Anticholinergicity and cognitive processing in chronic schizophrenia

Patients with chronic schizophrenia suffer from alterations in cholinergic functioning due to several factors, including the disease diathesis and pharmacologic treatments. Acetylcholine-cognition relationships are well explored in normals but are unclear in schizophrenia. Prior work indicated serum anticholinergicity does not cause global cognitive impairment in this group (Tracy et al., 1998a), raising the possibility that anticholinergicity normalizes an abnormal hyperactive cholinergic state. Serum anticholinergic levels were determined in 38 chronic schizophrenia patients using an established radioreceptor assay method. Six cognitive functions associated with cholinergic tone in normals were tested. The potential role of autonomic arousal and cigarette smoking were also assessed as both have been linked to cholinergic functioning. Regression analyses showed measures of inhibitory executive control and effortful memory accounted for a greater proportion of the variance in the anticholinergicity measure compared to the other variables. The data demonstrate a relationship between high anticholinergicity and worse performance on two types of attention-resource demanding cognitive processes and do not support the notion that reduced cholinergic tone normalizes a hyperactive cortical acetylcholine substrate. Relevant neuroanatomic structures and implications for models of cognitive deficits in schizophrenia are discussed.