OADES, R. D.,
RAO, M. L., BENDER, S., SARTORY, G., & MÜLLER, B.
(2000). Neuropsychological and conditioned blocking performance in
patients with schizophrenia: assessment of the contribution of neuroleptic
dose, serum levels and dopamine D2-receptor occupancy. Behavioural
Pharmacology, 11, 317-330.
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Introduction:
Patients with schizophrenia are widely reported to show impairments
of attention and neuropsychological performance, but the extent to which
this is attributable to medication and dopamine (DA) function remains
largely unexplored.
Methods:
We describe here the putative influence of 1) the dose of antipsychotic
medication (chlorpromazine equivalents, CPZ), 2) the antipsychotic serum
concentration (neuroleptic units in terms of butyrophenone displacement
from animal neostriatum) and 3) the approximated DA D2-receptor occupancy
in the brain (based on regression curves from 11 studies published for
5 neuroleptics) - - on conditioned blocking (CB) measures of attention
and performance on a neuropsycholog-ical battery. We studied 108 patients
with schizophrenia with 62 healthy controls.
Results:
1) Antipsychotic serum concentration and
D2-occupancy were higher in patients with a paranoid vs. non-paranoid
diagnosis, and in female vs. male patients (independent of symptom severity).
2) Controlling for D2-occupancy removed
the difference between high CB in paranoid and impaired low CB measures
of selective attention in nonparanoid patients.
3) Similar partial correlations for antipsychotic
drug dose and serum levels of DA D2-blocking activity with performance
on the trail-making and picture completion tests (negative) and the
block-design test (positive) showed the functional importance of DA-related
activity.
4) High estimates of D2-occupancy were
related to impaired verbal fluency - but - were associated with improved
recall of stories, especially in paranoid patients.
5) Non-dopaminergic aspects
of medication (i.e. CPZ-dependent but not D2-occupancy-associated) impaired
verbal recall in males (left-hemisphere function) and non-verbal performance
in females (reflecting right hemisphere function).
Conclusions:
This first study of its kind tentatively imputes a role for DA D2-related
activity in left frontal (e.g. CB and verbal fluency) and temporal lobe
functions (verbal recall), as well as in some non-verbal abilities mediated
more in the right hemisphere of patients with schizophrenia
. [This report was conceived
as the third of 5 reports on Project 1
(blocking), see also 1)
Schizophr. Res. (associations
with symptoms and onset), 2)
Cog.Neuropsychiat., (associations
with neuropsychology) :
(2 other reports still in preparation).
Our first blocking study in schizophrenia: a)
1996 Dev.Neuropsychol.,
b) 1996 J.Psychiat. Res. c)
1992 Acta Paedopsychiat. ]
The effect on CB of DA-depleting lesions in the Frontal cortex,
Septum and VTA in rats was reported in Oades
et al., 1987 .
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