Center for Clinical Research in Neuropsychiatry

Mt Claremont, Australia

Center for Clinical Research in Neuropsychiatry

Mt Claremont, Australia
SEARCH FILTERS
Time filter
Source Type

Mazhari S.,Center for Clinical Research in Neuropsychiatry | Mazhari S.,University of Western Australia | Mazhari S.,Kerman Medical University | Price G.,Center for Clinical Research in Neuropsychiatry | And 9 more authors.
Brain and Cognition | Year: 2011

Poor performance on the antisaccade task has been proposed as a candidate endophenotype in schizophrenia. Caveats to this proposal, however, include inconsistent findings in first-degree relatives of individuals with schizophrenia, and substantial heterogeneity in individuals with the disorder. In this study, we examined antisaccade performance in patients and relatives, and sought to establish whether antisaccade measures could differentiate between two patients clusters identified in the Western Australian Family Study of Schizophrenia with either pervasive cognitive deficits (CD) or cognitively spared (CS). Ninety-three patients (CD = 47, CS = 46), 99 relatives and 62 healthy controls carried out a standard antisaccade task. Results showed: (i) significantly greater error rate, and prolonged latencies to correct responses and self-correction saccades in patients compared with controls; (ii) high error rates in relatives of poorly performing patients; (iii) longer latencies of self-correction saccades in relatives compared to controls; and (iv) higher error rate and longer latencies of self-correction saccades in the CD subgroup compared with CS. Unaffected relatives as a group were unimpaired in error rate as compared to healthy controls. These findings suggest that the antisaccade error rate and latency of self-correction saccades are useful measures in specific applications of genetic research in schizophrenia, without fully meeting endophenotype co-familiality requirements. © 2011 Elsevier Inc.


Morgan V.A.,University of Western Australia | Croft M.L.,University of Western Australia | Valuri G.M.,University of Western Australia | Zubrick S.R.,University of Western Australia | And 6 more authors.
British Journal of Psychiatry | Year: 2012

Background: Recent evidence points to partially shared genetics of neuropsychiatric disorders. Aims: We examined risk of intellectual disability and other neuropsychiatric outcomes in 3174 children of mothers with schizophrenia, bipolar disorder or unipolar major depression compared with 3129 children of unaffected mothers. Method: We used record linkage across Western Australian population-based registers. The contribution of obstetric factors to risk of intellectual disability was assessed. Results: Children were at significantly increased risk of intellectual disability with odds ratios (ORs) of 3.2 (95% CI 1.8-5.7), 3.1 (95% CI 1.9-4.9) and 2.9 (95% CI 1.8-4.7) in the maternal schizophrenia, bipolar disorder and unipolar depression groups respectively. Multivariate analysis suggests familial and obstetric factors may contribute independently to the risk. Although summated labour/delivery complications (OR = 1.4, 95% CI 1.0-2.0) just failed to reach significance, neonatal encephalopathy (OR = 7.7, 95% CI 3.0-20.2) and fetal distress (OR = 1.8, 95% CI 1.1-2.7) were independent significant predictors. Rates of rare syndromes in children of mothers with mental disorder were well above population rates. Risk of pervasive developmental disorders, including autism, was significantly elevated for children of mothers with bipolar disorder. Risk of epilepsy was doubled for children of mothers with unipolar depression. Conclusions: Our findings provide epidemiological support for clustering of neuropsychiatric disorders. Further larger epidemiological studies are warranted.


Mazhari S.,Center for Clinical Research in Neuropsychiatry | Mazhari S.,University of Western Australia | Mazhari S.,Kerman Medical University | Price G.,Center for Clinical Research in Neuropsychiatry | And 7 more authors.
Psychiatry Research | Year: 2011

Abnormalities in measures of mid-latency auditory evoked responses (MLAER) have frequently been reported in schizophrenia, while few studies have examined whether these measures could distinguish cognitive subtypes of schizophrenia. The aim of this study was to investigate whether patterns of performance on MLAER measures could differentiate a cognitive subtype of patients characterized by pervasive cognitive deficits (CD) from patients with only mild cognitive deficits (CS) and controls. An auditory paired-click conditioning test was administered to 55 schizophrenia patients (26 CD, 29 CS) and 49 healthy controls. Amplitudes, latencies and sensory gating indices of the P50, N100, and P200 MLAER were analysed. The results showed that CD patients exhibited smaller S1 amplitudes of N100 and P200 than controls, while CS patients were comparable to controls. Binary logistic regression identified the P200 S1 amplitude as a significant predictor of patients' membership in the CD subtype. However, none of the other MLAER measures could differentiate the two subtypes of schizophrenia. These findings suggest that the abnormal pathophysiologic mechanisms underlying the electrophysiological brain responses to auditory stimulation are associated with the pervasive cognitive deficits, which characterize the CD subtype of schizophrenia. This finding might provide additional electrophysiological endophenotypes for future genetic research of schizophrenia. © 2011 Elsevier Ltd.


Mazhari S.,Center for Clinical Research in Neuropsychiatry | Mazhari S.,University of Western Australia | Badcock J.C.,Center for Clinical Research in Neuropsychiatry | Badcock J.C.,University of Western Australia | And 7 more authors.
Psychiatry Research | Year: 2010

Spatial working memory (SWM) dysfunction is a central finding in schizophrenia; however, more evidence of impaired maintenance over time is required. Consequently, the present study examined SWM maintenance over short unfilled delays, and with encoding equated. The influence of a vertical reference frame to support maintenance was also investigated. The performance of 58 patients with schizophrenia and 50 healthy controls was assessed using the Visuo-Spatial Working Memory (VSWM) Test across three unfilled delays (0, 2, and 4. s). Inaccuracy of direction and distance responses was examined at each delay duration. The results showed that performance was significantly less accurate for both distance and direction responses at 2 and 4. s delays in schizophrenia, but was not significantly different from controls at the 0. s delay. Patients showed a particularly marked loss of accuracy between the time interval of 0-2. s. Furthermore, schizophrenia participants exhibited significantly greater response variability at the vertical axis of symmetry than controls at the 2 and 4. s delays, but not at the 0. s delay. These data clearly show both impaired maintenance over time and difficulty using a vertical frame of reference in schizophrenia. The latter findings may reflect, in part, dysfunctional reference-related inhibition. © 2009 Elsevier Ireland Ltd.


Badcock J.C.,University of Western Australia | Badcock J.C.,Center for Clinical Research in Neuropsychiatry | Dragovic M.,University of Western Australia | Dragovic M.,Center for Clinical Research in Neuropsychiatry | And 3 more authors.
Schizophrenia Research | Year: 2011

Background: Formal thought disorder (TD) is a key symptom of schizophrenia with a significant impact on interpersonal relationships. Current cognitive models emphasize disordered language functioning and abnormalities accessing semantic representations. The cortical mechanisms for language and motor function are closely linked, hence action-related language may be impaired in TD, yet existing studies have focussed exclusively on object (noun) rather than action (verb) semantics. Method: In order to examine this issue both action (verb) and traditional semantic (tools, fruits, musical instruments) and phonological (FAS) fluency tasks were completed by individuals with schizophrenia (N = 53) and healthy controls (N = 69). Fluency performance was measured as the total number of correct words generated in 60. s. The Schizotypal Personality Questionnaire (SPQ) was used to index odd and disorganized speech, as well as positive and negative symptoms. Results: Fluency on all tasks was impaired in schizophrenia, compared to controls, with a similar effect size. Within the schizophrenia group Odd Speech was correlated with poor fluency for actions, tools and musical instruments but not fruit or phonological fluency. These action-related fluency deficits were also correlated with Constricted Affect and Social Anxiety but not with Unusual Perceptions/Odd Beliefs. Conclusion: These results point to a unique connection and possible common aetiology between action fluency and odd speech in schizophrenia rather than a general impairment in language/executive functions common to fluency tasks. The findings provide the first evidence of a specific role of action-based language production deficits in TD together with a joint effect on social interaction skills. © 2010.


Power B.D.,North Metropolitan Area Health Service | Power B.D.,Center for Clinical Research in Neuropsychiatry | Power B.D.,University of Western Australia | Dragovic M.,North Metropolitan Area Health Service | And 5 more authors.
Social Psychiatry and Psychiatric Epidemiology | Year: 2013

Purpose: To identify the external validators of patient clusters according to need in a long-stay inpatient population with schizophrenia. Methods: We recruited without exclusion 112 in-patients with chronic schizophrenia in a long-stay rehabilitation facility of a major psychiatric hospital in Perth, Western Australia. Case managers completed a number of measures for participants, including The Camberwell Assessment of Need-Short Appraisal Schedule, which evaluates health and social needs. Latent class analysis according to patient need was performed to identify clusters within the cohort. One way analysis of variance was used to identify the external validators of these clusters, using variables obtained from the additional study measures (Social Behaviour Schedule, Global Assessment of Function, Basic Everyday Living Skills, Behaviour Rating Inventory of Executive Function-Adult version). Results: Three distinct needs-based clusters with different external profiles were identified. A "low unmet needs" group (n = 50) with relatively intact executive function, with the least problematic behaviour and most independent functioning; a "high unmet need (drug abstinent)" group (n = 43) with greatest executive dysfunction, most problematic behaviour and least independent function; a "high unmet need (drug using)" group (n = 19), with less severe executive dysfunction, and intermediate relative to the other groups on measures of social behaviour and independent functioning. Conclusions: The clinical heterogeneity we have identified, which may well be explained by executive dysfunction, suggests further exploration of appropriate assessment and streams of care for those in the rehabilitation setting is warranted. © 2012 Springer-Verlag.


Martyr P.,Center for Clinical Research in Neuropsychiatry
Social History of Medicine | Year: 2011

How did the diagnosis and treatment of lunacy in Western Australia intersect with Indigenous control by whites, and attitudes to Indigenous Western Australians in general, in the late nineteenth and early twentieth centuries? Historical analyses of the pre-1960s period are fragmentary, but there seems to have been about 30 cases of Indigenous persons being charged or diagnosed with lunacy in the period from 1870 to 1914, the overwhelming majority of whom were from remote and sparsely-settled areas of Western Australia. The constant ill-treatment to which most Indigenous people were subjected by whites, combined with often-terrifying internecine warfare between local clans or families, makes these diagnoses problematic. There is little evidence that white professionals made any connection between this ill-treatment and the development of lunacy, nor is any consideration given by local medical practitioners to the idea that acknowledged signs of insanity among white settlers were not necessarily signs of insanity among Indigenous people. © 2011 The Author.


Jablensky A.,Center for Clinical Research in Neuropsychiatry | Morar B.,University of Western Australia | Wiltshire S.,University of Western Australia | Wiltshire S.,Oxford Genetics | And 6 more authors.
Genes, Brain and Behavior | Year: 2011

Neurocognitive dysfunction is a core feature of schizophrenia with particularly prominent deficits in verbal episodic memory. The molecular basis of this memory impairment is poorly understood and its relatedness to normal variation in memory performance is unclear. In this study, we explore, in a sample of cognitively impaired schizophrenia patients, the role of polymorphisms in seven genes recently reported to modulate episodic memory in normal subjects. Three polymorphisms (GRIN2B rs220599, GRM3 rs2189814 and PRKCA rs8074995) were associated with episodic verbal memory in both control and patients with cognitive deficit, but not in cognitively spared patients or the pooled schizophrenia sample. GRM3 and PRKCA acted in opposite directions in patients compared to controls, possibly reflecting an abnormal brain milieu and/or adverse environmental effects in schizophrenia. The encoded proteins balance glutamate signalling vs. excitotoxicity in complex interactions involving the excitatory amino acid transporter 2 (EAAT2), implicated in the dysfunctional glutamatergic signalling in schizophrenia. Double carrier status of the GRM3 and PRKCA minor alleles was associated with lower memory test scores and with increased risk of schizophrenia. Single nucleotide polymorphism (SNP) rs8074995 lies within the PRKCA region spanned by a rare haplotype associated with schizophrenia in a recent UK study and provides further evidence of PRKCA contribution to memory impairment and susceptibility to schizophrenia. Our study supports the utility of parsing the broad phenotype of schizophrenia into component cognitive endophenotypes that reduce heterogeneity and enable the capture of potentially important genetic associations. © 2011 The Authors. Genes, Brain and Behavior © 2011 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.


PubMed | Center for Clinical Research in Neuropsychiatry
Type: Journal Article | Journal: Psychiatry research | Year: 2011

Abnormalities in measures of mid-latency auditory evoked responses (MLAER) have frequently been reported in schizophrenia, while few studies have examined whether these measures could distinguish cognitive subtypes of schizophrenia. The aim of this study was to investigate whether patterns of performance on MLAER measures could differentiate a cognitive subtype of patients characterized by pervasive cognitive deficits (CD) from patients with only mild cognitive deficits (CS) and controls. An auditory paired-click conditioning test was administered to 55 schizophrenia patients (26 CD, 29 CS) and 49 healthy controls. Amplitudes, latencies and sensory gating indices of the P50, N100, and P200 MLAER were analysed. The results showed that CD patients exhibited smaller S1 amplitudes of N100 and P200 than controls, while CS patients were comparable to controls. Binary logistic regression identified the P200 S1 amplitude as a significant predictor of patients membership in the CD subtype. However, none of the other MLAER measures could differentiate the two subtypes of schizophrenia. These findings suggest that the abnormal pathophysiologic mechanisms underlying the electrophysiological brain responses to auditory stimulation are associated with the pervasive cognitive deficits, which characterize the CD subtype of schizophrenia. This finding might provide additional electrophysiological endophenotypes for future genetic research of schizophrenia.


PubMed | Center for Clinical Research in Neuropsychiatry
Type: Journal Article | Journal: Brain and cognition | Year: 2011

Poor performance on the antisaccade task has been proposed as a candidate endophenotype in schizophrenia. Caveats to this proposal, however, include inconsistent findings in first-degree relatives of individuals with schizophrenia, and substantial heterogeneity in individuals with the disorder. In this study, we examined antisaccade performance in patients and relatives, and sought to establish whether antisaccade measures could differentiate between two patients clusters identified in the Western Australian Family Study of Schizophrenia with either pervasive cognitive deficits (CD) or cognitively spared (CS). Ninety-three patients (CD=47, CS=46), 99 relatives and 62 healthy controls carried out a standard antisaccade task. Results showed: (i) significantly greater error rate, and prolonged latencies to correct responses and self-correction saccades in patients compared with controls; (ii) high error rates in relatives of poorly performing patients; (iii) longer latencies of self-correction saccades in relatives compared to controls; and (iv) higher error rate and longer latencies of self-correction saccades in the CD subgroup compared with CS. Unaffected relatives as a group were unimpaired in error rate as compared to healthy controls. These findings suggest that the antisaccade error rate and latency of self-correction saccades are useful measures in specific applications of genetic research in schizophrenia, without fully meeting endophenotype co-familiality requirements.

Loading Center for Clinical Research in Neuropsychiatry collaborators
Loading Center for Clinical Research in Neuropsychiatry collaborators