No association between serotonin 5-HT 1A receptors and spirituality among patients with major depressive disorders or healthy volunteers.

An earlier study (Borg et al., Am J Psychiatry 2003) found an inverse correlation between [carbonyl-(11)C]WAY-100635 ligand binding to 5-HT(1A) receptors and scores for self-transcendence, but no other of the six dimensions of the Temperament and Character Inventory, in a group of healthy males. The aim of this study was to investigate if the finding of an inverse correlation between spirituality and 5-HT(1A) could be seen in patients suffering from major depressive disorder or replicated among healthy volunteers. A total of 23 patients with major depressive disorder and 20 healthy volunteers were examined with PET using [carbonyl-(11)C]WAY-100635 as the radioligand. The personality traits were measured using the Finnish version of the Temperament and Character Inventory and correlated with ligand binding (BP). No significant correlations were found between the different Temperament and Character Inventory subscales and BP in any of the studied brain regions (amygdala, anterior cingulate cortex, dorsal raphe nuclei, dorsolateral prefrontal cortex, angular gyrus, inferior, middle, and superior temporal gyri, medial prefrontal cortex orbitofrontal cortex, hippocampus, insular cortex, subgenual anterior cingulate cortex, supramarginal gyrus, ventrolateral prefrontal cortex, and posterior cingulate cortex). These results do not support the idea that the serotonin system forms the biological basis of spiritual experiences among patients suffering from major depressive disorder or among healthy volunteers.

Measurement of striatal and thalamic dopamine D2 receptor binding with 11C-raclopride.

11C-Raclopride is a widely used positron emission tomography (PET) tracer for measurement of striatal D2 dopamine receptor binding characteristics. Recently, 11C-raclopride has also been used for quantification of thalamic D2 receptor binding. We studied reproducibility and validity issues on the thalamic D2 binding measurements using healthy volunteer test-retest data and simulated data. Eight healthy male volunteers received 11C-raclopride as a bolus injection in a standard test-retest design using 3-dimensional PET. The displacement of thalamic 11C-raclopride binding by the D2 receptor antagonist haloperidol was studied in two female schizophrenic patients. With regards to reproducibility and reliability, thalamic 11C-raclopride binding could be described with a simplified reference tissue model resulting in binding potentials (BPs) between 0.38 and 0.66. In comparison, the model failed to describe 11C-raclopride binding consistently in temporal cortex due to low specific signal. Measurement of thalamic 11C-raclopride BP was reproducible with a test-retest variability of 7.6+/-6.2% and reliable with an intraclass correlation coefficient (ICC) of 0.87. Comparable ICCs were observed in caudate and putamen (0.84-0.96). With regard to validity, subchronic low dose haloperidol treatment reduced specific 11C-raclopride binding equally in putamen and thalamus but a higher dose induced clearly higher D2 receptor occupancy in putamen than in thalamus. Noise simulations indicated that this can partly be explained by an over-estimation of thalamic D2 receptor BP in noisy conditions (low signal, high occupancy). The D2 receptor BP in putamen was clearly more resistant to noise. We conclude that the reproducibility and reliability of thalamic 11C-raclopride BP is good and equal to, or only slightly less than, those observed in caudate or putamen. However, the signal-to-noise ratio for quantification may become too low especially in receptor occupancy-type studies, leading to an artefactual underestimation of measured D2 receptor occupancy.

Extrastriatal dopamine D(2) receptors in Parkinson's disease: a longitudinal study.

Most antiparkinsonian drugs are known to act through central dopamine D(2) receptor agonism. A previous longitudinal positron emission tomography (PET) study has indicated that, in the striatum of Parkinson's disease (PD) patients, dopamine D(2) receptor binding declines at a relatively fast annual rate of 2-4% (compared to the rate of <1%/year in healthy individuals). In the present study, the examination of longitudinal changes in D(2) receptors was extended to extrastriatal brain regions in PD. Eight early PD patients were examined twice with PET, approximately 3 years apart, using a high-affinity extrastriatal D(2)/D(3) receptor tracer, [(11)C]FLB 457. Both the MRI-referenced region-of-interest method and the voxel-based statistical analysis method were used independently in the analysis. Regional D(2)-like availabilities (binding potentials) in the left dorsolateral prefrontal cortex, the left temporal cortex and the left and right medial thalami were significantly decreased at the second examination by 20-37% (corresponding to an annual decline of 6-11%). Thus, the annual loss of extrastriatal D(2) availability in PD is up to three times faster than the rate previously reported in the putamen. Our longitudinal study shows first evidence concerning cortical D(2) receptor loss in the progression of PD, although it is not possible to distinguish between the effects of the therapy and the disease.

Sex differences in extrastriatal dopamine d(2)-like receptors in the human brain.

OBJECTIVE: The study examined gender differences in extrastriatal dopamine D2-like receptor levels in the human brain in vivo. METHOD: [(11)C]FLB 457, a high-affinity radioligand for extrastriatal D(2)-like receptors, and a three-dimensional positron emission tomography system were used to measure D(2)-like receptor binding potentials in frontal cortex, temporal cortex, and thalamus in 12 healthy men and 12 healthy women. RESULTS: Women had higher D(2)-like receptor binding potentials than men in the three brain regions studied, and the difference in the frontal cortex was statistically significant. In a more detailed regional analysis, the difference between the sexes was most pronounced for the left and right anterior cingulate cortex. CONCLUSIONS: This study provides in vivo evidence for a gender difference in dopamine D(2)-like receptor levels, which could be reflected in gender-associated differences in clinical disorders linked to the dopamine system.

Age-related dopamine D2/D3 receptor loss in extrastriatal regions of the human brain.

Loss of dopamine D2-like receptors in the striatum has been associated with both normal human aging and impairment of cognitive and motor functions in the elderly. To investigate whether there are age-associated changes in dopamine D2 and D3 receptor subtypes (D2/3Rs) outside the striatum, a D2/3R selective high-affinity radioligand [11C]FLB 457 was used in positron emission tomography (PET) examinations for 24 normal healthy male subjects (age range 19-74 years). Significant age-related declines of D2/3Rs were detected in all the brain regions studied: the anterior cingulate cortex (decline of 13% per increase of a decade in age, P < 0.001). the frontal cortex (11%, P < 0.001), the lateral temporal cortex (10%, P < 0.001), the hippocampus (10%, P < 0.01), the medial temporal cortex (9%, P < 0.001), the amygdala (7%, P < 0.01), the medial thalamus (6%, P < 0.001) and the lateral thalamus (5%, P < 0.01). The rate of D2/3R decline was significantly faster in the frontal cortex as compared to the medial temporal cortex (P < 0.05, Bonferroni corrected) and as compared to the medial thalamus (P < 0.05, Bonferroni corrected). These results indicate that the previously demonstrated age-related decline in striatal dopamine D2 receptors extends to several extrastriatal regions in normal human males. Further, the rate of D2/3R decline may be faster in the frontal cortex as compared to the temporal and thalamic regions.

Extrastriatal dopamine D2 and D3 receptors in early and advanced Parkinson's disease.

OBJECTIVE: To investigate whether dopamine D2 and D3 receptor subtypes (D2/3Rs) outside the caudate-putamen are affected in PD. BACKGROUND: Alterations in striatal D2-like dopamine receptors in PD have been extensively demonstrated using PET, but there are no studies focusing on extrastriatal D2/3Rs. METHODS: Fourteen unmedicated patients with idiopathic early PD with predominantly left-sided symptoms, 14 levodopa-medicated patients with advanced PD, and 20 normal age-matched controls were examined using PET. PET scanning was performed with a novel high-affinity D2/3R radioligand ([11C]FLB 457) and a PET scanner in three-dimensional mode. RESULTS: In advanced PD, the binding potential of [11C]FLB 457 in the dorsolateral prefrontal cortex was decreased by 40% (p < 0.01), in the anterior cingulate cortex by 20% (p < 0.01), and in the medial thalamus by 17% (p < 0.05) compared with healthy controls. In early PD, the extrastriatal [11C]FLB 457 binding potentials were not significantly different compared with the control group. However, the binding potential in the anterior cingulate cortex (29%; p < 0. 05) was higher in early PD compared with advanced PD. CONCLUSIONS: These results imply that the D2/3 receptor subtypes outside the striatum are affected in advanced PD but not in the early stages of the disease, and that this receptor decline is present in the anterior cingulate cortex, the dorsolateral prefrontal cortex, and the thalamus.

Effects of clozapine metabolites and chronic clozapine treatment on rat brain GABAA receptors.

Similarly to clozapine, a clozapine metabolite, N-desmethylclozapine, but not clozapine N-oxide, antagonized brain gamma-aminobutyric acid type A (GABAA) receptors at high micromolar concentrations. However, daily subcutaneous injections of clozapine (10 and 25 mg/kg) and haloperidol (0.5 mg/kg) for 14 days failed to alter the modulation by GABA of rat cerebrocortical and cerebellar benzodiazepine ([3H]flunitrazepam) or convulsant (t-[35S]bicyclophosphorothionate) binding sites of the GABAA receptor. The results thus suggest that the GABAA receptor antagonism exerted by chronic in vivo clozapine treatment is weak as compared to this treatment's actions on certain monoamine receptors and is unlikely to be involved in the therapeutic actions of clozapine.

Serum iron, copper, zinc, ferritin, and ceruloplasmin after intense heat exposure.

Twelve voluntary adult subjects twice took a 30-min sauna bath, at a temperature of 80 degrees C with a 30-min rest between each, every 12 h for 1 week. Measurements of serum iron, copper, zinc, ferritin and ceruloplasmin were performed before the experiment, after the first and second 30 min in the sauna and at the end of the week. The first two sauna baths did not significantly change the concentrations of the trace elements measured. After the week the mean serum copper concentration had decreased from 15.0 (SD 1.7) mumol x 1-1 to 13.5 (SD 2.0) mumol x 1-1 (p less than 0.02). The mean zinc concentration decreased from 13.8 (SD 2.4) mumol x 1-1 to 9.8 (SD 1.8) mumol x 1-1 (p less than 0.001) during the week of the experiment. At the beginning of the study period two subjects had zinc concentrations below the reference values and after the week nine subjects had zinc concentrations below the reference values. The concentration of serum ferritin decreased from 142.2 (SD 103) micrograms x 1-1 to 111.3 (SD 89) micrograms x 1-1 (p less than 0.02) whereas the values of ceruloplasmin remained unchanged. Our findings confirm the earlier suggestion that heavy exposure to heat can cause a loss of some trace elements, especially zinc.

Acute phase proteins, humoral and cell mediated immunity in environmentally-induced hyperthermia in man.

The effects of repeated hyperthermia, caused by a Finnish sauna bath over 1 week, on the serum levels of some acute phase reactant proteins and on both humoral and cell-mediated immunity on twelve healthy young volunteers are presented. The mean rise in rectal temperature during each 30-min period in the bath was about 1.3 degrees C. Heat exposure caused significant increases in the serum concentrations of two of the acute phase reactant proteins, alpha1-antitrypsin (from a mean value of 1.8 (0.1) to 1.9 (0.2) g X l-1, p less than 0.01) and transferrin (from a mean value of 36.9 (3.4) to 38.3 (4.4) mumol X l-1, p less than 0.05), but no changes occurred in immunoglobulins or cell-mediated immunity. These findings suggest that environmentally induced hyperthermia can initiate the acute phase reaction associated with fever.