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)

Schizophrenia, the most severe psychiatric disorder, is characterized by heterogeneity of clinical signs, often categorized into positive and negative symptoms. Among a wide array of competing biological mechanisms, altered cerebral energy metabolism and mitochondrial dysfunction have been suggested to play an important role in the pathophysiology of schizophrenia. In this study we investigated mitochondrial complex I in platelets of 113 schizophrenic patients divided into three groups (acute psychotic episode, chronic active state and residual schizophrenia) and 37 control subjects. Complex I was analysed at the level of enzymatic activity, mRNA and protein levels by enzyme kinetics, RT-PCR and Western blot analyses, respectively. Complex I activity in platelets of schizophrenic patients altered with disease state presenting high specificity and sensitivity. Thus, increased activity was associated with psychotic symptomology, while its decrease was observed in patients with residual schizophrenia. The relationship between the clinical state and complex I activity in schizophrenia was further supported by its positive correlation with the severity of patients' positive symptoms assessed by clinical ratings. In addition, similar alterations were observed at the levels of mRNA and protein of the 24- and 51-kDa iron-sulfur flavoprotein subunits of the complex. Taken together these results point to the potential of platelet complex I to turn into a reliable novel marker for schizophrenia. At present, definitive diagnosis depends only on descriptive behavioral and symptomatic information, therefore a peripheral measurable specific marker will contribute to diagnosis and monitoring of the disease.
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PMID:State-dependent alterations in mitochondrial complex I activity in platelets: a potential peripheral marker for schizophrenia. 1239 53

Thirty-two female (mean age=52.9 years [SD=9.2]) patients with a diagnosis of residual schizophrenia and 19 female (mean age=51.1 years [SD=12.7]) control subjects were studied through cerebral Magnetic Resonance Imaging. Along the entire surface of the septum pellucidum, 1-mm coronal slices were performed in all subjects. The authors classified the cavum septum pellucidum into three types based on embryological development. The prevalence of a cavum was significantly higher in the patients with schizophrenia (Chi square 6.112. p < 0.05). No other significant associations with previously described morphological brain changes were found. Although this result was found in previous reports (DeGreef et al., 1992; DeLisi et al., 1993), our discussion focused on the neurodevelopmental theory of the septum pellucidum and its possible association with schizophrenia.
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PMID:Cavum septum pellucidum and its increased prevalence in schizophrenia: a neuroembryological classification. 1499 Jul 58

Long-term pharmacotherapy with antipsychotic agents is an important aspect of the management of schizophrenia. In patients responsive to the chosen treatment, maintenance therapy is usually conducted by halving the drug dose that has proven effective during the acute phase. This strategy is suitable for maintaining remission; moreover, it can improve the patients' quality of life. Records from over 1000 patients treated with clozapine during the past 22 years were examined; 782 of these patients were diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision (DSM-IV-TR) criteria (with the modification in early years). From this group, 181 patients were treated with clozapine for at least a year. The mean duration of long-term maintenance treatment with clozapine was 12.2+/-4.25 years (range: from 14.5 months to 18 years). Clozapine was administered in a daily dose of 50-200 mg (mean: 71.5+/-14.12 mg). In 76 schizophrenics, treatment was initiated with clozapine, whereas 105 patients were switched over from other treatments after their failure. The control group comprised 152 patients on long-term maintenance therapy with haloperidol. Clozapine administered for long-term maintenance therapy was effective both in paranoid and in catatonic schizophrenia. It also accomplished good results in patients with disorganized or residual schizophrenia, as well as in individuals with schizoaffective psychosis. Relapse rate was similar to that observed in the haloperidol group; however, patient compliance, side-effect profile, and therapeutic efficacy were all superior in the clozapine group. Long-term maintenance therapy with clozapine is successful. Compliance is good; schizophrenic patients are willing to take this atypical antipsychotic for years on end. Clozapine treatment is associated with a low relapse rate and a favorable safety profile.
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PMID:Clozapine maintenance therapy in schizophrenia. 1509 52

This study investigated serum brain-derived neurotrophic factor (BDNF) protein levels in schizophrenia patients and healthy control subjects and schizophrenia patients with various clinical phenotypes. During a 1-year period, 126 schizophrenic patients and 96 healthy control subjects were recruited. Serum BDNF protein levels were measured using an ELISA Kit. Psychiatric diagnoses were made according to DSM-IV criteria. One-way analysis of variance (ANOVA) showed no significant differences in serum BDNF protein levels between schizophrenia and healthy normals. Additionally, no significant differences existed in BDNF levels between schizophrenia patients for the following variables: with/without a suicide attempt; antipsychotic drug use, family tendency and disease onset before and after 25 years old. However, patients with catatonic schizophrenia had lower serum BDNF protein levels than patients with paranoid or residual schizophrenia. These analytical results suggested that BDNF might play an important role in the clinical subtypes of schizophrenia, but it needed further investigation in future.
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PMID:Associations between serum brain-derived neurotrophic factor levels and clinical phenotypes in schizophrenia patients. 1638 72

The concepts of partial recovery and remission have become increasingly important for the evaluation of the effectiveness of schizophrenia therapeutics. The relationship of baseline symptoms and changes in symptoms to remission of psychosis was evaluated. Fifty-six outpatients with residual schizophrenia completed a double-blind trial of olanzapine versus haloperidol and were then enrolled into a one-year open-label trial of olanzapine. Out of these 56 subjects, 13 (23%) met remission criteria at the beginning of the open-label treatment and were excluded. During the one-year study, 7/43 (16%) subjects met remission criteria. These subjects had significantly lower baseline ratings for tardive dyskinesia (TD) than subjects who did not achieve remission (1.8 +/- 1.5 vs. 4.2 +/- 4.6, P = 0.03). As expected, remitted subjects had significantly greater improvements in Brief Psychiatric Rating Scale total scores, positive subscale scores and scale for the Assessment of Negative Symptoms total scores. Remitted subjects also experienced a significantly greater improvement in depressive symptoms (P = 0.001), activation (P = 0.005), and Clinical Global Impressions scores (P < 0.001), as well as greater improvements in extrapyramidal symptoms (P = 0.007) and TD (P < 0.001). These results suggest that the relationship of depressive symptoms and improved side effects to the construct of remission in schizophrenia may deserve special attention. Future studies should aim to relate remission criteria to functional outcomes, cognition, and other important symptom domains.
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PMID:Remission in schizophrenia: the relationship to baseline symptoms and changes in symptom domains during a one-year study. 1858 42

A 58-year-old Japanese man developed psychomotor excitement and hallucinatory paranoia at age 53, which gradually developed to residual schizophrenia. He was administered various common tranquilizers until death. Myelodysplastic syndrome was noted 10 months before death. A routine autopsy was performed. The brain weighed 1365 g, and macroscopic observation revealed no remarkable findings. However, microscopic examination disclosed cells with enlarged and basophilic nuclei, and unusual astrocytes in the demyelinated foci, especially at the corticomedullary junctions in the temporal and occipital lobes. On the other hand, the white matter was relatively intact. Immunohistochemical analysis using anti-JC virus protein, VP-1 antibody, demonstrated JC virus-infected cells in not only abnormal glial cells and neurons but also normal-looking cells, which are suggestive of progressive multifocal leukoencephalopathy (PML). Immunostaining for GFAP revealed severe gliosis and some scattered abnormal enlarged nuclear cells in the lesions. Some clusters of CD8-positive lymphocytes were seen, which kill infected cells. PML could be considered a short-term disease preceding death, as "incidental PML" in this case. This is a rare autopsy case of early PML occurring in a schizophrenia patient with PML.
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PMID:Clinicopathological study of early progressive multifocal leukoencephalopathy incidentally found in a schizophrenia patient. 1917 Aug 97

There is increasing recognition that a person's spiritual or religious experiences contribute to quality of life (QOL). However, research exploring the relation between spirituality and QOL has mainly been in the context of chronic and life-threatening illnesses, and studies examining this important correlate of QOL in chronically mentally ill subjects are sparse. This study aimed to explore the relationship between spirituality and QOL, and to investigate if spirituality contributes to other domains of QOL (both physical and psycho-social) in subjects with residual schizophrenia. In a study with a cross-sectional design, 103 patients with residual schizophrenia were assessed with the Positive and Negative Syndrome scale, and their quality of life, spirituality and religiousness were assessed with the WHO Quality of Life-Spirituality, Religiousness and Personal Beliefs (WHOQOL-SRPB) scale. The SRPB domain and all its facets other than spiritual connection correlated significantly with all other domains of QOL and overall QOL. On regression analysis, the inner peace domain of spirituality explained 21.6 to 37.6% of variance of all QOL domains except the domain of level of independence. The spirituality domain explained 33.8% of the variance of the 'level of independence domain of QOL. Taken together, inner peace and spirituality facets explained 23 to 40% of the variance of the social relationships domain, the psychological domain and the level of independence domain of QOL. This study suggests that spirituality and religiosity have an important influence on overall QOL of patients with schizophrenia. Hence, besides pharmacological and non-pharmacological management for schizophrenia, clinicians should focus on this aspect and encourage their patients to follow their religious practices and spiritual beliefs.
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PMID:Contribution of spirituality to quality of life in patients with residual schizophrenia. 2199 71

Certain cytokines have been identified in the peripheral blood as trait markers of schizophrenia, while others are considered relapse-related state markers. Furthermore, data from peripheral blood, cerebrospinal fluid (CSF) and nuclear imaging studies suggest that (1) blood-brain barrier (BBB) dysfunction (e.g., immigration of lymphocytes into brain tissue and intrathecal antibody production) correlates with the development of negative symptoms, while (2) the brain's mononuclear phagocyte system (microglial cells) is activated during acute psychosis. Based on these neuroinflammatory hypotheses, we have quantified the numerical density of immunostained CD3+ T-lymphocytes, CD20+ B-lymphocytes, and HLA-DR+ microglial cells in the posterior hippocampus of 17 schizophrenia patients and 11 matched controls. Disease course-related immune alterations were considered by a separate analysis of residual (prevailing negative symptoms, n=7) and paranoid (prominent positive symptoms, n=10) schizophrenia cases. Higher densities of CD3+ and CD20+ lymphocytes were observed in residual versus paranoid schizophrenia (CD 3: left: P=0.047, right: P=0.038; CD20: left: P=0.020, right: P=0.010) and controls (CD3: left: P=0.057, right: P=0.069; CD20: left: P=0.008, right: P=0.006). In contrast, HLA-DR+ microglia were increased in paranoid schizophrenia versus residual schizophrenia (left: P=0.030, right: P=0.012). A similar trend emerged when this group was compared to controls (left: P=0.090, right: P=0.090). BBB impairment and infiltration of T cells and B cells may contribute to the pathophysiology of residual schizophrenia, while microglial activation seems to play a role in paranoid schizophrenia. The identification of diverse immune endophenotypes may facilitate the development of distinct anti-inflammatory schizophrenia therapies to normalize BBB function, (auto)antibody production or microglial activity.
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PMID:Different distribution patterns of lymphocytes and microglia in the hippocampus of patients with residual versus paranoid schizophrenia: further evidence for disease course-related immune alterations? 2291 59

Negative symptoms in schizophrenia are associated with decreased dopaminergic activity in the prefrontal cortex (PFC). It is hypothesized that increasing dopamine levels would alleviate negative symptoms. Termination of dopamine activity in the PFC is mainly via catechol-O-methyl tranferase (COMT) activity. Hence, inhibition of COMT activity with entacapone should reverse PFC dopaminergic transmission. To assess the efficacy of entacapone addition to antipsychotic treatment in patients with residual schizophrenia, we conducted a double-blind, randomised, placebo-controlled study for 12 wk of treatment with entacapone or placebo. Clinical measures (PANSS, CGI and QLS) were obtained at baseline and at weeks 4, 8 and 12 and cognitive functions were assessed by the RBANSS. Significant improvement over time in PANSS and QLS scores was observed in both groups. However, entacapone did not demonstrate a beneficial effect compared to placebo. Therefore, this study does not support a therapeutic role for entacapone in residual schizophrenia.
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PMID:Entacapone augmentation of antipsychotic treatment in schizophrenic patients with negative symptoms; a double-blind placebo-controlled study. 2422 65

The central serotonergic system is implicated in the pathogenesis of schizophrenia, where the imbalance between dopamine, serotonin and glutamate plays a key pathophysiological role. The dorsal raphe nucleus (DRN) is the main source of serotonergic innervation of forebrain limbic structures disturbed in schizophrenia patients. The study was carried out on paraffin-embedded brains from 17 (8 paranoid and 9 residual) schizophrenia patients and 28 matched controls without mental disorders. The transcriptional activity of ribosomal DNA (rDNA) in DRN neurons was evaluated by the AgNOR silver-staining method. An increased rDNA transcriptional activity was found in schizophrenia patients in the cumulative analysis of all DRN subnuclei (t test, P = 0.02). Further subgroup analysis revealed that it was an effect specific for residual schizophrenia versus paranoid schizophrenia or control groups (ANOVA, P = 0.002). This effect was confounded neither by suicide nor by antipsychotic medication. Our findings suggest that increased activity of rDNA in DRN neurons is a distinct phenomenon in schizophrenia, particularly in residual patients. An activation of the rDNA transcription in DRN neurons may represent a compensatory mechanism to overcome the previously described prefrontal serotonergic hypofunction in this diagnostic subgroup.
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PMID:Ribosomal DNA transcription in the dorsal raphe nucleus is increased in residual but not in paranoid schizophrenia. 2509 23


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