You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Acute Inflammatory Biomarker Profiles Predict Depression Risk Following Moderate to Severe Traumatic Brain Injury
Abstract 1:
Objective : To examine whether acute inflammation profiles predict posttraumatic depression ( PTD ) risk 6 and 12 months after traumatic brain injury . Setting : University-affiliated level 1 trauma center and community . Participants : Adults with moderate to severe traumatic brain injury ( acute serum levels : n = 50 ; acute cerebrospinal fluid ( CSF ) levels : n = 41 ) . Design : Prospect i ve cohort study . Main Measures : Patient Health Question naire ; inflammatory biomarkers ( interleukin [IL]-1&bgr ; , IL-4 , IL-5 , IL-6 , IL-7 , IL-8 , IL-10 , IL-12 , tumor necrosis factor & agr ; , soluble vascular adhesion molecule [ sVCAM-1 ] , soluble intracellular adhesion molecule [ sICAM-1 ] , soluble Fas [ sFAS ] ) . Results : Higher levels of acute CSF cytokine surface markers ( sVCAM-1 , sICAM-1 , and sFAS ) in an inflammatory biomarker risk ( IBR ) score were associated with a 3.920-fold increase in the odds of developing PTD at 6 months ( 95 % confidence interval : 1.163 - 8.672 ) . Having sICAM-1 , sVCAM-1 , or sFAS above the 75th percentile had a positive predictive value of 85.7 % for PTD risk at 6 months . An IBR score including inflammatory biomarkers IL-7 and IL-8 showed a trending association with 12-month PTD risk ( odds ratio = 3.166 , 95 % confidence interval : 0.936 - 10.708 ) . Conclusion : Acute CSF IBR scores show promise for identifying individuals at risk for PTD . Further research should assess acute CSF inflammatory biomarkers ' relationships to chronic inflammation as a mechanism of PTD and should explore anti-inflammatory treatments for PTD , as well as prevention and screening protocol s , and link inflammatory biomarkers to symptom tracking


Title 2:
Whole blood serotonin and platelet activation in depressed post-myocardial infarction patients.
Abstract 2:
Depression is an independent risk factor for post myocardial infa rct ion ( MI ) mortality . Abnormalities in platelet function have been proposed as one of the mechanisms involved in increased cardiovascular risk among patients with depression post-MI . Depression in somatically healthy patients has been associated with increased platelet activation . Some but not all studies showed changes in blood serotonin level . Increased platelet activation and blood serotonin level have been associated with increased risk of cardiac events in patients with MI . The goal of this study was to investigate whether 1 ) depressed post-MI patients have higher markers of platelet activation as measured by plasma levels of beta-thromboglobulin ( betaTG ) , platelet factor 4 ( PF4 ) and soluble CD40 lig and ( sCD40L ) and higher serotonin ( 5-HT ) levels than non-depressed post-MI patients and 2 ) treatment with the antidepressant mirtazapine decreases platelet activation . In this study , 25 depressed post-MI patients were asked for blood collection before start as well as after 8 weeks treatment with mirtazapine or placebo . The control group ( n=22 ) consisted of non-depressed post-MI patients , matched for age , gender and time elapsed since MI . Plasma levels of betaTG , PF4 and sCD40L were not statistically different between the groups , but 5-HT levels were significantly higher in depressed patients . Treatment with mirtazapine result ed in a non-significant decrease in betaTG and PF4 and platelet 5-HT levels . Platelet and whole blood 5-HT , but not platelet activation was significantly increased in depressed post-MI patients . Treatment with mirtazapine showed a non-significant decrease in platelet activation and platelet 5-HT


Title 3:
Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy.
Abstract 3:
OBJECTIVE Approximately 30 % of patients with depression fail to respond to a selective serotonin reuptake inhibitor ( SSRI ) . Few studies have attempted to define these patients from a biological perspective . Studies suggest that overall patients with depression show increased production of proinflammatory cytokines . We examined pro- and anti-inflammatory cytokine levels in patients who were SSRI resistant . METHODS Plasma concentrations of IL-6 , IL-8 , IL-10 , TNF-alpha and sIL-6R were measured with enzyme linked immunosorbent assays ( ELISA ) in DSM-1V major depressives who were SSRI resistant , in formerly SSRI resistant patients currently euthymic and in healthy controls . RESULTS Patients with SSRI-resistant depression had significantly higher production of the pro-inflammatory cytokines IL-6 ( p=0.01 ) and TNF-alpha ( p=0.004 ) compared to normal controls . Euthymic patients who were formerly SSRI resistant had proinflammatory cytokine levels which were similar to the healthy subject group . Anti-inflammatory cytokine levels did not differ across the 3 groups . CONCLUSION Suppression of proinflammatory cytokines does not occur in depressed patients who fail to respond to SSRIs and is necessary for clinical recovery


Title 4:
Higher CSF interleukin-6 and CSF interleukin-8 in current depression in older women. Results from a population-based sample
Abstract 4:
OBJECTIVE The literature regarding cerebrospinal fluid ( CSF ) cytokines in geriatric depression is sparse . The aim of this study was to examine associations between CSF interleukin-6 ( IL-6 ) , interleukin-8 ( IL-8 ) and depression in a population -based sample of older women who were followed for 17 years . METHODS 86 dementia-free women aged 70 - 84 years who participated in the Prospect i ve Population Study of Women in Gothenburg , Sweden took part in a lumbar puncture in 1992 - 3 .  CSF IL-6 and CSF IL-8 were measured . Psychiatric symptoms were rated with the Comprehensive Psychopathological Rating Scale at baseline and at three subsequent face-to-face examinations . Depression ( major or minor ) was diagnosed in accordance with DSM-IV/DSM-IV research criteria . RESULTS At baseline , women with ongoing major ( n=10 ) or minor depression ( n=9 ) had higher levels of CSF IL-6 ( p=0.008 ) and CSF IL-8 ( p=0.007 ) compared with those without depression ( n=67 ) . Higher CSF IL-8 was related to higher MADRS score ( p=0.003 ) . New cases of depression were observed in 9 women during follow-ups . No associations between CSF cytokine levels and future depression could be shown in women without depression at baseline . CONCLUSION Higher levels of CSF IL-6 and IL-8 were associated with current depression in this population -based sample .  CSF IL-6 and CSF IL-8 may play a role in depression in late life


Title 5:
Elevated Neuroimmune Biomarkers in Sweat Patches and Plasma of Premenopausal Women with Major Depressive Disorder in Remission: The POWER Study
Abstract 5:
BACKGROUND Major depressive disorder ( MDD ) is inconsistently associated with elevations in proinflammatory cytokines and neuropeptides . We used a skin sweat patch , recently vali date d in healthy control subjects , and recycling immunoaffinity chromatography to measure neuroimmune biomarkers in patients with MDD mostly in remission . METHODS We collected blood at 8:00 am and applied skin sweat patches for 24 hours in 21- to 45-year-old premenopausal women ( n = 19 ) with MDD ( 17/19 in remission ) and age-matched healthy controls ( n = 17 ) participating in the POWER ( Premenopausal , Osteopenia/Osteoporosis , Women , Alendronate , Depression ) Study . RESULTS Proinflammatory cytokines , neuropeptide Y , substance P , and calcitonin-gene-related peptide were significantly higher and vasoactive intestinal peptide , a marker of parasympathetic activity , was significantly lower in patients compared to controls , and depressive symptomatology strongly correlated with biomarker levels . All analytes were strongly correlated in the skin sweat patch and plasma in patients ( r = .73 to .99 ; p < .0004 ) . CONCLUSIONS The skin sweat patch allows detection of disrupted patterns of proinflammatory cytokines and neuropeptides in women with MDD in clinical remission , which could predispose to medical consequences such as cardiovascular disease , osteoporosis , and diabetes . This method permits measurement of cytokines in ambulatory setting s where blood collection is not feasible


Title 6:
Elevated platelet factor 4 and β-thromboglobulin plasma levels in depressed patients with ischemic heart disease
Abstract 6:
Clinical depression has recently been recognized as an independent risk factor for cardiac mortality in patients after myocardial infa rct ion . The underlying mechanisms of this increased mortality remain unclear . This study investigated the hypothesis that patients suffering from ischemic heart disease ( IHD ) and depression concurrently may have abnormal platelet activation result ing in an increased risk of thrombosis . Platelet factor 4 ( PF4 ) and beta-thromboglobulin ( beta-TG ) were measured in young healthy control subjects , in nondepressed patients with IHD , and in depressed patients with IHD .  Mean PF4 and beta-TG plasma levels in the IHD group with depression were found to be significantly higher than those of the control and IHD groups . This increase was not related to age , gender , racial difference , aspirin use , or severity of cardiac disease . This finding suggests that in depressed patients with IHD there is greater platelet activation , and may indicate an increased risk of thrombotic complications


Title 7:
Low Brain-Derived Neurotrophic Factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity
Abstract 7:
BACKGROUND Recent reports have suggested a role for brain-derived neurotrophic factor ( BDNF ) in psychiatric disorders . Decreased serum BDNF levels have been reported in major depression , but the cause of this decrease has not yet been investigated . The goal of this study was to assess blood BDNF and a platelet activation index , PF4 . METHODS Forty-three drug-free patients ( 27 female , 16 male ) diagnosed with major depression and 35 healthy control subjects ( 18 female , 17 male ) were assessed for plasma , serum , and blood BDNF content . Brain-derived neurotrophic factor and PF4 were assayed with enzyme-linked immunosorbent assay methods , and severity of depression was evaluated with the Montgomery-Asberg Depression Rating Scale . RESULTS Serum and plasma BDNF levels were decreased in depressed patients compared with control subjects . In whole blood , BDNF levels were unaltered in the depressed subjects compared with control subjects . The serum/blood BDNF ratio was lower in patients with major depression . Increased plasma but not serum PF4 levels were observed in depressed subjects compared with control subjects . CONCLUSIONS Our results suggest that an alteration of serum or plasma BDNF is not due to the change in blood BDNF but rather is probably related to mechanisms of BDNF release . Secretion of BDNF seems to be independent of platelet reactivity ; other mechanisms are therefore probably involved and need to be eluci date
Overall , our meta- analysis finds evidence linking abnormalities of blood chemokines with depression in humans .
Furthermore , we have demonstrated the possibility of classifying individuals with depression based on their inflammatory biomarker profile .