Effects of anticholinergic challenge on psychopathology and cognition in drug-free patients with schizophrenia and healthy volunteers

Several aspects of the neurobiology of schizophrenia, especially the background of the negative symptoms and cognitive deficits, are still insufficiently understood. Tandon and Greden (1989) postulated a central role of dopaminergic/cholinergic imbalance in pathophysiology of schizophrenia. The purpose of our study was to investigate the effects of an anticholinergic challenge (performed by application of biperiden, a central selective M1-muscarinic receptor antagonist) on psychopathology, cognition and attention in 12 unmedicated patients with schizophrenia and 12 healthy controls. The anticholinergic challenge resulted in a considerable increase in PANSS scores and in cognitive impairments, which were significantly more pronounced in patients than in healthy volunteers. Thereby, the PANSS total score increase showed a significant negative correlation with age in patients but not in controls. These results could be a hint to increased dopaminergic transmission after anticholinergic challenge. The age-related diminished reaction in patients could be a consequence of the age-dependent decline of steady state dopamine storage capacity. The neurocognitive impairments caused by a selective M1 receptor antagonismus are in concordance with the previously reported negative impact of anticholinergics on cognition. The more pronounced impairments in patients compared to the controls speak on behalf the initially assumption of dopaminergic/cholinergic imbalance in schizophrenia. This study was supported by DFG