In postmortem studies of patients with schizophrenia, D2 dopamine receptors in the basal ganglia have been observed to be more numerous than in patients with no history of neurological or psychiatric disease. Because most patients with schizophrenia are treated with neuroleptic drugs that block D2 dopamine receptors in the caudate nucleus, it has been suggested that this increase in the number of receptors is a result of adaptation to these drugs rather than a biochemical abnormality intrinsic to schizophrenia. With positron emission tomography (PET), the D2 dopamine receptor density in the caudate nucleus of living human beings was measured in normal volunteers and in two groups of patients with schizophrenia--one group that had never been treated with neuroleptics and another group that had been treated with these drugs. D2 dopamine receptor densities in the caudate nucleus were higher in both groups of patients than in the normal volunteers. Thus, schizophrenia itself is associated with an increase in brain D2 dopamine receptor density.
These data suggest the use of compensatory mental and neural strategies by subjects with ADHD in response to a disrupted ability to inhibit attention to nonrelevant stimuli and the use of internalized speech to guide behavior.
The neurotransmitter acetylcholine has been implicated in animal and human studies of delirium. This chapter will briefly review the clinical studies focussing on measurement of serum levels of anticholinergic activity in delirious states. Three approaches have been taken. First, to identify medications currently prescribed that have subtle anticholinergic effects. The current ‘list’ includes 48 commonly prescribed medications. Second, to associate serum anticholinergic activity with delirium in various clinical states including postcardiotomy delirium, postelectroconvulsive delirium, delirious elderly medical inpatients, and nursing home patients. Third, to intervene in patients with elevated anticholinergic activity by reducing known anticholinergics and correlating this reduction with clinical measures of cognition and delirium. Our most recent data investigates the impact of anticholinergics on demented patients. Rates of delirium were significantly higher in patients receiving larger numbers of anticholinergics.
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