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ABSTRACT: Many patients with schizophrenia show a limited symptomatic response to treatment with dopaminergic antipsychotics. This may reflect the additional involvement of non-dopaminergic neurochemical dysfunction in the pathophysiology of the disorder. We tested the hypothesis that brain glutamate levels would differ between patients with first-episode psychosis who were symptomatic compared with those with minimal symptoms following antipsychotic treatment. Proton magnetic resonance spectroscopy (1H-MRS) spectra were acquired at 3 Tesla in the anterior cingulate cortex and left thalamus in 15 patients with first-episode psychosis in symptomatic remission, and 17 patients with first-episode psychosis who were still symptomatic following at least one course of antipsychotic treatment. Metabolite levels were estimated in ratio to creatine (Cr) using LCModel. Levels of glutamate/Cr in the anterior cingulate cortex were significantly higher in patients who were still symptomatic than in those in remission (T(30)=3.02; P=0.005). Across the entire sample, higher levels of glutamate/Cr in the anterior cingulate cortex were associated with a greater severity of negative symptoms (r=0.42; P=0.017) and a lower level of global functioning (r=-0.47; P=0.007). These findings suggest that clinical status following antipsychotic treatment in schizophrenia is linked to glutamate dysfunction. Treatment with compounds acting on the glutamatergic system might therefore be beneficial in patients who respond poorly to dopaminergic antipsychotics.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 07/2012; 37(11):2515-21. · 6.99 Impact Factor
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Isabel Valli,
James Stone,
Andrea Mechelli,
Sagnik Bhattacharyya, Marie Raffin,
Paul Allen,
Paolo Fusar-Poli,
David Lythgoe,
Ruth O'Gorman,
Marc Seal,
Philip McGuire
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ABSTRACT: Both medial temporal cortical dysfunction and perturbed glutamatergic neurotransmission are regarded as fundamental pathophysiological features of psychosis. However, although animal models of psychosis suggest that these two abnormalities are interrelated, their relationship in humans has yet to be investigated.
We used a combination of functional magnetic resonance imaging and magnetic resonance spectroscopy to investigate the relationship between medial temporal activation during an episodic memory task and local glutamate levels in 22 individuals with an at-risk mental state for psychosis and 14 healthy volunteers.
We observed a significant between-group difference in the coupling of medial temporal activation with local glutamate levels. In control subjects, medial temporal activation during episodic encoding was positively associated with medial temporal glutamate. However, in the clinical population, medial temporal activation was reduced, and the relationship with glutamate was absent.
In individuals at high risk of psychosis, medial temporal dysfunction seemed related to a loss of the normal relationship with local glutamate levels. This study provides the first evidence that links medial temporal dysfunction with the central glutamate system in humans and is consistent with evidence that drugs that modulate glutamatergic transmission might be useful in the treatment of psychosis.
Biological psychiatry 10/2010; 69(1):97-9. · 8.93 Impact Factor
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ABSTRACT: Schizophrenia is a severe mental illness affecting approximately 1% of the population worldwide. Antipsychotic drugs are effective in symptom control in up to two-thirds of patients, but in at least one-third of patients the response is poor. The reason for this is not clear, but one possibility is that good and poor responders have different neurochemical pathologies, and may therefore benefit from different treatment approaches. In this selective review we summarise research findings investigating the biological differences between patients with schizophrenia who show a good or a poor response to treatment with antipsychotic drugs.
Journal of Psychopharmacology 11/2009; 24(7):953-64. · 3.04 Impact Factor
