شباهت عصبی بین اسکیزوفرنی مزمن و شدید فراموشی پیشانی گیجگاهی گونه رفتاری
|کد مقاله||سال انتشار||مقاله انگلیسی||ترجمه فارسی||تعداد کلمات|
|30189||2015||9 صفحه PDF||سفارش دهید||6610 کلمه|
Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)
Journal : Psychiatry Research, Volume 225, Issue 3, 28 February 2015, Pages 658–666
This study focuses on a group of patients with chronic schizophrenia who have a more severe form of the disorder, as indicated by socio-functional decline, treatment resistance, and recurrent hospitalisation. Previous research has suggested that the pattern and severity of cognitive deficits in people with severe chronic schizophrenia is similar to that observed in behavioural variant frontotemporal dementia (bvFTD). In the current study, we compared neurocognitive performance in 16 cognitive domains in 7 inpatients with severe chronic schizophrenia, 13 community-dwelling outpatients with chronic schizophrenia, 12 patients with bvFTD, and 18 healthy controls. Our findings revealed more similar cognitive profiles between the schizophrenia inpatient and bvFTD groups compared to the schizophrenia outpatient group, who outperformed the former groups. The current results provide preliminary evidence for a distinct schizophrenia subgroup, distinguishable from other chronic schizophrenia patients by poorer clinical and functional status, who have levels of cognitive impairment comparable to those seen in bvFTD patients.
Schizophrenia was first conceptualised by Emil Kraepelin as “dementia praecox”, a group of three disorders of “insanity” with adolescence-to-young-adulthood onset and a progressively deteriorating course culminating in dementia (Kraepelin, 1987 and McKenna, 2007). Kraepelin emphasised the involvement of the frontal and temporal lobes, as well as corresponding executive dysfunction, in dementia praecox. The current consensus is that schizophrenia is not a dementia, but Kraepelin׳s concept of dementia praecox may yet apply to some patients, especially those who are the most severely unwell. These are the patients subjected to recurrent hospitalisation and who are reliant on carers when living in the community. This subtype of schizophrenia has been termed “Kraepelinian schizophrenia” (Keefe et al., 1987) and “poor-outcome schizophrenia” (Mitelman and Buchsbaum, 2007). Some of these patients have cognitive and daily functioning levels similar to that seen in dementia, with a pattern resembling the behavioural variant frontotemporal dementia (bvFTD), including severe executive and memory impairments and fronto-temporal hypoperfusion (de Vries et al., 2001). A key clinical role of our specialist neuropsychiatry unit is to assess patients with chronic schizophrenia who are referred for investigations of possible dementia, due to functional decline over and above that expected in schizophrenia. It is noteworthy that these more severely-unwell schizophrenia patients are often excluded from research studies investigating cognition because of issues with “testability” and compliance. FTD, a younger-onset dementia, is the most common clinical syndrome associated with frontotemporal lobar degeneration (Neary et al., 2005). This pattern of neurodegeneration may manifest clinically as bvFTD or as one of several variants of language disorders – semantic dementia (SD), progressive non-fluent aphasia (PNFA), and logopenic progressive aphasia (LPA) (Gorno‐Tempini et al., 2004 and Gorno-Tempini et al., 2011). The current research focused only on the bvFTD population. The characteristic neuropsychiatric disturbances in bvFTD include behaviour and personality change, loss of empathy and insight, emotional blunting, apathy, and executive dysfunction (Gregory et al., 1998, Neary et al., 1998b and McKhann et al., 2001). These features are also seen in people with chronic schizophrenia (Weinberger, 1988 and McKenna, 2007), which can result in challenging differential diagnosis between the two disorders (Woolley et al., 2011), particularly when age of onset is younger in bvFTD compared to other dementias. The overlap in clinical presentation in bvFTD and schizophrenia mainly pertains to negative symptoms, although behavioural disinhibition is seen in both disorders. Frank psychosis is thought to be rare in bvFTD (Mendez et al., 2008), but the rates of occurrence may differ as a function of age. We have previously reported that younger patients with bvFTD can present initially with a schizophrenia-like psychosis (Velakoulis et al., 2009b). Some patients with late-onset schizophrenia (LOS) have been shown to have FTD-like neuropathological abnormalities (Velakoulis et al., 2009a). While grey and white matter abnormalities are typical of both schizophrenia and FTD (Shenton et al., 2001, Buchsbaum et al., 2006, Schroeter et al., 2008 and Looi et al., 2012), the current consensus is that these brain changes are progressive only in FTD. Nevertheless, schizophrenia may also be associated with progression in brain abnormalities (DeLisi, 2008) and there may be an absence of atrophy in a subset of patients with so-called non-progressive FTD (Kipps et al., 2007). Two very recent reviews have investigated the relationship between schizophrenia and FTD from a number of perspectives, including phenotypic or clinical overlaps and shared genetic and pathophysiologic mechanisms (Cooper and Ovsiew, 2013 and Harciarek et al., 2013). While a definitive link between the two disorders was not found (Cooper and Ovsiew, 2013), it remains a possibility that the same causal mechanisms are involved early in schizophrenia and late in FTD in some cases (Harciarek et al., 2013). In the absence of “hard” evidence supporting a relationship between schizophrenia and bvFTD, comparative studies in neuropsychology can provide useful information about the level and profile of impairment in each disorder. Such information has implications for daily functioning and disorder-specific brain-behaviour relationships (Goldberg et al., 2001) and for clinical differentiation between the disorders. Only a few studies have directly contrasted neurocognition in schizophrenia and bvFTD. Zakzanis et al. (2001) identified performance overlap on 34 out of 38 individual test variables between 32 patients with LOS (average age of onset was 48 years) and 12 bvFTD patients. bvFTD patients were significantly more impaired in letter fluency, category fluency, and concept formation/set-shifting, whereas LOS patients were significantly worse on digit span. A second study (Ziauddeen et al., 2011) compared 11 bvFTD patients and 12 patients with negative syndrome chronic schizophrenia patients in executive functioning – bvFTD patients had significantly reduced category fluency and inhibition ability, but the differences were not significant in letter fluency, cognitive estimation, letter-number sequencing, rule attainment, and on a naturalistic multi-tasking test. In a third study, probabilistic association learning, which is thought to rely on intact fronto-striatal function, was found to be equally impaired in nine bvFTD patients and 24 patients with schizophrenia/schizoaffective disorder (Weickert et al., 2013). Lastly, in a Dutch study, bvFTD patients were more impaired on the Mini-Mental State Examination (Folstein et al., 1975) and Frontal Assessment Battery (Dubois and Litvan, 2000) (a measure of executive functioning) than elderly schizophrenia patients (Sanders et al., 2012). Taken together, these studies imply that schizophrenia and bvFTD share many similarities on comprehensive neuropsychological testing, and the lack of a consistent pattern of deficits across studies is likely due to the different subtype of schizophrenia under study. In summary, there is increasing recognition of possible links between schizophrenia and bvFTD. We postulate that these overlaps may be most apparent in a poorly-functioning Kraepelinian subtype with a dementia-like cognitive and functional status. Kraepelinian patients may differ from those patients with chronic schizophrenia who with treatment eventually stabilise in their clinical picture and are able to maintain some degree of functional and occupational independence (although never quite recovering to pre-morbid levels). Functional and cognitive deficits are thought to be strongly associated in schizophrenia (Mitelman and Buchsbaum, 2007). Consistent with this, previous research has found inpatients with schizophrenia to be more impaired in both global cognition and specific cognitive domains compared to community-dwelling patients with schizophrenia (Irani et al., 2011). A pilot study has reported more impaired executive functioning and fine motor dexterity in Kraepelinian compared to non-Kraepelinian patients (Roy et al., 2003). In the current study, we aimed to compare the neurocognitive profiles of chronic schizophrenia outpatients (Scz), chronic schizophrenia inpatients conforming to the Kraepelinian schizophrenia subtype (KScz), patients with bvFTD and healthy controls (HC) across major cognitive domains. We hypothesised that (i) the KScz and bvFTD groups would demonstrate very similar performances across cognitive domains, whereas there would be greater difference in the Scz-bvFTD profiles in terms of severity of impairment, and (ii) compared to the control groups, the Scz group would be the least impaired among the patient groups.
نتیجه گیری انگلیسی
The current study identified that poorly-functioning patients with chronic schizophrenia can exhibit cognitive impairment as severe as that of people with frontotemporal dementia. While the current findings provide support for the existence of a subgroup of patients with severe chronic schizophrenia reminiscent of Kraepelinian “dementia praecox”, future research with larger samples is required to confirm these findings.