (Cooper and Ovsiew, 2013; Harciarek et al., 2013). Consistent with the locus of brain atrophy, patients with schizophrenia and FTD typically demonstrate executive dysfunction and selective memory deficits (Binetti et al., 2000; Fioravanti et al., 2005; Heinrichs and Zakzanis, 1998; Hodges and Patterson, 2007; McKenna, 2007). "
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    ABSTRACT: Objective: Previous research has suggested cognitive similarities between schizophrenia and frontotemporal dementia. In the current study, we compared neurocognition in a group of hospitalised patients with chronic schizophrenia, who may have a more severe form of schizophrenia resembling Emil Kraepelin's dementia praecox, with patients with frontotemporal dementia. We hypothesised minimal group differences in cognitive performance, and a large overlap in between-group score distributions in each cognitive domain. Methods: Retrospective neuropsychological data for 26 patients with severe chronic schizophrenia and 34 patients with frontotemporal dementia (behavioural variant) was collated. Neuropsychological measures were categorised into 16 cognitive domains. Raw scores were converted into standardised z-scores for each measure, which were then averaged across measures within each domain. In addition to difference analysis, equivalence testing was utilised, whereby overlap percentages were computed to reflect the amount of score distribution overlap in each domain between groups. Results: A statistically significant difference was observed only in the executive function sub-domain of Switching. Small-to-moderate and moderate effect sizes were noted in four other domains. Equivalence testing showed more than 85% of overlap in score distribution in most domains. Conclusions: Our findings suggest that some patients with severe chronic schizophrenia have cognitive deficits similar in degree and pattern to patients with frontotemporal dementia. The few differences observed between both groups of patients are important for differential diagnostic purposes. One limitation is the retrospective nature of the study. Suggestions for future research include longitudinal follow-up studies of these two patient populations and studies of aspects beyond neurocognition. An implication of our findings is that the 'dementia of schizophrenia' concept may be applicable to patients with severe chronic schizophrenia.
    Full-text · Article · Apr 2014 · Australian and New Zealand Journal of Psychiatry
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    • "Taken together, this suggests that, beyond the phenotypic similarities between SZ and FTLD, both conditions could share etiological, in particular genetic, determinants [35]. Some authors suggested that SZ and FTLD can also share common biochemical features (reviewed in [35]). C9ORF72 repeat expansions have been reported as a frequent cause of FTLD [36], with some patients exhibiting late-onset psychosis as the first clinical manifestation of the disease [37] [38] [39]. "
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    ABSTRACT: Background: Although numerous studies have assessed cognitive dysfunction in patients with schizophrenia, very few have focused on the diagnosis of dementia. Objective: Our objectives were to accurately diagnose dementia in a cohort of middle-aged patients with schizophrenia and to assess the type of dementia. Methods: 96 patients with schizophrenia (46 inpatients and 50 outpatients), aged 50 to 70 years, underwent a psychiatric, neurological, and neuropsychological evaluation at baseline and after a 20-month follow-up. We established a 3-step procedure: 1) diagnose dementia according to the DSM-IV criteria, using the Mattis Dementia Rating and Activities of Daily Living scales; 2) characterize dementia using brain imaging, perfusion by 99mTc-ECD-SPECT and laboratory tests including Alzheimer's disease cerebrospinal fluid biomarkers; and 3) search for genetic determinants. Results: Fourteen patients fulfilled the diagnostic criteria of dementia. Four were diagnosed with possible or probable behavioral-variant frontotemporal dementia (bvFTD), two with probable Alzheimer's disease, two with probable vascular dementia (including one due to CADASIL), one with CNS inflammatory disease, and six could not be fully characterized. Conclusions: The diagnosis of dementia in middle-aged patients with schizophrenia is challenging but possible, using a multistep procedure. The most frequent condition, bvFTD, could reflect the presence of an evolutive neurodegenerative process in some patients.
    Full-text · Article · Nov 2013 · Journal of Alzheimer's disease: JAD
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