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Biomedical subjects

Patrick D McGorry

Publications and source records attributed to Patrick D McGorry.

At least 73 records · Page 4Linked to original sources
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↗
PubMed2003

Incipient neurovulnerability and neuroprotection in early psychosis.

The objective of this study was to review the implications of altered regulatory mechanisms of progenitor cell generation and death for neurodevelopment and adult brain functioning in early intervention in schizophrenia and related disorders. MEDLINE databases were searched from 1966 to 2002 using the following key words: stem cells, progenitor cells, glia, neurogenesis, apoptosis, and combined with brain and schizophrenia. Necropsy evidence suggests alterations in synaptic connectivity and a reduction in glial cell numbers with no substantial signs of neuronal cell loss or necrotic neurodegeneration (gliosis). Neuroimaging data propose dynamic structural changes with some evidence of volume loss of the hippocampus during the transition to psychosis. Central and peripheral tissues of patients with schizophrenia give indirect evidence of reduced neurotrophic and anti-apoptotic factors relevant for generation, and atrophic degeneration of cells of glial and, in some brain areas, even neuronal origin. In vivo brain magnetic resonance spectroscopy data in schizophrenia support the loss of neuropil (reduction in n-acetylaspartate) and increased membrane turnover (decrease in phosphomonoesters [PMEs], increase in phosphodiesterases [PDEs]) at the onset of illness, which potentially corresponds with increased apoptotic activity of progenitor cells. In conclusion, dysfunctional regulation of generation and degeneration of progenitor cells of glial and, in some brain areas, neuronal origin may potentially explain early and late neurodevelopmental abnormalities in early psychosis. A reduced genesis or an increased death of glial cells in the grey matter may provide the cellular substrate for synaptic and dendritic changes resulting in local atrophy and disconnectivity. Neuroprotective strategies counteracting the loss or supporting the generation of progenitor cells may therefore be a potent therapeutic avenue to explore.

Animals↗
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

Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms.

BACKGROUND: Most disability produced by psychotic illnesses, especially schizophrenia, develops during the prepsychotic period, creating a case for intervention during this period. However, only recently has it been possible to engage people in treatment during this phase. METHODS: A randomized controlled trial compared 2 interventions in 59 patients at incipient risk of progression to first-episode psychosis. We termed this group ultra-high risk to emphasize the enhanced risk vs conventional genetic high-risk studies. Needs-based intervention was compared with specific preventive intervention comprising low-dose risperidone therapy (mean dosage, 1.3 mg/d) and cognitive behavior therapy. Treatment was provided for 6 months, after which all patients were offered ongoing needs-based intervention. Assessments were performed at baseline, 6 months, and 12 months. RESULTS: By the end of treatment, 10 of 28 people who received needs-based intervention progressed to first-episode psychosis vs 3 of 31 from the specific preventive intervention group (P=.03). After 6-month follow-up, another 3 people in the specific preventive intervention group became psychotic, and with intention-to-treat analysis, the difference was no longer significant (P=.24). However, for risperidone therapy-adherent patients in the specific preventive intervention group, protection against progression extended for 6 months after cessation of risperidone use. CONCLUSIONS: More specific pharmacotherapy and psychotherapy reduces the risk of early transition to psychosis in young people at ultra-high risk, although their relative contributions could not be determined. This represents at least delay in onset (prevalence reduction), and possibly some reduction in incidence.

Adolescent↗
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

First-episode mania: a neglected priority for early intervention.

OBJECTIVE: While first-episode (FE) psychosis has become an important field of research, FE affective psychoses, and mania in particular, have been relatively neglected. This paper summarizes current knowledge about FE mania and explores the potential for early intervention. METHOD: The main computerized psychiatric literature databases were accessed. RESULTS: When functional as well as symptomatic variables are considered, the outcome of mania is not as good as was formerly believed, a characteristic which is already present from the first episode. Various factors (lower socio-economic status, younger age at onset of illness, poor adherence to treatment, presence of comorbidity) have been identified as possible predictors of poor outcome. The prognostic value of the presence of psychotic symptoms and their congruence to mood, as well as the diagnostic subgroup, is less well established. This literature review also reveals striking similarities between manic and schizophreniform first episodes. Poor functional outcome in a significant proportion of patients following the first episode, high risk of suicide, high prevalence of comorbid diagnoses, worse outcome with a younger age at onset and with longer delay until treatment is initiated, and finally early presence of neuro-anatomical changes, are observed in both syndromes. CONCLUSIONS: This pattern justifies the development of early intervention strategies for FE manic patients and supports more exploratory research to identify prodromal symptoms, which might ultimately lead to even earlier focus on preventive interventions.

Adolescent↗
PubMed2002

Cannabis use is not associated with the development of psychosis in an 'ultra' high-risk group.

BACKGROUND: The association between cannabis use and the development of a first psychotic episode was studied in a group of 100 young people identified as being at very high risk for the onset of psychosis. METHOD: The 'ultra' high risk cohort was identified by the presence of subthreshold psychotic symptoms, or a combination of first-degree relative with a psychotic disorder and recent functional decline. Thirty-two per cent of the cohort developed an acute psychotic episode over the 12-month period after recruitment. As a component of a larger research study, the level of cannabis use by participants in the year prior to enrollment in the study was assessed at intake. RESULTS: Cannabis use or dependence in the year prior to recruitment to this study was not associated with a heightened risk of developing psychosis over the following 12-month period and therefore did not appear to contribute to the onset of a psychotic disorder. CONCLUSION: The results of this study suggest that cannabis use may not play an integral role in the development of psychosis in a high-risk group. While this study does not support a role for cannabis in the development of first-episode psychosis, we cannot conclude that cannabis use should be completely ignored as a candidate risk factor for onset of psychosis. A number of weaknesses of the study (the low level of cannabis use in the current sample, the lack of monitoring of cannabis use after intake) suggest that it may be premature to dismiss cannabis use as a risk factor for the development of psychosis and further research is urged in this area.

Adolescent↗
PubMed2002

The PACE Clinic: identification and management of young people at "ultra" high risk of psychosis.

Over the past decade, both clinical and research interest in the early stages of psychotic disorders has grown. This has been associated with research suggesting that early intervention in these disorders may limit their impact on the life of the affected individual and his or her family. It has also been recognized that the biological and psychological changes underpinning the development of psychotic disorders may already be active in the prepsychotic or prodromal phase. It has been suggested that efforts to prevent psychotic disorders should be focused on this phase of emerging illness. In this article, the authors review work conducted at the PACE Clinic in Melbourne, Australia since 1994. This clinical research program was established to develop strategies for identifying young people at high risk for developing a psychotic disorder within a short period. The program has also investigated biological and psychological processes thought to underlie the development of psychosis and evaluated potential preventive interventions.

Journal Article↗
PubMedDate not supplied

Early intervention in psychosis: a new evidence based paradigm.

OBJECTIVE: Even in countries whose mental health services are comparatively well resourced, the care offered to those in the early stages of psychotic illnesses is not what it could be. Patients often have to progress to chronicity before receiving adequate interventions, by which stage there has been great potential for harm, not only through the psychosis, but also to the quality of life of the individual who has often missed or not completed adequately, several important developmental tasks. Further, evidence indicates that delay in treatment is positively associated with poorer outcome. This paper puts the case for early intervention in psychosis. METHOD: Based on the experience of the Early Psychosis Prevention and Intervention Centre in Melbourne, the paper reviews the evidence for and the criticisms of, early intervention. Using the concept of indicated prevention, it suggests ways in which clinicians can improve the interventions available to those experiencing the onset of psychosis and suggests that pre-psychotic intervention may be possible. RESULTS: Evidence discussed in this paper indicates that the development of mental illness is a major health issue in young people; that there is a positive correlation between duration of untreated psychosis and outcome; that it is possible to identify a proportion of those at high risk of developing mental illness; that through intervention it may be possible to reduce the transition rate to illness. CONCLUSION: Primary prevention is beyond the capacity of our present knowledge. Indicated prevention in the form of early intervention and optimal, sustained treatment is a paradigm for which there is increasing supportive evidence. It is a paradigm which is appealing to clinicians, patients, families and which has the potential to reduce the secondary impact of serious mental illness such as suicide, stigma, isolation and reduction in social status.

Evidence-Based Medicine↗