Growth hormone responses to pyridostigmine in schizophrenia: evidence for cholinergic dysfunction

The hypothesis that increased central cholinergic neurotransmitter function may be present in schizophrenic illness and may underlie negative symptoms was tested using a neuroendocrine challenge approach. The cholinergic challenge used was the anticholinesterase pyridostigmine, thought to cause the release of growth hormone (GH) from the anterior pituitary by diminishing inhibitory somatostatin tone. Eleven patients, six neuroleptic-naive and five neuroleptic-free, satisfying DSM-III-R criteria for schizophrenia and 11 matched controls took part. Subjects received pyridostigmine (120 mg orally) and blood was sampled at 0, 60, 90, 120, and 180 min for GH estimation. Peak GH responses were significantly increased in the schizophrenic group compared to controls. There was no relationship between individual peak GH values and negative symptom ratings (Scale for the Assessment of Negative Symptoms). Neither could a relationship be established between other aspects of psychopathology or dyskinesias and GH responses. An increased pyridostigmine/GH response is also found in affective disorders and could be related to nonspecific symptoms common to all these diagnostic groups. This study suggests that schizophrenia may be associated with increased cholinergic neurotransmitter function but the relationship between this cholinergic dysfunction and schizophrenia may involve psychopathology not specific to schizophrenia.