PubMed Health⌕ Search

Biomedical subjects

C Pantelis

Publications and source records attributed to C Pantelis.

At least 19 recordsLinked to original sources
PubMed2006

Stress and HPA-axis functioning in young people at ultra high risk for psychosis.

It is thought that hypothalamic-pituitary-adrenal (HPA) axis functioning mediates between the experience of stress and development of psychotic symptoms. This study aimed to evaluate this model in a cohort of young people at ultra high risk (UHR) of psychosis. Information about the experience of psychological symptoms and recent stressful experiences was obtained from 23 young people who met UHR criteria. Plasma samples were taken to assess cortisol and glucocorticoid receptor numbers, and an MRI scan was also performed. Plasma cortisol levels were significantly and positively correlated with the experience of 'hassles' but not with the experience of stressful life events. Significant positive associations were also found between plasma cortisol levels and level of depression and anxiety. No significant relationships were found between plasma cortisol level and global psychopathology, psychotic symptomatology, functioning or pituitary and hippocampal volumes. These results suggest that the number of hassles experienced by young people at UHR of psychosis could be an important factor in raising their cortisol levels, which might, in turn, affect the severity of depressive and anxiety symptoms. No other relationships were found between plasma cortisol levels and the experience of psychotic symptoms, functioning or hippocampal and pituitary volumes. These results indicate possible impairment in HPA-axis functioning in the early stages of psychotic illness, but further investigation of the relationships between these parameters is required.

Adolescent↗
PubMed2005

Clinical deficits correlate with regional cerebral atrophy in progressive supranuclear palsy.

Most cerebral imaging studies of patients with progressive supranuclear palsy (PSP) have noted subtle atrophy, although the full extent of atrophy and any correlates to clinical features have not been determined. We used voxel-based morphometry analysis of grey matter, white matter and CSF on MRI brain scans to map the statistical probability of regional tissue atrophy in 21 patients with PSP, 17 patients with Parkinson's disease and 23 controls. PSP and Parkinson's disease cohorts were selected to approximate the mid-stages of their respective disease courses. Where regions of significant tissue atrophy were identified in a disease group relative to controls, the probability of tissue loss within those regions was correlated with global indices of motor disability, and behavioural and cognitive disturbance for that disease group. Minimal regional atrophy was observed in Parkinson's disease. PSP could be distinguished from both controls and Parkinson's disease by symmetrical tissue loss in the frontal cortex (maximal in the orbitofrontal and medial frontal cortices), subcortical nuclei (midbrain, caudate and thalamic) as well as periventricular white matter. For PSP, motor deficits correlated with atrophy of the caudate and motor cingulate, while behavioural changes related to atrophy in the orbitofrontal cortex and midbrain. These data suggest that intrinsic neurodegeneration of specific subcortical nuclei and frontal cortical subregions together contribute to motor and behavioural disturbances in PSP and differentiate this disorder from Parkinson's disease within 2-4 years of symptom onset.

Aged↗
PubMed2005

Reduced volume of parietal and frontal association areas in patients with schizophrenia characterized by passivity delusions.

BACKGROUND: In patients with schizophrenia, passivity delusions are characterized by a difficulty in determining the agency of purposive actions. Neuropsychological and functional neuroimaging data suggest that passivity delusions are associated with dysfunction of the parietal lobe association cortex. METHOD: Cortical volume calculated from magnetic resonance imaging data in a group of 12 patients with schizophrenia characterized by motor passivity delusions was compared statistically with the cortical volume of 11 patients without passivity delusions. RESULTS: Reduced cortical volume was observed in parietal and frontal association cortices in the passivity group. CONCLUSIONS: These data provide direct evidence for the involvement of the parietal lobe in the pathophysiology of passivity delusions in schizophrenia.

Adult↗
PubMed2004

Relationship of behavioural and symptomatic syndromes in schizophrenia to spatial working memory and attentional set-shifting ability.

BACKGROUND: Behavioural syndromes (thought disturbance, social withdrawal, depressed behaviour and antisocial behaviour) offer a different perspective from that of symptomatic syndromes on the disability that may be associated with schizophrenia. Few studies have assessed their relationship with neuropsychological deficits. We hypothesized that these syndromes may represent behavioural manifestations of frontal-subcortical impairments, previously described in schizophrenia. METHOD: Long-stay inpatients (n=54) and community patients (n=43) with enduring schizophrenia were assessed, using measures of symptoms and behaviour and tests of executive functioning. The relationship between syndromes and neuropsychological function was assessed using multiple regression and logistic regression analyses. RESULTS: Significant associations were found between performance on the spatial working memory task and the psychomotor poverty symptomatic syndrome, and between attentional set-shifting ability and both disorganization symptoms and the thought disturbance behavioural syndrome. These results were not explained by the effect of premorbid IQ, geographical location, length of illness or antipsychotic medication. Length of illness was an independent predictor of attentional set-shifting ability but not of working memory performance. CONCLUSION: The specific relationship between negative symptoms and spatial working memory is consistent with involvement of the dorsolateral prefrontal cortex. The associations between difficulty with set-shifting ability and both disorganization symptoms and behaviours may reflect inability to generalize a rule that had been learned and impaired ability to respond flexibly. The specific relationship of illness duration to set-shifting ability may suggest progressive impairment on some executive tasks. The nature of these relationships and their neurobiological and rehabilitation implications are considered.

Adult↗
PubMed2003

Spatial working memory ability is a marker of risk-for-psychosis.

BACKGROUND: Working memory has been identified as a core cognitive deficit in schizophrenia that is associated with negative symptoms, but it is unclear whether it is impaired prior to onset of psychosis in symptomatic patients. METHOD: Thirty-eight young people at ultra high-risk (UHR) of developing psychosis (of whom nine later became psychotic) were compared with 49 healthy controls on tests of spatial working memory (SWM) and delayed matching-to-sample (DMTS). RESULTS: Both SWM and DMTS performance was significantly poorer in the UHR groups. Those who later became psychotic generally performed more poorly than those who did not, although this did not reach significance for any measure. A significant association between SWM errors and negative symptoms was seen in the later-psychotic group only (P = 0.02). CONCLUSIONS: Spatial working memory abilities are impaired in those at high-risk for psychosis. The relationship between working memory and negative symptoms may be useful as a predictive tool.

Adolescent↗
PubMed2002

Visuospatial memory and learning in first-episode schizophreniform psychosis and established schizophrenia: a functional correlate of hippocampal pathology?

BACKGROUND: Despite a number of studies that have indicated impaired memory function in patients with schizophrenia, there have been few that have used a sensitive measure of right medial temporal lobe pathology. Given the reported findings of reduced hippocampal volume in schizophrenia, we used a theoretically sensitive test of the right medial temporal lobe to determine the nature of the visuospatial memory deficit in the disorder. METHODS: Seventy-six patients (37 with a first-episode schizophreniform psychosis, and 39 with established schizophrenia) were compared with 41 comparison subjects on a number of tests of visuospatial memory. These included spatial working memory, spatial and pattern recognition memory and a pattern-location associative learning test. RESULTS: Both patient groups displayed recognition memory deficits when compared to the comparison group. However, only those patients with established schizophrenia (of 9 years duration on average) were impaired on the associative learning test. CONCLUSIONS: The results indicate either a progressive decline in visuospatial associative learning ability over the course of the disorder, or that poor visuospatial associative learning is a marker for poor prognosis. In addition, these results have implications for our understanding of the role of the right medial temporal lobe in the pathophysiology of schizophrenia.

Adolescent↗
PubMed2002

Impairments of response conflict monitoring and resolution in schizophrenia.

BACKGROUND: It has been argued recently that the attentional dysfunction in schizophrenia occurs as a result of an inability to inhibit automatic attentional shifts to compelling external stimuli. However, this hypothesis is based on performance on paradigms that require overt or covert shifts of spatial attention. METHOD: We investigated responses to foveally presented stimuli in patients with schizophrenia and healthy controls as they performed unidimensional and bidimensional versions of the flanker task. In both tasks, centrally presented target stimuli were flanked by peripheral stimuli that were either congruent or incongruent with the behavioural goal of the subject. In the bidimensional task, the flanking stimuli could be congruent and incongruent on multiple stimulus characteristics. RESULTS: On the unidimensional flanker task, the behavioural goal modulated the responses of the schizophrenia group such that response times (RTs) to target stimuli that were flanked by congruent stimuli were faster than RTs to target stimuli flanked by incongruent stimuli. However, on the bidimensional flanker task, the responses of schizophrenia patients were no longer constrained by the behavioural goal and RTs to both congruent and incongruent stimuli were equivalent. CONCLUSIONS: It appears that the attentional dysfunction in schizophrenia may reflect difficulty in resolving multiple and simultaneous response conflicts. These findings suggest a possible role for the anterior cingulate cortex in the attentional impairments associated with schizophrenia.

Adult↗
PubMed2002

Incidental radiological findings on brain magnetic resonance imaging in first-episode psychosis and chronic schizophrenia.

OBJECTIVE: To investigate whether patients with first-episode psychosis or chronic schizophrenia have an increased incidence of magnetic resonance imaging (MRI) brain abnormalities compared with control subjects. METHOD: Totally 340 clinical MRI reports [Controls (n=98), first-episode psychoses (n=152), chronic schizophrenia (n=90)] were reported by a neuroradiologist blind to diagnosis and subsequently categorized using referral criteria (immediate, urgent, routine or no referral). RESULTS: Thirty percent of all scans were reported by a neuroradiologist as abnormal, but the majority required no referral. Patients with chronic schizophrenia were more likely to have clinically significant abnormal scans than patients with first episode psychosis or control subjects. In four patients the MRI findings led to the discovery of previously unsuspected pathology. CONCLUSION: Patients with chronic schizophrenia have an increased prevalence of incidental brain abnormalities. A small proportion of patients with chronic schizophrenia and first-episode psychosis benefitted directly from MRI scanning.

Adult↗
PubMed2002

Frontal atrophy correlates with behavioural changes in progressive supranuclear palsy.

Regional brain volumes were measured in 21 patients with progressive supranuclear palsy (PSP), 17 patients with Parkinson's disease and 23 controls using 3D MRI-based volumetry. Cortical, subcortical and ventricular volume measures were correlated with global indices of motor disability and cognitive disturbance. All MRI measures, including hippocampal volume, were preserved in Parkinson's disease. Patients with PSP could be distinguished from both Parkinson's disease and controls by whole brain volume loss, ventricular dilatation and disproportionate atrophy of the frontal cortex. Caudate nucleus volume loss additionally differentiated PSP from controls, but was modest in severity and proportionate to whole brain volume loss. The present study identifies disease-specific differences in the topography of brain atrophy between PSP and Parkinson's disease, and has potential implications for the in vivo radiological differentiation of these two disorders. In PSP, the variance in frontal grey matter volume related to measures of behavioural disturbance, confirming the use of behavioural tests for ante-mortem case differentiation and suggesting that intrinsic cortical deficits contribute to these clinical disturbances.

Aged↗
PubMed2001

Selective bilateral hippocampal volume loss in chronic schizophrenia.

BACKGROUND: The hippocampus is implicated in the pathophysiology of schizophrenia; however, volumetric changes are subtle and have limited diagnostic specificity. It is possible that the shape of the hippocampus may be more characteristic of schizophrenia. METHODS: Forty-five patients with chronic schizophrenia and 139 healthy control subjects were scanned using magnetic resonance imaging. Hippocampi were traced manually, and two-dimensional shape information was analyzed. RESULTS: Two shape factors were found to be adequate to represent variance in the shape of the hippocampus. One of these factors, representing volume loss behind the head of the hippocampus, provided a degree of discrimination between patients with chronic schizophrenia and healthy control subjects; however, overall hippocampal volume following appropriate adjustment for brain volume showed a similar level of discrimination. Patients with chronic schizophrenia were best characterized using these two measures together, but diagnostic specificity was only moderate. CONCLUSIONS: This study identified that less of the hippocampus was distributed in its posterior two-thirds in patients with chronic schizophrenia, and specifically in the region just posterior to the hippocampal head. Group discrimination on the basis of hippocampal volume and shape measures was moderately good. A full three-dimensional analysis of hippocampal shape, based on large samples, would be a useful extension of the study.

Adolescent↗
PubMed2001

A longitudinal study of hippocampal volume in first episode psychosis and chronic schizophrenia.

Brain abnormalities have been identified in patients with schizophrenia, but what is unclear is whether these changes are progressive over the course of the disorder. In this longitudinal study, hippocampal and temporal lobe volumes were measured at two time points in 30 patients with first episode psychosis (mean follow-up interval=1.9 years, range 0.54-4.18 years) and 12 with chronic schizophrenia (mean follow-up interval=2.3 years, range 1.03-4.12 years) and compared to 26 comparison subjects (mean follow-up interval 2.2 years, range 0.86-4.18 years). Hippocampal, temporal lobe, whole-brain and intracranial volumes (ICV) were estimated from high-resolution magnetic resonance images. Only whole-brain volume showed significant loss over the follow-up interval in both patient groups. The rate of this volume loss was not different in the first episode group compared to the chronic group. There were no changes in either hippocampal or temporal lobe volumes. The negative findings for the hippocampus and temporal lobes may mean that the abnormalities in these regions are stable features of schizophrenia. Alternatively, the period before the onset of frank psychotic symptoms may be the point of greatest risk for progressive change.

Adolescent↗
PubMed2001

Bimanual coordination in chronic schizophrenia.

Anomalies of movement are observed both clinically and experimentally in schizophrenia. While the basal ganglia have been implicated in its pathogenesis, the nature of such involvement is equivocal. The basal ganglia may be involved in bimanual coordination through their input to the supplementary motor area (SMA). While a neglected area of study in schizophrenia, a bimanual movement task may provide a means of assessing the functional integrity of the motor circuit. Twelve patients with chronic schizophrenia and 12 matched control participants performed a bimanual movement task on a set of vertically mounted cranks at different speeds (1 and 2 Hz) and phase relationships. Participants performed in-phase movements (hands separated by 0 degrees ) and out-of-phase movements (hands separated by 180 degrees ) at both speeds with an external cue on or off. All participants performed the in-phase movements well, irrespective of speed or cueing conditions. Patients with schizophrenia were unable to perform the out-of-phase movements, particularly at the faster speed, reverting instead to the in-phase movement. There was no effect of external cueing on any of the movement conditions. These results suggest a specific problem of bimanual coordination indicative of SMA dysfunction per se and/or faulty callosal integration. A disturbance in the ability to switch attention during the out-of-phase task may also be involved.

Adult↗
PubMed2001

Abnormal executive function in attention deficit hyperactivity disorder: the effect of stimulant medication and age on spatial working memory.

OBJECTIVE: This study sought to examine the factors associated with spatial working memory and the use of strategies to impairments in spatial working memory in children with attention deficit hyperactivity disorder (ADHD). The developmental trajectories for spatial working memory in medicated and medication naïve children with ADHD were investigated. In addition, the effect of psychostimulant medication on deficits in spatial working memory was examined. METHOD: A cross-sectional study compared performance between 21 psychostimulant medicated children with ADHD, 27 medication naïve children with ADHD and 26 matched control subjects on computerized tests of spatial memory and spatial working memory. RESULTS: Compared with the controls, performance in medication naïve children with ADHD was significantly worse on the spatial working memory task. There was no difference in performance between the medicated children with ADHD and the control subjects on this same task, despite the ongoing symptoms of ADHD in the former group. The pattern of normal and abnormal performance in the ADHD groups was age-independent. CONCLUSIONS: Deficits in executive functions related to spatial working memory do occur in children with ADHD, although the magnitude of these deficits is not related to the child's age or the level of ADHD symptoms. These deficits were not present in the current sample of children who were receiving psychostimulant medication.

Age Factors↗
PubMed2001

Treatment of psychogenic polydipsia: comparison of risperidone and olanzapine, and the effects of an adjunctive angiotensin-II receptor blocking drug (irbesartan).

OBJECTIVE: Our objective was to determine the outcome of novel strategies in managing a case of severe polydipsia. CLINICAL PICTURE: The patient was a 39-year-old male with a 20-year history of paranoid schizophrenia who, despite only mild residual psychotic symptoms, had been hospitalized for the previous 10 years because of severe polydipsic behaviour complicated by water intoxication. TREATMENT: Novel antipsychotic agents, risperidone and olanzapine, as well as the specific angiotensin-II receptor blocking drug, irbesartan were employed at selected intervals in a study lasting nearly 3 years. A strict behavioural management programme was ongoing, in which diurnal weight change and the number of breaches of weight limits, requiring management in a low-stimulus environment, were documented on a daily basis. Summary measures of diurnal weight change and behavioural intervention were charted against changes in treatment. OUTCOME: Polydipsic behaviour improved on risperidone up to 4 mg daily, but was not sustained. Olanzapine was similarly successful in stabilizing polydipsia, and improvement was achieved with the addition of irbesartan. CONCLUSION: We suggest that the D2-sparing profiles of receptor binding achieved with low-dose risperidone and olanzapine may account for this beneficial effect. The benefit derived with irbesartan implicates the involvement of brain angiotensin systems centrally in helping to regulate drinking behaviour.

Adult↗
PubMed2001

Hemispheric and gender-related differences in the gross morphology of the anterior cingulate/paracingulate cortex in normal volunteers: an MRI morphometric study.

The sulci and gyri found within the anterior cingulate (AC), and across the cerebrum generally, have been found to vary in location and complexity from one individual to the next, making it difficult to analyze imaging data accurately and systematically. In this study, we examined the nature of morphometric variance in the AC of the left and right cerebral hemispheres using high-resolution structural magnetic resonance imaging (MRI) acquired from 176 healthy volunteers. Depending on the presence of a paracingulate sulcus (PCS) and its antero-posterior extent, three types of AC patterns were identified: 'prominent', 'present' and 'absent'. Hemispheric comparisons across the whole sample showed the PCS to be more commonly 'prominent' in the left hemisphere and more commonly 'absent' in the right hemisphere. There was a significant gender difference, such that males showed an asymmetric pattern characterized by increased fissurization of the left AC, while females showed greater symmetry, with less fissurization of the left AC. Overall cerebral morphology, namely hemispheric volume and hemispheric fissurization, were also measured and used as independent variables as well as covariates in the analyses in order to ascertain the specificity of the results regarding AC morphology. Results showed that cerebral volume for males was larger on the right than on the left while fissurization showed the reverse asymmetry of greater leftward fissurization. In contrast, females were symmetric in both respects. The findings regarding AC morphology could not be explained by differences in these overall cerebral measures or by differences in age and handedness within the population. The results suggest that in the normal male brain, there exist morphological asymmetries at both the global and local levels that are less apparent in the female brain. The findings have implications for future studies examining the organization, development and functional anatomy of the AC.

Adolescent↗
PubMed2001

Stability of olfactory identification deficits in neuroleptic-naive patients with first-episode psychosis.

OBJECTIVE: Olfactory identification deficits and their relationship to negative symptoms in patients with schizophrenia were examined in patients with recent-onset psychosis, the majority of whom were neuroleptic naive. METHOD: Seventy-four inpatients with a first episode of psychosis (27 with schizophrenia or schizophreniform disorder, nine with schizoaffective disorder, 17 with affective psychoses, and 21 with other psychoses), 49 of whom had not received antipsychotic medication, were compared to 38 age- and gender-matched normal subjects. Olfactory identification ability was assessed with the University of Pennsylvania Smell Identification Test. Forty patients and 13 comparison subjects were reassessed at 6 months to examine whether olfactory deficits were specific to schizophrenia or schizophreniform disorder and were stable over time. RESULTS: At baseline, the patients had significant impairment in olfactory identification ability compared to the normal subjects. This difference persisted after controlling for gender, premorbid or current IQ, smoking history, cannabis use, or the effects of medication. Diagnostic subgroups did not differ in olfactory identification ability. The deficits remained stable at 6-month follow-up and were associated with negative symptoms at both time points. No relationship was found between olfactory identification ability and length of either untreated psychosis or illness prodrome. CONCLUSIONS: Impairment in olfactory identification ability was apparent from the outset of psychotic illness and was not specific to schizophrenia or schizophreniform disorder. No change in the degree of this deficit was found after patients were stabilized and had responded to medication. The deficit could not be explained by peripheral factors that might contribute to olfactory identification ability, suggesting that it reflects central mechanisms.

Adolescent↗
PubMed2001

Spatial working memory deficits in schizophrenia: relationship with tardive dyskinesia and negative symptoms.

OBJECTIVE: This study examined the interrelationship between negative symptoms, orofacial tardive dyskinesia, and specific neurocognitive processes, particularly those involved in memory and executive function, in patients with schizophrenia. METHOD: A set of computerized neurocognitive tasks, the Cambridge Neuropsychological Test Automated Battery, was used to assess executive and memory function in 54 hospitalized patients with chronic schizophrenia. Analysis of covariance was used to examine differences between groups with or without the topographical syndromes of orofacial tardive dyskinesia and between groups with high or low negative symptom scores. Principal-components and path analyses were used to examine further the influence of negative symptoms and orofacial tardive dyskinesia on performance on tests of memory and executive function. RESULTS: Both orofacial tardive dyskinesia and negative symptoms were significantly and independently associated with deficits on measures of spatial working memory span derived from principal-components analysis, but only orofacial tardive dyskinesia was associated with deficits on measures of spatial working memory strategy. Both were also associated with impairment on the delayed-matching-to-sample task, a test of memory. These associations were not explained by deficits in global intellectual function. Path analysis suggested that the relationships between the clinical symptoms and performance on the delayed-matching-to-sample task were mediated entirely through their relationship with the spatial working memory measures. CONCLUSIONS: In schizophrenia, orofacial tardive dyskinesia and evident negative symptoms are relatively independent markers of compromise of the cerebral systems that mediate spatial working memory. Candidate neural circuits include the frontal-striatal-thalamic systems, particularly those involving the dorsolateral prefrontal cortex.

Adult↗