***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 Major depressive disorder ( MDD ) has been associated with alterations in immune function . Suppression of natural killer ( NK ) cell activity ( NKCA ) reliably characterizes immunological alterations observed in MDD . Antidepressant pharmacotherapy has been associated with modulation of NKCA . Previous investigations into antidepressant modulation of NKCA have not employed r and omized double-blind placebo controlled design s. Thus , it is unknown whether treatment-associated changes in immune function are due to drug , placebo , or spontaneous remission effects . The present investigation examined the effect of antidepressant treatment on NKCA utilizing a r and omized double-blind placebo controlled experimental design . METHOD Patients ( N = 16 ) met DSM-IV criteria for MDD and were r and omly assigned to drug ( N = 8 ; citalopram , 20 mg/day ) or placebo ( N = 8) under double-blind conditions . Severity and pattern of depressive symptoms were assessed by the Hamilton Depression Rating Scale ( HDRS ) . NK cell function was measured using a st and ard chromium-release assay and NK cell number assessed by flow cytometry . HDRS scores , NK cell function , and NK cell numbers were collected at 0 , 1 , 2 and 4 weeks of treatment . RESULTS Clinical response was associated with augmented NKCA independent of treatment condition . Failure to respond to treatment result ed in significantly reduced NKCA over treatment interval . CONCLUSIONS The present results suggest that alterations in the depressive syndrome , regardless of therapeutic modality , may be sufficient to modulate NKCA during antidepressant trials and thus may significantly impact on co-morbid health outcomes in MDD Altered cytokine secretion as a mechanism in the etiology of depression is still obscure . The serotonin transporter ( 5-HTT ) may play an important role in the termination of serotonergic neurotransmission by serotonin ( 5-HT ) uptaking into presynaptic neurons and representing as an initial action site for selective 5-HTT reuptake inhibitors ( SSRI ) . In our study , we evaluated whether cytokines and 5-HTT acted as biological markers for depression . Blood sample s were collected from 42 participants . The differences in cytokine and 5-HTT mRNA expressions of leukocytes were assessed between the patients with major depression ( n=20 ) and the healthy controls ( n=22 ) , along with the measurements prior and after treatment with a SSRI , fluoxetine , for 3 months in the follow-up patient group ( n=8 ) . The results revealed that the mRNA expressions of IL-1beta , IL-6 , IFNgamma , TNFalpha , and 5-HTT were higher in the depressed patients than those of the healthy controls . The higher level of mRNA expressions of IFNgamma and 5-HTT diminished after fluoxetine treatment . Furthermore , we found a positive correlation between 5-HTT and cytokines mRNA expressions in total participants , which suggested that pro-inflammatory cytokines and 5-HTT might play critical roles in the pathogenesis of major depression and that their levels were affected by chronic treatment with 5-HTT inhibitors OBJECTIVE Major depressive disorder has been linked with inflammatory processes , but it is unclear whether individual differences in levels of inflammatory biomarkers could help match patients to treatments that are most likely to be beneficial . The authors tested the hypothesis that C-reactive protein ( CRP ) , a commonly available marker of systemic inflammation , predicts differential response to escitalopram ( a serotonin reuptake inhibitor ) and nortriptyline ( a norepinephrine reuptake inhibitor ) . METHOD The hypothesis was tested in the Genome-Based Therapeutic Drugs for Depression ( GENDEP ) study , a multicenter open-label r and omized clinical trial . CRP was measured with a high-sensitivity method in serum sample s from 241 adult men and women with major depressive disorder r and omly allocated to 12-week treatment with escitalopram ( N=115 ) or nortriptyline ( N=126 ) . The primary outcome measure was the score on the Montgomery-Åsberg Depression Rating Scale ( MADRS ) , administered weekly . RESULTS CRP level at baseline differentially predicted treatment outcome with the two antidepressants ( CRP-drug interaction : β=3.27 , 95 % CI=1.65 , 4.89 ) . For patients with low levels of CRP ( < 1 mg/L ) , improvement on the MADRS score was 3 points higher with escitalopram than with nortriptyline . For patients with  higher CRP levels , improvement on the MADRS score was 3 points higher with nortriptyline than with escitalopram . CRP and its interaction with medication explained more than 10 % of individual-level variance in treatment outcome . CONCLUSIONS An easily accessible peripheral blood biomarker may contribute to improvement in outcomes of major depressive disorder by personalizing treatment choice There is significant variability in antidepressant treatment outcome , with ∼30–40 % of patients with major depressive disorder ( MDD ) not presenting with adequate response even following several trials . To identify potential biomarkers of response , we investigated peripheral gene expression patterns of response to antidepressant treatment in MDD . We did this using Affymetrix HG-U133 Plus2 microarrays in blood sample s , from untreated individuals with MDD ( N=63 ) ascertained at a community outpatient clinic , pre and post 8-week treatment with citalopram  , and used a regression model to assess the impact of gene expression differences on antidepressant response . We carried out technical validation of significant probesets by quantitative reverse transcriptase PCR and conducted central nervous system follow-up of the most significant result in post-mortem brain sample s from 15 subjects who died during a current MDD episode and 11 sudden-death controls . A total of 32 probesets were differentially expressed according to response to citalopram treatment following false discovery rate correction . Interferon regulatory factor 7 ( IRF7 ) was the most significant differentially expressed gene and its expression was upregulated by citalopram treatment in individuals who responded to treatment . We found these results to be concordant with our observation of decreased expression of IRF7 in the prefrontal cortex of MDDs with negative toxicological evidence for antidepressant treatment at the time of death . These findings point to IRF7 as a gene of interest in studies investigating genomic factors associated with antidepressant response BACKGROUND After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor ( SSRI ) , it is not known whether switching to one antidepressant is more effective than switching to another . METHODS We r and omly assigned 727 adult out patients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSRI citalopram  to receive one of the following drugs for up to 14 weeks : sustained-release bupropion ( 239 patients ) at a maximal daily dose of 400 mg , sertraline ( 238 patients ) at a maximal daily dose of 200 mg , or extended-release venlafaxine ( 250 patients ) at a maximal daily dose of 375 mg . The study was conducted in 18 primary and 23 psychiatric care setting s. The primary outcome was symptom remission , defined by a total score of 7 or less on the 17-item Hamilton Rating Scale for Depression ( HRSD-17 ) at the end of the study . Scores on the Quick Inventory of Depressive Symptomatology - Self Report ( QIDS-SR-16 ) , obtained at treatment visits , determined secondary outcomes , including remission ( a score of 5 or less at exit ) and response ( a reduction of 50 percent or more on baseline scores ) . RESULTS Remission rates as assessed by the HRSD-17 and the QIDS-SR-16 , respectively , were 21.3 percent and 25.5 percent for sustained-release bupropion , 17.6 percent and 26.6 percent for sertraline , and 24.8 percent and 25.0 percent for extended-release venlafaxine . QIDS-SR-16 response rates were 26.1 percent for sustained-release bupropion , 26.7 percent for sertraline , and 28.2 percent for extended-release venlafaxine . These treatments did not differ significantly with respect to outcomes , tolerability , or adverse events . CONCLUSIONS After unsuccessful treatment with an SSRI , approximately one in four patients had a remission of symptoms after switching to another antidepressant . Any one of the medications in the study provided a reasonable second-step choice for patients with depression . ( Clinical Trials.gov number , NCT00021528 . ) In a controlled study , such immunological parameters as whole blood production of the cytokines interleukin-6 ( IL-6 ) and tumor-necrosis factor-α ( TNF-α ) were assessed in 24 in patients with a major depressive disorder ( MDD ) both before and again under treatment . After a 6-week treatment period with amitriptyline , patients were classified as responders or nonresponders according to their psychopathological outcome as evaluated by the Hamilton and the Montgomery – Asberg Depression Rating Scales . Pre-treatment levels of c-reactive protein ( CRP ) were significantly higher in both patient subgroups than in the control subjects . In comparison to the controls , unstimulated pretreatment production of IL-6 was significantly decreased in the responders ; whereas it was significantly increased in the nonresponder subgroup . Post-treatment values did not differ significantly among the patient and control groups . Pretreatment levels of TNF-α were increased in both patient subgroups , with a significant decrease during treatment only in the responder subgroup . Pretreatment levels of IL-6/105 mononuclear cells and the ratio between lymphocytes and monocytes acted as independent variables with regard to the clinical response . Our data indicate that unstimulated secretion of TNF-α is related to the psychopathological improvement ; whereas , IL-6 levels might dichotomize the patients into subsequent responders and nonresponders already at admission OBJECTIVE Depression in older adults is often associated with cognitive abnormalities and may predict later development of a primary cognitive disorder . This double-blind , r and omized , placebo-controlled pilot study was design ed to assess the safety and efficacy of galantamine augmentation of antidepressant treatment for depressive and cognitive symptoms in older adults with major depression . METHODS Thirty-eight , non-demented older adults ( age > 50 ) with major depression were r and omized to receive galantamine or placebo augmentation of st and ard antidepressant pharmacotherapy ( venlafaxine XR or citalopram ) .  Mood and cognitive status were monitored for 24 weeks using the 24-item Hamilton Rating Scale for Depression and the Repeatable Battery for the Assessment of Neuropsychological Status . RESULTS Both groups showed significant improvements in mood and cognition over 24 weeks , but no significant difference was found in change over time between groups . An exploratory post-hoc analysis suggested that patients r and omized to galantamine had lower depression scores compared to patients in the placebo group after 2 weeks of treatment . Dropout was high with more subjects r and omized to antidepressant plus galantamine  withdrawing early from the study . CONCLUSIONS This pilot study failed to demonstrate a benefit for galantamine augmentation of antidepressant medication in the treatment of depression in older adults . Future studies should explore strategies for reducing dropout in such longitudinal trials and more carefully assess time to response with cholinesterase inhibitor augmentation OBJECTIVE Some evidence indicates that an immune response with an increased production of proinflammatory cytokines often accompanies major depression . The objective of this study was to examine the serum levels of IL-6 in patients with major depression and the changes occurring in IL-6 levels during treatment with selective serotonin reuptake inhibitors ( SSRI ) . METHOD Twenty-three patients with a DSM-IV diagnosis of major depressive disorder and 23 healthy matched controls were included in the study . The severity of depression was measured with the Hamilton rating scale for depression . Blood sample s for IL-6 levels were obtained at baseline and at week 6 of treatment and IL-6 concentrations were evaluated using a solid phase s and wich enzyme immunoassay . All patients were treated with an SSRI . RESULTS The IL-6 levels showed no statistically significant difference between the patients and the controls at baseline . However , IL-6 levels after treatment with SSRIs were significantly lower compared with the baseline IL-6 levels of both the patients and the controls . CONCLUSION The results of this study suggest that proinflammatory cytokines show some changes during the course of treatment of major depression . These findings might also be considered as supporting the hypothesis of a modulatory role of antidepressants on the immune system Depressed mood has been associated with reduced natural killer cell activity ( NKCA ) . Further , amelioration of depressive symptoms by pharmacotherapy has result ed in augmented NKCA . Serotonin , an indoleamine implicated in the pathophysiology of affective disorders , enhances NKCA in vitro and lymphocytes possess serotonin transporters and receptors . The present study evaluated NKCA  in depressed out patients before and during treatment with the selective serotonin reuptake inhibitor ( SSRI ) fluoxetine ( Prozac ® ) . Further , the SSRIs , fluoxetine and paroxetine ( Paxil ® ) , were also incubated in vitro with lymphoid cells to evaluate possible direct effects of SSRIs on NKCA . Depressed out patients were administered fluoxetine  ( 20 mg/day ) for 4 weeks  . NKCA and 
    Output:
    
Antidepressants appear , in general , to reduce pro-inflammatory factor levels , particularly C-reactive protein ( CRP ) , tumour necrosis factor (TNF)-α , interleukin (IL)-1β and IL-6 .