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Region Hovedstaden - en del af Københavns Universitetshospital

Pan European Collaboration on Antipsychotic Naïve Schizophrenia II (PECANS II)/Improving treatment of patients with schizophrenia – glutamatergic disturbances as a possible marker of choice-of-treatment

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Summary
Insufficient response to antipsychotic drugs constitutes one of the major challenges in the treatment of patients suffering from schizophrenia and therefore other targets than the dopamine D2 receptor are highly warranted. Glutamate constitutes the main excitatory neurotransmitter in the brain and growing evidence supports that glutamatergic disturbances substantially contribute to the pathophysiology of schizophrenia. However, the relation between disturbances in glutamatergic turnover and specific clinical symptoms is largely unknown, and as a result the efforts to relieve symptoms of schizophrenia by agents modulating glutamate neurotransmission have not yet been successful.
Aripiprazole is a first-line antipsychotic drug, and the only drug, which is a partial dopamin D2 receptor agonist. Interestingly, it has been shown to reduce glutamate release in the rat prefrontal cortex.
In humans, proton magnetic resonance spectroscopy (1H-MRS) can be used to assess glutamate levels. The few existing 1H-MRS studies of patients with schizophrenia suggest increased levels of glutamate and increased glutamate turnover in the anterior cingulate cortex (ACC) of antipsychotic-naïve and minimally treated young patients with schizophrenia. Moreover, glutamatergic dysfunction in ACC has also been associated with insufficient response to antipsychotic treatment.
The objective of this study is to investigate the glutamatergic turnover in a cortical and subcortical region in a large cohort of initially antipsychotic-naïve first-episode patients with schizophrenia and matched healthy controls. The glutamatergic turnover will be related to clinical symptoms and level of functioning before and after 6 weeks of treatment with aripiprazole.
Results from this study will add important pathophysiological insights into the implications of glutamatergic disturbances before antipsychotic treatment is initiated. The monotherapeutic design with aripiprazole will provide pivotal new insights into the interaction between glutamatergic disturbances, clinical symptoms and level of functioning. Thus, the present study constitutes a pertinent step towards improving the treatment options for patients suffering from schizophrenia.
StatusAfsluttet
Periode01/09/201331/12/2018
FinansieringskildeIntern støtte (Offentlig)
ForskningsprogramGraduate School of Health and Medicial Sciences
Beløb1.500.000,00 Danske Kroner
Årstal2013

    Forskningsområder

  • Sundhedsvidenskab - Schizophrenia Spectrum and Other Psychotic Disorders, Neuroimaging

ID: 41328512