ABSTRACT
BACKGROUND: Recent findings suggest that dopaminergic abnormalities found in psychotic disorders may be secondary to nitric oxide dysfunctions. Nitric oxide seems to influence glutamatergic and dopaminergic neurotransmission, both of which have been associated with psychosis. OBJECTIVE: To search and review published works which examined the influence of nitric oxide in psychotic disorders subjects. METHODS: The research was executed in the on-line collections of Pubmed and ISI Web of Science. The key aspects utilized were "Psychotic Disorders AND Nitric Oxide", "Psychosis AND Nitric Oxide","Schizotypal Personality Disorder AND Nitric Oxide", "Delusional Disorder AND Nitric Oxide", "Brief Psychotic Disorder AND Nitric Oxide", "Schizophreniform Disorder AND Nitric Oxide", "Schizoaffective Disorder AND Nitric Oxide", and "Schizophrenia AND Nitric Oxide". Empirical works utilizing human subjects, published in the last 10 years, in English language were included. RESULTS: Initially, the search yielded a total of 95 studies. Then, 39 were elected according to the inclusion requirements. The selected articles were divided into five groups: biochemical studies (n=15; 38.5%), genetic studies (n=11; 28.2%), postmortem studies (n=6; 15.4%), clinical trials (n=6; 15.4%), and case reports (n=1; 2.5%). The studies evaluated only schizophrenic or schizoaffective disorder subjects. The great majority of them found evidence of nitric oxide dysfunctions in psychosis. CONCLUSIONS: The results of the review strengthen the idea that nitric oxide has a key participation in psychotic disorders and deserves deeper investigation as a target for future pharmacological intervention.
Subject(s)
Nitric Oxide/metabolism , Psychotic Disorders/pathology , Antipsychotic Agents/therapeutic use , Arginine/analogs & derivatives , Arginine/therapeutic use , Brain/metabolism , Clinical Trials as Topic , Humans , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase/metabolism , Phosphodiesterase 5 Inhibitors/therapeutic use , Psychotic Disorders/drug therapy , Psychotic Disorders/metabolism , Schizophrenia/drug therapy , Schizophrenia/metabolism , Schizophrenia/pathology , Sildenafil Citrate/therapeutic useABSTRACT
BACKGROUND: Better treatments for schizophrenia are urgently needed. The therapeutic use of the nitric oxide (NO)-donor sodium nitroprusside (SNP) in patients with schizophrenia has shown promising results. The role of NO in schizophrenia is still unclear, and NO modulation is unexplored in ketamine (KET) animal models to date. In the present study, we compared the behavioral effects of pre- and post-treatment with SNP, glyceryl trinitrate (GTN), and methylene blue (MB) in the acute KET animal model of schizophrenia. The present study was designed to test whether acute SNP, GTN, and MB treatment taken after (therapeutic effect) or before (preventive effect) a single KET injection would influence the behavior of rats in the sucrose preference test, object recognition task and open field. RESULTS: The results showed that KET induced cognitive deficits and hyperlocomotion. Long- term memory improvement was seen with the therapeutic GTN and SNP treatment, but not with the preventive one. MB pretreatment resulted in long-term memory recovery. GTN pre-, but not post-treatment, tended to increase vertical and horizontal activity in the KET model. Therapeutic and preventive SNP treatment consistently decreased KET-induced hyperlocomotion. CONCLUSION: NO donors - especially SNP - are promising new pharmacological candidates in the treatment of schizophrenia. In addition, we showed that the potential impact of NO-related compounds on KET-induced behavioral changes may depend on the temporal window of drug administration.
Subject(s)
Antipsychotic Agents/pharmacology , Methylene Blue/pharmacology , Nitroglycerin/pharmacology , Nitroprusside/pharmacology , Schizophrenia/drug therapy , Acute Disease , Animals , Cognition Disorders/drug therapy , Cognition Disorders/physiopathology , Dietary Sucrose/administration & dosage , Disease Models, Animal , Exploratory Behavior/drug effects , Male , Motor Activity , Nitric Oxide Donors/pharmacology , Rats, Wistar , Recognition, Psychology/drug effects , Schizophrenia/physiopathology , Schizophrenic Psychology , Taste Perception/drug effects , Treatment OutcomeABSTRACT
We report the case of an adult male patient with Tourette syndrome, self-injurious behavior and depression, refractory to conventional treatment, and whose symptoms remitted after electroconvulsive therapy. Serial Technetium 99m-Ethyl-Cysteinate-Dimer single photon emission tomographies were applied, before, during, and after electroconvulsive therapy. The neural substrates of this treatment process were further analyzed by woxel-wise subtracted single photon emission tomography images.
Subject(s)
Brain/diagnostic imaging , Electroconvulsive Therapy , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Tomography, Emission-Computed, Single-Photon , Tourette Syndrome/diagnostic imaging , Tourette Syndrome/therapy , Adult , Brain/blood supply , Brain/physiopathology , Brain Mapping , Brief Psychiatric Rating Scale , Cerebral Cortex/blood supply , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/physiopathology , Combined Modality Therapy , Cysteine/analogs & derivatives , Depressive Disorder/diagnostic imaging , Depressive Disorder/physiopathology , Depressive Disorder/therapy , Humans , Male , Neurologic Examination , Organotechnetium Compounds , Psychotropic Drugs/administration & dosage , Regional Blood Flow/physiology , Self-Injurious Behavior/diagnostic imaging , Self-Injurious Behavior/physiopathology , Self-Injurious Behavior/therapy , Subtraction Technique , Tourette Syndrome/physiopathologyABSTRACT
The hypothesis that schizophrenia involves aberrant inter-hemispheric communication has a long pedigree, however its precise role remains unclear. We therefore report the case of a total agenesis of the corpus callosum in a 21-year-old man with childhood-onset schizophrenia. The presence of schizophrenia with very early onset on absence of corpus callosum offers an opportunity to examine neurodevelopmental model and theories regarding to interhemispheric communication in the pathogenesis of psychosis.
A hipótese que a esquizofrenia envolve comunicação inter-hemisférica aberrante possui longa tradição, entretanto seu papel permanece incerto. Nós relatamos um caso de agenesia total do corpo caloso em um homem de 21 anos portador de esquizofrenia de início na infância. A associação de esquizofrenia de início precoce na ausência de corpo caloso oferece uma oportunidade para exame do modelo neurodesenvolvimental e de teorias que envolvem a comunicação interemisférica na patogênese da psicose.
Subject(s)
Adult , Humans , Male , Corpus Callosum/abnormalities , Schizophrenia, Childhood/etiology , Electroencephalography , Magnetic Resonance Imaging , Schizophrenia, Childhood/pathologyABSTRACT
The hypothesis that schizophrenia involves aberrant inter-hemispheric communication has a long pedigree, however its precise role remains unclear. We therefore report the case of a total agenesis of the corpus callosum in a 21-year-old man with childhood-onset schizophrenia. The presence of schizophrenia with very early onset on absence of corpus callosum offers an opportunity to examine neurodevelopmental model and theories regarding to interhemispheric communication in the pathogenesis of psychosis.
Subject(s)
Agenesis of Corpus Callosum , Schizophrenia, Childhood/etiology , Adult , Electroencephalography , Humans , Magnetic Resonance Imaging , Male , Schizophrenia, Childhood/pathologySubject(s)
Antipsychotic Agents/therapeutic use , Clinical Trials, Phase I as Topic , Randomized Controlled Trials as Topic , Schizophrenia/drug therapy , Acute Disease , Antipsychotic Agents/adverse effects , Benzodiazepines/adverse effects , Benzodiazepines/therapeutic use , Dose-Response Relationship, Drug , Dyskinesia, Drug-Induced/etiology , Humans , Olanzapine , Patient Dropouts , Perphenazine/adverse effects , Perphenazine/therapeutic use , Treatment OutcomeABSTRACT
Cannabidiol (CBD), one of the major products of the marijuana plant, is devoid of marijuana's typical psychological effects. In contrast, potential antipsychotic efficacy has been suggested based on preclinical and clinical data (Zuardi et al., 2002). In this report, we further investigated the efficacy and safety of CBD monotherapy in three patients with treatment-resistant schizophrenia (TRS). This was an in-patient study. All patients were given placebo for the initial 5 days, and from the 6th to 35th day (inclusive) they received CBD (initial oral dose of 40 mg reaching 1280 mg/day). On the 36th day, CBD treatment was discontinued and replaced by placebo for 5 days, which was subsequently switched to olanzapine for over 15 days. Efficacy, tolerability and side effects were assessed. One patient showed mild improvement, but two patients didn't show any improvement during CBD monotherapy. All patients tolerated CBD very well and no side effects were reported. These preliminary data suggest that CBD monotherapy may not be effective for TRS.
