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OADES, R. D., KLIMKE,
A., HENNING, U., & RAO, M. L.,
(2002). Relations of clinical features, subgroups and medication
to serum monoamines in schizophrenia. Human Psychopharmacology
: Clinical and Experimental, 17, 15-27 . -
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text (view).
The original publication (cited above: doi: 10.1002/hup.368 ) is available
at http://www3.interscience.wiley.com/journal/89016248/issue
Introduction :
Plasma and serum indices of monoaminergic activity
reflect partly the illness of schizophrenia (e.g. relationship of HVA
levels to the deficit syndrome) and sometimes the individual symptoms
(e.g. HVA levels with features of anhedonia) . But, such studies
have rarely taken both the metabolites and the parent monoamines or
inter - amine ratios into account. [ HVA = metabolite of dopamine (DA)]
Aims :
We hypothesised that a comparison of the major symptom dimensions expressed
with measures of neurotransmitter activity (with and without control
for the antipsychotic drug treatment) would show differential patterns
of activity reflecting a) the sub-groups of schizophrenia, and
would thus, b) be useful for the design of pharmacological treatments.
Methods :
Dopamine (DA), noradrenaline (NA),
serotonin (5-HT), their three major metabolites (HVA, MHPG, 5-HIAA)
and prolactin (PRL) were measured in the serum of 108 patients with
schizophrenia and 63 healthy controls matched for age, gender and socio-economic
factors. DA D2-receptor blocking activity was estimated from a regression
of butyrophenone displacement in pig striatum in vitro on to PET reports
of drug-binding in vivo. Symptoms were factor-analysed into 4 dimensions
(disorganised / thought disordered, non-paranoid / negative, ideas-of-reference,
and paranoid / positive dimensions) .
Results :
1/ Patients' DA activity did not
differ from controls': but their 5-HT activity increased, and NA activity
decreased. Further the DA / 5-HT metabolite ratio (HVA/5-HIAA) was lower.
Increased DA-D2 receptor occupancy was predicted by decreased DA metabolism
and its ratio to 5-HT metabolism (HVA/5-HIAA).
2/ Comparing responses to atypical
vs. typical neuroleptic drugs patients showed higher levels of NA, of
DA metabolites and the DA/5-HT metabolite ratios (HVA/5-HIAA).
3/ In paranoid patients increased
DA D2-occupancy was associated with lower DA metabolism, but this in
non-paranoid patients this was unrelated to the recorded increase of
D/5-HT metabolite ratio (HVA/5-HIAA) and NA metabolism (MHPG).figure
3)
4/ Low DA / 5-HT metaboite ratios
(HVA / 5-HIAA), high prolactin, and low DA metabolism characterised
thought-disordered patients.
5/ High DA/5-HT metabolite ratios
(HVA / 5-HIAA) paralleled many ideas-of reference. The metabolic differences
were sensitive to statistical control for D2-receptor occupancy and
PRL levels.
Conclusions
:
The role of DA in paranoid patients, and opposing changes
(and significant role) of 5-HT in patients with
thought disorder vs. ideas of reference point both to the mechanisms
underlying these different symtom features typical of some sub-groups
of patients with schizophrenia, and to the type of medication strategy
that might be appropriate.
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