***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 Many studies have implicated prenatal infection in the etiology of schizophrenia . Cytokines , a family of soluble polypeptides , are critically important in the immune response to infection and in other inflammatory processes . The goal of this study was to determine whether second-trimester levels of four cytokines-interleukin-8 ( IL-8 ) , interleukin-1beta ( IL-1beta ) , interleukin-6 ( IL-6 ) , and tumor necrosis factor-alpha (TNF-alpha)-are higher in the mothers of offspring who later developed schizophrenia spectrum disorders than in matched comparison subjects . METHOD The authors conducted a nested case-control study of maternal serum cytokine levels in a large birth cohort , born 1959 - 1967 . Cases ( N=59 ) were subjects diagnosed with schizophrenia spectrum disorders ( mostly schizophrenia and schizoaffective disorder ) who had available second-trimester maternal serum sample s. Comparison subjects ( N=105 ) were members of the birth cohort , had not been diagnosed with a schizophrenia spectrum disorder or major affective disorder , and were matched to subjects with schizophrenia for date of birth , gender , length of time in the cohort , and availability of maternal sera . Maternal second-trimester serum levels of IL-8 , IL-1beta , IL-6 , and TNF-alpha were determined by s and wich enzyme-linked immunosorbent assay . RESULTS The second-trimester IL-8 levels in mothers of offspring with schizophrenia spectrum disorders were significantly higher than those of the mothers of comparison subjects . There were no differences between subjects with schizophrenia and comparison subjects with respect to maternal levels of IL-1beta , IL-6 , or TNF-alpha . CONCLUSIONS Using prospect ively collected prenatal sera in a large and well-characterized birth cohort , the authors have documented a significant association between maternal IL-8 level during the second trimester and risk of schizophrenia spectrum disorders in the offspring . These findings provide further support for a substantive role of in utero infection or inflammation in the etiology of schizophrenia . Moreover , these results may have important implication s for elucidating the mechanisms by which disrupted fetal development raises the risk of this disorder 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 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 . ) 
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Some early mechanistic evidence does associate select chemokines with the neurobiological processes , including neurogenesis , modulation of the neuroinflammatory response , regulation of the hypothalamus-pituitary-adrenal axis , and modulation of neurotransmitter systems .
This early evidence however does not clearly demonstrate any specificity for a certain psychiatric disorder , but is primarily relevant to mechanisms which are shared across disorders .
Notable exceptions include CCL11 that has recently been shown to impair hippocampal function in aging - of distinct relevance to Alzheimer 's disease and depression in the elderly , and pre-natal exposure to CXCL8 that may disrupt early neurodevelopmental periods predisposing to schizophrenia .
Pro-inflammatory chemokines , such as CCL2 , CCL7 , CCL8 , CCL12 , and CCL13 , have been shown to drive chemotaxis of pro-inflammatory cells to the inflamed or injured CNS .
Likewise , CX3CL has been implicated in promoting glial cells activation , pro-inflammatory cytokines secretion , expression of ICAM-1 , and recruitment of CD4 + T-cells into the CNS during neuroinflammatory processes .