***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND C-reactive protein ( CRP ) , intercellular adhesion molecule-1 ( ICAM-1 ) , vascular cell adhesion molecule-1 ( VCAM-1 ) , and E-selectin are systemic inflammatory markers ( IM ) that positively correlate with cardiovascular ( CV ) risk . Despite the known CV effects of atypical antipsychotics , there is limited prospect i ve data on IM changes during treatment . METHODS The IM outcomes were compared between  antipsychotic treatment groups in the CATIE ( Clinical Antipsychotic Trials of Intervention Effectiveness ) schizophrenia trial phase 1 with subjects with laboratory assessment s at baseline and 3 months ( n = 789 ) . RESULTS There were significant treatment differences in CRP , E-selectin , and ICAM-1 at 3 months , with a differential impact of baseline values on the CRP and ICAM-1 results . In overall comparisons , quetiapine and olanzapine had the highest median levels for CRP , and olanzapine for E-selectin and ICAM-1 .  Olanzapine was significantly different after baseline adjustment than perphenazine ( p = .001 ) for E-selectin , and in those with low baseline CRP ( < 1 mg/L ) , olanzapine was significantly different than perphenazine ( p < .001 ) , risperidone ( p < .001 ) , and ziprasidone ( p = .002 ) for CRP .  Perphenazine had the lowest 3-month ICAM-1 levels in subjects with baseline ICAM-1 above the median , but the differences were not statistically significant versus olanzapine ( p = .010 ) , quetiapine ( p = .010 ) , and risperidone ( p = .006 ) after controlling for multiple comparisons . The 18-month repeated measures CRP analysis confirmed the significantly higher values for olanzapine in those with low baseline CRP . CONCLUSIONS This analysis provides further evidence for differential antipsychotic metabolic liabilities as measured by changes in systemic inflammation . C-reactive protein might emerge as a useful target for CV risk outcomes in schizophrenia patients Recent trials support the hypothesis of the role of inflammation in the pathogenesis of schizophrenia . The overall therapeutic benefit of anti-inflammatory medication , in particular cyclo-oxygenase-2 ( COX-2 ) inhibitors in schizophrenia , is still controversial . There are suggestions that therapy with COX-2 inhibitors may influence the early stages of the disease . Taking these findings into account , we conducted a double-blind , placebo-controlled , r and omized trial of celecoxib augmentation to amisulpride treatment in patients with a first manifestation of schizophrenia . Forty-nine patients diagnosed with schizophrenia were r and omly assigned . They were treated either with amisulpride ( 200 - 1000 mg ) plus celecoxib ( 400 mg ) or amisulpride ( 200 - 1000 mg ) plus placebo . Inclusion criterion was the diagnosis of schizophrenia during the past two years according to DSM-IV . The trial lasted six weeks . At weekly intervals an assessment of the psychopathology was performed using the Positive and Negative Symptom Scale ( PANSS ) and the Global Clinical Impression Scale ( CGI ) . A significantly better outcome was observed in the patient group treated with amisulpride plus celecoxib compared to the group with amisulpride plus placebo  ( PANSS negative : p=0.03 ; PANSS global ; p=0.05 and PANSS total : p=0.02 ) . In addition , ratings by the CGI scale during therapy with amisulpride and celecoxib showed a significantly better result ( p < or = 0.001 ) . A significantly superior therapeutic effect could be observed in the celecoxib group compared to placebo in the treatment of early stage schizophrenia . This is the first time an improvement in patients ' negative symptoms has been demonstrated with celecoxib . In future , further trials are needed to investigate the effect of COX-2 inhibitors on prodromal and negative symptoms of schizophrenia OBJECTIVE To determine bone mass using quantitative phalangeal bone ultrasound in institutionalized schizophrenic patients under chronic treatment with antipsychotic drugs .  METHODS A total of 73 patients with schizophrenia ( 25 women , mean age 59.84 + /- 17.01 years ; 48 men , mean age 61.89 + /- 12.95 years ) and 73 healthy subjects ( 25 women , mean age 60.37 + /- 17.16 years ; 48 men , mean age 61.24 + /- 13.09 years ) participated in the study . Bone status was assessed using an ultrasound device that measures the amplitude-dependent speed of sound ( Ad-SoS ) in metres per second . Measurements were made on the phalanges ( II-V ) of the non-dominant h and , and the mean value was computed . RESULTS The schizophrenic women had higher levels of prolactin ( PRL ) , parathyroid hormone ( PTH ) , alkaline phosphatase ( AlPh ) , and tartrate-resistant acid phosphatase ( TRAP ) ( all p < 0.0001 ) , and lower 25-hydroxyvitamin D(25(OH)D3 ) levels ( p < 0.0001 ) and Ad-SoS values ( p < 0.05 ) than controls . Ad-SoS was higher in schizophrenic men ( p < 0.05 ) . CONCLUSIONS Schizophrenic women in treatment with antipsychotic drugs  had a loss of phalangeal bone mass that was associated with the levels of vitamin D or PTH , and increased bone turnover In an attempt to define potential immunological dysfunctions in schizophrenia , we determined the production of interleukin-2 ( IL-2 ) , interleukin-4 ( IL-4 ) , interferon-γ ( IFN-γ ) , and soluble IL-2 receptor ( sIL-2R ) in a whole-blood assay after stimulation with phytohemagglutinin ( PHA ) as well as the serum concentrations of sIL-2R . Because CD4+CD45RO+T cells are the main producers of IFN-γ , we determined the percentage of these cells , as well as of pan T , CD4+T , and CD8+T cells , by flow cytometry . A whole-blood count was performed in addition . Two groups of patients were examined , paranoid-type and residual-type schizophrenics . The numbers of both monocytes and neutrophils , but not of lymphocytes , were increased significantly in the schizophrenic sample .  The IFN-γ production of the schizophrenics as a whole group , and of the paranoid patients , was reduced significantly in comparison with the control group ( p≤0.05 ) . The residual patients produced less IFN-γ than the controls , but more than the paranoid patients . The latter differences did not reach statistical significance . The production of IL-4 , which physiologically antagonizes the production of IFN-γ , was not significantly higher in the patient group . No changes in the lymphocyte sub population s were observed . The production of IL-2 showed a trend toward reduction in paranoid patients , but not in residual schizophrenics . The serum sIL-2R levels were elevated slightly in schizophrenics when compared with controls . In order to rule out a possible effect of cortisol on cytokine production , 20 schizophrenic were compared with 20 age- and gendermatched controls . However , neither elevated cortisol levels were detected in the schizophrenic sample , nor significant intercorrelations between cortisol levels and cytokine production , or levels of sIL-2R , respectively . In summary , our data reinforce the possibility of immune dysfunction in schizophrenia and point to the possible relevance of disease subgroups in this respect OBJECTIVE Abnormalities in the immune system in schizophrenia have been described . However , important findings such as high levels of activating cytokines in the CSF and signs of CNS inflammation have been controversial . The authors conducted a trial of the new selective cyclooxygenase-2 inhibitor celecoxib , an immunomodulatory drug , in schizophrenic patients to evaluate its therapeutic effects . METHOD In a prospect i ve , double-blind evaluation , 50 patients with an acute exacerbation of schizophrenia were r and omly assigned to either risperidone plus celecoxib or risperidone plus placebo . After a washout period , 25 patients received 2 - 6 mg/day of risperidone plus placebo and 25 received risperidone plus 400 mg/day of celecoxib for 5 weeks . The treatment effect was calculated by analysis of covariance . There were no significant differences between groups in age , sex , duration or severity of disease or psychopathology , or risperidone dose or plasma level . RESULTS Over 5 weeks , both groups of patients showed significant improvement in scores on the Positive and Negative Syndrome Scale and on all subscales . However , the celecoxib group showed significantly greater improvement in the total score . CONCLUSIONS Additional treatment with celecoxib has significant positive effects on the therapeutic action of risperidone with regard to total schizophrenia psychopathology . Moreover , the fact that treatment with an immunomodulatory drug showed beneficial effects on schizophrenia symptoms indicates that immune dysfunction in schizophrenia is not just an epiphenomenon but is related to the pathomechanism of the disorder . However , a nonimmunological therapeutic effect of celecoxib mediated by the N-methyl-D-aspartic acid receptor has to be taken into account The alteration of T helper 1 ( TH1 ) and TH2 responses and related cell-mediated immunity has been supposed to be associated with the immunological pathogenesis in the development of schizophrenia . Increasing evidence suggested the alteration of cytokines in accordance with the antipsychotic treatment as well , so that this study aim ed at investigating the aberration of TH1 and -2 cytokines before and after antipsychotic treatment in patients with schizophrenia . Thirty-five schizophrenic patients with antipsychotic naïve or free more than 2 months participated in the study . We measured the plasma levels of tumor necrosis factor-alpha ( TNF-alpha ) and interleukin (IL)-2 ( TH1 ) , and IL-6 , IL-10 and IL-13 ( TH2 )  at the time of admission and after an 8-week antipsychotic treatment . The IL-6 ( p = 0.001 ) and -13 ( p = 0.004 ) levels were significantly decreased after antipsychotic treatment than those of before antipsychotic treatment . The total and general PANSS score changes were correlated with the change of IL-6 ( r = 0.598 , corrected p < 0.05 ; r = 0.550 , corrected p = 0.005 , respectively ) . The baseline IL-6 level was correlated with change of general PANSS score ( r = 0.449 , corrected p = 0.044 ) , whereas changes of other PANSS scores were not correlated with any other baseline cytokine levels . The baseline total PANSS score was correlated with the baseline levels of IL-13 ( r = 0.776 , corrected p < 0.005 ) . The baseline total and general PANSS scores were correlated with the baseline levels of IL-6 ( r = 0.689 , corrected p < 0.005 ; r = 0.653 , corrected p < 0.005 ) . The correlations between the baseline levels of cytokines and the duration of illness and the age at onset were not found . Our study supports that TH-2 arm cytokines may be involved in the improvement of psychopathology and symptomatologies of schizophrenia and that antipsychotic drugs may suppress some TH-2 cytokines in patients with schizophrenia 
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However , evidence is limited regarding the causal connection between atypical antipsychotic drugs and the changes in glucose and lipid metabolism that could trigger the onset of physical ill health , including diabetes and heart disease .
Indeed , there is evidence that there is a metabolic predisposition to diabetes in patients with schizophrenia that is exacerbated by obesity and thereby contributes to cardiovascular disease and other co-morbid illnesses .
It is concluded that the effects of inflammatory mediators on the brain causally contribute to the pathology of schizophrenia and the ill health that accompanies the disorder