Investigation into cognitive function in first episode psychosis and chronic schizophrenia patients. An investigation into cognitive deficits associated with first episode psychosis and chronic schizophrenia patients in South Asian and Caucasian populations as assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB).
AuthorSaleem, Majid M.
SupervisorNeill, Joanna C.
Cambridge Neuropsychological Test Automated Battery (CANTAB)
The University of Bradford theses are licenced under a Creative Commons Licence.
InstitutionUniversity of Bradford
DepartmentSchool of Pharmacy
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AbstractRationale Cognitive deficits are now recognised as a major symptom of schizophrenia with a number of studies reporting profound deficits in cognitive function in both chronic and first episode patients. Recent advances in cognitive remediation therapy have provided the opportunity for patients to improve their cognitive function and therefore improve their functional outcome. Aim The aim of the present study was to investigate cognitive deficits using the Cambridge Neuropsychological Test Automated Battery (CANTAB®) in first episode psychosis and chronic schizophrenia patients. In the first episode population the effect of ethnicity on cognition was also examined. In the chronic schizophrenia study comparisons between severity of deficits with first episode psychosis patients were also made. The effects of cognitive remediation therapy were also examined in a sample of first episode patients. Methods A total of 35 patients and 30 healthy controls were recruited into the first episode study, 17 patients and 17 controls into the chronic schizophrenia study and 11 patients into the cognitive remediation study. The first episode psychosis patients were recruited from the Bradford and Airedale Early Intervention Service and the chronic patients from the Leeds Partnership NHS Foundation Trust. The control subjects were matched as closely as possible in terms of intelligence and demographics to the patient groups. The Wechsler Test of Adult Reading (WTAR) was used to estimate subjects pre-morbid IQ. The severity of symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). All subjects who took part in the study completed a comprehensive battery of neuropsychological tests from the CANTAB®. Patients in the cognitive remediation study participated in group therapy sessions using X-cog®. Results There were no significant differences found between There were no significant differences found between patients and controls in relation to intelligence or demographics in all studies. The effect of ethnicity was shown to be not significant in the first episode study. Results show that patients performed significantly worse than controls across all iv cognitive domains tested in all studies. A correlation between negative symptoms and executive function was found in both first episode and chronic schizophrenia patients. Comparisons between first episode psychosis and chronic schizophrenia patients in cognition showed no significant differences, however significant differences were found in levels of negative symptoms and age between the two groups with chronic patients scoring higher on negative symptoms and being older. In the cognitive remediation study a significant improvement was observed in patients in the domain of executive function and a reduction in negative symptoms following completion of the intervention. Conclusion First episode and chronic schizophrenia patients display significant cognitive deficits across all domains when tested using the CANTAB®. Some of these deficits appear to be independent of the length of the illness but dependent on negative symptoms. This study demonstrates that cognitive deficits exist across all patient groups regardless of age, gender, pre-morbid IQ, years in education and ethnicity. Cognitive remediation therapy has also been shown to be effective in improving cognitive functioning in patients.
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Exploration of cognitive and neurochemical deficits in an animal model of schizophrenia. Investigation into sub-chronic PCP-induced cognitive deficits using behavioural, neurochemical and electrophysiological techniques; and use of receptor-selective agents to study the pharmacology of antipsychotics in female rats.Neill, Joanna C.; Woolley-Roberts, Marie; McLean, Samantha L. (University of BradfordSchool of Pharmacy, 2010-10-19)Cognitive dysfunction is a core characteristic of schizophrenia, which can often persist when other symptoms, particularly positive symptoms, may be improved with drug treatment. The non-competitive NMDA receptor antagonist, phencyclidine (PCP), is a psychomotor stimulant drug that has been shown to induce symptoms characteristic of schizophrenia in humans and animals. The aim of these studies was to use the sub-chronic PCP model in rats to investigate cognitive dysfunction in behavioural tests which have been highlighted as relevance by the MATRICS initiative (MATRICS.ucla.edu). The main tests used were attentional set-shifting, operant reversal learning, and novel object recognition tasks. The pharmacology of antipsychotics was studied in the reversal learning task using receptor selective compounds. Following this, experiments were carried out using in vitro electrophysiology and in vivo microdialysis in an attempt to investigate the mechanisms underpinning the PCP-induced cognitive deficits. The attentional set-shifting task is a test of executive function, the extra-dimensional shift (EDS) phase relates to the ability to shift attention to a different stimulus dimension; this is impaired in patients with schizophrenia. The studies presented in chapter 2 showed that sub-chronic PCP administration impaired attentional set-shifting performance selectively in the EDS phase, a deficit which was significantly attenuated by sub-chronic administration of clozapine and risperidone, but not haloperidol. The effect of PCP was also shown to be more robust in female rats compared to males. A deficit in set-shifting ability was also observed in isolation reared rats. However, the deficits produced by PCP were more robust than the deficit produced by isolation rearing. The reversal learning task is another test of executive function. Chapter 3 reported that sub-chronic PCP administration impairs reversal learning ability in an operant task, as demonstrated by reduced percent correct responding in the reversal phase of the reversal learning task. It was found that a D1 agonist (SKF-38398), a 5-HT1A partial agonist (buspirone), a 5-HT2C antagonist (SB-243213A) and an agonist and positive allosteric modulator of the alpha 7 nACh receptor (PNU-282987 and PheTQS respectively) are able to reverse the sub-chronic PCP-induced deficit in reversal learning. Although many antipsychotics have affinity for muscarinic M1 and histamine H1 receptors, selective agents at these receptors were not able to improve the PCP-induced deficit. In chapter 4, the atypical antipsychotics, clozapine and risperidone, when given alone to naïve rats had no effect on reversal learning. Haloperidol when given to naïve rats impaired performance at the highest dose. Sub-chronic PCP was again found to impair reversal learning performance. Investigative experiments revealed that the 2 min time-out could be important as a cue. Following a double reversal, olanzapine-treated rats lost the ability to switch between the rules, whereas clozapine and risperidone-treated rats could perform the double reversal. Experiments with the extended (15 min) reversal phase could allow the investigation of the time-course effects of antipsychotics or selective compounds. The studies presented in chapter 5 found a reduction in gamma oscillations in the CA3 region of the hippocampus, following sub-chronic PCP treatment (2-5 weeks post treatment) that was paralleled by a deficit in parvalbumin immunoreactive (IR) cell density, at a similar time point (2 weeks post treatment). In contrast, a time-dependent increase in gamma oscillations was observed (6-8 weeks post treatment), at which point parvalbumin IR cell density was unchanged (8 weeks post treatment). Gamma oscillations were unchanged in the prefrontal cortex (PFC) following the PCP treatment regime. Locomotor activity tests were also carried out to ensure that the sub-chronic PCP treatment was successful. In-vivo microdialysis revealed that vehicle-treated rats show an increase in dopamine in the PFC which is selective for the retention trial of the novel object recognition task. PCP-treated rats were unable to distinguish between the novel and familiar objects and the increase in dopamine observed in vehicle rats was absent. As a control experiment it was also shown that sub-chronic PCP did not induce anxiety-like symptoms in the elevated plus maze and open field tests. These studies suggest that sub-chronic PCP induces cognitive deficits in behavioural tasks, and these deficits may be due to GABAergic mediated processes in the hippocampus and dopaminergic dysfunction in the PFC. These behavioural and neurochemical results are concurrent to findings observed in schizophrenia.
Development of a patient-reported outcome measure (PROM) for post-stroke cognitive rehabilitation: using qualitative interviews to inform design and contentPatchick, E.; Horne, Maria; Vail, A.; Bowen, A. (2015-12)Background Improving cognition is service users' top research priority for life after stroke, and future research should include outcomes that they deem important. Patient perspectives on outcomes are collected using patient-reported outcome measures (PROMs). There is currently no patient-centred PROM specific for cognitive rehabilitation trials. Objective Inform PROM development by exploring stroke survivor perspectives on the important, measurable impacts of persisting post-stroke cognitive problems. Design Qualitative semi-structured interviews in participants' homes. Participants Purposive sample of 16 cognitively impaired stroke survivors at least six months post-stroke. Methods Interviews used a schedule and communication aids developed through patient consultation. Interviews were transcribed verbatim with non-verbal communication recorded using field notes. Data were analysed using a framework approach to find commonalities to shape the focus and content of an outcome measure. Results Participants identified important impacts of their ‘invisible’ cognitive problems, outside of other stroke-related impairments. Cognitive problems exacerbated emotional issues and vice versa. Changes in self-identity and social participation were prominent. Impact was not spoken about in terms of frequency but rather in terms of the negative affect associated with problems; terms like ‘bothered’ and ‘frustration’ were often used. Conclusions The results support the development of a PROM specifically designed to address the impact of cognitive problems. It should: include items addressing a comprehensive range of cognitive skills; ask questions about mood, self-identity and social participation; use accessible wording that respondents understand and endorse; measure impact rather than frequency; and explore perceived impact on carers.