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5-HT2A receptor antagonism may be crucial to the action of atypical antipsychotics. Previous work has related 5-HT2A receptor blockade to clinical efficacy and protection from extrapyramidal side-effects.
We developed a SPET imaging protocol for assessing 5-HT2A receptor binding using the selective ligand 1231-5-1-R91150. Six healthy volunteers, five clozapine- and five risperidone-treated subjects with DSM–IV schizophrenia were studied. Multi-slice SPET was performed on each subject.
Cortex: cerebellum ratios were significantly lower in both clozapine-and risperidone-treated subjects compared with the healthy volunteers in all cortical regions. There was no difference in occupancy between the two drug-treated groups. No correlation was found between the percentage change in the Global Assessment Scale (GAS) and 5-HT2A receptor binding indices in the drug-treated groups.
Clozapine and risperidone potently block 5-HT2A receptors in vivo. The lack of relationship between receptor binding indices and change in GAS suggests that 5-HT2A receptor blockade may be unrelated to clinical improvement. Future studies will substantiate this finding by studying 5-HT2A receptor binding in large groups of patients treated with both typical and novel atypical antipsychotics.
We compared regional cerebral blood flow (rCBF) in three groups of patients with DSM–III–R anxiety disorders.
Fifteen patients with obsessive–compulsive disorder (OCD), 15 with panic disorder with agoraphobia (PA), and 16 with post-traumatic stress disorder (PTSD) and a similar group of healthy controls were assessed on brain-dedicated high-resolution SPET.
MANOVA revealed significant rCBF differences between diagnostic groups (F=4.4; d.f.=3, 57; P=0.007) and between cerebral regions (F=6.4; d.f.=1, 57; P=0.01) in OCD and PTSD compared with PA and healthy controls, limited to bilateral superior frontal cortices and right caudate nuclei. Whole brain blood flow correlated positively with anxiety (r=0.24, n=46, P=0.05). Beck depression scores correlated significantly negatively with left caudate rCBF (r= –0.24, n=46, P=0.05) and right caudate rCBF (r= –0.31, n=46, P=0.02). PTSD syndrome severity correlated significantly negatively with the left caudate (r=-0.49, n=16. P=0.03) and with right caudate rCBF (r=-0.7, n=16, P=0.001)
Functional rCBF differences in anxiety disorders could relate to repetitive, intrusive, distressing mental activity, prominent in both OCD and PTSD.
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