Purpose Serotonergic brain regions play a crucial role in the modulation of emotion, and serotonergic dysfunction may contribute to several neurological disorders. [123I]ADAM is a novel SPECT tracer which binds with high affinity to serotonin transporters (SERT). The objective of this study was to compare different methods for the quantification of tracer binding and to develop a simplified single-scan protocol for this tracer, as well as to investigate its potential for characterisation of the transporter occupancy versus plasma concentration curve of a selective serotonin re-uptake inhibitor (SSRI).Methods Dynamic SPECT scans were performed on 16 healthy volunteers after administration of 150 MBq [123I]ADAM. Data were acquired from the time of injection until 5.5 h after injection in 30- or 45-min sessions. Each subject was scanned twice: with and without pre-treatment with the SSRI citalopram in various dosage regimens. The plasma concentration of citalopram (Cp) was determined from venous samples. Images were reconstructed by filtered back-projection with scatter and attenuation correction. Tracer binding was quantified for midbrain, striatum and thalamus using cerebellum as a reference region. Quantification was done by kinetic modelling, graphical analysis and multi-linear regression, as well as by the ratio method, with binding potential (BP2) as the outcome measure. The SERT occupancy by citalopram was determined relative to the baseline scan for each subject, and the occupancy versus Cp curve was fitted with the Emax model.Results The highest binding of [123I]ADAM was in midbrain (mean baseline BP2±SD=1.31±0.29), with lower binding in thalamus (0.79±0.16) and striatum (0.66±0.13). There was good agreement between BP2 values obtained by different quantification methods. Using the ratio method, the best agreement with kinetic modelling was obtained with data from the time interval [200,260] min after injection. The fitting of the midbrain occupancy curve yielded a maximum occupancy of 84% and a plasma concentration required to reach 50% of the maximum of 2.5 ng/ml, with a goodness-of-fit variability of 13% (SD).Conclusion Binding of [123I]ADAM to SERT in midbrain can be quantified with a single scan starting 200 min after injection. However, the variability of estimated occupancy values may be too high for critical assessment of occupancy of SERT by SSRI. 相似文献
This review discusses common mental health disorders and their associations with cardiovascular disease risks. Commonly found mental health disorders include depression, anxiety, and personality types. The link between depression and cardiovascular disease mortality has been established. Depression is also common in patients with heart failure. In addition to discussing psychological disorders, a review of psychotropic drugs is also included. Drugs are described for therapy for depression and anxiety, as well as associations with cardiovascular drug-drug interactions. Drug-drug interactions are more common and potentially dangerous in elderly patients, in whom the conditions often coexist. The most common drug-drug interactions involve the P450 system of enzymes. 相似文献
We found previously that alcohol-preferring (P) rats have fewer serotonin (5-HT) neurons and fibers in key brain regions than alcoholnonpreferring (NP) rats. Because 5-HT uptake blockers increase synaptic 5-HT content and 5-HT1A receptor antagonists increase 5-HT release by disinhibiting 5-HT autoinnervation, in the present study, our intent was to determine whether increased synaptic 5-HT content and/or 5-HT release in P rats would effectively reduce alcohol consumption. In experiment 1, the 5-HT antagonist WAY 100635 (WAY) was tested on adult female P rats maintained on 24-hr free-choice access to ethanol (10% v/v) and water. Twice daily doses of WAY (0.05, 0.1, 0.5, and 1.0 mg/kg, subcutaneously) were administered to each rat in a counterbalanced order. Baseline ethanol intake, derived from the mean ethanol intakes of the three previous non-drug days, was approximately 8 g/kg/day. Results indicated that 0.05,0.1, and 0.5 mg/kg doses of WAY reduced 24-hr ethanol drinking by 25-30% ( p < 0.01) without affecting 24-hr water intake or body weight In the second experiment, the effects of WAY (0.5 mg/kg), fluoxetine (1.0 mg/kg), or a combination of both were tested in another group of female P rats. WAY and fluoxetine, each alone, reduced ethanol drinking by around 20% and, when combined, decreased ethanol intake by 50%, whereas the body weight and the total fluid intake were not significantly affected. Taken together, these results indicate that both fluoxetine and WAY preferentially reduce ethanol drinking in the P line of rats and, when administered together, reduce ethanol intake in an additive manner. It is proposed that coadministration of these two compounds with distinct mechanisms of action may be a new strategy for reducing alcohol intake. 相似文献
BACKGROUND: Interruptions in SSRI treatment have been associated with adverse effects that can resemble depressive illness. We hypothesized that brain regions implicated in depression, with extensive serotonergic innervation, would exhibit changes in activity associated with emergence of symptoms following drug discontinuation. METHODS: Subjects meeting DSM-IV criteria for remitted major depression on 20 mg/day of either fluoxetine or paroxetine were recruited into this 6-week study. During weeks 2 and 6, subjects underwent a 3-day period in which either active drug or placebo was substituted for their medication under double-blind conditions. Cerebral blood volume (CBV) maps were obtained via dynamic susceptibility magnetic resonance imaging at the end of each double-blind period. RESULTS: In the paroxetine group, change in CBV in left medial superior frontal region and left caudate nucleus correlated significantly with change in Discontinuation Emergent Symptom Scale and Hamilton Depression Rating Scale (HDRS; R2 = 0.66, p =.0007; R2 = 0.51, p =.006; and R2 = 0.43, p =.015; R2 = 0.32, p =.043, respectively). CONCLUSIONS: These data demonstrate that changes in regional CBV of left prefrontal cortex and left caudate nucleus correlate with the emergence of discontinuation symptoms and increased HDRS after interruption of paroxetine treatment. 相似文献
BACKGROUND: Evidence is accumulating that pharmacological blockade of the substance P preferring neurokinin-1 (NK1) receptor reduces anxiety. This study compared the effects of an NK1 receptor antagonist, citalopram, and placebo on brain activity and anxiety symptoms in social phobia. METHODS: Thirty-six patients diagnosed with social phobia were treated for 6 weeks with the NK1 antagonist GR205171 (5 mg), citalopram (40 mg), or matching placebo under randomized double-blind conditions. GR205171 was administered for 4 weeks preceded by 2 weeks of placebo. Before and after treatment, regional cerebral blood flow (rCBF) during a stressful public speaking task was assessed using oxygen-15 positron emission tomography. Response rate was determined by the Clinical Global Impression Improvement Scale. RESULTS: Patients improved to a larger extent with the NK1 antagonist (41.7% responders) and citalopram (50% responders), compared with placebo (8.3% responders). Within- and between-group comparisons showed that symptom improvement was paralleled by a significantly reduced rCBF response to public speaking in the rhinal cortex, amygdala, and parahippocampal-hippocampal regions. The rCBF pattern was corroborated in follow-up analyses of responders and subjects showing large state anxiety reduction. CONCLUSIONS: Short-term administration of GR205171 and citalopram alleviated social anxiety. Neurokinin-1 antagonists may act like serotonin reuptake inhibitors by attenuating neural activity in a medial temporal lobe network. 相似文献
Objective: The Finnegan scoring list (FSL) is widely used to screen for poor neonatal adaptation in infants exposed to anti-depressants in utero. However, the large number of FSL-items and differential weighing of each item is time consuming. The aim of this study was to shorten and simplify the FSL yet preserving its clinimetric properties.
Methods: This observational study examined infants exposed to an anti-depressant during pregnancy admitted for at least 72?h on a maternity ward. Trained nurses completed the FSL three times daily. Items for the adapted FSL were selected through forward analysis whereby the number of selected items was based on the area under the curve (AUC). Internal validity was assessed by cross-validation.
Results: 183 infants met the inclusion criteria. By forward analysis eight equally-weighed items resulted in an AUC of 0.91. In cross-validation, the mean AUC was 0.89 for 8 items. This adapted FSL had a sensitivity of 97.7% and specificity of 37.0% and a sensitivity of 41.9% and specificity of 86.2% regarding a cut-off of, respectively, 1 and 2.
Conclusions: An adapted FSL with eight equally-weighed items has acceptable clinimetric properties and can serve as an easy to apply screening tool in infants exposed to anti-depressants during pregnancy. 相似文献
A number of plant species are used in Danish folk medicine for treatment of depression and anxiety.
Materials and methods
Aqueous and ethanolic extracts of 17 plant species were tested for affinity to the serotonin transporter and for inhibition of MAO-A—both targets for antidepressive treatment.
Results
An ethanolic extract of aerial parts of Borago officinalis had affinity to the serotonin transporter. Ten extracts, from eight plants, had IC50 values below 25 μg/ml extract in the MAO-A assay. The most active extracts in the MAO-A assay were the ethanol extract of seeds of Trigonella foenum-graecum (IC50 4 μg/ml); ethanol extract of leaves of Apium graveolens (IC50 5 μg/ml) and the water extract of aerial parts of Calluna vulgaris (IC50 8 μg/ml).
Conclusions
Besides Borago officinalis, which toxicity profile excludes it from further development as an herbal drug, none of the plants had potential as serotonin reuptake inhibitors. Several plants had MAO-A inhibitory activity. 相似文献
The aim of the present study was to retrospectively identify sexual dysfunction changes in the patients under mirtazapine-augmented serotonin reuptake inhibito (SSRI) treatment. The study comprised medical records of 20 outpatients, under mirtazapine-augmented SSRI treatment for their major depressive disorder, who had been selected among the patients that had developed sexual dysfunction to previous treatment as monotherapy, with SSRI for at least six weeks. These drugs were maintained and mirtazapine were added (15-45 mg/day). There was a significant difference in scores between baseline and week 4 or week 8 on the both Hamilton Depression Rating and Arizona Sexual Experience Scale. According to Clinical Global Impression-Improvement, 68.4% of the patients were responders. The use of low-dose mirtazapine as an add-on treatment to SSRIs appears to be an effective and well-tolerated augmenttaion for sexual dysfunction caused by SSRIs. 相似文献