***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 Background C-reactive protein ( CRP ) is associated with immune , cardiometabolic , and psychiatric traits and diseases . Yet it is inconclusive whether these associations are causal . Methods and Findings We performed Mendelian r and omization ( MR ) analyses using two genetic risk scores ( GRSs ) as instrumental variables ( IVs ) . The first GRS consisted of four single nucleotide polymorphisms ( SNPs ) in the CRP gene ( GRSCRP ) , and the second consisted of 18 SNPs that were significantly associated with CRP levels in the largest  genome-wide association study ( GWAS ) to date ( GRSGWAS ) . To optimize power , we used summary statistics from GWAS consortia and tested the association of these two GRSs with 32 complex somatic and psychiatric outcomes , with up to 123,865 participants per outcome from population s of European ancestry . We performed heterogeneity tests to disentangle the pleiotropic effect of IVs . A Bonferroni-corrected significance level of less than 0.0016 was considered statistically significant . An observed p-value equal to or less than 0.05 was considered nominally significant evidence for a potential causal association , yet to be confirmed . The strengths ( F-statistics ) of the IVs were 31.92–3,761.29 and 82.32–9,403.21 for GRSCRP and GRSGWAS , respectively . CRP GRSGWAS showed a statistically significant protective relationship of a 10 % genetically elevated CRP level with the risk of schizophrenia ( odds ratio [ OR ] 0.86 [ 95 % CI 0.79–0.94 ] ; p < 0.001 ) . We vali date d this finding with individual-level genotype data from the schizophrenia GWAS ( OR 0.96 [ 95 % CI 0.94–0.98 ] ; p < 1.72 × 10−6 ) . Further , we found that a st and ardized CRP polygenic risk score ( CRPPRS ) at p-value thresholds of 1 × 10−4 , 0.001 , 0.01 , 0.05 , and 0.1 using individual-level data also showed a protective effect ( OR < 1.00 ) against schizophrenia ; the first CRPPRS ( built of SNPs with p < 1 × 10−4 ) showed a statistically significant ( p < 2.45 × 10−4 ) protective effect with an OR of 0.97 ( 95 % CI 0.95–0.99 ) . The CRP GRSGWAS showed that a 10 % increase in genetically determined CRP level was significantly associated with coronary artery disease ( OR 0.88 [ 95 % CI 0.84–0.94 ] ; p < 2.4 × 10−5 ) and was nominally associated with the risk of inflammatory bowel disease ( OR 0.85 [ 95 % CI 0.74–0.98 ] ; p < 0.03 ) , Crohn disease ( OR 0.81 [ 95 % CI 0.70–0.94 ] ; p < 0.005 ) , psoriatic arthritis ( OR 1.36 [ 95 % CI 1.00–1.84 ] ; p < 0.049 ) , knee osteoarthritis ( OR 1.17 [ 95 % CI 1.01–1.36 ] ; p < 0.04 ) , and bipolar disorder ( OR 1.21 [ 95 % CI 1.05–1.40 ] ; p < 0.007 ) and with an increase of 0.72 ( 95 % CI 0.11–1.34 ; p < 0.02 ) mm Hg in systolic blood pressure , 0.45 ( 95 % CI 0.06–0.84 ; p < 0.02 ) mm Hg in diastolic blood pressure , 0.01 ml/min/1.73 m2 ( 95 % CI 0.003–0.02 ; p < 0.005 ) in estimated glomerular filtration rate from serum creatinine , 0.01 g/dl ( 95 % CI 0.0004–0.02 ; p < 0.04 ) in serum albumin level , and 0.03 g/dl ( 95 % CI 0.008–0.05 ; p < 0.009 ) in serum protein level . However , after adjustment for heterogeneity , neither GRS showed a significant effect of CRP level ( at p < 0.0016 ) on any of these outcomes , including coronary artery disease , nor on the other 20 complex outcomes studied . Our study has two potential limitations : the limited variance explained by our genetic instruments modeling CRP levels in blood and the unobserved bias introduced by the use of summary statistics in our MR analyses . Conclusions Genetically elevated CRP levels showed a significant potentially protective causal relationship with risk of schizophrenia . We observed nominal evidence at an observed p < 0.05 using either GRSCRP or GRSGWAS — with persistence after correction for heterogeneity — for a causal relationship of elevated CRP levels with psoriatic osteoarthritis , rheumatoid arthritis , knee osteoarthritis , systolic blood pressure , diastolic blood pressure , serum albumin , and bipolar disorder . These associations remain yet to be confirmed . We can not verify any causal effect of CRP level on any of the other common somatic and neuropsychiatric outcomes investigated in the present study . This implies that interventions that lower CRP level are unlikely to result in decreased risk for the majority of common complex outcomes This r and omized within-subject , double blind study aim ed to compare the effects of a single dose of two different antipsychotics ( haloperidol and aripiprazole ) on cortisol , interleukin (IL)-6 and hippocampal regional Cerebral Blood Flow ( rCBF ) in the same 17 healthy male individuals . Subjects received a single dose of haloperidol ( 3 mg ) , aripiprazole ( 10 mg ) and placebo , in a r and omized order on three study appointments . We measured salivary cortisol levels at multiple time points , IL-6 levels from plasma sample s , and resting cerebral blood flow ( rCBF ) , using a pulsed continuous arterial spin labeling ( pCASL ) sequence ( 1.5 T ) . We found significantly lower cortisol levels in the haloperidol condition ( F(2,32)=5.78 , p=0.007 ) , than in either placebo ( p=0.013 ; CI=0.45 , 0.406 ) or aripiprazole ( p=0.037 ; CI=-0.520 , -0.014 ) . Interleukin-6 levels were also lower following haloperidol ( F(2,22)=4.19 , p=0.048 ) in comparison with placebo ( p=0.02 ; CI=0.14 , 1.8 ) , but not with aripiprazole . Finally , we found a greater rCBF in the right ( peak voxel : T=6.47 , p<0.0001 ) and left ( peak voxel T=5.17 , p<0.01 ) hippocampus following haloperidol compared with placebo , and at trend level also in the left hippocampus following aripiprazole compared with placebo ( T=4.07 , p=0.057 ) . These differences in hippocampal rCBF after both antipsychotics were no longer evident ( haloperidol ) or present at trend level ( aripiprazole ) , after controlling for cortisol and IL-6 levels . Our findings suggest that haloperidol can directly regulate the hypothalamic-pituitary-adrenal ( HPA ) axis and immune system through a pharmacological action via D2 receptor antagonism . Finally , our data suggest that the increased hippocampal rCBF is a manifestation of the reduction in IL-6 and cortisol which follows the administration of haloperidol BACKGROUND Weight gain and metabolic abnormalities occur in chronic schizophrenia patients treated with atypical antipsychotics .  The purpose of the study was to evaluate changes in serum levels of C-reactive protein ( CRP ) , insulin and cytokines ( IL-6 , TNF-α , IL-1β , IFN-γ , sTNF-R1 , IL-12 , IL-23 , IL-1Ra , TGF-β1 , IL-4 , and IL-10 ) after switching to aripiprazole . METHODS Cytokine , hsCRP and insulin measurements were performed in patients ( n=17 ) on day 0 and day 28 of the study using st and ard ELISA assays . The psychopathological status was assessed using PANSS . WC and BMI were measured and calculated , respectively . RESULTS We observed high clinical efficacy in aripiprazole linked to a 2.7 % weight loss . There were statistically significant reductions in PANSS scores and body parameters ( p<0.001 ) . After 28 days we detected a significant reduction in hsCRP ( p<0.001 ) , insulin ( p<0.001 ) , IL-1β , IL-6 , TNF-α , sTNF-R1 , IL-12 , IL-23 , IL-1Ra , TGF-β1 , IL-4 ( p<0.001 ) , IFN-γ ( p<0.05 ) and a significant elevation of IL-10 ( p<0.001 ) . There was a significant negative correlation between IL-10 levels and PANSS positive , negative and total scores after the study ( p=0.022 , p=0.003 , p=0.008 , respectively ) . CONCLUSIONS Aripiprazole limits inflammatory processes by enhancing anti-inflammatory signaling . Aripiprazole also reduces the risk of metabolic abnormalities Chronic functional constipation is common in infants , and the bacterial composition of stools in this condition is not known . The study aims were to : ( i ) investigate the composition of the intestinal ecosystem in chronic functional constipation ; ( ii ) establish whether the addition of the water‐holding agent calcium polycarbophil to the diet induces an improvement in constipation ; and ( iii ) determine the composition of the intestinal ecosystem after the use of this agent . In total , 42 children ( 20F , 22 M ; mean age : 8.6 ± 2.9 y ) were studied . Twenty‐eight children with functional chronic constipation without anatomical disorders were treated double‐blind in r and om sequence for 1 month with an oral preparation of calcium polycarbophil ( 0.62 g /twice daily ) or placebo . Intestinal flora composition was evaluated by st and ard microbiological methods and biochemical assays on faecal sample s collected before and after treatment . Fourteen healthy children were studied as controls . The results show that ( i ) the constipated children presented a significant increase in clostridia and bifidobacteria in faeces compared to healthy subjects – different species of clostridia and enterobacteriaceae were frequently isolated ; no generalized overgrowth was observed ; Clostridia outnumbered bacteroides and E. coli mean counts by 2–3log , while bacteroides and E. coli 
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While meta-analyses including case-control studies suggest a clear association between CRP and SZ , one other study has suggested that CRP-associated genes were associated with a lower risk of SZ onset .
Increased CRP has been significantly associated with positive symptoms in acute phase psychosis , while studies including community-dwelling stabilized subjects did not find such an association .
Abnormal CRP has been associated with a wide range of cognitive impairment in SZ stabilized individuals .
Body Mass index has been extensively associated with increased CRP in SZ subjects ; and increased CRP has been identified as a risk factor for metabolic syndrome and cardiovascular risk in SZ subjects .
Conclusion : In the light of the above-mentioned studies , increased hs-CRP may be reasonably suggested as a marker for SZ onset risk , as well as a risk factor for increased positive symptoms , cognitive impairment , hypovitaminosis D , microbiota disturbances , cardiovascular and metabolic syndrome risk in SZ subjects , and increased nicotine dependence in SZ smokers .