Psychopathological correlates of reduced dopamine receptor sensitivity in depression, schizophrenia, and opiate and alcohol dependence

Abstract

A dysfunction of central dopaminergic neurotransmission has been found in various neuropsychiatric diseases, and may be associated with a common psychopathological correlate. One hypothesis suggests that dopaminergic stimulation of the brain reward system reinforces behavior because it is experienced as pleasurable, and that dopaminergic dysfunction leads to anhedonia, the inability to experience pleasure. An alternative hypothesis assumes that dopaminergic stimulation does not promote pleasure or "liking" of a reward but rather mediates "wanting" of a reward, and suggests that dopaminergic dysfunction is associated with a failure to be motivated by stimuli that indicate reward. We measured negative symptoms, psychomotor slowing and dopamine receptor sensitivity in twelve drug-free patients with major depression, seventeen alcohol-dependent and sixteen opiate-dependent patients, ten schizophrenics with neuroleptic medication, and ten healthy controls. The sensitivity of central dopamine receptors was assessed with the growth hormone response to apomorphine application. Psychomotor slowing was measured in a reaction-time test and anhedonia and other negative symptoms were assessed with self-rating scales and the Scale for the Assessment of Negative Symptoms. Patients with major depression, alcohol dependence and neuroleptic medication displayed a reduced sensitivity of central dopamine receptors compared to control subjects. Anhedonia was not a common correlate of dopamine receptor dysfunction. Instead, affective flattening was associated with both dopamine receptor sensitivity and psychomotor slowing. Our findings thus do not support the anhedonia hypothesis of central dopaminergic dysfunction. Rather, affective flattening may result from the lack of an emotional response towards reward-indicating stimuli. These findings indicate that patients with dopaminergic dysfunction are not unable to experience pleasure, but may fail to be motivated by environmental stimuli to seek reward.