The cortical serotonin2 receptors studied with positron-emission tomography and [18F]-setoperone during depressive illness and antidepressant treatment with clomipramine.

BACKGROUND: Changes in serotonin (5-HT)2 receptor densities were reported in depression by postmortem studies and following treatment with tricyclic antidepressants in animal studies. Here, 5-HT2 receptors were studied in vivo in depressed patients. METHODS: Cortical 5-HT2 receptors were investigated prospectively using positron-emission tomography and [18F]-setoperone in 7 depressed patients, before and after at least 3 weeks of clomipramine (CMI), 150 mg daily. They were compared to 7 age-matched controls. RESULTS: There was no significant difference between the untreated patients and the controls, except in the frontal region, where the [18F]-setoperone specific binding was slightly lower in patients. After CMI treatment, depression scores significantly improved and [18F]-setoperone specific binding decreased in cortical regions, suggesting receptor occupancy and/or receptor regulation, by CMI; however, no clinical score correlated with the 5-HT2 receptor measurements either in the untreated or in the treated conditions. CONCLUSIONS: These data substantiate the view that tricyclic antidepressants such as clomipramine significantly interact with cortical 5-HT2 serotoninergic receptors in actual therapeutic situations.

Frontal dysfunction in neurologically normal chronic alcoholic subjects: metabolic and neuropsychological findings.

BACKGROUND: Neuropsychological and imaging studies suggest that frontal dysfunction may occur in apparently normal chronic alcoholic subjects. METHODS: To investigate this issue further, we performed neuropsychological and fluorodeoxy-glucose-PET studies in 17 chronic alcoholics without patent neurological and psychiatric complications. RESULTS: Metabolic abnormalities were found in the mediofrontal and in the left dorsolateral prefrontal cortex, but not in the orbitofrontal cortex. Neuropsychological testing revealed significantly reduced verbal fluency and impaired performance on the Stroop test. The mediofrontal hypometabolism correlated with the reduction in verbal fluency and the time necessary to perform the interference condition of the Stroop test. The left dorsolateral prefrontal hypometabolism correlated with the number of errors on the Stroop test. CONCLUSION: These data indicate that circumscribed frontal dysfunctions may occur in chronic alcoholic subjects before clinically obvious neurological complications, and may account for some of the alcohol-related neuropsychological and behavioural impairments.

Presynaptic dopaminergic function in the striatum of schizophrenic patients.

The dopaminergic hypothesis of schizophrenia postulates increased brain dopaminergic activity. Two previous studies reported increased 18F-DOPA uptake with positron emission tomography in schizophrenic patients (n = 5, n = 7). In the present study, striatal dopaminergic function was assessed in vivo in six untreated schizophrenics and seven control subjects, comparable for age and sex. The 18F-fluoro-L-DOPA (18F-DOPA) uptake rate constant Ki was determined in the caudate and putamen using coregistered positron emission tomography and magnetic resonance imaging. No difference between groups for mean Ki was found. The variability of the 18F-DOPA uptake values was higher in the caudate (p < 0.01) and in the putamen (p < 0.001) in schizophrenic patients than in control subjects, suggesting that schizophrenia is a disorder involving heterogeneous states of the striatal presynaptic dopaminergic function.

In vivo characteristics of dopamine D2 receptor occupancy by amisulpride in schizophrenia.

The relationship between the daily oral dose of the benzamide amisulpride and the striatal D2-dopamine receptors occupancy was investigated in 11 schizophrenic patients using positron emission tomography with 76Br-bromolisuride. The patients were studied before and during chronic treatment with amisulpride over a wide range of doses. The test-retest variability of the method was estimated to be 5.8% in a group of four patients receiving placebo. A curvilinear relationship was demonstrated between the amisulpride doses and the D2-receptor occupancy. A range of 70-80% occupancy of the striatal D2 receptors, suggested as an optimal interval for therapeutic action on positive psychotic symptoms, was obtained with doses of amisulpride ranging between 630 and 910 mg per day, while an occupancy of 85%, suggested to be associated with pronounced extrapyramidal side-effects, was reached with 1,100 mg per day.

Peduncular 'rubral' tremor and dopaminergic denervation: a PET study.

Lesions causing so-called rubral tremors frequently involve the substantia nigra or the nigrostriatal fibers, suggesting dopaminergic denervation as possibly contributory. We examined this hypothesis using PET and [18F]-fluorodopa in six patients with a contralateral tremor following a peduncular lesion. The denervation revealed by PET was even more marked than in severe parkinsonian patients. All patients showed partial to complete improvement with levodopa therapy. PET evaluation of D2-receptors with [76Br]bromolisuride showed no asymmetry of the D2 binding despite the important asymmetry of 18F-fluorodopa uptake. Our results indicate an important involvement of the nigral dopaminergic system in peduncular tremors that appears to be independent of postsynaptic dopamine receptors.

Delusional misidentification: a clinical, neuropsychological and brain imaging case study.

The case of a young woman with a disorder involving Capgras syndrome, Frégoli syndrome, intermetamorphosis, and the subjective-doubles syndrome is reported. Neuropsychological assessment showed a low efficiency in the complex visuospatial organization tasks and in non-verbal memory. MRI found a left lenticular hypodensity, and two PET scans performed in the symptomatic and recovered states showed significant changes and asymmetries in cerebral glucose metabolism in the frontal, parietal, and subcortical regions. These findings are discussed with respect to recent models of delusional misidentification syndromes.

Central D2 receptors and negative symptoms of schizophrenia.

Most in vivo studies of striatal D2 receptor (SD2R) density with positron emission tomography in schizophrenia have attempted to relate this variable to the diagnosis of the illness. In the present study, a relationship between SD2R and clinical dimensions of this psychosis was searched for in a highly selected group of young negative schizophrenics (8 drug-naïve and 2 drug-free). The SD2R density index measured in vivo using 76Br-bromolisuride and PET correlated negatively (r = 0.80, P < 0.01) with a psychomotor dimension of schizophrenia involving blunted affect and alogia. The mean SD2R index of the patients did not differ from that of age-matched control subjects. Therefore, this behavioural dimension accounts for the variance of the SD2R, suggesting that the striatal dopamine system modulates symptoms such as flattened affect and alogia.

[Positron-emission tomographic study of the dopaminergic system in a case of secondary unilateral tremor after mesencephalic hematoma]. / Etude du système dopaminergique en tomographie par émission de positons dans un cas de tremblement unilatéral secondaire à un hématome mésencéphalique.

A 30 year-old woman developed a postural and rest tremor of the left hand following a right peduncular post-traumatic hematoma. Two years later, positron emission tomography showed a marked decrease in [18F] fluorodopa uptake contrasting with a normal [76Br] bromolisuride uptake in the right striatum. This suggests that: 1) chronic unilateral dopaminergic striatal denervation may occur without persistent D2 dopaminergic receptor upregulation in humans; and 2) symptomatic mesencephalic tremor may be, at least in part, related to dopaminergic striatal denervation.

[Brain imaging and schizophrenia]. / Imagerie cérébrale et schizophrénie.

Brain structures and brain function have been investigated by the new brain imaging techniques for more than ten years. In Psychiatry, these techniques could afford a new understanding of mental diseases. In schizophrenic patients, CAT scanner and RMI pointed out statistically significant ventricular enlargements which are presently considered as evidence for abnormalities in brain maturation. Functional imaging techniques reported metabolic dysfunctions in the cortical associative areas which are probably linked to the cognitive features of schizophrenics.