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)

Proteins and peptides can be sequenced from the carboxy terminus with isothiocyanate reagents to produce amino acid thiohydantoin derivatives. Previous studies in our laboratory indicated that the use of trimethylsilyl isothiocyanate (TMS-ITC) as a coupling reagent significantly improved the yields and reaction conditions and reduced the number of complicating side products [Hawke et al. (1987) Anal. Biochem. 166, 298]. The present study further explores the conditions for formation of the peptidylthiohydantoins by TMS-ITC and examines the cleavage of these peptidylthiohydantoin derivatives into a shortened peptide and thiohydantoin amino acid derivative. Schizophrenia-related peptide (Thr-Val-Leu) was used as a model peptide and was treated with acetic anhydride and TMS-ITC at 50 degrees C for 30 min, and the peptidylthiohydantoin derivatives were isolated by reverse-phase HPLC and characterized by FAB-MS. The purified derivatives were subjected to a variety of cleavage conditions, and rate constants for hydrolysis were determined. Hydrolysis with acetohydroxamate as reported originally by Stark [(1968) Biochemistry 7, 1796] was found to give excellent cleavage of the terminal thiohydantoin amino acid, but also led to the formation of stable hydroxamate esters of the shortened peptide which are poorly suited for subsequent rounds of degradation. Hydrolysis with 2% aqueous triethylamine under mild conditions (1-5 min at 50 degrees C) was found to be more suitable for carboxy-terminal sequence analysis by the thiocyanate method. The shortened peptide, which could be isolated and subjected to a second round of degradation, and the released thiohydantoin amino acid are formed in good yield (90-100%). Several other small peptides containing 15 different C-terminal amino acid side chains were also investigated in order to examine any interfering reactions that might occur when these side chains are encountered in a stepwise degradation using the thiocyanate chemistry. Quantitative yields of peptidylthiohydantoins were obtained for all the amino acids examined with the following exceptions: low yields were obtained for C-terminal Glu or Thr, and no peptidylthiohydantoins were obtained for C-terminal Pro or Asp. Asparagine was found to form cyclic imides (64%) at the penultimate position (C-2) during hydrolysis of the peptidylthiohydantoins by 2% aqueous triethylamine. Cleavage of C-terminal Asn under these conditions led to the formation of the expected shortened peptide (69%), but also to the formation of a shortened peptide (31%) with a C-terminal amide. Problems with Glu and Thr could be solved by minimizing the reaction time with acetic anhydride.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Carboxy-terminal sequencing: formation and hydrolysis of C-terminal peptidylthiohydantoins. 233 84

Dopamine is implicated in movement, learning, and motivation, and in illnesses such as Parkinson's disease, schizophrenia, and drug addiction. Little is known about the control of dopamine release in humans, but research in experimental animals suggests that the prefrontal cortex plays an important role in regulating the release of dopamine in subcortical structures. Here we used [(11)C]raclopride and positron emission tomography to measure changes in extracellular dopamine concentration in vivo after repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex in healthy human subjects. Repetitive TMS of the left dorsolateral prefrontal cortex caused a reduction in [(11)C]raclopride binding in the left dorsal caudate nucleus compared with rTMS of the left occipital cortex. There were no changes in binding in the putamen, nucleus accumbens, or right caudate. This shows that rTMS of the prefrontal cortex induces the release of endogenous dopamine in the ipsilateral caudate nucleus. This finding has implications for the therapeutic and research use of rTMS in neurological and psychiatric disorders.
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PMID:Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus. 1145 78

Low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) can depress the excitability of the cortex locally and has been proposed for the treatment of disorders such as schizophrenia and epilepsy. Some have speculated that the depressant effect is related to long-term depression (LTD) of cortical synapses. Because in vitro LTD can be enhanced by pretreatment of synapses with higher-frequency stimulation, we hypothesized that if rTMS depression had mechanisms in common with LTD, higher-frequency priming would increase it also. In 25 healthy volunteers in two experiments, we measured motor-evoked potentials (MEPs) from TMS of the motor cortex to define the baseline response. Subthreshold rTMS (6 Hz, fixed rate or frequency modulated) was used to prime the motor cortex, followed by suprathreshold 1 Hz stimulation for 10 min at just above the MEP threshold. Over the next 60 min, we recorded MEPs every 10 sec and found significant increases in the amount of cortical depression with both types of 6 Hz priming rTMS relative to sham. The MEP depression from 6 Hz-primed 1 Hz rTMS showed no evidence of decay after 60 min. Pretreatment with 6 Hz primes both 1 Hz rTMS depression and LTD. Although not conclusive evidence, this strengthens the case for overlapping mechanisms and suggests a potent new technique for enhancing low-frequency rTMS depression that may have experimental and clinical applications.
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PMID:Priming stimulation enhances the depressant effect of low-frequency repetitive transcranial magnetic stimulation. 1464 80

Transcranial magnetic stimulation as mapping method offers the possibility to measure aspects of motor cortex excitability painlessly and non-invasively. Using this neurophysiological tool, new insights into the effects of central-acting drugs are possible. Particularly striking seems to be the potential of this approach to gain new insights into neurobiological processes associated with neuropsychiatric diseases like schizophrenia or major depression. In combination with genetic aspects, TMS is able to bridge the gap between molecular research and clinical approach.
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PMID:[The neuronal level of motor activity: determination of motor cortex excitability by TMS]. 1581 20

Brain imaging studies performed over the past 20 years have generated new knowledge about the specific brain regions involved in the brain diseases that have been classically labeled as psychiatric. These include the mood and anxiety disorders, and the schizophrenias. As a natural next step, clinical researchers have investigated whether the minimally invasive brain stimulation technologies (transcranial magnetic stimulation [TMS] or transcranial direct current stimulation [tDCS]) might potentially treat these disorders. In this review, we critically review the research studies that have examined TMS or tDCS as putative treatments for depression, mania, obsessive-complusive disorder, posttraumatic stress disorder, panic disorder, or schizophrenia. (Separate controversy articles deal with using TMS or tDCS to treat pain or tinnitus. We will not review here the large number of studies using TMS or tDCS as research probes to understand disease mechanisms of psychiatric disorders.) Although there is an extensive body of randomized controlled trials showing antidepressant effects of daily prefrontal repetitive TMS, the magnitude or durability of this effect remains controversial. US Food and Drug Administration approval of TMS for depression was recently granted. There is much less data in all other diseases, and therapeutic effects in other psychiatric conditions, if any, are still controversial. Several issues and problems extend across all psychiatric TMS studies, including the optimal method for a sham control, appropriate coil location, best device parameters (intensity, frequency, dosage, and dosing schedule) and refining what subjects should be doing during treatment (activating pathologic circuits or not). In general, TMS or tDCS as a treatment for most psychiatric disorders remains exciting but controversial, other than prefrontal TMS for depression.
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PMID:Controversy: Repetitive transcranial magnetic stimulation or transcranial direct current stimulation shows efficacy in treating psychiatric diseases (depression, mania, schizophrenia, obsessive-complusive disorder, panic, posttraumatic stress disorder). 2063 99

The default mode network is a group of brain regions that are active when an individual is not focused on the outside world and the brain is at "wakeful rest." It is thought the default mode network corresponds to self-referential or "internal mentation". It has been hypothesized that, in humans, activity within the default mode network is correlated with certain pathologies (for instance, hyper-activation has been linked to schizophrenia and autism spectrum disorders whilst hypo-activation of the network has been linked to Alzheimer's and other neurodegenerative diseases. As such, noninvasive modulation of this network may represent a potential therapeutic intervention for a number of neurological and psychiatric pathologies linked to abnormal network activation. One possible tool to effect this modulation is Transcranial Magnetic Stimulation: a non-invasive neurostimulatory and neuromodulatory technique that can transiently or lastingly modulate cortical excitability (either increasing or decreasing it) via the application of localized magnetic field pulses. In order to explore the default mode network's propensity towards and tolerance of modulation, we will be combining TMS (to the left inferior parietal lobe) with functional magnetic resonance imaging (fMRI). Through this article, we will examine the protocol and considerations necessary to successfully combine these two neuroscientific tools.
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PMID:Combining transcranial magnetic stimulation and FMRI to examine the default mode network. 2124 84

Non-pharmacological biological therapies of schizophrenia have dramatically developed over the last eight decades. Starting from a historical perspective authors aim to give an overview about the development of convulsive therapy. Recommendations of the most influential guidelines and the controversies in the worldwide clinical practice are discussed and clinical conditions responsive to electroconvulsive therapy are reviewed. Finally, the place of the new neurostimulation techniques, particularly TMS is outlined.
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PMID:Non-pharmacological biological therapies in schizophrenia. 2218 92

This special theme issue of Schizophrenia Bulletin presents a series of related articles focusing on auditory hallucinations, prepared by members of the International Consortium on Hallucination Research [InCoHR] working groups. The InCoHR is a large collaborative framework that serves as a platform for researchers to meet and collaborate on multidisciplinary projects relating to auditory hallucinations [AH] and discuss methodological issues facing transdiagnostic research. Laroi et al. observe the similarities in characteristic features of AHs in different clinical and nonclinical groups, but they also note that differences exist, reflecting the contribution of disease-related process. Waters et al. use findings of shared cognitive impairments across different diagnostic groups with AHs to propose a novel theoretical cognitive framework. Allen et al. describe that the neurobiological substrates of AHs include neural systems involved in language processing, as well as sensory and nonsensory brain regions and that studies are increasingly using fine-grain analysis of patients' characteristics in analyzing neuroimaging data. Ford et al. discuss different neurophysiological approaches and describes hallucination-related alterations in activity in temporal and frontal regions of the brain and particularly in auditory cortical areas. Finally, Sommer et al. review different treatment options for AHs in schizophrenia and other disorders, including pharmacological treatment, cognitive-behavioral therapy [CBT] and acceptance and commitment therapy [ACT], transcranial magnetic stimulation [TMS], and electroconvulsive therapy [ECT]. These related publications describe the current substance and direction of research on AHs across different diagnostic groups.
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PMID:Multidisciplinary approaches to understanding auditory hallucinations in schizophrenia and nonschizophrenia populations: the International Consortium on Hallucination Research. 2283 51

One Hertz (1 Hz) repetitive transcranial magnetic stimulation (rTMS) is an effective therapy for auditory verbal hallucinations (AVH). Theta burst protocols (TBS) show longer after-effects. This single-blind, randomized controlled study compared continuous TBS with 1Hz rTMS in a 10-day treatment. Patients were diagnosed with schizophrenia or schizoaffective disorder. TBS demonstrated equal clinical effects compared to 1Hz TMS.
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PMID:Theta burst transcranial magnetic stimulation for the treatment of auditory verbal hallucinations: results of a randomized controlled study. 2364 82

Transcranial magnetic stimulation is an established method to probe inhibitory and facilitatory networks within the human motor cortex. Reduced motor-cortical inhibition is a common finding in schizophrenia patients. Based on neuropathological findings, the reduced cortical inhibition in schizophrenia has been linked mainly to alterations in GABAergic neurotransmission. The aim of this study was to investigate the impact of disease state on intracortical inhibitory and facilitatory networks measured by TMS in schizophrenia. Cortical excitability was investigated in a pooled cross-sectional sample of recent-onset-schizophrenia (RO-SZ), chronically-ill schizophrenia patients (CH-SZ) and healthy controls (HC) using single- and paired-pulse TMS applied to the left primary motor cortex. The sample included 41 RO-SZ, 42 CH-SZ and 59 HC. Analyses were focused on resting motor threshold (RMT), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP). There was a significant difference regarding the mean CSP durations across our three study groups (p=0.002). Subgroup comparisons revealed a shorter CSP in HC compared to RO-SZ (p<0.001). Three group comparisons of SICI (p=0.098) and RMT (p=0.075) showed differences at a trend-level. An overall comparison between HC and all patients showed a significantly reduced SICI (p=0.031) and prolonged CSP (p=0.003) in schizophrenia patients. This is the largest and first cross-sectional investigation of various excitability parameters in schizophrenia patients. These findings indicate general alterations of cortical inhibition, with differences between recent-onset and chronically-ill schizophrenia patients.
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PMID:Impairments in motor-cortical inhibitory networks across recent-onset and chronic schizophrenia: a cross-sectional TMS Study. 2450 48


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