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

Latent inhibition consists of a decrement in conditioning to a stimulus as a result of its prior non-reinforced pre-exposure. Based on evidence pointing to the involvement of the hippocampus and the nucleus accumbens in latent inhibition disruption, it has been proposed that latent inhibition depends on the integrity of the subicular input to the nucleus accumbens. Since fibers originating in the subiculum and destined for the nucleus accumbens run through the fimbria-fornix, we assessed the effects of radiofrequency lesion or transection of the fimbria-fornix, on latent inhibition. The effectiveness of both lesions was demonstrated by the total disappearance of acetylcholinesterase staining in the hippocampus and of retrogradely labeled cells in the hippocampus/subiculum following the injection of the retrograde tracer biotin-dextran amine into the shell subregion of the nucleus accumbens. Likewise, in accord with previously documented behavioral effects of lesions to the hippocampus and related structures, both lesions increased spontaneous activity and disrupted performance in Morris water maze, and the radiofrequency lesion facilitated the acquisition of two-way active avoidance. In spite of the above, latent inhibition remained unaffected by both fimbria-fornix lesions, indicating that the critical projections subserving latent inhibition are not those traversing the fimbria-fornix from the hippocampus/subiculum to the nucleus accumbens. The implications of these results for the neural circuitry of latent inhibition and the latent inhibition model of schizophrenia are discussed.
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PMID:The effects of radiofrequency lesion or transection of the fimbria-fornix on latent inhibition in the rat. 1039 42

Rigorous experimental design can minimize the high risk of false positives and false negatives in the behavioral phenotyping of a new transgenic or knockout mouse. Use of well established, quantitative, reproducible behavioral tasks, appropriate Ns, correct statistical methods, consideration of background genes contributed by the parental strains, and attention to litter and gender issues, will maximize meaningful comparisons of -/-, +/-, and +/+ genotypes. Strategies developed and used by our laboratory are described in this review. Preliminary observations evaluate general health and neurological reflexes. Sensory abilities and motor functions are extensively quantitated. Specific tests include observations of home cage behaviors, body weight, body temperature, appearance of the fur and whiskers, righting reflex, acoustic startle, eye blink, pupil constriction, vibrissae reflex, pinna reflex, Digiscan open field locomotion, rotarod motor coordination, hanging wire, footprint pathway, visual cliff, auditory threshold, pain threshold, and olfactory acuity. Hypothesis testing then focuses on at least three well-validated tasks within each relevant behavioral domain. Specific tests for mice are described herein for the domains of learning and memory, feeding, nociception, and behaviors relevant to discrete symptoms of human anxiety, depression, schizophrenia, and drug addiction. An example of our approach is illustrated in the behavioral phenotyping of C/EBPdelta knockout mice, which appear to be normal on general health, neurological reflexes, sensory and motor tasks, and the Morris water task, but show remarkably enhanced performance on contextual fear conditioning.
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PMID:Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests. 1044 92

Recent in vivo diffusion brain imaging studies of schizophrenic patients have revealed microstructural abnormalities, with low diffusion anisotropy present throughout much of cortical white matter. Brain anisotropy is produced when proton movement reflects physically restricted water movement, for example, by myelin sheaths. Conditions that increase self-diffusion, such as edema, may also alter the longitudinal and transverse relaxation time of protons, and it is possible that such changes could explain the observed anisotropy diminution seen in schizophrenia. To test this possibility, we calculated pixel-by-pixel transverse relaxation time (T2) and proton density (PD) maps for gray matter and white matter across eight 5-mm-thick axial slices of fast spin echo MRI in 10 control men (age 30-57 years) and 10 men with schizophrenia (age 32-64 years). Schizophrenics had significantly longer mean white matter T2 (84.0 vs. 81.9 ms, P<0.03) and gray matter T2 (95.1 vs. 92.2, P = 0.003); their mean white and gray matter PD values were not significantly different from those of controls. Correlations were not significant between anisotropy and T2 in either grey or white matter but were significant between anisotropy and PD in white matter. T2 relaxation times are longer in schizophrenics than in controls in both gray and white matter whereas anisotropy reduction is restricted to white matter. Taken together, these results suggest that the process producing prolonged T2 does not fully account for the abnormally low anisotropy observed selectively in white matter in this group of schizophrenic patients.
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PMID:Brain gray and white matter transverse relaxation time in schizophrenia. 1051 64

A 36-y-o patient with schizophrenia, who had consumed gradually increasing quantities of oolong tea that eventually reached 15 L each day, became delirious and was admitted to a psychiatric hospital. After abstinence from oolong tea his delirium resolved. He was transferred to our hospital when he was discovered to have acute renal failure with hyponatremia (118 mEq/L) and severe rhabdomyolysis (creatine phosphokinase, 227,200 IU/L). On admission rhabdomyolysis had begun to improve despite a worsening of the hyponatremia (113 mEq/L). With aggressive supportive therapy, including hypertonic saline administration and hemodialysis, the patient fully recovered without detectable sequelae. The clinical course suggests that caffeine, which is present in oolong tea, was mainly responsible for the rhabdomyolysis as well as the delirium, although severe hyponatremia has been reported to cause rhabdomyolysis on rare occasions. We hypothesize that caffeine toxicity injured the muscle cells, which were fragile due to the potassium depletion induced by the coexisting hyponatremia, to result in unusually severe rhabdomyolysis. The possibility of severe rhabdomyolysis should be considered in a patient with water intoxication due to massive ingestion of caffeine-containing beverages.
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PMID:Severe rhabdomyolysis following massive ingestion of oolong tea: caffeine intoxication with coexisting hyponatremia. 1059 46

1. Increased water intake and output is more common among psychiatric patients, especially those with schizophrenia, than in the general population. Animal studies suggest that polydipsia and polyuria derive, in part, from dopamine dysregulation. Stimulated by these observations this study sought to elucidate relationships among water homeostasis, monoamine metabolism, and electrolyte excretion in schizophrenic patients with and without paranoid hallucinatory symptoms (PH vs. NP), thought to reflect hyper- and hypo-dopaminergic states respectively, and to compare these with those shown by patients with obsessive compulsive disorder (OCD). 2. 24 hr-urine samples for electrolyte, monoamine and metabolite measures were taken from 14 schizophrenic patients with PH symptoms, 13 with predominantly nonparanoid (NP) symptoms, 11 OCD patients and 27 healthy controls (matched for age, weight and creatinine production). Water intake and serum electrolytes was sampled during psychological testing. 3. PH patients drank 2-3 times more than the others in a 3-4 hr test, yet 24 hr-urinary volumes were 75% larger in both PH and NP patients than in the two comparison groups. 4. Daily potassium excretion was a bit higher in PH patients, but concentrations of sodium, potassium and phosphate tended to be lower in PH and NP patients than in the others. 5. Positive associations of electrolyte with homovanillic acid excretion were consistent across groups and not directly related to medication. But associations of electrolyte excretion with noradrenergic activity in controls were absent in psychotic patients and associations with serotonin in OCD patients were absent in the other groups. 6. Increased water intake and output in PH patients along with the disturbed association with noradrenergic metabolism are consistent with altered autonomic activity in these patients. 7. The independence of measures of water homeostasis from dopaminergic medication indicates that the associations in clinically responding PH patients of polydipsia with DA function (decreased DA levels) may be pertinent to this subgroup but not to schizophrenia in general.
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PMID:Subclinical polydipsia and polyuria in young patients with schizophrenia or obsessive-compulsive disorder vs normal controls. 1063 61

A 32-year-old woman with chronic schizophrenia who took 8-10 liters of water for three years due to thirsty, admitted to our hospital because of convulsion and muscle weakness. Neurological finding on admission showed a mild disturbance of consciousness, moderate proximal muscle weakness, and muscle pain. Laboratory examination revealed marked serum hyponatremia(102 mEq/l) and high value of creatin kinase (1,259 IU/l). The level of creatin kinase reached a peak(39,700 IU/l) at the 5th hospital day. An analysis of the muscle biopsy specimen showed necrotic muscle fibers and opaque fibers, that was compatible with rhabdomyolysis. T 2 weighted magnetic resonance imaging of the brain showed a transient high signals in bilateral putamen but not in pons. She was diagnosed to have rhabdomyolysis due to water intoxication. The present case is the first rhabdomyolysis in Japan that was confirmed by muscle biopsy at an acute stage of water intoxication related with schizophrenia.
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PMID:[A case of rhabdomyolysis with water intoxication confirmed by muscle biopsy]. 1068 92

The frontostriatal system (dorsolateral prefrontal cortex, lateral orbitofrontal cortex, anterior cingulate, supplementary motor area, and associated basal-ganglia structures) is subject to a range of neurodevelopmental disorders: Tourette's syndrome (TS), obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), autism, and probably depression. The system is responsible for our adaptive responses (initiation, execution, or withholding) to environmental situations, and the above disorders, involving effectively excessive release or withholding of various types of response, are all a consequence of changes in specific frontostriatal regions. The disorders all have a genetic component, and their persistence in the genome indicates that their clinical manifestations may also be associated, perhaps in low levels in close relatives, with certain adaptive advantages in given situations. Thus autism is associated with computational careers, depression with literary creativity, SCZ with lateral thinking and the Odyssean personality, ADHD with an Ice-Age readiness to respond, OCD with a focused range of interests, and TS with competitive sports and jazz improvisation. The disorders are all highly comorbid, and which one predominantly manifests may depend on how the frontostriatal system happens to be compromised as a result of inherited genetic predispositions and environmental contingency. We review the adaptive nature of the various subclinical manifestations and the evidence for concomitant phenomena (possibly epiphenomena): alterations in structural, functional, and behavioral lateralization in each syndrome. Indeed it is not clear that altered lateralization in frontostriatal disorders of a neurodevelopmental origin generally has any adaptive significance; it may often simply serve as a marker for altered regulatory function of the frontostriatal system, alterations which in low genetic dosage or penetrance continue to play an adaptive role in clinically unaffected close relatives of probands, but which, in high dosage or penetrance in the probands themselves, are generally deleterious.
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PMID:The neurodevelopmental frontostriatal disorders: evolutionary adaptiveness and anomalous lateralization. 1085 79

The annexins are water soluble proteins possessing a hydrophilic surface, which belong to a family of proteins which (a) bind ('annex') both calcium and phospholipids, and (b) form voltage-dependent calcium channels within planar lipid bilayers. Annexins types are diverse (94 annexins in 45 species) and they belong to an enormous multigene family that ranges throughout all eukaryotic kingdoms. Although the structure of these proteins is now well known their functional and physiological roles remain largely unknown and circumstantial. Various experimental approaches provided evidence that annexins function as Ca(2+) channels that could act as regulators of membrane fusion. The identity of annexins is derived from the conserved 34 kDa C-terminal domain which comprises four repeats - except for annexin VI, with eight repeats - of a sequence of approximately seventy amino acids, which holds the area known as the 'endonexin fold', with its identifying GXGTDE. Annexins have been placed into three subgroups of (1) tetrad core and short amino terminal, (2) tetrad core and long amino terminal, and (3) octad core and short amino terminal. The repeats are highly conserved, each forming a compact alpha-helical domain comprising five alpha-helices wound in a right-handed superhelix. Four domains are formed, arranged in a nearly flat and cyclical array, with domains I and IV, and II and III respectively forming two tightly organised modules with almost twofold symmetry. A hydrophilic pore lies at the centre of the molecule, forming a prominent ion channel coated with charged and highly conserved residues. The annexin molecule is slightly curved, with both a convex and a concave face. The cation/anion permeability ratios and the selectivity sequence of the ion channels formed by several annexins confirm the selectivity of the annexins for Ca(2+) over other divalent cations, and reveals the importance of structural sites, e.g. amino acid positions 17, 78, 95 and 112 for the identification of the ion channel's position, function and regulation. Some are sensitive to low doses of the phenothiazine drugs, trifluoperazine (an anti-schizophrenia drug) and promethazine (anti nausea drug) La(3+) and Cd(2+), (blockers of voltage-gated Ca(2+) channels) nifedipine (an inhibitor of non-activating Ca(2+) channels). There are two main competing models used to explain in vitro ion channel activity of annexins: one involves changes in the conductance of ion via electrostatic disturbance of the membrane surface; the other involves a much more extensive alteration in protein structure and a correspondingly deeper penetration into the membrane.
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PMID:Biophysical and molecular properties of annexin-formed channels. 1095 28

Functional brain imaging studies have reported decreased frontal activations in schizophrenia, but hemispheric dominance for language has rarely been assessed. To investigate regional activation and lateralization during word production, we determined normalized regional cerebral blood flow (rCBF) variations with positron emission tomography (PET) and H2(15)O (water labeled with the isotope oxygen 15) in 14 negative schizophrenia patients and 14 volunteers. Subjects were scanned during two trials of three conditions: rest, vocalized verbal fluency, and spontaneous word production. Images were analyzed using an anatomical volumes of interest method, and the two groups' changes were compared, using rest as a baseline. Differences in the lateralization of changes were detected in homologous frontal and inferior parietal regions. The lateralization effects in patients arose from lower activations in the left frontal regions, abnormal right inferior frontal activations, and weaker right inferior parietal deactivation, during the word production tasks. The right hemisphere changes correlated negatively with the performance in verbal fluency. Thus in negative schizophrenia patients, while the activations were less focused on the left hemisphere regions usually engaged in word generation, rCBF changes in the right hemisphere might reflect a compensatory functional pattern.
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PMID:Altered hemispheric functional dominance during word generation in negative schizophrenia. 1099 8

The assessment of cerebral functions has long been the domain of positron-emission tomography and single photon emission computed tomography. The use of rapid imaging sequences and contrast agents enables physiological and pathophysiological cerebral processes to be assessed and monitored by magnetic resonance imaging. Both T1- and T2-weighted contrast-enhanced fast imaging sequences can be used to assess tissue perfusion, vascularity, and microcirculation by applying models developed in nuclear medicine. The diffusion of water molecules and hemodynamic aspects of the macrovasculature can also be monitored. Functional magnetic resonance (MR) imaging enables the visualization of neuronal function and activity, and MR spectroscopy makes possible the metabolic mapping of lesions and surrounding tissue. The advantages of MR techniques includes their low invasiveness, multiplanar imaging ability, and lack of radiation. This contribution discusses the clinical use of functional MR imaging methods and their role in neuroradiological diseases. Measuring perfusion and diffusion allows detailed insight into the pathophysiology of cerebral ischemia and is already being used routinely in acute ischemic stroke. Dynamic MR angiography enables the hemodynamic assessment of vascular malformations. In CNS neoplasms these imaging techniques can improve lesion characterization and the selecting, planning, and monitoring of therapy. Functional MR imaging techniques have also revolutionized the study of psychiatric illness; however, their clinical utility here is still limited. Initial results in patients with dementia and schizophrenia have provided insight into the pathophysiological changes of these diseases.
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PMID:[Functional magnetic resonance tomography in neuroradiology]. 1110 7


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