We measured regional cerebral glucose metabolism using 2-[18F]-fluoro-2-deoxy-D-glucose and positron emission tomography in depressed and nondepressed patients with early Huntington's disease (HD), compared with appropriately matched controls. Caudate, putamen, and cingulate metabolism was significantly lower in patients with HD than in control subjects, independent of mood state. Orbital frontal-inferior prefrontal cortex hypometabolism, however, differentiated depressed patients from both nondepressed patients and normal controls. These findings implicate selective dysfunction of the paralimbic regions of the frontal lobes in the mood disorder of HD. The metabolic pattern is similar to that in depression associated with Parkinson's disease, suggesting that the integrity of pathways linking paralimbic frontal cortex and the basal ganglia may be integral to the normal regulation of mood.
Detailed studies of the properties of 3H-3-N-methylspiperone (NMSP) binding in rat and human brain homogenates were performed at 37 degrees C. In homogenates of rat striatum and frontal cortex and human caudate and frontal cortex tissues, the specific binding was found to be saturable. Rat caudate contained 33.2 pmol/gm wet-weight tissue and displayed an equilibrium dissociation constant (Kd) of 8.7 X 10(-11) M; rat frontal cortex contained 18.5 pmol/gm wet-weight tissue and displayed a Kd of 1.5 X 10(-10) M. Human caudate contained 8.96 pmol/gm wet-weight tissue and displayed a Kd of 1.1 X 10(-10) M; human frontal cortex possessed 9.8 pmol/gm wet-weight tissue and a Kd of 4.4 X 10(-10) M. Kinetic studies revealed a very rapid rate of association in all the tissues studied. The rate of dissociation was relatively slow in all 4 tissue preparations; the dissociation rate was somewhat slower in rat striatum and human caudate relative to rat and human frontal cortex. This was consistent with the somewhat higher affinity, relative to frontal cortex, displayed by 3H-NMSP in rat striatal and human caudate tissue. The pharmacological properties of the specific binding in rat striatal and human caudate tissues were very similar and indicated the presence of brain D2 dopamine receptors. In rat and human frontal cortex tissue homogenates, the pharmacological characteristics of the specific binding indicated the presence of 5-HT2 receptors.
Patients with right-hemisphere strokes (N = 9) more than 1 year after injury had greater cortical binding of (3-N-[11C]methyl)spiperone than a similar group of patients with left-hemisphere strokes (N = 8) or normal control subjects (N = 17). The higher S2 serotonin receptor binding occurred in uninjured regions of the right parietal and temporal cortex. The ratio of binding in the ipsilateral to contralateral cortex showed a significant negative correlation with severity of depression scores in the left temporal cortex. These findings suggest that the biochemical response of the brain may be different depending on which hemisphere is injured and that some depressions may be a consequence of the failure to upregulate serotonin receptors after stroke.
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