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)

We recently proposed a new psychostimulant animal model of the progressive pathophysiological changes of schizophrenia. Studies using that model produced a treatment strategy for preventing progression. Lamotrigine (LTG) blocks repeated high-dosage methamphetamine (METH)-induced initiation and expression of prepulse inhibition deficit and development of apoptosis in the medial prefrontal cortex (mPFC). Moreover, it inhibits METH-induced increases in extracellular glutamate levels in the mPFC (Nakato et al., 2011, Neurosci. Lett.). Abnormal behavior induced by METH or NMDA receptor antagonists is regarded as an animal model of schizophrenia. This study examined the effects of LTG on the development of behavioral sensitization to METH and cross-sensitization to dizocilpine (MK-801) by repeated administration of high-dose METH (2.5mg/kg, 10 times s.c.). Rats were injected repeatedly with LTG (30mg/kg) after 120min METH administration (2.5mg/kg). Repeated co-administration of LTG blocked the development of behavioral cross-sensitization to MK-801 (0.15mg/kg), but it did not prevent behavioral sensitization to METH (0.2mg/kg). The LTG-induced prevention of increased glutamate by high-dose METH might be related to the former finding. Combined results of our previous studies and this study suggest that LTG is useful to treat schizophrenia, especially at a critical point in its progression.
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PMID:Lamotrigine blocks repeated high-dose methamphetamine-induced behavioral sensitization to dizocilpine (MK-801), but not methamphetamine in rats. 2194 44

Ketamine acts as an N-methyl-D-aspartate receptor antagonist and evokes psychotomimetic symptoms resembling schizophrenia in healthy humans. Imaging markers of acute ketamine challenge have the potential to provide a powerful assay of novel therapies for psychiatric illness, although to date this assay has not been fully validated in humans. Pharmacological magnetic resonance imaging (phMRI) was conducted in a randomized, placebo-controlled crossover design in healthy volunteers. The study comprised a control and three ketamine infusion sessions, two of which included pretreatment with lamotrigine or risperidone, compounds hypothesized to reduce ketamine-induced glutamate release. The modulation of the ketamine phMRI response was investigated using univariate analysis of prespecified regions and a novel application of multivariate analysis across the whole-brain response. Lamotrigine and risperidone resulted in widespread attenuation of the ketamine-induced increases in signal, including the frontal and thalamic regions. A contrasting effect across both pretreatments was observed only in the subgenual prefrontal cortex, in which ketamine produced a reduction in signal. Multivariate techniques proved successful in both classifying ketamine from placebo (100%) and identifying the probability of scans belonging to the ketamine class (ketamine pretreated with placebo: 0.89). Following pretreatment, these predictive probabilities were reduced to 0.58 and 0.49 for lamotrigine and risperidone, respectively. We have provided clear demonstration of a ketamine phMRI response and its attenuation with both lamotrigine and risperidone. The analytical methodology used could be readily applied to investigate the mechanistic action of novel compounds relevant for psychiatric disorders such as schizophrenia and depression.
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PMID:Quantifying the attenuation of the ketamine pharmacological magnetic resonance imaging response in humans: a validation using antipsychotic and glutamatergic agents. 2337 Jul 94

A 28-year-old woman diagnosed with schizophrenia was admitted to hospital due to progressing dyspnoea for months. At admission, she was oxygen-dependent, and a high-resolution computed tomography revealed ground glass opacities. She had no obvious exposures besides having been treated with lamotrigine for several years. A psychiatrist doubted the diagnosis, and the lamotrigine treatment was tapered. After some months, she became clinically stable without further need of oxygen. Lamotrigine can cause pneumonitis, and this side effect should be suspected in patients who are being treated with lamotrigine and presenting with progressive dyspnoea. Crucial treatment is to remove the exposure.
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PMID:[Lamotrigine-induced pneumonitis]. 2796 26

30% of people with schizophrenia do not respond to antipsychotics. In these cases, treatment with clozapine is indicated, but only 40% of this subpopulation responds to treatment, thus forming a subgroup of resistant patients who do not respond to clozapine and are therefore referred to as ultra-resistant. Between 12 and 20% of people with schizophrenia are ultra-resistant. The objective of this work is to review the possible treatment for ultra-resistance and its scientific evidence. From the review carried out, it is clear that: 1) The addition of a second antipsychotic to clozapine has a partial response, and there is no antipsychotic that shows significant difference compared to others. 2) Of the antiepileptics, the one that generates a slight clinical improvement is sodium valproate, but even so, a complete response is not achieved. Lamotrigine, in turn, generates a therapeutic response in studies with mild to moderately symptomatic patients. 3) The use of inhibitors of d-amino oxidase, such as sodium benzoate, only achieved a slight clinical improvement without achieving a comprehensive therapeutic response. 4) The addition of memantine was not effective. 5) The addition of electroconvulsive therapy generates significant therapeutic response in severely symptomatic patients for both the positive and negative symptomatic dimensions. Electroconvulsive therapy does not generate cognitive alterations, produces improvement in immediate and long-term verbal memory and in executive functions. Currently more robust evidence concerning therapeutic approaches to ultrarresistant schizophrenia are lacking. In particular, randomized and controlled studies with significant number of patients will be valuable of help to make decisions in this subpopulation with an important impairment in their functionality and quality of life.
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PMID:[Approaches for the treatment of people with schizophrenia that do not respond to clozapine or ultra-resistant schizophrenia. Review of the evidence.] 3196 29


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