***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 Cognitive deficits form core features in schizophrenia . Several studies have shown improvements in prefrontal cognitive function by α 2 -agonists in schizophrenia . In the present study , it was investigated whether clonidine ( an α 2 -adrenoceptor agonist ) could normalize sensorimotor gating deficits in schizophrenia . METHODS In a double blind , placebo controlled , r and omized , yet balanced , cross-over experiment , 20 male schizophrenia patients on stable medication were assessed in an auditory prepulse inhibition ( PPI ) , sensitization , and habituation of the startle reflex paradigm on 5 occasions : once after oral administration of placebo and after a single dose of 25 , 50 , 75 , and 150 µg of clonidine . Their results were compared with 20 age- and gender-matched healthy volunteers , who received no treatment . RESULTS In the placebo treatment , patients showed deficient PPI and sensitization , yet normal habituation compared with the controls . Except the highest dose , all dosages of clonidine significantly increased percentage PPI in the patients compared with placebo , to such levels that it no longer differed significantly from the healthy controls . However , none of the dosages increased sensitization or influenced habituation . CONCLUSIONS This is the first study to show that even a single low dose of clonidine added to the medical treatment of patients with schizophrenia who are clinical ly stable on their antipsychotic medication not only significantly ameliorates their PPI deficits , but also normalizes them . The results have a potentially high clinical relevance for the medical treatment of schizophrenia Adjunctive mirtazapine improved negative symptoms of schizophrenia  in several studies . Recently , we found an improvement also in positive symptoms when mirtazapine was added to first generation antipsychotics ( FGAs ) in a 6 week r and omized controlled trial ( RCT ) . The short duration of that trial was its limitation . This study aim ed to explore whether longer treatment is worthwhile Major depressive disorder ( MDD ) has been associated with alterations in the noradrenergic system and impaired memory function . In turn , enhanced memory function has been associated with noradrenergic stimulation . In this study , we examined whether noradrenergic stimulation would differentially improve memory function in patients with MDD and healthy controls . In a placebo-controlled crossover study , 20 patients with MDD and 18 age- and sex-matched healthy controls received either placebo or 5 mg of yohimbine , an alpha-2-adrenoceptor antagonist that causes increased noradrenergic activity , orally before memory testing . A word list paradigm was used to test memory consolidation . Furthermore , the autobiographical memory test assessing memory retrieval and a working memory test were administered . Salivary alpha-amylase and blood pressure were measured . Yohimbine improved memory consolidation ( word list learning ) across groups ( main effect of yohimbine : p = 0.05 ) . This effect was more prominent in depressed patients compared with controls ( post hoc t-test : MDD p = 0.01 , controls p = 0.77 ) . Memory retrieval ( autobiographical memory specificity ) and working memory were not affected by yohimbine . Across groups , yohimbine administration result ed in an increase in blood pressure and alpha-amylase . In sum , these results further support the hypothesis that noradrenergic stimulation enhances memory consolidation . The mechanism by which yohimbine leads to stronger memory consolidation in depressed patients compared with healthy controls remains to be eluci date BACKGROUND Due to their favorable side-effect profile , atypical antipsychotic agents offer important therapeutic advantages in mood disorders .  Ziprasidone , an atypical antipsychotic agent with strong 5-HT(1A ) agonist activity , may be particularly useful when used in conjunction with st and ard antidepressants in treatment-resistant depression . The purpose of this study is to test this hypothesis in depressed out patients who have not experienced significant clinical improvement following an adequate trial of a selective serotonin reuptake inhibitor ( SSRI ) . METHOD Twenty patients with major depressive disorder ( MDD ) who had failed to experience a clinical response to an adequate trial of an SSRI were treated with open-label ziprasidone in addition to their SSRI for 6 weeks between February 2002 and December 2002 . MDD was diagnosed with the Structured Clinical Interview for DSM-IV Axis I disorders . Clinical response was defined as a 50 % or greater decrease in depressive symptoms during the course of the trial ( baseline to endpoint ) , as measured by the HAM-D-17 total score . RESULTS Thirteen of 20 patients ( 65.0 % ) completed the trial . Using a completer analysis , 8 patients ( 61.5 % ) were classified as responders . An intent-to-treat ( ITT ) analysis result ed in 10 responders ( 50.0 % ) . The overall proportion of remitters was 5 of 13 ( 38.5 % ) using a completer analysis and 5 of 20 ( 25.0 % ) using the ITT analysis . Ziprasidone administration appeared to be safe , with no clinical ly significant QTc prolongation or severe adverse events observed in any of the study participants . CONCLUSION These results suggest a possible augmentation role for ziprasidone when used in conjunction with SSRIs in SSRI-resistant MDD BACKGROUND The comparative antidepressant effects of clozapine and other atypical antipsychotics for schizophrenia remain elusive , leading us to examine this question using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness phase 2E . METHODS Ninety-nine patients who discontinued treatment with olanzapine , quetiapine , risperidone , or ziprasidone because of inadequate efficacy were r and omly assigned to open-label treatment with clozapine ( n=49 ) or double-blind treatment with another atypical antipsychotic not previously received in the trial ( olanzapine [ n=19 ] , quetiapine [ n=15 ] , or risperidone [ n=16 ] ) . The primary outcome was the Calgary Depression Scale for Schizophrenia ( CDSS ) total score . Antidepressant effects of clozapine and the other atypical antipsychotics were compared in patients with chronic schizophrenia and those with a major depressive episode ( MDE ) at baseline ( i.e. ≥6 on the CDSS ) , using mixed models . RESULTS No differences in the baseline CDSS total scores were found between the treatment groups regardless of presence of an MDE . Clozapine was more effective than quetiapine in antidepressant effects for chronic schizophrenia ( p<.01 for the whole sample and p=.01 for those with an MDE ) , and comparable to olanzapine and risperidone . CONCLUSION The present findings suggest that clozapine demonstrates superior antidepressant effects to quetiapine and comparable effects to olanzapine and risperidone in chronic schizophrenia regardless of presence of MDE . Given the indication of clozapine for treatment-resistant schizophrenia ( TRS ) and the negative impacts of depressive symptoms on clinical outcomes in schizophrenia , further research is warranted to investigate antidepressant effects of clozapine in TRS with an MDE 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 Background The Mental Health Biomarker Project ( 2010–2014 ) selected commercial biochemistry markers related to monoamine synthesis and metabolism and measures of visual and auditory processing performance . Within a case – control discovery design with exclusion criteria design ed to produce a highly characterised sample , results from 67 independently DSM IV-R-diagnosed cases of schizophrenia and schizoaffective disorder were compared with those from 67 control participants selected from a local hospital , clinic and community catchment area . Participants underwent protocol -based diagnostic-checking , functional-rating , biological sample - collection for thirty c and i date markers and sensory-processing assessment . Results Fifteen biomarkers were identified on ROC analysis . Using these biomarkers , odds ratios , adjusted for a case – control design , indicated that schizophrenia and schizoaffective disorder were highly associated with dichotic listening disorder , delayed visual processing , low visual span , delayed auditory speed of processing , low reverse digit span as a measure of auditory working memory and elevated levels of catecholamines . Other nutritional and biochemical biomarkers were identified as elevated hydroxyl pyrroline-2-one as a marker of oxidative stress , vitamin D , B6 and folate deficits with elevation of serum B12 and free serum copper to zinc ratio . When individual biomarkers were ranked by odds ratio and correlated with clinical severity , five functional domains of visual processing , auditory processing , oxidative stress , catecholamines and nutritional-biochemical variables were formed . When the strengths of their inter-domain relationships were predicted by Lowess ( non-parametric ) regression , predominant bidirectional relationships were found between visual processing and catecholamine domains . At a cellular level , the nutritional-biochemical domain exerted a pervasive influence on the auditory domain as well as on all other domains . Conclusions The findings of this biomarker research point towards a much-required advance in Psychiatry : quantification of some theoretically-underst and able , translationally-informative , treatment-relevant underpinnings of serious mental illness . This evidence reveals schizophrenia and schizoaffective disorder in a somewhat different manner , as a conglomerate of several disorders many of which are not currently being assessed-for or treated in clinical setting s. Currently available remediation techniques for these underlying conditions have potential to reduce treatment-resistance , relapse-prevention , cost burden and social stigma in these conditions . If replicated and vali date d in prospect i ve trials , such findings will improve progress-monitoring and treatment-response for schizophrenia and schizoaffective disorder No studies have compared mirtazapine with duloxetine in patients with major depressive disorder ( MDD ) . Fifty-six patients were nonr and omly assigned to a 4-week treatment with either 15 to 45 mg/day of mirtazapine ( n = 22 ) or 20 to 60 mg/day of duloxetine ( n = 34 ) . The primary efficacy measurements were the Hamilton Rating Scale for Depression ( HRSD ) and the Montgomery – Åsberg Depression 6-point Rating Scale ( MADRS ) scores . The second efficacy measurements were the response and remission rates of treatment . Tolerability assessment s were also performed . Fifty-six patients ( 43 male ; age , 43.6 years ) were recruited . There was no significant difference in the discontinuation rate between the mirtazapine and duloxetine treatment groups ( P = 0.867 ) . Both mirtazapine and duloxetine significantly improved the HRSD and MADRS scores from baseline ( P < 0.0001–0.0004 ) . While mirtazapine was superior to duloxetine in the reduction of HRSD scores ( P = 0.0421 ) , there was no significant change in MADRS scores in terms of between-group differences ( P = 0.171 ) . While more somnolence was observed with mirtazapine ( P = 0.0399 ) , more nausea was associated with duloxetine ( P = 0.0089 ) . No serious adverse events were observed for either antidepressant . Mirtazapine and duloxetine were safe and well-tolerated treatments for Japanese patients with MDD . Double-blind controlled studies are needed to further explore the efficacy and safety of mirtazapine and duloxetine in Japanese patients with MDD BACKGROUND Sensory gating deficits are 
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Overall , the studies provided indirect evidence that α-AR activity may play an important role in aberrant regulation of cognition , arousal , and valence systems associated with MDD and schizophrenia .
Characterization of the NE pathway in patients may provide clinicians with information for more personalized therapy of these heterogeneous diseases .
Current clinical studies do not provide direct evidence to support the role of NE α-ARs in the pathophysiology of MDD and schizophrenia and in the treatment response of patients with these diseases , in particular with relation to specific valence systems .