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Christos Pantelis

Publications and source records attributed to Christos Pantelis.

54 records · Page 3Linked to original sources
PubMed2003

Moyamoya disease in a patient with schizophrenia.

We present the case of a 23-year-old Vietnamese male with a 2-year history of a psychotic illness marked by prominent negative symptoms, fatuousness and disturbed behavior. Neuroimaging revealed a prominent vascular flow void affecting the middle and anterior cerebral arteries, with associated increased collateral supply to the frontal cortex, consistent with Moyamoya disease. Neurological examination was unremarkable; however, neuropsychological assessment revealed significant executive dysfunction, including stimulus-driven behavior. Whilst the diagnosis of schizophrenia and Moyamoya disease may be coincidental, an interaction between the 2 diseases may have led to some of the atypical features of this case, including prominent executive dysfunction and marked sensitivity to psychotropic medication. We discuss the nature of possible interactions between the 2 conditions. This case also highlights the importance of re-evaluating patients with atypical or treatment-resistant psychoses for cerebral pathology.

Adult↗
PubMed2003

Early and late neurodevelopmental disturbances in schizophrenia and their functional consequences.

OBJECTIVE: The evidence from structural imaging studies supports the notion that schizophrenia arises from an early abnormality in brain development. In this paper we review the timing of structural changes in schizophrenia and argue that schizophrenia is a neuro-developmental disorder with limited progressive brain changes occurring during the evolution and early phase of psychosis. METHOD: The available cross-sectional and longitudinal studies are reviewed, along with data from our own research. RESULTS: The current literature, including our own data, suggests that structural brain changes are apparent premorbidly, consistent with a neurodevelopmental lesion. These are prominent in frontal and cingulate regions, and appear related to premorbid neuropsychological deficits in executive function. However, there appear to be additional brain changes over the transition to illness and beyond. CONCLUSIONS: We propose first, that an early neurodevelopmental insult interacts with either normal or abnormal postpubertal brain maturation to produce further (late neurodevelopmental) brain structural and functional changes; and second, that the effect of such neurodevelopmental lesions will have different consequences for functions that normally develop early in life, such as memory, compared with functions developing later, such as executive functions. A model is presented suggesting that the structural and functional abnormalities in schizophrenia can be understood as a consequence of the neurodevelopmental stage at which brain changes occur.

Brain↗
PubMed2003

Normative data from the CANTAB. I: development of executive function over the lifespan.

The study of executive function within a developmental framework has proven integral to the advancement of knowledge concerning the acquisition and decline of higher skill processes. Still in its early stages, there exists a discontinuity in the literature between the exploration of executive capacity in young children and the elderly. Research of age-related differences utilising a lifespan approach has been restricted by the lack of assessment tools for the measurement of executive skills that are applicable across all age levels. This paper addresses these issues using the computer-based Cambridge Neuropsychological Test Automated Battery (CANTAB) to identify periods of development in executive capacities using a normative sample of 194 participants ranging in age from 8 to 64 years. Findings of executive function in children as young as 8 years of age were extended, with functional gains found in the efficiency of working memory capacity, planning and problem-solving abilities, between the ages of 15 and 19 years and again at 20-29 years of age. Cognitive flexibility was assessed at adult-levels in even the youngest children. Declines in performance on all tasks were revealed for the 50-64 year old sample, providing support for the vulnerability of executive skills to normal aging.

Adolescent↗
PubMed2003

A review and new report of medial temporal lobe dysfunction as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric family study of the parahippocampal gyrus.

A central question in schizophrenia research is which brain abnormalities are independent of psychosis and which evolve before and after psychosis begins. This question can be addressed by longitudinal neuroimaging studies beginning in the prodrome, but at present there is only one published study. We reviewed the literature on structural brain imaging in persons with chronic and first episode schizophrenia, nonpsychotic persons at genetic high risk, and persons thought to be at risk for imminent psychosis ("prodromal" persons). Medial temporal lobe (MTL), especially hippocampal, volume alterations are among the most robust brain vulnerabilities for schizophrenia. Because verbal declarative memory (VDM) deficits are prominent and the parahippocampal gyrus (PHG) is considered to be centrally involved with the hippocampus in VDM processing, we analyzed PHG data from a family study of schizophrenia. Patients with schizophrenia and nonpsychotic relatives from "multiplex" families (families with multiple persons with schizophrenia) had significantly smaller right parahippocampal anterior (PHa) volumes than controls. Marginally significant findings were observed for the left PHa. Unexpectedly, relatives from "simplex" families (families with only one person with schizophrenia) had significantly larger PH posterior volumes than controls and did not differ from controls on PHa. Results provide some support for the hypothesis that the vulnerability to schizophrenia includes abnormal volumes of the PHG. These data provide additional support for the hypothesis that some MTL abnormalities in schizophrenia are independent of psychosis, at least in families with presumably high genetic loading. Implications of genetic risk studies for prodromal research are discussed.

Adult↗
PubMed2003

Proton magnetic resonance spectroscopy in first episode psychosis and ultra high-risk individuals.

The underlying neurobiology of emerging psychotic disorders is not well understood. Recent neuroimaging findings have suggested that some brain areas are affected prior to the onset of psychosis, while changes occur in other brain regions during the transition to illness. Further, previous research using magnetic resonance spectroscopy (MRS) has generally demonstrated that there are changes to the brain chemistry of patients with schizophrenia. However, it is unclear whether these changes are present prior to or at the onset of the disorder, and to what extent they are specific to schizophrenia. In this study, we assessed the left medial temporal and left dorsolateral prefrontal regions of 56 patients in their first episode of a psychotic disorder, 30 young people at ultra high-risk (UHR) of developing psychosis, and 21 healthy controls, using proton MRS. Six of the UHR group developed a first episode psychosis over the study period. No differences were identified between the first episode and control groups for any metabolite ratio in either region of interest. This may reflect intact neuronal circuits in the early phase of psychotic disorders. There were also no differences between the UHR and control groups for the medial temporal region. However, there was a significant elevation of the NAA/Creatine and the Choline/Creatine ratios in the dorsolateral prefrontal region of the UHR group, which was interpreted as a decline in creatine indicative of hypometabolism. This finding did not discriminate between those UHR individuals who later became psychotic and those who did not.

Adolescent↗
PubMed2003

Impairment of olfactory identification ability in individuals at ultra-high risk for psychosis who later develop schizophrenia.

OBJECTIVE: Previous investigation has revealed stable olfactory identification deficits in neuroleptic-naive patients experiencing a first episode of psychosis, but it is unknown if these deficits predate illness onset. METHOD: The olfactory identification ability of 81 patients at ultra-high risk for psychosis was examined in relation to that of 31 healthy comparison subjects. Twenty-two of the ultra-high-risk patients (27.2%) later became psychotic, and 12 of these were diagnosed with a schizophrenia spectrum disorder. RESULTS: There was a significant impairment in olfactory identification ability in the ultra-high-risk group that later developed a schizophrenia spectrum disorder but not in any other group. CONCLUSIONS: These findings suggest that impairment of olfactory identification is a premorbid marker of transition to schizophrenia, but it is not predictive of psychotic illness more generally.

Adolescent↗
PubMed2003

Morphology of the anterior cingulate cortex in young men at ultra-high risk of developing a psychotic illness.

BACKGROUND: The anterior cingulate cortex (ACC) is consistently implicated in the pathophysiology of schizophrenia, and our own work has identified morphological anomalies in the ACC of people with this disorder. AIMS: To examine whether ACC morphological anomalies are present in a group at ultra-high risk of psychosis and whether such anomalies can be used to predict the subsequent development of a psychotic illness. METHOD: Magnetic resonance imaging of 75 healthy volunteers and 63 people at ultra-high risk of developing a psychotic disorder (all right-handed males) was used to examine ACC sulcal and gyral features. RESULTS: Compared with the controls, significantly fewer people in the ultra-high risk group had a well-developed left paracingulate sulcus and significantly more had an interrupted left cingulate sulcus. There was no difference between those who did (n=21) and did not (n=42) subsequently develop a psychotic illness. CONCLUSIONS: Although ACC anomalies are present in young people considered to be at ultra-high risk of psychosis, they do not identify individuals who subsequently make the transition to psychosis.

Adult↗
PubMed2002

Prediction and prevention of transition to psychosis in young people at incipient risk for schizophrenia.

The treatment of psychotic disorders, particularly schizophrenia, had been viewed with pessimism until a recent shift in focus from established or chronic illness to earlier phases of illness around the onset highlighted opportunities for enhanced recovery. Associated with this change in focus of research and clinical efforts has been the recognition that the biological and social changes underpinning the development of psychotic disorders may already be active in the pre-psychotic or prodromal phase. It has therefore been suggested that efforts toward the prevention of psychotic disorders should focus on the emerging illness. This article provides a review of work that has been conducted at the PACE Clinic in Melbourne, Australia since 1994. This clinical research program was established to develop strategies for the identification of young people at high risk of developing a psychotic disorder within a short period of time- primarily by virtue of recent mental state changes. Additionally, biological and psychological processes that have been proposed to underlie the development of illness have been investigated and potential preventive interventions have been evaluated.

Adolescent↗
PubMed2002

Non-reduction in hippocampal volume is associated with higher risk of psychosis.

Previous research using MRI scans has shown reduced hippocampal volumes in chronic schizophrenia and first-episode psychosis compared to well subjects. There are few MRI volumetric studies of high-risk cohorts and no studies that have compared structural measures between high-risk subjects who later developed a psychotic illness and those who did not. Therefore, the question of whether structural changes to the hippocampi precede the onset of an acute psychotic episode has not been answered. Hippocampal and whole brain volumes of 60 people at ultra high-risk (UHR) of developing a psychotic episode (identified through state and trait criteria) were obtained through MRI scan and compared with subjects with first episode psychosis (FEP: n=32), and no mental illness (n=139). Thirty-three percent (n=20) of the UHR cohort developed a psychotic disorder during the 12-month period following the MRI scan. The UHR group as a whole, like the FEP group, had significantly smaller left and right hippocampal volumes than the normal comparison group. Contrary to our initial hypothesis, the left hippocampal volume of the UHR subjects who developed a psychotic disorder was larger than the UHR-non-psychotic subgroup and the FEP group, but no differences were found between the UHR-psychotic and normal groups. The right hippocampus of the UHR-non-psychotic group was significantly smaller than the Normal group but not different to the FEP group. Furthermore, a larger left hippocampal volume of the UHR cohort at intake was associated with the subsequent development of acute psychosis rather than smaller volumes. These results contradicted the expected outcomes, which had been influenced by the neurodevelopmental model of the development of psychosis and an earlier study comparing hippocampal volumes of first episode, chronic schizophrenia and normal populations. One implication of these results is that a process of dynamic central nervous system change may occur during the onset phase of schizophrenia and related disorders, rather than earlier in life as suggested by the neurodevelopmental model. Alternatively, selection factors associated with the UHR cohort may have created a bias in the results. Replication of these results is required in other high-risk cohorts.

Acute Disease↗
PubMed2002

Increased duration of illness is associated with reduced volume in right medial temporal/anterior cingulate grey matter in patients with chronic schizophrenia.

It is unclear whether the neuroanatomical abnormalities associated with schizophrenia change over the course of the disorder. We addressed this issue by examining whether the magnitude of structural brain abnormalities in patients with chronic schizophrenia was related to their duration of illness. Thirty-nine subjects with schizophrenia (34 male, 5 female, range of illness duration 2-31 years) were scanned using magnetic resonance imaging. Images were segmented into grey and white matter, cerebrospinal fluid and dura/blood vessels using the Structural Magnetic Resonance Toolkit (SMaRT). Voxel-based analysis identified brain areas whose volume varied significantly with time since the first onset of psychosis. Right medial temporal, medial cerebellar and bilateral anterior cingulate grey matter volume, and white matter volume in the right posterior limb of the internal capsule, were all negatively correlated with illness duration (p < 0.002). Conversely, illness duration was positively correlated with the volume of the right globus pallidus (p < 0.002). These correlations were not a function of chronological age or age at illness onset. The inverse correlation between right frontal, temporal and cerebellar volumes and the time since the onset of schizophrenia could reflect progressive tissue loss following the first episode of the disorder.

Adult↗
PubMed2002

Paracingulate morphologic differences in males with established schizophrenia: a magnetic resonance imaging morphometric study.

BACKGROUND: Our previous work on sulcal-gyral brain morphology in healthy volunteers revealed that males were characterized by greater cortical folding in the left versus right anterior cingulate cortex. Given the evidence showing an absence or reversal of normal anatomical asymmetries in patients with schizophrenia, the current study examined the anterior cingulate cortex sulcal-gyral patterns in patients with schizophrenia. METHODS: Using high-resolution magnetic resonance imaging, we examined anterior cingulate cortex surface morphology in a group of 55 patients with established schizophrenia and 75 healthy controls. All subjects were male and right-handed. Depending on the presence of a paracingulate sulcus and its antero-posterior extent, three types of anterior cingulate cortex sulcal patterns were identified: "prominent," "present," and "absent." Measures of overall cerebral hemispheric folding were used as independent variables and as covariates to ascertain the specificity of the findings to the anterior cingulate cortex. RESULTS: Examination of anterior cingulate cortex morphology showed that, compared with controls, patients with schizophrenia lacked the leftward anterior cingulate cortex sulcal asymmetry, which was explained by reduced folding in the left anterior cingulate cortex. These differences were over and above differences in cortical folding across the entire left hemisphere. CONCLUSIONS: These findings suggest that, in male patients with schizophrenia, there is a disturbance in the neurodevelopment of the left anterior cingulate cortex, as well as a more general aberration of left hemisphere development.

Adult↗
PubMed2002

The cognitive neuropsychiatric approach to investigating the neurobiology of schizophrenia and other disorders.

In this paper, we examine a cognitive neuropsychiatric approach to understanding neuropsychiatric disorders by examining recent data in schizophrenia. By understanding and applying this approach, we suggest that the processes underlying the neurobiology of a range of other psychiatric disorders can be understood. Further, an assessment of the brain-behaviour relationships through this emerging discipline provides testable models for further study, using a range of techniques including functional and other imaging techniques.

Cognition Disorders↗
PubMed2002

Implications of lipid biology for the pathogenesis of schizophrenia.

OBJECTIVE: Preclinical and clinical data suggest that lipid biology is integral to brain development and neurodegeneration. Both aspects are proposed as being important in the pathogenesis of schizophrenia. The purpose of this paper is to examine the implications of lipid biology, in particular the role of essential fatty acids (EFA), for schizophrenia. METHODS: Medline databases were searched from 1966 to 2001 followed by the cross-checking of references. RESULTS: Most studies investigating lipids in schizophrenia described reduced EFA, altered glycerophospholipids and an increased activity of a calcium-independent phospholipase A2 in blood cells and in post-mortem brain tissue. Additionally, in vivo brain phosphorus-31 Magnetic Resonance Spectroscopy (31P-MRS) demonstrated lower phosphomonoesters (implying reduced membrane precursors) in first- and multi-episode patients. In contrast, phosphodiesters were elevated mainly in first-episode patients (implying increased membrane breakdown products), whereas inconclusive results were found in chronic patients. EFA supplementation trials in chronic patient populations with residual symptoms have demonstrated conflicting results. More consistent results were observed in the early and symptomatic stages of illness, especially if EFA with a high proportion of eicosapentaenoic acid was used. CONCLUSION: Peripheral blood cell, brain necropsy and 31P-MRS analysis reveal a disturbed lipid biology, suggesting generalized membrane alterations in schizophrenia. 31P-MRS data suggest increased membrane turnover at illness onset and persisting membrane abnormalities in established schizophrenia. Cellular processes regulating membrane lipid metabolism are potential new targets for antipsychotic drugs and might explain the mechanism of action of treatments such as eicosapentaenoic acid.

Fatty Acids, Essential↗
PubMed2002

Thalamic and caudate volumes in monozygotic twins discordantfor schizophrenia.

OBJECTIVE: The thalamus and caudate nucleus are key subcortical structures in the fronto-striato-thalamic pathways that have been implicated in the pathogenesis of schizophrenia. Previous studies have been inconsistent in identifying structural and functional abnormalities in these structures. However, methodologies in these studies have been unreliable and some have not adequately matched patients and controls. METHODS: Using algebraically-manipulated double-echomagnetic resonance (MR) images, we developed a reliable method to estimate caudate and thalamic volumes in a group of 13 monozygotic(MZ) twins; eight discordant for schizophrenia and five normal.Initially, volumes were measured on four image types: proton density(PD), T2-weighted, summed (PD + T2) and subtracted (PD-T2) to determine the most reliable method. RESULTS: There was a significant method by region interaction, where caudate volumes measured on PD images were significantly larger than those measured on T2-weighted images, while the opposite was found for thalamic volumes. However, there was no interaction of method by diagnosis. Test-retest reliability was highest for the summed images. Using summed images to measure the volumes of the caudate and thalamus in each twin, we found significantly increased caudate volumes in affected twins compared to their unaffected cotwins,but no significant difference in thalamic volume. CONCLUSIONS: Our results in a small sample of MZ twins discordant for schizophrenia do not support the presence of structural abnormalities in the thalamus. The findings in the caudate are consistent with previously reported effects of antipsychotic medication. We also report a reliable method for assessing the volumes of subcortical structures. However, volumetric estimates of brain structures may be dependent on which method is used and the structure being assessed. Such interactions need to be considered in future studies investigating brain structural abnormalities in schizophrenia and other disorders.

Adult↗
PubMed2002

Anterior cingulate activation during Stroop task performance: a PET to MRI coregistration study of individual patients with schizophrenia.

OBJECTIVE: The authors used single-subject functional imaging analyses to 1) corroborate the findings of anterior cingulate hypoperfusion during an attentional task in schizophrenia and 2) examine whether anterior cingulate activation is associated with underlying morphology. METHOD: Five healthy subjects and six patients with schizophrenia underwent positron emission tomography scanning while they performed the Stroop task. The medial-frontal lobes were masked out for analysis, and activation peaks were individually coregistered to each subject's magnetic resonance imaging scan. RESULTS: Healthy subjects showed activations in both limbic and paralimbic anterior cingulate regions. Patients with schizophrenia showed only paralimbic activations, and these were apparent only in patients having a paracingulate sulcus. CONCLUSIONS: These findings suggest that 1) patients with schizophrenia have limbic-anterior cingulate hypoperfusion during attentional tasks and 2) paralimbic activation is associated with underlying morphology.

Adult↗