***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: Objective : Interferon ( IFN ) beta has repeatedly shown benefit in multiple sclerosis ( MS ) in reducing the rate of relapse , the disease activity as shown with magnetic resonance imaging and , to some degree , the progression of disability ; however , it is unknown how much the therapeutic response depends on the dose , the subgroup involved , and the disease stage . This multicentre , double blind , placebo controlled study explored the dose−response curve by examining the clinical benefit of low dose IFN beta-1a ( Rebif ® ) , 22 μg subcutaneously once weekly , in patients with secondary progressive MS . Methods : A total of 371 patients with clinical ly definite SPMS were r and omised to receive either placebo or subcutaneous IFN beta-1a , 22 μg once weekly , for 3 years . Clinical assessment s were performed every 6 months . The primary outcome was time to sustained disability , as defined by time to first confirmed 1.0 point increase on the Exp and ed Disability Status Scale ( EDSS ) . Secondary outcomes included a sensitive disability measure and relapse rate . Results : Treatment had no beneficial effect on time to confirmed progression on either the EDSS ( hazard ratio ( HR ) = 1.13 ; 95 % confidence interval ( CI ) 0.82 to 1.57 ; p = 0.45 for 22 μg v placebo ) or the Regional Functional Status Scale ( HR = 0.93 ; 95 % CI 0.68 to 1.28 ; p = 0.67 ) . Other disability measures were also not significantly affected by treatment . Annual relapse rate was 0.27 with placebo and 0.25 with IFN ( rate ratio = 0.90 ; 95 % CI 0.64 to 1.27 ; p = 0.55 ) . The drug was well tolerated with no new safety concerns identified . No significant gender differences were noted . Conclusions : This patient population was less clinical ly active than SPMS population s studied in other trials . Treatment with low dose , IFN beta-1a ( Rebif ® ) once weekly did not show any benefit in this study for either disability or relapse outcomes , including a subgroup with preceding relapses . These results add a point at one extreme of the dose−response spectrum of IFN beta therapy in MS , indicating that relapses in this phase may need treatment with higher doses than in the initial phases OBJECTIVE To assess efficacy , safety , and tolerability of every-other-day interferon beta-1b treatment in patients with a first clinical event suggestive of multiple sclerosis ( MS ) ( clinical ly isolated syndrome ) . METHODS We conducted a multicenter , r and omized , double-blind , placebo-controlled trial . Patients with a first clinical demyelinating event and at least two clinical ly silent brain MRI lesions were r and omized to interferon beta-1b ( IFNB-1b ) 250 mug subcutaneously ( SC ) every other day ( EOD ) ( n = 292 ) or placebo ( n = 176 ) , until clinical ly definite MS ( CDMS ) was diagnosed or they had been followed for 24 months . RESULTS After 2 years , 45 % of placebo patients had converted to CDMS ( Kaplan-Meier estimate ; primary outcome measure ) and 85 % fulfilled the McDonald criteria ( co- primary outcome measure ) . Overall interferon beta-1b delayed the time to diagnosis of CDMS ( p < 0.0001 ) and McDonald MS ( p < 0.00001 ) . Hazard ratios ( 95 % CI ) were 0.50 ( 0.36 to 0.70 ) for CDMS and 0.54 ( 0.43 to 0.67 ) for McDonald MS favoring treatment with IFNB-1b . Treatment was well tolerated , as indicated by the low rate of patients dropping out of the study before CDMS was reached ( 6.6 % overall , 7.2 % in the IFNB-1b group ) . CONCLUSIONS Interferon beta-1b 250 mug subcutaneously every other day delayed conversion to clinical ly definite multiple sclerosis , and should be considered as a therapeutic option in patients presenting with a first clinical event suggestive of multiple sclerosis Our previously reported multicenter , blinded , r and omized , controlled study of two doses of interferon beta-1b ( IFNB ) in 372 patients demonstrated a reduction in relapse frequency and severity and in MRI activity . We now report the results of the continuation of that study . The median time on study was 46.0 months for the placebo arm , 45.0 months for 1.6 million international units ( MIU ) , and 48.0 months for 8 MIU . IFNB had a persistent beneficial effect on exacerbation rate and MRI burden of disease and was relatively free of long-term side effects . There was a one-third reduction in exacerbation rate in the 8-MIU treatment arm , compared with placebo , in each of 5 years . Serial annual MRI was done in all patients , and 217 of the patients had either a fourth- or fifth-year scan . There was no significant progression of lesion burden in the 8-MIU arm in each successive year compared with baseline ( at 4 years , p = 0.917 ) , whereas a highly significant increase in lesion area occurred in the placebo arm ( p = 0.0001 ) . Among the 154 noncompleters , there was no systematic bias recognized that favored either treatment arm for the outcome measures of exacerbation rate , disability , or MRI activity . Dropouts in the placebo group had higher exacerbation rates and accumulation of MRI lesion burden than did dropouts in the other treatment arms , which probably reduced the power of the study to demonstrate treatment effects on these measures in the later years of the trial . ( ABSTRACT TRUNCATED AT 250 WORDS Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Major depressive disorder is associated with increases in infectious disease risk as well as the incidence of inflammatory disorders . Declines of natural killer ( NK ) cell activity are reliably found in depression , whereas other studies report evidence of inflammation in depressed patients . The potential association between NK activity and circulating markers of immune activation has not been previously examined in the context of major depression . In this study , we measured  levels of NK activity , circulating levels of interleukin-6 ( IL-6 ) , soluble interleukin-2 receptor , and acute phase proteins  in 25 male patients with current major depressive disorder and 25 age , gender , and body weight comparable controls . As compared to controls , patients with major depressive disorder showed lower NK activity ( p = .05 ) and higher circulating levels of IL-6 ( p < .05 ) . Levels of NK activity were not correlated with IL-6 or with other markers of immune activation . The independent effect of depression on inflammatory markers and natural killer immune responses has implication s for underst and ing individual differences in the adverse health effects of major depressive disorder The concentration of cytokines such as Interleukin-6 ( IL-6 ) has been reported to be elevated in depressed and schizophrenic patients and , in healthy persons , upon stress . Interleukin-6 plasma levels were determined in depressed ( n = 12 ) and schizophrenic ( n = 32 ) patients during the acute state of illness and after remission at approximately 8 weeks after admission and were compared with healthy controls ( n = 12 ) . Patients were diagnosed according to DSM-III-R by the Structured Clinical Interview ( SLID ) . Severity of illness was assessed for depression by the Montgomery Asberg Depression Rating Scale ( MADRS ) and for schizophrenia by the Brief Psychiatric Rating Scale ( BPRS ) . Interleukin-6 plasma concentrations were elevated during the acute state either of depression or of schizophrenia if compared to controls . After remission , IL-6 concentrations in depressed and in schizophrenic patients had decreased and did not differ significantly from controls . We hypothesize that the elevated IL-6 levels during the acute state of depression or schizophrenia may reflect an unspecific stress response The relationship between plasma kynurenine ( KYN ) concentration and  anxiety and depression in psychiatric patients was examined . KYN has been reported as a probable endogenous anxiogen in animal models of anxiety . Thirty patients with affective states were studied . The Hamilton Anxiety Scale ( HAM-A ) , Hamilton Depression Scale ( HAM-D ) ,  Dexamethazone Suppression Test ( DST )  and  Diazepam Test ( DT ) were used to differentiate two groups with prevalence of anxious or depressive symptomatology . It was found that in endogenous anxiety , the plasma KYN concentration is increased and in endogenous depression , it is decreased ( resp . , 1.94 micrograms/ml and 0.62 microgram/ml , versus normal 0.9 + /- 0.07 microgram/ml ) . After treatment this concentration became normal in both groups . In this study KYN concentration correlated significantly with the severity of anxiety . The results suggest that the increase of plasma KYN concentration in anxiety may be used as an additional criterion to differentiate endogenous anxiety with depressive mood from endogenous depression in clinical practice . DT and DST have also appeared to be reliable factors in differentiation of anxiety and depression BACKGROUND Treatment with interferon beta has been shown to help patients with established multiple sclerosis , but it is not known whether initiating treatment at the time of a first clinical demyelinating event is of value . METHODS We conducted a r and omized , double-blind trial of 383 patients who had a first acute clinical demyelinating event ( optic neuritis , incomplete transverse myelitis , or brain-stem or cerebellar syndrome ) and evidence of prior sub clinical demyelination on magnetic resonance imaging ( MRI ) of the brain . After initial treatment with corticosteroids , 193 patients were r and omly assigned to receive weekly intramuscular injections of 30 microg of interferon beta-1a and 190 were assigned to receive weekly injections of placebo . The study end points were the development of clinical ly definite multiple sclerosis and changes in findings on MRI of the brain . The trial was stopped after a preplanned interim efficacy analysis . RESULTS During three years of follow-up , the cumulative probability of the development of clinical ly definite multiple sclerosis was significantly lower in the interferon beta-1a group than in the placebo group ( rate ratio , 0.56 ; 95 percent confidence interval , 0.38 to 0.81 ; P=0.002 ) . As compared with the patients in the placebo group , patients in the interferon beta-1a group had a relative reduction in the volume of brain lesions ( P<0.001 ) , fewer new or enlarging lesions ( P<0.001 ) , and fewer gadolinium-enhancing lesions ( P<0.001 ) at 18 months . CONCLUSIONS Initiating treatment with interferon beta-1a at the time of a first demyelinating event is beneficial for patients with brain lesions on MRI that indicate a high risk of clinical ly definite multiple sclerosis There is now some evidence that i ) the availability of plasma tryptophan , the precursor of serotonin , is significantly lower in pregnant women at the end of term and the first few days after delivery than in nonpregnant women ; and ii ) both pregnancy and the early puerperium are accompanied by activation of the inflammatory response system . The aims of the present study were to examine the effects of pregnancy and delivery on plasma kynurenine , a major tryptophan catabolite synthesized after induction of indoleamine-2 , 3 dioxygenase ( IDO ) by pro-inflammatory cytokines . We measured plasma kynurenine and tryptophan and immune markers , such as serum interleukin-6 ( IL-6 ) , IL-8 and the leukemia inhibitory factor-receptor ( LIF-R ) in healthy , nonpregnant and pregnant women at the end of term and one and three days after delivery .  Plasma kynurenine was significantly lower in pregnant women at the end of term than in nonpregnant women , findings which may be attributed to lower plasma tryptophan at the end of term . The kynurenine/tryptophan ( K/T ) quotient was significantly higher in the pregnant women at the end of term and in the early puerperium than in nonpregnant women . In the early puerperium there was a significant increase in plasma kynurenine and the K/T quotient . The increases in plasma kynurenine and the K/T quotient were significantly more pronounced in women whose anxiety and depression scores significantly increased in the puerperium . The changes from the end of term to the early puerperium in plasma kynurenine and the K/T quotient were significantly related to those in the immune markers . It is concluded that 1 ) lower plasma kynurenine at the end of term is the consequence of lower plasma tryptophan ; 2 ) the increased K/T quotient at the end of term and in the early puerperium indicates inflammation-induced degradation of tryptophan along the kynurenine pathway ; and 3 ) that depressive and anxiety symptoms in the early puerperium are ( causally ) related to an increased catabolism of tryptophan into kynurenine , a phenomenon which probably results from immune activation Background : The beneficial effect of interferon beta on exacerbations in relapsing-remitting MS has been demonstrated repeatedly , but results concerning disability vary . Object 
    Output:
    
The review ed studies conclude that there is not a clear relationship between IFNβ and depression .
A history of depression is a risk factor for developing depression during the first 6 months of treatment , nevertheless , it is not sufficient to contraindicate it .
It is suggested that these patients would have fewer functional reserve remaining to deal with stressful life events , which could precipitate a depressive disorder