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The role of histamine dysfunction in sensory and cognitive deficits in schizophrenia

Final Report Summary - SCHIZOAMINE (The role of histamine dysfunction in sensory and cognitive deficits in schizophrenia)

The overall aims and objectives of this project are to investigate the role of the histaminergic neurotransmitter system in sensory and cognitive symptoms characterizing schizophrenia. An established role of histamine provides a new drug target for the symptoms of schizophrenia. The objective is to increase histaminergic activity using combined H1-agonist and H3-antagonist in healthy volunteers, and measure the consequent performance on sensory and cognitive tasks and associated brain activity. Betahistine is a drug that has been used over 40 years to treat Meniere’s disease and acts as a H3-antagonist/H1-agonist. Betahistine enters the central nervous system where it increases histamine neurotransmission, and where it may be able to enhance cognitive functioning. Betahistine’s effects on psychomotor performance have been assessed in several studies. However, these studies found no change in performance after oral doses ranging from 48 mg to three times 72 mg. These studies have measured the effects 2 hours after the last or only dose, while betahistine has been shown to have a very short Tmax (30 min)(Obecure, Clinical Study Report, 2010). Therefore, the effects may have been missed by these studies. For the present studies it was chosen to administer betahistine twice with doses separated by 30 minutes. In the present study it is hypothesised that betahistine increases histamine neurotransmission and performance on tasks depending on frontal lobe activity and on performance, which is typically impaired in schizophrenia. To test this hypothesis healthy volunteers were recruited to perform tasks of working memory and associative learning after betahistine or placebo, while their brain activity was measured using fMRI.

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