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Articles by P. McGuire
Total Records ( 4 ) for P. McGuire
  D. P Prata , A Mechelli , M. M Picchioni , C. H. Y Fu , T Toulopoulou , E Bramon , M Walshe , R. M Murray , D. A Collier and P. McGuire
 

Context  The dopamine transporter plays a key role in the regulation of central dopaminergic transmission, which modulates cognitive processing. Disrupted dopamine function and impaired executive processing are robust features of schizophrenia.

Objective  To examine the effect of a polymorphism in the dopamine transporter gene (the variable number of tandem repeats in the 3' untranslated region) on brain function during executive processing in healthy volunteers and patients with schizophrenia. We hypothesized that this variation would have a different effect on prefrontal and striatal activation in schizophrenia, reflecting altered dopamine function.

Design  Case-control study.

Setting  Psychiatric research center.

Participants  Eighty-five subjects, comprising 44 healthy volunteers (18 who were 9-repeat carriers and 26 who were 10-repeat homozygotes) and 41 patients with DSM-IV schizophrenia (18 who were 9-repeat carriers and 23 who were 10-repeat homozygotes).

Main Outcome Measures  Regional brain activation during word generation relative to repetition in an overt verbal fluency task measured by functional magnetic resonance imaging. Main effects of genotype and diagnosis on activation and their interaction were estimated with analysis of variance in SPM5.

Results  Irrespective of diagnosis, the 10-repeat allele was associated with greater activation than the 9-repeat allele in the left anterior insula and right caudate nucleus. Trends for the same effect in the right insula and for greater deactivation in the rostral anterior cingulate cortex were also detected. There were diagnosis x genotype interactions in the left middle frontal gyrus and left nucleus accumbens, where the 9-repeat allele was associated with greater activation than the 10-repeat allele in patients but not controls.

Conclusions  Insular, cingulate, and striatal function during an executive task is normally modulated by variation in the dopamine transporter gene. Its effect on activation in the dorsolateral prefrontal cortex and ventral striatum is altered in patients with schizophrenia. This may reflect altered dopamine function in these regions in schizophrenia.

  S Benetti , A Mechelli , M Picchioni , M Broome , S Williams and P. McGuire
 

Recent neuroimaging studies have reported deficits in functional integration between prefrontal cortex and the hippocampal formation in schizophrenia. It is unclear whether these alterations are a consequence of chronic illness or its treatment, and whether they are also evident in non-psychotic subjects at increased risk of the disorder. We addressed these issues by investigating prefrontal–hippocampal interactions in patients with first episode schizophrenia and subjects with an At Risk Mental State (ARMS). Using functional Magnetic Resonance Imaging, we measured brain responses from 16 individuals with an ARMS, 10 patients with first episode schizophrenia and 14 healthy controls during a delayed matching to sample task. Dynamic causal modelling was used to estimate the effective connectivity between prefrontal cortex and anterior and posterior hippocampal regions. The normal pattern of effective connectivity from the right posterior hippocampus to the right inferior frontal gyrus was significantly decreased in both first episode patients and subjects with an ARMS (ANOVA; F = 8.16, P = 0.01). Interactions between the inferior frontal gyrus and the anterior part of the hippocampus did not differ across the three groups. Perturbed hippocampal–prefrontal interactions are evident in individuals at high risk of developing psychosis and in patients who have just developed schizophrenia. This suggests that it may be a correlate of increased vulnerability to psychosis and that it is not attributable to an effect of chronic illness or its treatment.

  R Gafoor , D Nitsch , P McCrone , T. K. J Craig , P. A Garety , P Power and P. McGuire
 

Background

Early specialised care may improve short-term outcome in first-episode non-affective psychosis, but it is unclear if these benefits endure.

Aims

To assess the long-term effect of early intervention in psychosis.

Method

Individuals with first-episode psychosis were randomised to specialised care or care as usual (trial number: ISRCTN73679874). Outcome after 5 years was assessed by case-note review.

Results

There were no significant differences in the admission rate (coefficient 0.096, 95% CI –0.550 to 0.742, P = 0.770) or the mean number of bed days (coefficient 6.344, 95% CI –46 to 58.7, P = 0.810).

Conclusions

These findings that specialist intervention did not markedly improved outcome at 5 years accord with those from a larger OPUS study. The sample size of this study was small and these results should be generalised with caution. More research is needed.

 
 
 
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