Kirsten B. Bojesen

​MD​​

​​PECANS II (Pan European Collaboration on Antipsych​otic Naïve Schizophrenia II) 

- Glutamatergic and GABAergic disturbances as markers of choice-of-treatment

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. 

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 the two connected areas ACC and thalamus 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 the antipsychotic compound aripiprazole. 

The Ph.D. project is part of PECANS II that is a collaborative study between Center for Neuropsychiatric Schizophrenia Research (CNSR), Copenhagen Universuty Hospital, Psychiatric Center Glostrup and Functional Imaging Unit (FIU), Glostrup Hospital​.

Inclusion is expected to start in January 2014 and last until December 2018.

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.

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