D2 dopamine receptor occupancy, risperidone plasma level and extrapyramidal motor symptoms in previously drug-free schizophrenic patients.

RATIONALE: A relationship between high D2 occupancy (above 80%) and extrapyramidal-motor symptoms under neuroleptic treatment has been observed in several neuroimaging studies. OBJECTIVES: We investigated the striatal dopamine D2 receptor occupancy, risperidone plasma level and extrapyramidal-motor symptoms in drug-free schizophrenic patients. METHODS: Ten schizophrenic patients were treated with 3 - 6 mg risperidone daily. After four weeks administration, a [(123)I]iodobenzamide ([(123)I]IBZM)-single photon emission tomography (SPET) scan for determination of D2 receptor occupancy was carried out (in eight responders) and compared to a control group. Plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (active moiety) were determined by high performance liquid chromatography and electrochemical detection. Extrapyramidal-motor symptoms were assessed by means of the Simpson-Angus-Scale and a handwriting test before treatment and coincident with the scan. RESULTS: The D2 receptor occupancy (Mean 62%, SD 13%) positively correlated with the plasma level of the risperidone active moiety as well as with the reduction in handwriting area. Multiple linear regression revealed an inherent relationship with a coefficient of determination of r = 0.956 (p = 0.02). No clinical relevant extrapyramidal-motor symptoms were observed. CONCLUSIONS: In drug-free schizophrenic responders, the simultaneous assessment of both plasma level and reduction in handwriting area may be a useful clinical tool for a surrogate estimate of D2 receptor occupancy under risperidone treatment. This may help to minimize or even prevent extrapyramidal-motor symptoms.

[The 100th anniversary of Gustav Wilhelm Störring's "Lectures on Psychopathology". A review of his early years]. / Vor 100 Jahren erschienen die "Vorlesungen über Psychopathologie..." von Gustav Wilhelm Störring. Ein Rückblick auf seine frühen Jahre.

The aim of this essay is to retell the life and work of philosopher and psychiatrist Gustav Wilhelm Störring (1860-1946) during his early years in Leipzig and Erdmannshain. His "Lectures on Psychopathology and its Impact on Normal Psychology", written 100 years ago, are acknowledged as his most important work. With this book Störring stands in opposition to many of his contemporaries, which is illustrated with his concept of mania. In some aspects, however, his ideas coincide with those of other well-known psychiatrists such as Emil Kraepelin. Both were inclined to the idea that psychiatry and psychology could mutually stimulate each other. Störring's work in Wundt's laboratory of experimental psychology had a major impact on his work. Wundt's ideas gave impetus to a lot of his work and also influenced papers Störring was to write later on. Störring's biography is followed until 1902 when he was appointed professor of philosophy of Zurich University, in which his friend Ernst Meumann was substantially involved. In Leipzig Störring had started his work as Flechsig's assistant at the hospital of psychiatry and neurology of Leipzig University. In 1897 he founded his own sanitarium for mentally and neurologically ill in Erdmannshain, a village near Leipzig, which he managed together with his wife Marie, née Bonacker. With the help of Wundt Störring qualifies as a university lecturer. During the years regarded here, however, he got more and more attracted to philosophical matters, thus turning away from neurosciences. In time he started to regard his work as physician as nothing more than necessary for making his living. His relationship with Wundt, who together with his laboratory of experimental psychology had previously made him wish to come to Leipzig, cooled down, at least on the part of the first. That puts an end to Störring's early years not only from the point of view of his biography but also from his work.

[Diminution of hand writing area and D2-dopamine receptor blockade. Results from treatment with typical and atypical neuroleptics]. / Verkleinerung der Handschriftfläche und D2-Dopaminrezeptorblockade. Ergebnisse unter Behandlung mit typischen und atypischen Neuroleptika.

Beside the typical extrapyramidal motor symptoms such as rigidity, tremor, and dyskinesia, a reduction in handwriting area may occur under neuroleptic therapy. To date, the nature of the relationship between a reduction in handwriting area and striatal D2 dopamine receptor occupancy has remained unclear, and it is not known whether such a reduction also occurs under treatment with atypical neuroleptic drugs. In 23 schizophrenic patients treated with haloperidol, haloperidol decanoate, risperidone, and clozapine, the handwriting are was examined using a planimetric computer program. 123I-iodobenzamide (IBZM) single photon emission tomography (SPET) was used to measure the D2 dopamine receptor occupancy. A statistically significant correlation was found between a reduction in handwriting area and D2 dopamine receptor occupancy (r = 0.86; P < 0.0001). The curve derived from the plotted data resulted in a hyperbolic function. The regression was present regardless of whether the patients were treated with typical or atypical neuroleptic drugs.

Haloperidol serum concentrations and D2 dopamine receptor occupancy during low-dose treatment with haloperidol decanoate.

The aim of this study was to examine the relationship between serum concentrations of haloperidol and central D2 receptor occupancy in eight schizophrenic patients treated with low doses of haloperidol decanoate. The accompanying psychopathology was assessed. During a 4-week interval after administration of haloperidol decanoate (dose range 30-70 mg), serum concentrations of haloperidol were determined once a week by using a sensitive high-performance liquid chromatography method. The patients' D2 receptor occupancy was determined with single-photon emission computed tomography on two separate occasions. One week after depot administration the mean haloperidol serum concentration was 7.3 nmol/l (range 3.9-22.7 nmol/l) and the mean D2 receptor occupancy was 75% (range 52-100%). After 4 weeks the mean haloperidol serum concentration had decreased to 1.8 nmol/l (range 0-5.7 nmol/l) and the mean D2 receptor occupancy to 53% (range 12-89%). Differences were seen in two subgroups, defined by their history of neuroleptic exposure before inclusion into the study. Patients treated with depots of haloperidol decanoate for months showed higher D2 receptor occupancy and corresponding higher serum haloperidol concentrations at week 4 than did patients who had a history of oral haloperidol treatment. Because the difference in the dynamics of D2 receptor occupancy could be reflected by corresponding serum concentrations of haloperidol, it seems useful to involve haloperidol drug monitoring as a possible surrogate marker for D2 receptor occupancy in optimizing low-dose treatment with haloperidol decanoate.