Endophenotyping with spectroscopy: Genetic modulation and treatment response

Coordinator:    Prof. Dr. Karl Mann                                                                               Prof. Dr. Jürgen Gallinat
Institution: ZI Mannheim                                                                                         Klinik für Psychiatrie und Psychotherapie Charité - Universitätsmedizin Berlin
Chronic intake of ethanol is associated with a compensatory up-regulation of glutamatergic neurotransmission. Several lines of evidence indicate a direct interaction of glutamate and dopamine systems for normal and addictive behavior.

The specific biological phenotype of altered glutamatergic response during acute alcohol withdrawal will be assessed in alcohol dependent patients recruited from

1) the Central Institute of Mental Health, Mannheim and

2) and the Department of Psychiatry, Charité University Medicine Berlin.

All patients will undergo an initial MR spectroscopic scan, and a second scan follows after 14 days of controlled abstinence (inpatient treatment). Healthy controls with little or no alcohol consumption (biomarkers within the normal range) will undergo MRS of which 20 will be scanned again after 14 days to determine the reliability of the endophenotype parameters.
It was demonstrated that during alcohol withdrawal, augmented glutamate levels can be suppressed by acamprosate treatment and that in parallel, various withdrawal signs are reduced by this treatment. Evidence has emerged, suggesting that individuals, who exhibit a “hyper-glutamatergic state”, will in fact respond to acamprosate treatment. It would thus be an important step towards an individualized treatment of alcohol dependent patients if MRS will proof to be a suitable tool to screen for a “hyper-glutamatergic endophenotype”.   

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