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

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine with functions in nerve cell growth, differentiation, and apoptosis. There are several studies showing that a TNF-alpha--G308A promoter polymorphism, which possibly affects TNF-alpha transcription, is associated with schizophrenia, although negative results also exist. Our aim was to investigate the relationship between the TNF-alpha --G308A promoter polymorphism, the risk of schizophrenia, and the age of onset of schizophrenia, and the TNF-alpha -G308A polymorphism was therefore studied in 149 southern Finnish patients with a DSM-IV diagnosis of schizophrenia and in 393 healthy controls. The allele and genotype frequencies did not differ significantly between the patient and control groups (P=0.10 and 0.12, respectively), but the frequency of G/G homozygotes was statistically significantly higher in male patients than in male controls (chi(2)=5.03, d.f.=1, P=0.025) with an odds ratio of 2.00 (95% confidence interval: 1.08--3.70). No such difference was seen in female patients (P=0.79) or in the whole study group (P=0.064). The age of onset of schizophrenia did not differ significantly between the different TNF-alpha genotypes (ANOVA: F=0.45, P=0.64). In conclusion, we did not find a clear association between the TNF-alpha --G308A polymorphism and schizophrenia in the whole study group. However, TNF-alpha --G308A G/G homozygosity was modestly associated with schizophrenia in male patients.
 ...
PMID:Tumor necrosis factor-alpha --G308A polymorphism in schizophrenia in a Finnish population. 1592 74

Proton magnetic resonance spectroscopy (1H-MRS) studies of schizophrenia suggest an effect of the disease or of antipsychotic medications on brain N-acetyl aspartate (NAA), a marker of neuronal viability. We studied in rat the effect of haloperidol on NAA, glutamate, and glutamine in several brain regions where metabolite reductions have been reported in chronically medicated patients with schizophrenia. Two groups of 16 rats each were treated with haloperidol depo (38 mg/kg/month) and vehicle for 6 months and were killed. Concentrations of metabolites were determined by high-resolution magic angle proton magnetic resonance spectroscopy (HR-MAS 1H-MRS) at 11.7 T in ex-vivo punch biopsies from the following brain regions: medial frontal and cingulate cortex, striatum, nucleus accumbens, dorsal and ventral hippocampus, amygdala, and temporal cortex. Factorial ANOVA of NAA concentrations revealed no significant effect of drug group (F(1,212) = 1.5; p = 0.22) or a group by brain region interaction (F(7,212) = 1.0; p = 0.43). There was a significant main effect of region (F(7,212) = 17.8; p < 0.001) with lower NAA in the striatum. A prolonged exposure to the dopamine D2 receptor blockade effects of haloperidol does not result in changes in NAA, glutamate, glutamine, and other metabolites in the proton spectrum. These results are consistent with the only other two studies of the effect of antipsychotic drugs on NAA in the rat brain. The documented lower NAA in chronically treated schizophrenia patients is most likely not a simple effect of antipsychotic medications.
 ...
PMID:Long-term treatment of rats with haloperidol: lack of an effect on brain N-acetyl aspartate levels. 1613 64

The profile and time-course of symptom response in acute schizophrenia is unclear. For the present study, we hypothesized that the time-course would be nonlinear. A meta-analysis was performed using randomized, controlled clinical trials of five atypical antipsychotics reported in nine electronic databases. Studies were of subjects experiencing an acute exacerbation of illness, with multiple BPRS or PANSS data-points as outcome measures. A mixed factorial repeated-measures ANOVA was used. Twenty-one published clinical trials were identified. Reduction in total symptoms from baseline to 4 wk was associated with a linear decline in symptomatology (F=23.4, d.f.=1, 7, p=0.002) without attenuation of effect. In contrast, from baseline to 6 wk the linear symptom reduction (F=76.5, d.f.=1, 12, p<0.001) eventually flattened at the end of the trial (F=87.2, d.f.=1, 12, p<0.001). Secondary analyses showed a similar pattern for typical antipsychotics, and the same profile for risperidone and olanzapine as for atypical agents as a whole. Inclusion of LOCF data altered the results at 4 wk, but not 6 wk; completion rates had no effect on results. In conclusion, this meta-analysis confirms our hypothesis for 6-wk data. The profile of symptom change is one of linear symptom reduction until 4 wk, with a flattening of treatment effects by 6 wk. A curvilinear profile of schizophrenia symptom reduction has possible implications with respect to trial design and clinical decision-making.
 ...
PMID:A meta-analysis of profile and time-course of symptom change in acute schizophrenia treated with atypical antipsychotics. 1631 78

Smaller medial temporal lobe volume is a frequent finding in studies of patients with schizophrenia, but the relative contributions of the hippocampus and three surrounding cortical regions (entorhinal cortex, perirhinal cortex, and parahippocampal cortex) are poorly understood. We tested the hypothesis that the volumes of medial temporal lobe regions are selectively changed in schizophrenia. We studied 19 male patients with schizophrenia and 19 age-matched male control subjects. Hippocampal and cortical volumes were estimated using a three-dimensional morphometric protocol for the analysis of high-resolution structural magnetic resonance images, and repeated measures ANOVA was used to test for region-specific differences. Patients had smaller overall medial temporal lobe volumes compared to controls. The volume difference was not specific for either region or hemisphere. The finding of smaller medial temporal lobe volumes in the absence of regional specificity has important implications for studying the functional role of the hippocampus and surrounding cortical regions in schizophrenia.
 ...
PMID:Hippocampal and parahippocampal volumes in schizophrenia: a structural MRI study. 1631 77

Cross-section research suggests reported childhood abuse in schizophrenia spectrum disorders is linked with graver symptom levels and social dysfunction. To examine this prospectively, we compared biweekly ratings of positive and emotional discomfort symptoms and weekly accounts of hours worked over 4 months of rehabilitation of 12 participants with schizophrenia or schizoaffective disorder and childhood sexual abuse history and 31 with schizophrenia or schizoaffective disorder and no childhood sexual abuse history. Repeated-measures ANOVA revealed the abuse group had consistently higher levels of both symptom components and poorer participation in vocational rehabilitation. A time by group effect was observed for hours of work, with the abuse group working increasingly fewer hours over time. Participants reporting abuse also were more likely to perform poorly on a test of executive function and to have particularly higher levels of hallucinations and anxiety over time. Clinical and theoretical implications are discussed.
 ...
PMID:Reported history of child sexual abuse in schizophrenia: associations with heightened symptom levels and poorer participation over four months in vocational rehabilitation. 1631

Evidence suggests that neuroactive steroids may be candidate modulators of schizophrenia pathophysiology and therapeutics. We therefore investigated neuroactive steroid levels in post-mortem brain tissue from subjects with schizophrenia, bipolar disorder, nonpsychotic depression, and control subjects to determine if neuroactive steroids are altered in these disorders. Posterior cingulate and parietal cortex tissue from the Stanley Foundation Neuropathology Consortium collection was analyzed for neuroactive steroids by negative ion chemical ionization gas chromatography/mass spectrometry preceded by high-performance liquid chromatography. Subjects with schizophrenia, bipolar disorder, nonpsychotic depression, and control subjects were group matched for age, sex, ethnicity, brain pH, and post-mortem interval (n = 14-15 per group, 59-60 subjects total). Statistical analyses were performed by ANOVA with post-hoc Dunnett tests on log transformed neuroactive steroid levels. Pregnenolone and allopregnanolone were present in human post-mortem brain tissue at considerably higher concentrations than typically observed in serum or plasma. Pregnenolone and dehydroepiandrosterone levels were higher in subjects with schizophrenia and bipolar disorder compared to control subjects in both posterior cingulate and parietal cortex. Allopregnanolone levels tended to be decreased in parietal cortex in subjects with schizophrenia compared to control subjects. Neuroactive steroids are present in human post-mortem brain tissue at physiologically relevant concentrations and altered in subjects with schizophrenia and bipolar disorder. A number of neuroactive steroids act at inhibitory GABA(A) and excitatory NMDA receptors and demonstrate neuroprotective and neurotrophic effects. Neuroactive steroids may therefore be candidate modulators of the pathophysiology of schizophrenia and bipolar disorder, and relevant to the treatment of these disorders.
 ...
PMID:Neuroactive steroids are altered in schizophrenia and bipolar disorder: relevance to pathophysiology and therapeutics. 1631 20

Disturbances in learning are prominent in schizophrenia. The present study examined the effect of committing mistakes (errors) on learning in schizophrenia. Subjects included schizophrenia and schizoaffective disorder patients (n = 36) and healthy adults (n = 22) who were administered a word-stem completion task under "errorfree" (no guessing) and "errorful" (guessing) conditions. The data were analyzed using a 2 (group) x 2 (order) x 2 (condition) repeated-measures ANOVA and by comparing standard residualized scores between patients and controls. The results from the ANOVA revealed a significant group x condition interaction with patients showing greater impairment relative to controls on the errorful versus errorfree condition. Similarly, contrasts of standard residualized scores revealed patients' scores on the errorful condition to be deviant from that of healthy adults. The findings implicate problems in the ability to self-correct and suggest that rehabilitation efforts incorporating errorless learning methods may benefit persons with schizophrenia.
 ...
PMID:An "errorful" learning deficit in schizophrenia? 1644 79

Studies have reported beneficial effects of cholinergic enhancers, e.g., rivastigmine, on memory in schizophrenia but others have not. Possibly, these discrepancies are related to the lack of specificity of the tests used. This study investigated the effect of rivastigmine on memory in schizophrenia using event-related potentials (ERPs). Eighteen patients treated with atypical antipsychotic received rivastigmine adjuvant therapy in a randomized, crossover design. They were assessed at baseline (T1) and on two subsequent occasions (T2 and T3), where one half of the subjects were taken rivastigmine and the other half not. ERPs were recorded during a recognition memory task on each session. Behavioral and ERP data were analyzed using mixed ANOVA models first at T1 to detect potential group differences and for the trial (T1-T2) to determine the influence of rivastigmine, i.e., sessionxgroup interactions. The results showed no group difference at T1 except a trend for one group to be less efficient than the other on RT measures. When controlling for this difference the results on the trial data showed a trend for a benefit of rivastigmine on the RT memory effect. ERP analysis revealed that rivastigmine affects the amplitudes of two components elicited within 150-300 ms over posterior (reduced N2b) and frontal sites (enhanced P2a). It also enhances the magnitude of the memory (old/new) effect on two later components over posterior (N400) and frontal sites (F-N400). These results suggest that rivastigmine improves selective attention by enhancing interference inhibition processes (P2a) and lowering the reactivity to incoming stimulus (N2b). It also improves the integration of information with knowledge (N400) and with its context (F-N400). Generally, this study showed that the beneficial effect of rivastigmine on memory is not unitary but rather comes from its action at different time points within information processing cascade.
 ...
PMID:Are cholinergic enhancers beneficial for memory in schizophrenia? An event-related potentials (ERPs) study of rivastigmine add-on therapy in a crossover trial. 1658 Jul 65

Though often overlooked clinically, social anxiety appears to be unusually common in schizophrenia and may represent a barrier to quality of life and wellness. To explore the possible roots of social anxiety in schizophrenia, we concurrently assessed delusions using the Positive and Negative Syndrome Scale, flexibility of abstract thought using the Wisconsin Card Sorting Test, capacity for interpersonal relations using the Quality of Life Scale and social anxiety using the Liebowitz Social Anxiety Scale among 71 participants with schizophrenia or schizoaffective disorder. ANOVA revealed participants classified as having both significant delusions and impairments in flexibility of abstract thought (n=11) had significantly higher levels of social anxiety and fewer psychological resources for interpersonal relationships than participants with only one or neither of these difficulties. Groups did not differ on demographic variables, awareness of illness or negative symptoms. Clinical and theoretical implications are discussed.
 ...
PMID:Association of delusions and lack of cognitive flexibility with social anxiety in schizophrenia spectrum disorders. 1682 53

Disordered or maladaptive meta-cognitive processing appears to be a prominent feature for some individuals with a diagnosis of schizophrenia. We sought to establish whether healthy individuals distinguished either in terms hallucination proneness (HP) or level of schizotypy could also be differentiated on the sub-scales of the Meta-cognitions Questionnaire (MCQ), or a modified version of it in which items about worry were replaced with items specifically related to thinking. A total of 106 healthy volunteers completed the Oxford and Liverpool Inventory of Feelings and Experiences and Launay-Slade hallucination scale, the Schizotypal Personality Questionnaire and two versions of the MCQ: the original which assesses five domains of meta-cognition and an adapted version in which items relating to worry had been replaced by items relating to thinking or reflecting on thinking (MCQ-th). ANOVA indicated highly significant differences between three groups of individuals differentiated in terms of high, medium and low proneness to hallucinations on four of the five MCQ sub-scales, and three of the four MCQ-th factors. Regression analyses indicated that the MCQ factors encompassing (1) a sense of uncontrollability of thinking (and the perceived attendant dangers of this) and (2) negative beliefs about thinking related to suspicion and punishment were the strongest predictors of high schizotypy. Individuals who score higher on a measure of HP are more likely to display patterns of meta-cognitive processing that resemble, in certain respects, those reported in individuals with a diagnosis of schizophrenia. High schizotypy predicts a negative appraisal about both the controllability and consequences of thinking.
 ...
PMID:Hallucination proneness, schizotypy and meta-cognition. 1693 18


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>