***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 This study aim ed to explore effects of adjunctive N-acetylcysteine ( NAC ) treatment on inflammatory and neurogenesis markers in unipolar depression . METHODS We embarked on a 12-week clinical trial of NAC ( 2000 mg/day compared with placebo ) as an adjunctive treatment for unipolar depression . A follow-up visit was conducted 4 weeks following the completion of treatment . We collected serum sample s at baseline and the end of the treatment phase ( week 12 ) to determine changes in interleukin-6 ( IL6 ) , C-reactive protein ( CRP ) and brain-derived neurotrophic factor ( BDNF ) following NAC treatment . RESULTS NAC treatment significantly improved depressive symptoms on the Montgomery-Asberg Depression Rating Scale ( MADRS ) over 16 weeks of the trial . Serum levels of IL6 were associated with reductions of MADRS scores independent of treatment response . However , we found no significant changes in IL6 , CRP and BDNF levels following NAC treatment . CONCLUSION Overall , this suggests that our results failed to support the hypothesis that IL6 , CRP and BDNF are directly involved in the therapeutic mechanism of NAC in depression . IL6 may be a useful marker for future exploration of treatment response OBJECTIVE The purpose of this study was to identify genetic variants underlying the considerable individual differences in response to antidepressant treatment . The authors performed a genome-wide association analysis of improvement of depression severity with two antidepressant drugs . METHOD High- quality Illumina Human610-quad chip genotyping data were available for 706 unrelated participants of European ancestry treated for major depression with escitalopram ( N=394 ) or nortriptyline ( N=312 ) over a 12-week period in the Genome-Based Therapeutic Drugs for Depression ( GENDEP ) project , a partially r and omized open-label pharmacogenetic trial . RESULTS Single nucleotide polymorphisms in two intergenic regions containing copy number variants on chromosomes 1 and 10 were associated with the outcome of treatment with escitalopram or nortriptyline at suggestive levels of significance and with a high posterior likelihood of true association . Drug-specific analyses revealed a genome-wide significant association between marker rs2500535 in the uronyl 2-sulphotransferase gene and response to nortriptyline . Response to escitalopram was best predicted by a marker in the interleukin-11 ( IL11 ) gene . A set of 72 a priori-selected c and i date genes did not show pharmacogenetic associations above a chance level , but an association with response to escitalopram was detected in the interleukin-6 gene , which is a close homologue of IL11 . CONCLUSIONS While limited statistical power means that a number of true associations may have been missed , these results suggest that efficacy of antidepressants may be predicted by genetic markers other than traditional c and i date s. Genome-wide studies , if properly replicated , may thus be important steps in the elucidation of the genetic basis of pharmacological response Rationale The inflammatory hypothesis of depression states that increased levels of pro-inflammatory cytokines triggered by external and internal stressors are correlated to the acute depressive state . This hypothesis also suggests that pharmacotherapy partly acts in depression through anti-inflammatory effects . Transcranial direct current stimulation ( tDCS ) is a novel , promising , non-invasive somatic treatment for depression , although its antidepressant mechanisms are only partly understood . Objectives We explored the effects of tDCS and sertraline over the immune system during an antidepressant treatment trial . Methods In a 6-week , double-blind , placebo-controlled trial , 73 antidepressant-free patients with unipolar depression were r and omized to active/sham tDCS and sertraline/placebo ( 2 × 2 design ) . Plasma levels of several cytokines ( IL-2 , IL-4 , IL-6 , IL-10 , IL-17a , IFN-γ , and TNF-α ) were determined to investigate the effects of the interventions and of clinical response on them . Results All cytokines , except TNF-α , decreased over time , these effects being similar across the different intervention-groups and in responders vs. non-responders . Conclusions tDCS and sertraline ( separately and combined ) acute antidepressant effects might not specifically involve normalization of the immune system . In addition , being one of the first placebo-controlled trials measuring cytokines over an antidepressant treatment course , our study showed that the decrease in cytokine levels during the acute depressive episode could involve a placebo effect , highlighting the need of further placebo-controlled trials and observational studies examining cytokine changes during depression treatment and also after remission of the acute depressive episode 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 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 OBJECTIVE Selective serotonin reuptake inhibitors ( SSRIs ) are widely used to treat depression , but the rates , timing , and baseline predictors of remission in " real world " patients are not established . The authors ' primary objectives in this study were to evaluate the effectiveness of citalopram , an SSRI , using measurement-based care in actual practice , and to identify predictors of symptom remission in out patients with major depressive disorder . METHOD This clinical study included out patients with major depressive disorder who were treated in 23 psychiatric and 18 primary care " real world " setting s. The patients received flexible doses of citalopram prescribed by clinicians for up to 14 weeks . The clinicians were assisted by a clinical research coordinator in the application of measurement-based care , which included the routine measurement of symptoms and side effects at each treatment visit and the use of a treatment manual that described when and how to modify medication doses based on these measures . Remission was defined as an exit score of < or=7 on the 17-item Hamilton Depression Rating Scale ( HAM-D ) ( primary outcome ) or a score of < or=5 on the 16-item Quick Inventory of Depressive Symptomatology , Self-Report ( QIDS-SR ) ( secondary outcome ) . Response was defined as a reduction of > or=50 % in baseline QIDS-SR score . RESULTS Nearly 80 % of the 2,876 out patients in the analyzed sample had chronic or recurrent major depression ; most also had a number of comorbid general medical and psychiatric conditions . The mean exit citalopram dose was 41.8 mg/day . Remission rates were 28 % ( HAM-D ) and 33 % ( QIDS-SR ) . The response rate was 47 % ( QIDS-SR ) . Patients in primary and psychiatric care setting s did not differ in remission or response rates . A substantial portion of participants who achieved either response or remission at study exit did so at or after 8 weeks of treatment . Participants who were Caucasian , female , employed , or had higher levels of education or income had higher HAM-D remission rates ; longer index episodes , more concurrent psychiatric disorders ( especially anxiety disorders or drug abuse ) , more general medical disorders , and lower baseline function and quality of life were associated with lower HAM-D remission rates . CONCLUSIONS The response and remission rates in this highly generalizable sample with substantial axis I and axis III comorbidity closely resemble those seen in 8-week efficacy trials . The systematic use of easily implemented measurement-based care procedures may have assisted in achieving these results 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 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 Major depressive disorder ( MDD ) is a psychiatric condition characterized by hypercortisolism and variations in circulatory cytokines . Previously it has been reported that administration of selective serotonin reuptake inhibitors ( SSRI ) in MDD patients modify cortisol and cytokine levels but these studies only evaluated changes over a short time period . This work reports the long-term effects of administration of SSRI on the cortisol levels and pro-/anti-inflammatory cytokine profile in a group of MDD patients treated for 52 weeks . A total of 31 patients diagnosed with MDD received anti depressant treatment with SSRI . HDRS and BDI were administered over a year , and levels of interleukin IL-1beta , IL-10 , IL-2 , IFN-gamma , IL-4 , IL-13 , and 24-h urine cortisol were determined at weeks ( W 
    Output:
    
These findings suggested that alterations in peripheral cytokine levels were associated with antidepressant treatment outcomes in MDD .