Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nuclear medicine has a place in the study of brain trauma, brain tumours, stroke, dementia epilepsy and depression. The development of new tracers labelled with widely available radionuclides, such as technetium-99m (99Tc) and iodine-123, has played a key role here. Practical methodology can now be implemented in the routine setting. Additional applications are reviewed in the context of brain death, encephalitis, post-viral fatigue syndrome, Parkinson's disease and schizophrenia.
 ...
PMID:The role of nuclear medicine in neurology and psychiatry. 146 80

Using a brain-dedicated triple-headed single-photon emission tomography (SPET) system, a sequential whole-volume imaging protocol has been devised to evaluate the regional distribution of iodine-123 iomazenil binding to GABAA receptors in the entire brain. The protocol was piloted in eight normal volunteers (seven males and one female; mean age, 24.8 +/- 3.9 years). The patterns obtained were largely compatible with the known distribution of GABAA receptors in the brain as reported in autoradiographic studies, with cerebral cortical regions, particularly the occipital and frontal cortices, displaying the highest 123I-iomazenil uptake. Measures of time to peak uptake and tracer washout rates presented with the same pattern of regional variation, with later times to peak and slower washout rates in cortical regions compared to other brain areas. Semiquantitative analysis of the data using white matter/ventricle regions as reference demonstrated a plateau of specific 123I-iomazenil binding in neocortical and cerebellar regions from 60-75 min onwards. These data demonstrate the feasibility of sequential, dynamic whole-volume 123I-iomazenil SPET imaging. The protocol may be particularly useful in the investigation of neuropsychiatric conditions which are likely to involve more than one focus of GABA abnormalities, such as anxiety disorders and schizophrenia.
 ...
PMID:In vivo imaging of GABAA receptors using sequential whole-volume iodine-123 iomazenil single-photon emission tomography. 769 49

To examine the relationship between functional abnormality of the brain and the development of epileptic psychosis, regional cerebral blood flow (rCBF) patterns with single photon emission computed tomography (SPECT) using N-isopropyl-(iodine-123)-p-iodoamphetamine (123I-IMP) were serially examined in interictal stages with and without the psychotic state in 2 medicated patients with temporal lobe epilepsy with schizophrenia-like syndrome. Both patients had epileptic EEG foci in the left temporal lobe and schizophrenia-like syndrome in Bruens' classification of epileptic psychosis, mainly consisting of auditory hallucinations and delusions of persecution and reference accompanying the enhancement of interictal epileptic discharges. In both patients, the SPECT scans obtained in the stages without the psychotic state revealed focal hypoperfusion images in the left temporal lobe regionally consistent with the EEG foci. On the other hand, the SPECT scans in the stages with the psychotic states revealed focal hyperperfusion images in the left temporal lobe or amygdala in case 1, and a normal perfusion pattern without asymmetric images of the right and left temporal lobes in case 2. These results suggest that temporo-limbic dysfunction, in particular hyperfunction in the temporo-limbic system in the left dominant hemisphere, arises at the time of the psychotic state in epileptic psychosis.
 ...
PMID:123I-IMP SPECT brain imaging in epileptic psychosis: a study of two cases of temporal lobe epilepsy with schizophrenia-like syndrome. 827 3

This paper describes the application of a multivariate statistical technique to investigate striatal dopamine D2 receptor concentrations measured by iodine-123 iodobenzamide (123I-IBZM) single-photon emission tomography (SPET). This technique enables the automatic segmentation of dynamic nuclear medicine images based on the underlying time-activity curves present in the data. Once the time-activity curves have been extracted, each pixel can be mapped back on to the underlying distribution, considerably reducing image noise. Cluster analysis has been verified using computer simulations and phantom studies. The technique has been applied to SPET images of dopamine D2 receptors in a total of 20 healthy and 20 schizophrenic volunteers (22 male, 18 female), using the ligand 123I-IBZM. Following automatic image segmentation, the concentration of striatal dopamine D2 receptors shows a significant left-sided asymmetry in male schizophrenics compared with male controls. The mean left-minus-right laterality index for controls is -1.52 (95% CI -3.72-0.66) and for patients 4.04 (95% CI 1.07-7.01). Analysis of variance shows a case-by-sex-by-side interaction, with F=10.01, P=0. 005. We can now demonstrate that the previously observed male sex-specific D2 receptor asymmetry in schizophrenia, which had failed to attain statistical significance, is valid. Cluster analysis of dynamic nuclear medicine studies provides a powerful tool for automatic segmentation and noise reduction of the images, removing much of the subjectivity inherent in region-of-interest analysis. The observed striatal D2 asymmetry could reflect long hypothesized disruptions in dopamine-rich cortico-striatal-limbic circuits in schizophrenic males.
 ...
PMID:Multivariate cluster analysis of dynamic iodine-123 iodobenzamide SPET dopamine D2 receptor images in schizophrenia. 902 Nov 6

This study reports the application of Nile blue (NB), a farred oxazine label, as a precolumn derivatization reagent for the measurement of free levels of phenylacetic acid (PAA) in plasma. The measurement of PAA in psychiatric populations is important because it provides a marker for 2-phenylethylamine (PEA), which has been implicated in the pathogenesis of schizophrenia and major depression. PAA was derivatized with NB through an amide linkage in the presence of 2-chloro-1-methylpyridinium iodide (carboxylic acid activator, CMP) and triethylamine (base catalyst, TEA), respectively. The formation of the NB-PAA derivative was confirmed using normal phase and reversed phase thin-layer chromatography, reversed phase liquid chromatography, and electrospray mass spectrometry. The formation of the NB-PAA derivative was optimized using a sequential single factor approach. The optimal conditions for the formation and chromatographic separation of the derivative were determined to be 8.0 nmol/mL NB, 390 nmol/mL CMP, 2 mumol/mL TEA, a reaction time of 45 min, and a reaction temperature of 25 degrees C. This derivatization scheme was performed in a phase transfer catalysis mode that enabled the simultaneous extraction, preconcentration, and derivatization of the analyte in a single step. The limit of derivatization of PAA was determined to be 1.0 x 10(-9) M in phosphate-buffered saline, a PAA-free matrix. This derivatization was limited not by the kinetics of the reaction but by the chromatographic separation of the derivative from a side reaction product. The method was used to estimate endogenous free levels of PAA in human plasma samples. The levels of PAA in four sources of plasma were determined to be within 30-70 ng/mL using the method of standard addition and reflected levels that have been reported in the literature. The limit of detection of the derivative was determined to be 7.33 x 10(-11) M using a laboratory-constructed HPLC-VDLIF detector.
 ...
PMID:Visible diode laser-induced fluorescence detection of phenylacetic acid in plasma derivatized with Nile blue and using precolumn phase transfer catalysis. 925 52

Invasion of the air passage, especially with intraluminal involvement of well-differentiated thyroid carcinoma, is rare. Establishing a patent airway before surgery is necessary, but difficult and risky. We report a case of thyroid cancer with intraluminal invasion of the trachea. A 62-year-old schizophrenic woman presented with blood-tinged sputum and dyspnea. She had undergone a thyroid lobectomy 8 years previously. Computed tomography and bronchoscopy showed a protruding mass in the upper trachea and limited movement of the bilateral vocal folds. Emergency tracheostomy was performed to relieve impending apnea. Fine-needle aspiration of the left protruding thyroid gland showed papillary carcinoma. Because the tumor diffusely infiltrated the thyroid gland and intermingled with fibrosis due to the previous thyroid operation, and because there was limited movement of bilateral vocal folds, the patient underwent total laryngectomy, total thyroidectomy, total parathyroidectomy, and tracheal resection. Neither radioactive iodine nor external irradiation were given because of anticipated poor compliance due to schizophrenia. The postoperative course was smooth and thyroid hormone and calcium were supplemented regularly. The patient has lived well and without local recurrence for more than 3 years since the operation. She can speak with an artificial larynx.
 ...
PMID:Intraluminal involvement of thyroid cancer in the trachea. 958 83

Neuronal nicotinic receptors (nAChRs) have been implicated in pathology associated with neurological diseases and aberrant cognitive states such as addiction and schizophrenia. The design of subtype-specific cholinergic drugs is dependent on identification of key amino acids that play a significant role in determining subunit-specific agonist efficacy. 1,1-Dimethyl-4-phenylpiperazinium (DMPP) and a series of piperazium (PIP)-derived cholinergic agonists (1,1 dimethyl-4-acetylpiperizinium iodide, EthylPIP, PropylPIP, and ButylPIP) were used to identify a site (position 84) in homomeric neuronal nAChRs, which is a partial determinant of pharmacological specificity. In contrast to absolutely conserved amino acids within the nicotinic superfamily, the amino acid in position 84 can be polar or nonpolar. The addition of one methylene to PropylPIP to form ButylPIP eliminated channel activation of but not binding to the chick alpha7 homomeric nAChR (leucine in position 84). In rat alpha7 (glutamine in position 84), ButylPIP was an agonist. 1, 1-Dimethyl-4-phenylpiperazinium, a structural analog of ButylPIP, activates the rat alpha7 but is a weak partial agonist of the chick alpha7. Mutation of the chick alpha7 (L84Q) restored activation by ButylPIP, and the corresponding mutation in rat alpha7 (Q84L) abolished activation by ButylPIP. These mutations had moderate effects on the apparent affinity for acetylcholine, increasing its affinity for chick alpha7 and decreasing it for rat alpha7. Thus, the amino acid in position 84 (a residue on the periphery of the highly conserved loop A of the cys-loop superfamily of receptors) can potentially be exploited to produce subtype-specific drugs and can provide insights into the structure of the binding domain.
 ...
PMID:Identification of a new amino acid residue capable of modulating agonist efficacy at the homomeric nicotinic acetylcholine receptor, alpha7. 988 91

We studied central cannabinoid CB1 receptors in a schizophrenic patient using the pyrazole derivative AM281 labelled with the positron-emitting nuclide iodine-124. A dynamic positron emission tomography (PET) acquisition with simultaneous blood sampling was performed up to 1.5 h post-injection. The classical Logan plot analysis was applied to generate a three-dimensional map of distribution volume (DV). The map was spatially normalised into the Montreal Neurological Institute stereotactic space. Using a volume of interest (VOI) template, mean values of DV were extracted from multiple grey matter regions and white matter (as a reference). As a measure of regional receptor availability, ratios of DV in grey matter to DV in white matter minus one (DVR-1) were calculated. The highest receptor binding was observed in the striatum and the pallidum (DVR-1: 0.35-0.37). Binding in basal ganglia regions was lower on the left than the right side. Moderately high binding was seen in the frontal cortex (0.22), the temporal cortex (0.18) and the cerebellum (0.15). In conclusion, 124I-AM281 PET can be used to reveal areas with prominent CB1 receptor binding. Nevertheless, limited image contrast and relatively high radiation exposure (physical half-life of 124I: 4 days) have to be taken into account. Asymmetric receptor binding may possibly reflect pathologic changes in schizophrenia.
 ...
PMID:Feasibility of central cannabinoid CB1 receptor imaging with [124I]AM281 PET demonstrated in a schizophrenic patient. 1691 17

Sarcosine is an amino acid involved in one-carbon metabolism and a promising therapy for schizophrenia because it enhances NMDA receptor (NMDAR) function by inhibiting glycine uptake. The structural similarity between sarcosine and glycine led us to hypothesize that sarcosine is also an agonist like glycine. We examined this possibility using whole-cell recordings from cultured embryonic mouse hippocampal neurons. We found that sarcosine is an NMDAR co-agonist at the glycine binding site. However, sarcosine differed from glycine because less NMDAR desensitization occurred with sarcosine than with glycine as the co-agonist. This finding led us to examine whether the physiological effects of NMDAR activation with these two co-agonists are the same. The difference in desensitization probably accounts for rises in intracellular Ca(2+), as assessed by the fluorescent indicator fura-FF, being larger when NMDAR activation occurred with sarcosine than with glycine. In addition, Ca(2+)-activated K(+) currents following NMDAR activation were larger with sarcosine than with glycine. Compared to glycine, NMDAR-mediated autaptic currents decayed faster with sarcosine suggesting that NMDAR deactivation also differs with these two co-agonists. Despite these differences, NMDAR-dependent neuronal death as assessed by propidium iodide was similar with both co-agonists. The same was true for neuronal bursting. Thus, sarcosine may enhance NMDAR function by more than one mechanism and may have different effects from other NMDAR co-agonists.
 ...
PMID:The glycine transport inhibitor sarcosine is an NMDA receptor co-agonist that differs from glycine. 1956 42

The serotonin 5-HT(1B) receptors regulate the release of serotonin and are involved in various disease states, including depression and schizophrenia. The goal of the study was to evaluate a high affinity and high selectivity antagonist, [(11)C]P943, as a positron emission tomography (PET) tracer for imaging the 5-HT(1B) receptor. [(11)C]P943 was synthesized via N-methylation of the precursor with [(11)C]methyl iodide or [(11)C]methyl triflate using automated modules. The average radiochemical yield was approx. 10% with radiochemical purity of >99% and specific activity of 8.8+/-3.6 mCi/nmol at the end-of-synthesis (n=37). PET imaging was performed in non-human primates with a high-resolution research tomograph scanner with a bolus/infusion paradigm. Binding potential (BP(ND)) was calculated using the equilibrium ratios of regions to cerebellum. The tracer uptake was highest in the globus pallidus and occipital cortex, moderate in basal ganglia and thalamus, and lowest in the cerebellum, which is consistent with the known brain distribution of 5-HT(1B) receptors. Infusion of tracer at different specific activities (by adding various amount of unlabeled P943) reduced BP(ND) values in a dose-dependent manner, demonstrating the saturability of the tracer binding. Blocking studies with GR127935 (2 mg/kg iv), a selective 5-HT(1B)/5-HT(1D) antagonist, resulted in reduction of BP(ND) values by 42-95% across regions; for an example, in occipital region from 0.71 to 0.03, indicating a complete blockade. These results demonstrate the saturability and specificity of [(11)C]P943 for 5-HT(1B) receptors, suggesting its suitability as a PET radiotracer for in vivo evaluations of the 5-HT(1B) receptor system in humans.
 ...
PMID:High-resolution imaging of brain 5-HT 1B receptors in the rhesus monkey using [11C]P943. 2015 20


1 2 Next >>