抑郁症炎症标志物,文献综述
REVIEW
In?ammation and clinical response
to treatment in depression:A meta-analysis R.Strawbridge a,n,D.Arnone a,A.Danese b,c,A.Papadopoulos a, A.Herane Vives a,e,A.J.Cleare a,d
a Affective Disorders Research Group,Centre for Affective Disorders,Psychological Medicine,
Institute of Psychiatry,King's College London,London,UK
b Social,Genetic&Developmental Psychiatry Centre,Institute of Psychiatry,King's College London, London,UK
c Department of Child&Adolescent Psychiatry,Institute of Psychiatry,King's College London,London,UK
d National Institut
e for Health Research(NIHR)Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and Institute o
f Psychiatry,King's College London,London,UK e Psychiatric University Clinic,University of Chile,Santiago,Chile
Received24February2015;accepted12June2015
KEYWORDS Depression;
In?ammation; Biological markers; Depressive disorder; Treatment-resistant Abstract
The depressive state has been characterised as one of elevated in?ammation,which holds promise for better understanding treatment-resistance in affective disorders as well as for future developments in treatment strati?cation.Aiming to investigate alterations in the in?ammatory pro?les of individuals with depression as putative biomarkers for clinical response,we conducted meta-analyses examining data from35studies that investigated in?ammation before and after treatment in depressed patients together with a measure of clinical response.There were suf?cient data to analyse IL-6,TNFαand CRP.Levels of IL-6decreased with antidepressant treatment regardless of outcome,whereas persistently elevated TNFαwas associated with prospectively determined treatment resistance.Treatment non-responders tended to have higher baseline in?ammation,using a composite measure of in?ammatory markers.Our?ndings suggest that elevated levels of in?ammation are contributory to treatment https://www.wendangku.net/doc/f514085680.html,bining in?ammatory biomarkers might prove a useful tool to improve diagnosis and detection of treatment refractoriness,and targeting persistent in?ammation in treatment-resistant depres-sion may offer a potential target for the development of novel intervention strategies.
&2015Elsevier B.V.and ECNP.All rights reserved.
https://www.wendangku.net/doc/f514085680.html,/locate/euroneuro
https://www.wendangku.net/doc/f514085680.html,/10.1016/j.euroneuro.2015.06.007 0924-977X/&2015Elsevier B.V.and ECNP.All rights
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n Correspondence to:Affective Disorders Research Group,Centre for Affective Disorders,Department of Psychological Medicine, Institute of Psychiatry,Psychology&Neuroscience,King's College London,London SE58AZ,UK.Tel.:+442078485305.
E-mail address:Becci.strawbridge@https://www.wendangku.net/doc/f514085680.html,(R.Strawbridge).
European Neuropsychopharmacology(2015)25,1532–1543
1.Introduction
An aberrant in?ammatory pro?le has been widely demon-strated in depressive disorders and is believed to contribute to some of the biological mechanisms associated with disease onset and treatment response(Dowlati et al., 2010;Miller et al.,2009;Smith,1991).Recent evidence suggests that levels of in?ammation might be modi?able with pharmacological treatment(Hannestad et al.,2011; Hiles et al.,2012;Janssen et al.,2010)and preliminary evidence indicates that treatment resistance might be associated with heightened in?ammation.Additionally, non-steroidal anti-in?ammatory drugs might be bene?cial as adjunctive treatments in unipolar(Akhondzadeh et al., 2009;Muller et al.,2006)and bipolar(Nery et al.,2008) disorders and the TNFαantagonist in?iximab may particu-larly bene?t depressed individuals with a history of treat-ment resistance and high in?ammation(Raison et al.,2013). Treatment non-response contributes greatly to the burden of affective illnesses(Gibson et al.,2010);it is common, affecting at least a third of patients(Warden et al.,2007), and is generally associated with poorer long-term outcomes (Fekadu et al.,2009).To improve the rate and robustness of clinical response in depression there is a need for novel treatment strategies(Kupfer et al.,2012),including enhan-cing the personalisation of treatment provision using stra-ti?cation.As such,research has been increasingly focusing on the importance of effectively screening for predictors of response across depressed populations,and using putative biomarker signatures prior to treatment provision may help to identify objective biological differences between patients who do or do not respond to treatments.Measuring ‘panels’of biomarkers may assist with the discovery of biological signatures for disorders such as depression (Schmidt et al.,2011),which also may be supported using meta-analytic techniques that provide greater statis-tical power than individual https://www.wendangku.net/doc/f514085680.html,bining these two approaches may be useful for identifying in?ammatory relationships with depressed state and response to treat-ment,particularly as studies measuring different(but similar)data points cannot otherwise be compared in a high-powered analysis.We describe a new methodology of combining in?ammatory data from different biomarkers together to enable a substantially higher statistical power.
Another important factor in this relationship is whether in?ammatory pro?les within a depressed state might differ between individuals with unipolar and bipolar diagnoses: although this has not been established there is some indicative evidence that in?ammation is not elevated in bipolar depressed state(Munkholm et al.,2013),as opposed to mania and euthymia.
1.1.Aim of the study
With the aim of expanding on previous work,we investi-gated studies measuring in?ammatory biomarkers in depres-sion in relation to treatment response and hypothesised that (a)non-responsive patients would have higher levels of in?ammation at baseline than responders;(b)patients would show a decrease in levels of in?ammation after a course of treatment,but that;(c)treatment refractoriness would be characterised by persistently high levels of in?ammation.
2.Experimental procedures
2.1.Criteria for study inclusion
A systematic search of the literature was conducted to obtain all studies that measured in?ammatory responses in depression at baseline and following a course of treatment,and that also assessed treatment response.A priori inclusion criteria required eligible studies to be in English,measure in vivo at least one peripheral biomarker purporting to measure in?ammation in human subjects classi?ed as being in a depressive episode according to a clinician-rated standardised measure of depression symptomatology(e.g.HRSD,MADRS,IDS)alongside a standardised measure of clinical response to a treatment(and where relevant,a comparison of in?ammation between responder and non-responder groups at one timepoint or more).T o ensure we measured naturally occurring in?ammation we excluded any studies which included a psychological or physiological stressor,or induced in?amma-tion either by a targeted agent or by speci?c immunomodulatory drugs (e.g.non-steroidal anti-in?ammatory drugs would be excluded,but not psychotropic medications).For this reason we also excluded papers reporting relevant comparisons in speci?cally physically ill samples (though we included studies which did not necessarily exclude indivi-duals who had physical illnesses).Subjects were required to be of any adult age to be considered eligible.
2.2.Systematic search
We searched the databases PubMED(1960-),EMBASE(1974-),and PsycINFO(1967-),with the aim of eliciting all studies measuring peripheral markers of in?ammation in patients with unipolar or bipolar depression and in relation to treatment response and/or clinical improvement,ful?lling our inclusion criteria.The full search process is depicted in Figure1.Studies were retrieved by RS and inclusion/exclusion of studies agreed by consensus(with AC, AP).Studies were also scrutinised for potentially relevant citations. In case of incomplete information study authors were contacted to request additional data not available in the original manuscript. 2.3.Assessment of quality
Research reports were assessed using seven criteria,adapted from those developed by the Evidence-Based Medicine Working Group that had been modi?ed for use in prognostic investigations(Fekadu et al.,2009)and the Cochrane Collaboration's Risk of Bias tool for trial designs(Higgins et al.,2011).Studies can score either positively(+1),negatively(à1) or neutrally(no score change)on each of the following domains:Cohort formation,sample size,trial/follow-up length,collection of biological data,study completion data,design of treatment provision,objective clinical assessment.This resulted in a ranking fromà7to+7(see T able1),which we used as a brief indicator of methodological rigour in individual studies,within the limitations of this approach.
https://www.wendangku.net/doc/f514085680.html,posite biomarker calculation
It was clear that the variation between studies of in?ammatory biomarkers investigated would lead to low-powered meta-analyses of individual biomarkers.Based on the consideration that all selected biomarkers should measure the same latent construct(in?ammation) and thus be correlated,we planned analyses to incorporate all possible available data.This novel method should at present be considered a preliminary test of the predictive validity of a combination of biomark-ers as a measure of overall in?ammatory response.The‘composite
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measure’provides a preliminary and perhaps coarse representation of in?ammation and its relationship with response to treatment in affective disorders,and will therefore require consideration when interpreting results.However,this method not only permits a higher powered meta-analysis,but also enables a broader perspective to be taken on the putative relationship between in?ammatory pro?les and clinical response to antidepressant treatments in people with depression.
T o prevent bias in the composite in?ammation analysis towards studies measuring multiple biomarkers,one entry per eligible study was required for each analysis.It was also important not to bias our results towards particular biomarkers.We therefore employed a method to utilise the maximum data available by averaging together all relevant biomarkers within each study prior to entering into the meta-analysis.Eligible markers were de?ned as pro-in?ammatory cytokines(Cameron and Kelvin,2000;Hodge-Dufour et al.,1998),as follows:tumour necrosis factor(TNFα),interferon-αorβ(IFNα/IFNβ), interleukins1(IL-1α/IL-1β)or6(IL-6),c-reactive protein(CRP)which was also included as a direct marker of in?ammation.
For each included study,mean data values for each eligible biomarker were?rst converted into pg/ml(except for CRP which was converted into mg/L),and then all relevant variables pooled to create the‘composite’measure using a pooling method embedded in the software Comprehensive Meta-analysis(version2.2.021),for merging multiple data points within subjects(using the mean of the selected outcomes).The composite data calculated for each study, roughly representing the levels of in?ammation for each compar-ison,provided a single-entry per study into each meta-analysis. 2.5.Statistical analysis
Meta-analyses were conducted where suf?cient data were available in at least3studies for each primary comparison.For all possible biomarkers,the comparisons conducted were as follows:
1.Responder vs.non-responders at baseline(pre-treatment).
2.In?ammatory changes alongside treatment in responders.
3.In?ammatory changes alongside treatment in non-responders.
Additional secondary comparisons that were conducted on the above biomarkers were patients vs.controls at baseline and in?ammatory change in all patients over treatment(not distinguish-ing between responder and non-responder groups).
Aside from the effect-size calculations for the composite analyses, statistical analysis methodology was conducted using Stata11.0(Stata Corp,College Station,T exas)and supplemented by‘Metan’software downloadable from the Centre for Statistics in Medicine,Oxford,UK,as reported previously(Arnone et al.,2009).Standardised mean differ-ences were calculated using Cohen's d statistic and standardised effect sizes were then combined using the inverse variance method.Random effects analyses(DerSimonian and Laird,1986)were used throughout to weight each study.The presence of heterogeneity was tested using the Q-test and its magnitude estimated using I2,which can be interpreted as the proportion of effect size variance due to heterogeneity(Higgins et al.,2003).Publication bias,which describes the tendency of small studies to report large effect sizes,was examined using Egger's test (Egger et al.,1997)with the signi?cance level set at p o0.05.T o further investigate causes for heterogeneity,meta-regression analyses were performed in the primary analyses(outlined below).Potential con-founders considered were;sex(%),age,baseline symptom severity, clinical setting(inpatient/outpatient),medication status on study-entry, standardised/naturalised treatment in study,length of treatment,study year,and study quality assessment.The ST A T A module"metareg"was used throughout and the REML(restricted maximum likelihood)method used to estimate the model parameters.
3.Results
The literature search yielded a total of2053articles,of which35met inclusion criteria(see Figure1and Table1
for Figure1Flow chart of selection process for inclusion of studies.
R.Strawbridge et al. 1534
details and reasons for exclusion).All included studies investigated unipolar major depression except for one that only included bipolar diagnosed patients in a depressive episode (Tsai et al.,2014),and three that included both bipolar and unipolar depression (Himmerich et al.,2006;Landmann et al.,1997;Maes et al.,1995)but did
not
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In ?ammation and clinical response
compare in ?ammation between the two groups.Three biomarkers were suf ?ciently researched to be included in primary analyses:interleukin-6(IL-6)in 12studies (Basterzi et al.,2005;Carvalho et al.,2012;Fornaro et al.,2011;Frommberger et al.,1997;Kubera et al.,2000;Lanquillon et al.,2000;Maes et al.,1997a ;Maes et al.,1995;Marques-Deak et al.,2007;Mikova et al.,2001;Yoshimura et al.,2009;Yoshimura et al.,2013),TNF αin 11studies (Eller et al.,2008,2009;Fornaro et al.,2013;Himmerich et al.,2006;Landmann et al.,1997;Lanquillon et al.,2000;Mikova et al.,2001;Piletz et al.,2009;Song et al.,2009;T uglu et al.,2003;Yoshimura et al.,2009)and CRP in 8studies (Chang et al.,2012;Harley et al.,2010;Lanquillon et al.,2000;O'Brien et al.,2006;Piletz et al.,2009;Tsai et al.,2014;T uglu et al.,2003;Uher et al.,2014).
3.1.Description of studies
All 35studies were longitudinal in design,measuring in ?ammatory markers at baseline and following up patients over the course of treatment.All but two studies (Carvalho et al.,2012;Uher et al.,2014)repeated in ?ammation measurements after treatment.Most articles dichotomised patients at study-end into responders and non-responders (Basterzi et al.,2005;Basterzi et al.,2010;Carvalho et al.,2012;Chang et al.,2012;Eller et al.,2008,2009;Fornaro et al.,2011;Fornaro et al.,2013;Frank et al.,2004;Himmerich et al.,2006;Kook et al.,1995;Landmann et al.,1997;Lanquillon et al.,2000;Maes et al.,1997a ;Maes et al.,1997b ;Mikova et al.,2001;O'Brien et al.,2006;Pariante and Miller ,1995;Seidel et al.,1996;Song et al.,2009;Yoshimura et al.,2009;Yoshimura et al.,2013).For
these studies,the criterion for response was Z 50%reduc-tion of score on the adopted depression severity rating scale.Seven studies reported results in responders only (Frommberger et al.,1997;Hernandez et al.,2008;Maes et al.,1995;Marques-Deak et al.,2007;Piletz et al.,2009;Tsai et al.,2014;T uglu et al.,2003),and seven studies described clinical improvements using a continuous out-come measure (Harley et al.,2010;Himmerich et al.,2010;Kubera et al.,2000;Mizruchin et al.,1999;O'Brien et al.,2006;Schleifer et al.,1999;Uher et al.,2014).Studies were heterogeneous in terms of in ?ammatory biomarkers mea-sured and patient samples,including the presence of psychiatric comorbidity,the degree of baseline treatment refractoriness and medication status at baseline.All studies investigated only pharmacological treatment,except one that compared pharmacological with psychological inter-ventions (Harley et al.,2010);this found that high CRP was associated with good clinical response in antidepressant therapy but with poor response after psychotherapy.There were insuf ?cient studies to compare in ?ammatory markers in unipolar and bipolar depression.Meta-analyses largely demonstrated signi ?cant levels of heterogeneity (I 2)and lack of publication bias (all p 40.05);see ?gures and Table 2.
3.2.Baseline in ?ammation and subsequent treatment-response
Elevated baseline in ?ammation was found in depression vs.healthy controls with all three in ?ammatory markers:IL-6(p =0.003),TNF α(p =0.02)and CRP (p o 0.0001),as well as the composite analysis (p =0.017).However ,no signi ?
cant
R.Strawbridge et al.
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differences in levels of baseline in ?ammation were identi-?ed between those subsequently responding or not respond-ing to treatment:this was shown in TNF α(p =0.57),CRP (p =0.76),and IL-6(p =0.19),though the latter was numeri-cally higher in non-responders.The composite measure of in ?ammation at baseline showed higher levels were present in people subsequently not responding to treatment,which approached statistical signi ?cance (p =0.073).This ?nding remained when con ?ning the analysis solely to unipolar patients (i.e.removing the study which contained some
Egger’s test for publication bias: p=0.07, I 2 test for heterogeneity: p<0.001
Egger’s test for publication bias: p=0.27, I 2
test for heterogeneity: p<0.001
Figure 2TNF αchange in responders (Fig.2A)vs.non-responders (Fig.2B).Egger's test for publication bias:p =0.07,I 2test for heterogeneity:p o 0.001and Egger's test for publication bias:p =0.27,I 2test for heterogeneity:p o 0.001.
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In ?ammation and clinical response
bipolar depressed patients(Himmerich et al.,2006); p=0.071).We performed a meta-regression on the compo-site measure which showed that the effect of elevated in?ammation on treatment non-response was more accen-tuated in outpatient vs.inpatient settings(b=à0.494, p=0.012),and in studies with a higher quality rating (b=0.137,p=0.009).
3.3.Effects of treatment and treatment-response on in?ammation
There was no change evident in TNFαlevels when simply looking at the effects of treatment i.e.when responders and non-responders were grouped together(p=0.42).How-ever,there was a differential effect when treatment response was taken into account:levels of TNFαsigni?-cantly decreased in treatment responders(p=0.008)but not in non-responders(p=0.9);see Figure2.These analyses included one study where both unipolar and bipolar patients were included(Himmerich et al.,2006);exclusion of this study did not alter TNFαresults(responders,p=0.008;non-responders,p=0.66).Meta-regression analyses s uggested that decreased levels of TNFαin responders positively correlated with year of publication,suggesting a stronger effect in more recent studies(b=0.205,p=0.026)with a trend in non-responders(b=0.21,p=0.056).
In the studies measuring IL-6,there was an overall reduction following treatment irrespective of treatment response(p=0.03;see Figure3).When separate analyses were conducted for responders and non-responders how-ever,non-signi?cant decreases were seen after treatment in both responders(p=0.53)and non-responders(p=0.11).IL-6analyses included8patients diagnosed with bipolar depression(Maes et al.,1995);exclusion of the study containing these patients(as within-study bipolar/unipolar patient data was unavailable)from the analyses did not change the responders'subgroup results(p=0.8),and no non-responders were included in this article,but the overall analysis showed a slightly lowered signi?cance value(k=9, ES=à0.54,CIà1.12/0.03,p=0.06).
Meta-regressions indicated a correlation in responders between age and IL-6change over treatment;studies with a higher mean age report smaller reductions in IL-6levels with treatment(b=0.113,p=0.011).In non-responders the degree of change in measured IL-6levels was more sig-ni?cant in older studies(b=0.236,p=0.024).
There was no effect of treatment,or of treatment-response,on levels of CRP or on the composite in?ammation measure.However,meta-regressions run on the composite analyses unanimously suggested that studies in which not all subjects were unmedicated at baseline showed greater variance in in?ammatory changes alongside treatment: (for all depressed subjects:b=1.23,p=0.017;for respon-ders only:b=1.101,p=0.432;for non-responders only: b=1.215,p=0.053.)
3.4.Unipolar and bipolar depression
Only T sai et al.(2014)included solely bipolar diagnosed patients who were in a depressive episode and it was not possible to undertake a meta-analysis comparing unipolar vs.bipolar depression in the four studies identi?ed(Himmerich et al., 2006;Landmann et al.,1997;Maes et al.,1995)due to disparate study methodologies or insuf?cient information being available.T sai et al.(2014)identi?ed a non-signi?cant increase in levels of in?ammation from acute depression to euthymia.In Maes et al.(1995),eight patients of the61included were bipolar patients in a depressed mood state,and the authors reported no correlations between bipolarity,IL-6and depression severity(Maes et al.,1995).The other two articles including bipolar depressed patients did not report results separately nor any comparisons between the unipolar and bipolar diagnosed subjects.As can be seen above,removal of bipolar subjects from primary meta-analyses did not substantially affect the results.
4.Discussion
To our knowledge this is the?rst meta-analysis to investi-gate systematically the relationship between in?ammation and treatment resistance in depression,both as a predictive marker and in maintenance of the illness.We found that prospectively-determined treatment resistance is asso-ciated with continued elevations in in?ammation,in that there is a decrease in TNFαlevels over time in treatment-responsive but not in treatment-resistant patients.We also examined a novel method for merging related in?ammatory biomarker data,and its relation to treatment-resistance in affective disorders,?nding a trend towards higher in?am-mation being associated with a poorer response to anti-depressant treatment.
4.1.In?ammation and major depression
Although not the primary focus of the study,we have replicated previous?ndings that depression as a whole is associated with increased in?ammation.In?ammatory ele-vations in depression have been reliably demonstrated across numerous reviews(Dowlati et al.,2010;Hannestad et al.,2011;Hiles et al.,2012;Miller et al.,2009)and there exist many plausible mechanisms by which this may occur. The causative effect of psychological and physiological stress on the in?ammatory response has been well docu-mented and this system interacts bidirectionally with other systems implicated in mood disorders,including HPA-axis activity and cortisol release(Miller et al.,1999),serotoner-gic pathways(Maes et al.,2011),neurogenesis and neuroin-?ammation(Harry and Kraft,2012).There is additional evidence that in?ammation is a causal factor in the onset of depression,supported by replicated?ndings that adminis-tration of in?ammatory cytokines(particularly IFNαtreat-ment for hepatitis C)can induce depressive symptoms or clinical depression in many patients(Raison et al.,2005).
An important area of uncertainty is the degree to which depression occurring as part of a bipolar disorder may differ compared to a unipolar disorder.There is a paucity of research to this end,and we were not able to identify suf?cient studies to test the hypothesis that in?ammatory markers may differentiate between unipolar and bipolar disorder.There is clear evidence of differential treatment strategies being appropriate in unipolar and bipolar depres-sion(Pacchiarotti et al.,2013)and due to the unanswered
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question of whether raised levels of in ?ammation are more speci ?c to unipolar depression,therapeutic intervention in this domain may not be appropriate in bipolar depression.This is clearly an area which requires further investigation.
4.2.In ?ammation and treatment resistance
The results of the meta-analysis demonstrate a role of in ?ammation in treatment-resistant depression:there were signi ?cant decreases in TNF α(towards control levels)seen only in treatment responders,whereas treatment resistance was associated with persistently elevated TNF α.This implies that maintenance of heightened levels of in ?ammation may at least contribute to treatment refractoriness,and thus that anti-in ?ammatory agents might provide a mechanism for treatment resistance in individuals with persistent high levels of TNF α.This is strengthened by recent preliminary ?ndings that a TNF αantagonist,in ?iximab,can improve depression in some treatment-resistant patients (Raison et al.,2013);when strati ?ed by pre-treatment levels of in ?ammation,in ?iximab appears to be most anti-depressant in those with higher pre-treatment in ?ammation.This association between TNF αmodi ?cation and response may account for the lack of signi ?cant ?ndings in a previous meta-analysis (Hannestad et al.,2011)which did not consider differential patterns of alteration in responders vs.non-responders.
We also found that,regardless of treatment response,antidepressant treatment can have anti-in ?ammatory effects,
notably a reduction in IL-6.This may also occur in bipolar depression as indicated by the reduced signi ?cance found when removing Maes et al.(1995)whose sample was partly comprised of bipolar patients.The anti-in ?ammatory effects of antidepressants have been reported in preclinical (Connor et al.,1999)and in vitro (Xia et al.,1996)studies as well as clinical samples (Hannestad et al.,2011;Hiles et al.,2012).Indeed,it has been suggested that these anti-in ?amma-tory effects may be one of the many mechanisms by which antidepressants exert their therapeutic effect (Janssen et al.,2010).It may be,therefore,that this anti-in ?ammatory effect of antidepressants is suf ?cient in many cases to reverse the overall in ?ammatory response seen in depression.However ,in those with more severe or chronic illnesses,this effect may not in itself be suf ?cient to normalise the in ?ammation,which may then in turn act as a maintaining factor in the illness.It should also be noted that psychological interventions alone have also been reported to reduce in ?ammation alongside depressive symptoms (Thornton et al.,2009).
https://www.wendangku.net/doc/f514085680.html,posite biomarker measurement
While meta-regressions conducted on individual biomarkers may have been insuf ?ciently powered to illustrate factors important in modifying the comparisons,the composite meta-regressions highlight the potential importance of medication status in the relationship between in ?ammation and treatment-resistance in depression.Our ?ndings may also suggest that speci ?c medications and their mechanisms
Egger’s test for publication bias: p=0.47, I 2
test for heterogeneity: p<0.001
Figure 3
IL-6alterations over treatment.Egger's test for publication bias:p =0.47,I 2test for heterogeneity:p o 0.001.
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In ?ammation and clinical response
might explain some of the heterogeneity within results, something that we were not able to explore further.A comprehensive understanding of pharmacological effects on in?ammation,and treatment-response,will require sub-stantially larger samples of depressed individuals before, during and after treatment with a range of separate antidepressant medications.
The composite measures showed that patients with higher levels of in?ammation responded less well to sub-sequent treatment,though this?nding did not reach statistical signi?cance.Despite the lack of signi?cant results from the composite analyses,we suggest this approach is still worthwhile;due to the complexity of interactions between human biomarkers(as well as the heterogeneity of affective disorders),it is arguable that such methods will be more likely to detect robust and clinically useful biological indicators to predict the likelihood of treatment successes.There may be a number of methods for calculat-ing this composite measurement,and identi?cation of an optimal approach requires further investigation.We parti-cularly highlight the dif?culty surrounding which biomarkers should be classi?ed as those representing in?ammation,and inconsistencies within the literature on this subject.We believe that this can evolve through the use of large datasets,advanced modelling techniques,and/or new dis-coveries made in biochemical mechanisms.
4.4.Clinical implications
As outlined earlier,treatment resistance is a common clinical problem in affective disorders,and it is likely that there are several contributing factors in each individual patient.An important approach is to rule out alternative diagnoses that may explain the depressive symptoms,and to evaluate organic factors that may be of relevance.The results of this meta-analysis add to the suggestion that it may also be important to evaluate the presence of raised levels of in?ammation.We have shown that elevated in?ammatory markers predict a poorer response to antidepressants,and that those who do not respond to antidepressant treatments show persistently elevated in?ammation.We suggest that there is now a clear imperative for research to investigate whether targeting this elevated in?ammation will improve the outcome in treatment resistant depression,and if so,in which particular groups of patients.
Studies have rarely measured all potential in?ammatory markers,and we do not yet know whether there are speci?c aspects of the in?ammatory response that are relevant to depression or whether an approach such as that taken here of combining measures of in?ammation is most likely to be of clinical relevance.We also suggest that in?ammation is likely to represent just one of several potential novel treatment targets in these dif?cult to treat cases of dep-ression,and that other approaches based upon other maintain-ing factors such as HP A axis disturbance(Juruena et al.,2009; Markopoulou et al.,2009)may also suggest differential treat-ment approaches on an individual level.Indeed,combining a range of in?ammatory and other markers might be useful in enhancing treatment personalisation and diagnostic accuracy in the future,and complements current strategies to link clinical syndromes more closely to underlying neurobiological and other substrates(Insel,2014).The bene?ts of this approach have been comprehensively outlined by Schmidt et al.(2011),which advocates the investigation of‘panels’of biomarkers(including for in?ammatory,neurogenesis,endocrine and other systems) in order to improve the recognition of different patient subtypes and ultimately increase treatment response.
4.5.Limitations
There are several limitations in the interpretation of ?ndings from this work.Our assessments using Egger's test indicate that our analyses are not likely to have been in?uenced by publication bias.However,due to the rela-tively small number of studies included in this work it is not possible to fully exclude the possibility of selective pub-lication of positive studies.It is also notable that there were a large range of treatments,in?ammatory markers and variation in patient characteristics between included stu-dies,limiting the conclusiveness and generalisability of the present?ndings.In particular,the treatments studied were almost exclusively pharmacological,and therefore the results may not apply to other forms of treatment.In addition,depression is a highly diverse condition and this was evident in the signi?cant levels of heterogeneity present in analyses,with factors including severity,depres-sive subtype,and degree of treatment resistance likely contributing to variation in in?ammatory pro?les.We exp-lored possible sources of heterogeneity with meta-regre-ssion analyses and found some associations with effect sizes, notably those present in the composite analyses,and that IL-6reductions with treatment were more prominent in younger samples.This may be a proxy for an earlier stage within the longitudinal course of affective illness or a representation of treatment naivety;both of these factors are associated with improved clinical response(Kornstein and Schneider,2001).However,it is important to bear in mind that heterogeneity could only partially be explained by the confounders we considered in meta-regressions; indeed,it is likely that there is signi?cant heterogeneity due to the very nature of depression itself.Moreover,this reinforces our message that further progress will be facili-tated by de?ning more homogeneous groups for study,for example those with raised in?ammatory markers and/or speci?c symptom pro?les.
Utilising standardised treatment approaches,and the inclu-sion of psychological treatments as well as pharmacological, could improve our understanding of how different treatments can resolve in?ammation.Furthermore,the relationship between in?ammatory and other biological systems is clearly complex and multifaceted.Concurrent assessment of some of the parameters interacting with the in?ammatory response in depression,such as the endocrine system,might prove useful in providing a fuller understanding of neurobiological dysfunc-tion and treatment in depression.
Author disclosures
Role of funding source
This paper presents independent research partly funded by the National Institute for Health Research(NIHR)and the NIHR
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Biomedical Resource Centre for Mental Health;the NIHR had no further involvement in the methodology,?ndings or development of this paper.
Contributors
R Strawbridge,Prof.Cleare&Dr.Papadopoulos conceived the design and methodology.R Strawbridge conducted the systematic review and meta-analysis,as well as primarily writing the manu-script.Dr.Arnone advised on and contributed to meta-analytic procedures.Dr.Danese and Dr.Papadopoulos provided expertise on in?ammatory mechanisms,and Prof.Cleare supplied further exper-tise regarding data interpretation and treatment-resistant depres-sion.All authors contributed and approved the?nal manuscript. Con?ict of interest
Prof.Cleare and Dr Arnone receive support from the NIHR Biome-dical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and Institute of Psychiatry,Psychol-ogy&Neuroscience,King's College London.Dr Arnone's research is currently supported by the Academy of Medical Sciences(grant number AMS-SGCL8).The authors report no further potential or actual con?icts of interest.The views expressed are those of the authors and not necessarily those of the NHS,the NIHR,the Department of Health or the Academy of Medical Sciences. Acknowledgements
We thank Dr.Rudolf Uher,Dr.Reiji Yoshimura,Dr.Livia Carvalho, Professor Hubertus Himmerich,Dr.Po-See Chen,Dr.Tony Harley, and Dr.Marcus Ising for kindly providing us with data from their studies.
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抑郁症
抑郁症 文章目录*一、抑郁症的概述*二、抑郁症的典型症状*三、抑郁症的病因病机*四、抑郁症的检查诊断鉴别方法*五、抑郁症的并发症*六、抑郁症的防治方案 抑郁症的概述 1、定义抑郁症又称抑郁障碍,以显著而持久的心境低落为主要临床特征,是心境障碍的主要类型。临床可见心境低落与其处境不相称,情绪的消沉可以从闷闷不乐到悲痛欲绝,自卑抑郁,甚至悲观厌世,可有自杀企图或行为;甚至发生木僵;部分病例有明显的焦虑和运动性激越;严重者可出现幻觉、妄想等精神病性症状。每次发作持续至少2周以上、长者甚或数年,多数病例有反复发作的倾向,每次发作大多数可以缓解,部分可有残留症状或转为慢性。 2、别称抑郁障碍、抑郁性障碍、忧郁症。 3、发病部位全身。 4、传染性无传染性。 5、高发人群成人。
抑郁症的典型症状 1、抑郁症的典型症状早期症状:情绪低落、心情压抑、焦虑、兴趣丧失、精力不足、悲观失望、自我评价过低等 晚期症状:现悲观厌世、绝望、幻觉妄想、身体功能减退、并伴有严重的自杀企图,甚至自杀行为。 2、抑郁症的分类隐匿性抑郁症: 隐匿性抑郁症患者情绪低下,他们偶尔也会感到忧郁,但是这些症状不是很明显。常有各种躯体不适症状表现,如纳呆、心悸、胸闷、中上腹不适、气短、出汗、消瘦、失眠。中青年和儿童中比较常见。 内源性抑郁症: 内源性抑郁症患者常见的表现有懒、呆、变、忧、虑。患者的动作减少,思维迟钝,构思困难,记忆力、注意力下降,脑功能减退;性格明显改变;情绪抑郁悲观,精力、体力不足;多思多虑,焦急不安,心神不宁等。 反应性抑郁症: 反应性抑郁症患者是我们生活中常见的抑郁症,在生活中突遇天灾人祸、失恋婚变、生病、事业挫折等,心理能力差的人容易患反应性抑郁症。此类抑郁症为“有因而生”,去除病因后能迅速康复。
抑郁
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属,这与遗传疾病的一般规律相符。 生化因素:儿茶酚胺假说:主要指抑郁症的发生可能与大脑 突触间隙神经递质5-羟色胺(5-HT)和去甲肾上腺素(NE)的浓度下降有关;由于很多抗抑郁剂,如选择性5-羟色胺再摄取抑制剂(SSRI)或者选择性5-羟色胺和去甲肾上腺素再摄取抑制剂(SNRI)等使用后,虽然大脑突触间隙这些神经递质的浓度很快升高,但 抗抑郁的效果一般还是需要2周左右才会起效,因此又有了5-HT 和NE受体敏感性增高(超敏)的假说; 心理-社会因素:各种重大生活事件突然发生,或长期持续存在会引起强烈或者(和)持久的不愉快的情感体验,导致抑郁症的产生。 抑郁的检查诊断鉴别方法 1、抑郁的检查方法抑郁类量表包括些抑郁的自评量表和他评量表,自评量表如贝克抑郁自评问卷(BDI)、Carroll抑郁量表(CRS)、流调中心用抑郁量表(CED-S)、抑郁自评量表(SDS);他评量表如汉密顿抑郁量表(HRSD)、抑郁状态问卷(DIS)、抑郁症状量表(DSS);还有为特定人群设计的爱丁堡产后抑郁量表(EPDS)、老年抑郁量表(GDS)、医院焦虑抑郁量表(HADS)等。这些量表可以帮助诊断是否有抑郁症状,用于抑郁的临床筛查;评定抑郁症 状的严重程度;还可以用来观察在治疗过程中抑郁的病情变化, 作为疗效的判定指标。当您需要进行测试时,请参看具体的量表
急性脓毒症凝血病
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中医对抑郁症的认识和治疗概述 作者：肖怡， 赵志付 作者单位：中国中医科学院广安门医院中医心身医学科,100053 刊名： 北京中医药 英文刊名：BEIJING JOURNAL OF TRADITIONAL CHINESE MEDICINE 年，卷(期)：2008,27(9) 被引用次数：3次 参考文献(15条) 1.张伯臾中医内科学 1985 2.虢周科.福文俊中医关于抑郁症的辨证论治探讨[期刊论文]-中国中医药现代远程教育 2006(11) 3.彭计红.梅晓云抑郁症的辨证分型概况[期刊论文]-南京中医药大学学报(自然科学版) 2004(01) 4.于皎辨证治疗抑郁症46例疗效观察及护理体会[期刊论文]-河南中医 2006(03) 5.施毅中医对抑郁证的认识与治疗[期刊论文]-实用中西医结合临床 2005(04) 6.周恒台辨证治疗抑郁症体会[期刊论文]-山西中医 2005(06) 7.刘浩.刘锋.江成鹏抑郁症的中医药治疗进展[期刊论文]-河南中医 2006(02) 8.安春平.程伟近年来抑郁症的中医病机、证候研究概述[期刊论文]-中医药信息 2007(01) 9.杨林论肝郁与抑郁症[期刊论文]-陕西中医 2000(06) 10.张永雷.李燕董湘玉老师温胆汤加减临床应用经验举隅[期刊论文]-贵阳中医学院学报 2007(04) 11.张金茹小柴胡汤治疗抑郁症40例[期刊论文]-北京中医 2003(05) 12.张华臧佩林教授治疗抑郁症经验介绍[期刊论文]-新中医 2007(03) 13.付强.周永红王新陆教授治愈抑郁症案举隅[期刊论文]-中华中医药学刊 2006(11) 14.张世筠从心论治抑郁症49例[期刊论文]-天津中医药 2005(04) 15.赵志付.熊抗美.刘国刚柔辨证的中医心身医学研究[期刊论文]-天津中医药 2003(04) 本文读者也读过(10条) 1.张华.李海波.王继伟抑郁症中医研究概况[期刊论文]-中医杂志2006,47(11) 2.包祖晓.彭草云.田青.高新颜.陈宝君.钟宇峰.李黎.BAO Zu-xiao.PENG Cao-yun.TIAN Qing.GAO Xin-yan.CHEN Bao-jun.ZHONG Yu-Feng.LI Li古代中医认识抑郁症的历史沿革[期刊论文]-中医药学报2010,38(3) 3.走罐治疗失眠40例[期刊论文]-中国针灸2000,20(6) 4.虢周科.福文俊中医关于抑郁症的辨证论治探讨[期刊论文]-中国中医药现代远程教育2006,4(11) 5.卢帅军.瞿融中医对抑郁症再认识[期刊论文]-实用中医内科杂志2007,21(6) 6.闫东升.崔娟.石和元中医学对抑郁症的认识[期刊论文]-江苏中医药2007,39(8) 7.韩毳.李晓泓抑郁症与中医肝脏关系探讨[期刊论文]-山东中医杂志2001,20(5) 8.李德平.王宝玲腹针治疗抑郁症44例[期刊论文]-上海针灸杂志2005,24(3) 9.周英特种针法治疗失眠症概况[期刊论文]-甘肃中医2008,21(5) 10.王小云.沈碧琼.张春玲中医综合疗法治疗女性抑郁症60例[期刊论文]-广东医学2001,22(6) 引证文献(3条) 1.王晓叶中医方剂治疗抑郁症的临床观察[期刊论文]-中国保健营养（下旬刊） 2013(9)
湖泊沉积物记录的湖水古盐度定量研究进展_曾承
湖泊沉积物记录的湖水古盐度定量研究进展 曾 承 1,2,3,4 ,安芷生1,刘卫国1 ,余俊清 (1.中国科学院地球环境研究所 黄土与第四纪地质国家重点实验室 陕西西安 710075;2.襄樊学院地理系 湖北襄樊 441053;3.中国科学院盐湖研究所 青海西宁 810008; 4.中国科学院研究生院 北京 100039) 摘 要:湖水古盐度的定量反演,可以促进过去全球变化研究由定性走向定量。内陆干旱半干旱地区湖泊尤其是封闭湖泊的盐度取决于流域降水,径流和蒸发的平衡关系,并直接表现为湖泊水位的变化。关于湖水的古盐度反演,长期以来已经根据多湖泊沉积环境指标加以揭示,包括湖泊沉积物中介形虫壳体的元素地球化学特性、硅藻-古盐度转换函数、介形虫壳体的形态学特征及其与生长环境的关系以及实验模拟等。各种方法有不同的适用条件和适用范围及一定的局限性,对此做了归纳和评述。关键词:湖泊沉积物,古盐度,定量研究 中图分类号:P597.2 文献标识码:A 文章编号:1008-858X (2007)04-0013-07 研究过去全球变化的目的是获得和解释各类古气候环境记录信息,认识地球系统环境的变化过程与机理,从而为预测未来气候环境变迁物理模型的建立提供基础资料,并有效地减少预测中的不确定性。这里,一个关键点和难点是古气候要素的定量化复原,准确的预测需要古气候要素研究从定性走向定量,这是过去全球变化研究中的一个发展方向。湖水古盐度的定量反演,可以促进过去全球变化研究由定性走向定量。 内陆干旱半干旱地区,湖泊尤其是封闭湖泊的盐度取决于流域降水,径流和蒸发平衡关系,并直接表现为湖泊水位的变化[1-4],关于过去湖水的古盐度反演,长期以来已经根据多湖泊沉积环境指标加以揭示。湖泊沉积物中介形虫壳体的元素地球化学特性已成功地用于古盐度的定量恢复[5-13]。近年来国际上通过利用硅藻组合-湖水化学数据库,建立硅藻-古盐 度转换函数,在定量恢复湖水古盐度方面取得很大进展[1,14-18],硅藻已被成功应用于古盐度的定量恢复,并被证实为推算过去湖水盐度最有效的生物指标[2-3]。最近,介形虫壳体的形态学特征及其与生长环境的关系也已引起了有关学者的关注,并利用这一关系进行了古盐度定量重建的初步研究[19-20]。 鉴于湖水古盐度定量重建的重要性,本文对前人的主要研究成果做了归纳及相应评述。 1 利用介壳元素地球化学特征定 量模拟湖水古盐度 1.1 原 理 湖泊沉积物碳酸盐中的微量元素如镁、锶等的研究对于确定古湖泊的物理化学条件有效而且简单易行,是确定湖泊水体古盐度的上好 收稿日期:2007-04-09 基金项目:国家重点基础研究发展规划项目(2004CB720200);国家自然科学基金项目(40599420,40673012,40571173);中国科学 院地球环境研究所黄土与第四纪地质国家重点实验室基金项目(SKLLQG0713);湖北省教育厅科学技术研究项目(B200625003);湖北省高等学校省级教学研究项目(20050291) 作者简介:曾承(1975-),男,博士研究生,讲师,主要从事地球化学和环境变化研究。 第15卷 第4期2007年12月 盐湖研究JOURNAL OF SALT LAKE RE SE ARCH Vol .15 No .4 Dec . 2007
人为什么会得抑郁症,抑郁症根本原因大揭秘!
人为什么会得抑郁症，抑郁症根本原因大揭 秘！ 只有真正了解自己，才能更好地改变自己！——题记 抑郁症的根本原因是什么？ 一个人对待事物的看法会影响情绪，所以，人们对事物的看法往往不是来自于事物本身，而是来自于你对事物的看法。比如，一块奶油面包，它在一个乞丐眼里可能是人间美味，可是在一个正在减肥的女人眼中，那就是一块非常恐怖的大脂肪球了。同样的，小时候我们可能会为了没得到一小块糖果而哭闹，而长大后会觉得那很很幼稚。 这就是思维及看法对人的情绪影响。这就是人们情绪状态的起因。 那么，我们继续来分析抑郁症。
对抑郁症患者的看法及信念进一部分析，我们就会发现他们的一个共同追求——完美主义！ 正是因为渴求所有人都接受他，所以才会过于担心别人对自己的看法！ 正是因为希望自己是十全十美的人，所以才会对自己哪怕一点点的缺点都耿耿于怀！ 正是因为觉得自己比别人，甚至比所有人都强，所以才会对自己的失败及不如人的地方难以释怀！ 正是因为想成为理想中的自己，所以才会对自己百般挑剔、不满！ 正是因为这些种种的自我要求，才使得患者不断苛求、攻击、憎恨现实中的自己。同时，也是通过自我攻击来维护虚幻的自我形象。 抑郁症的根本原因——完美主义的现实表现 活在幻想中的完美，总比在现实中的残酷要来的好。 抑郁症患者往往会有如下的一些负面信念——如只有成功，我才叫活出自己;只有跟所有人都合的来，我才是可爱的;只有超越身边的人，我才是有价值的！ 这就比如现实中的一些老好人，不会拒绝别人，为人很“善良”，做事总是尽善尽美，即便要吃亏也往往让自己吃亏。但即便这样委曲求全求得了个“现世安稳”，自己仍然活在紧张和不安中，害怕别人“了解”他之后就会离开。 从中我们可以看到，他所谓的“好”仅仅是一种博取他人认可的手段，为了赢得别人对他的肯定与接纳不惜隐藏真实的自己去讨好他
脓毒症与生物标志物
脓毒症与生物标志物 脓毒症（sepsis），即脓毒血症，是由致病菌感染引起的系统性炎症反应综合征（SIRS）。此病发病急，死亡率高。多数患者在入院时表现不具备特异性，据以往的一般检测指标（如T、R、HB及白细胞计数等）结果和细菌培养加药敏实验以判断病情及指导治疗，因所需的时间较长，只能经验性使用抗生素、入住ICU等治疗措施，即使采用这样的方法，死亡率仍较高。为此便开始了更好的标志物研究。直到目前，用于评估脓毒症潜在用途的生物标志物多达170多种[1]。脓毒症标志物如此繁多，来源范围广，从宏观到微观，预计今后研究的发展趋势为微观领域。现就近几年来对脓毒症的诊断和预后有一定价值的主要标志物及其应用作一综述。 1 氧化-抗氧化与炎症因子标志物 脓毒症发生有多种机制，其中一种称之为炎症-抗炎因子平衡学说，在机体受到有害刺激时，会释放促炎细胞因子，同时抗炎系统也被启动，释放内源性抗炎因子对炎症反应进行牵制和调节，但在脓毒血症时，平衡受到破坏，炎症反应失控，炎性因子大量释放导致全身炎症反应，进而导致多器官衰竭，或者表现为抗炎反应过度亢进，拮抗炎症细胞因子生成及作用，影响免疫细胞功能，导致机体处于失衡状态[2]。此过程离不开炎症因子的作用，如肿瘤坏死因子（TNF-α）、白介素类（IL）等。但是，炎症反应并不能完全解释脓毒症的病理生理，因此另一种学说-脂质氧化应激与抗氧化认为脂多糖（LPS）起了重要作用，核因子-KB （NF-KB）与其蛋白抑制物IKB平时以一种无活性的形式存在于胞浆中，被活化后，能诱导许多氧化物的转录，如一氧化氮合酶（NOS）、超氧化物歧化酶（SOD）、选择性环氧酶（COX-2）等[3]，这些转录产物的失衡进一步加重脓毒症的病理损害，导致微循环障碍甚至脓毒症休克。Raspé C[4]通过实验发现，用选择性NF-KB抑制剂预先处理脓毒症小鼠，发现诸如TNF-α，IL-1β，IL-6，IFN-γ之类的促炎因子释放有显著性的下降，说明在机体组织很有可能是转录因子NF-KB通过减少促炎因子的释放来调节炎症反应的过程。 TNF-α是在炎症过程中通过不断放大的级联反应所产生的一种炎症介质，能激活吞噬细胞的吞噬功能和刺激其他细胞分泌炎症因子如IL-1、IL-6、IL-7等，陈氏等[5]发现TNF-α、NF-KB在脓毒症大鼠肝脏中浓度较高，而SOD浓度却明显较低，经给予抗感染、抗氧化治疗后，NF-KB和TNF-α浓度均有所降低，而SOD的浓度却升高了，或许脓毒症正是炎症反应与氧化应激的双重作用，那么对这些炎症因子或氧化-过氧化产物进行检测，就有可能对脓毒症病情的发展有所掌握。如血浆SOD活性就能够成为脓毒症的一项检测指标，指导病情和预后[6]。 降钙素原（PCT）是一种多肽，其化学结构上有几种阳离子氨基酸，能直接中和细菌的LPS，从而减少主要炎症介质的产生，由LPS诱导的Th1，调节性T 细胞及单核细胞的级联激活所产生的主要炎症因子，PCT对其有显著的抑制作用[7]。因此一直以来被认为是脓毒症较好的标志物，在重症感染发生时其浓度迅
湖泊沉积物中风成和水成组分定量判据的初步研究_以青海湖为例_董吉宝
第16卷第4期 2010年12月地质力学学报JOURNAL OF GEOMECHANICS Vol.16No.4 Dec.2010 文章编号：1006- 6616（2010）04-0402-10收稿日期：2010- 05-07作者简介：董吉宝（1985-），男，博士研究生，主要从事第四纪地质与便于变化研究，E-mail ：dib@https://www.wendangku.net/doc/f514085680.html, 。 湖泊沉积物中风成和水成组分定量 判据的初步研究 ———以青海湖为例 董吉宝1，2，安芷生1，卢凤艳1， 2（1.中国科学院地球环境研究所黄土与第四纪地质国家重点实验室，陕西西安 710075； 2.中国科学院研究生院，北京100049）摘要：对青海湖沉积物进行物质来源进行聚类分析，并对周边风成黄土与现代湖 泊表层沉积物进行粒度分析，在此基础上，以青海湖周边典型风成黄土作为风成组 分端元，以青海湖表层沉积物作为水成组分端元，首次利用已知端元的粒度分布特 征对青海湖沉积物中典型粒度分布进行拟合，进而估算了其中风成和水成组分的比 例。结果表明，青海湖沉积物粒度分布特征可分为三大类： 1.水成组分占主导； 2.风成组分占主导（风成黄土主导）； 3.两者以不同比例混合。希望此方法能成 为未来湖泊沉积物中不同组分的定量判据和古环境的解读提供新途径。 关键词：青海湖；粒度；风成组分；定量判据；聚类分析 中图分类号：P588.2文献标识码：A 沉积物的粒度特征记录了沉积环境、搬运动力等信息，因而常被用于沉积物成因类型的判别［1 4］。利用沉积物的粒度特征判别沉积环境的方法可分为定性法和定量法两大类。自上世纪50、60年代至今，已有很多学者尝试以粒度特征定性-半定量地判别沉积环境，并取得了丰硕的成果，提出了许多不同的方法，如Q 1-Md-Q 3法、概率累计曲线法、结构散点图法、判别函数法、C-M 图法、因子分析法、BP 神经网络的方法、分维值法［1 2，5 17］等等，其中结 构散点图法、判别函数法和C-M 图法在国内的应用较多 ［3 4，18 20］。但随着研究的不断深入，定性-半定量的方法已不能满足需求，人们越来越希望定量地区分沉积环境中的不同来源的贡献比例，其中，以沉积物粒度数据为基础而进行的定量判别方面已取得了丰硕的成果，并得到了广泛的运用 ［21 33］例如，孙东怀等［21 26］，殷志强等［27］、Prins M. A.等［29 33］，基于各自的理解，建立了不同的定量分离方法。此外，也有其他学者从地球化学角度做了积极有益的研究和探索［34 35］。 以粒度数据为基础的定量判据研究虽已取得了不少成果，但判别的方法和结果仍然存在不足之处，有待进一步改进，如基于不同的函数分布进行拟合的方法，由于函数分布并不能完全代表真实环境中沉积物的粒度分布，因此，拟合的结果必然存在一定的偏差。基于此考虑，本文试图以青海湖为例，利用已知沉积类型的粒度数据作为端元，定量判别湖泊沉积物
谈湖泊沉积物粒度的环境含义
谈湖泊沉积物粒度的环境含义 论文关键词:湖泊沉积物 ;粒度 ;气候 ;环境 论文摘要:气候特征是冰期和相对温暖的间冰期交替发生。湖泊沉积物以其连续性好、敏感性强和高分辨率的特点,在恢复和重塑各种短时间尺度(千年、百年、十年)的气候和环境演化序列上,具有其它自然历史记录无法替代性。本文主要研究沉积物粒度的环境含义,古气候特征,尘暴,构造运动等环境信息很好的保存在湖泊沉积物粒度上。因此,本文通过对湖泊沉积物粒度的研究进而推断当时的环境特征。 由于湖泊沉积物是记录湖泊及其流域气候环境信息的有效载体,并具有连续性好、分辨率高、包含信息量丰富等特点,它记录了构造运动、气候变化、生态演化,尘暴等丰富的信息 ,这对地球环境的研究有非常重要的意义。本文试从湖泊沉积物粒度对当时的气候,尘暴和构造隆升进行分析.重建区域气候和历史环境,帮助认识地球上正在发生的各种变化.为未来的全球变化提供类比模式。 1湖泊沉积物粒度所反映的气候含义 近年研究表明,不同的湖泊沉积所反映的气候含义是不同的,区分封闭性湖泊和非封闭性的外流湖和洼地湖沉积。以下就是对这两种情况的研究。 1.1封闭性湖泊沉积物粒度所反映的气候意义
由于湖泊的相对封闭的地理表现形式,所以湖泊沉积在所有沉积中独具特色。它可提供时问范围达百万年、时间分辨率迭年至十年的高精度环境信息,因而在过去全球变化研究中具有重要地位。 对于封闭性的湖泊,陆源碎屑物是沉积物的主要物质来源,沉积物来源比较单一,因而湖水物理能量成为控制沉积物粒度分布的主要因素.按照理想的湖泊沉积作用模式,从湖岸至湖心,随着水深的逐步增大,湖水物理能量(水动力条件) 由强变弱,沉积物颗粒逐渐变细且平行于湖岸线呈环带状分布,即从湖岸至湖心大致出现砾-砂-粉砂粘土的沉积规律.因为在气候干旱期,湖泊的水位下降,湖面收缩,采样点离岸边的距离较近,水动力条件较强,可以带动粗颗粒物质到此处,而且此时的浅水强动力条件使细粒物质难以稳定沉降,因而在该位置沉积的颗粒较粗;反之,在气候湿润期,湖泊水位上升,湖面扩张,采样点离岸边的距离较远,粗颗粒物质难以到达,而且此时的深水弱动力条件有利于细颗粒物质沉降,因而在该位置沉积的颗粒较细,沉积物粒径减小。所以,沉积物粒径的大小反映气候的变化,沉积物粒径增大反映了采样点离湖岸的距离减小,湖泊水位下降,指示气候干旱,反之,沉积物粒径减小则反映采样点离湖岸的距离增大,湖泊水位上升,指示气候湿润。一般来讲,沉积物粒度的变化受水动力条件制约,而水动力条件往往受气候环境变化的影响。气候变化最直接的反映就是气温和降水。因而,气温和降水变化都会影响到入湖补给水动力大小以及湖面高低,进而影响沉积物粒度分布。 我国大部分湖泊是外流湖或洼地湖,与封闭型湖泊相比湖面波动较
抑郁症讲稿完整版68055
抑郁症讲稿 大家好！我是维英，很高兴代表我们组和大家一起来学习。至于学习的内容，我们先来看一个视频。（视频）相信看完视频你们已经猜到我今天要讲的内容了吧。（学生回答抑郁症）那一讲到抑郁症大家会想到哪个明星呢？没错，就是他（乔任梁），他给予我们的一直都是阳光开朗的一面，但当他离开的时候我们才发现原来抑郁症一直困扰着他，抑郁症也是造成他自杀的罪魁祸首，或许你们会觉得抑郁症只会发生在张国荣、乔任梁这些明星身上，其实不然，抑郁症离我们很近。 就在今年年初，北京邮电大学的研究生孙腾霄在与工商银行签约前11小时从宿舍爬上了10楼，结束了他的生命.孙腾霄是校园风云人物，被称为“孙神”.无论在哪个区域成就都非常厉害，本应该在去年毕业并和中国银行签约，可是在论文那关被怀疑有抄袭的可能。于是延迟毕业一年. 在被延迟的那年里，其他同学都顺利毕业就职，而自己却被滞留，陷入了低谷，当每次联系同学和女朋友时候，其他人都在忙，没有很多时间和他聊天.后来他渐渐不与大家沟通，失眠，厌食，去医院诊断为“抑郁症”。当他很辛苦地熬过了一年，快顺利毕业并和工商银行签约，可在结果出来的前一天，他担心自己会出现同样的状况，于是凌晨留在了“活着真的很痛苦，不想再伤害家人了...”从10楼跳下.
正如案例一样，随着科技高速发展，社会对学生要求越来越高，使高校学生课程增多负担加重，尤其对于我们医学生而言，更是年年期末似高考，相信大家都有所感触。在备考的时候，面对枯燥乏味的书本知识，我们难免会心情烦躁，这算不算抑郁症的早期症状？也许很多人对抑郁症只有一个模糊的概念，那今天我就跟大家来学习抑郁症，通过学习后大家就能对其有更深入的了解。 我们这节课的学习目标是掌握抑郁症的临床表现，护理措施，健康指导，对于熟悉和了解的部分的内容大家看一下。 那我们现在先来了解一下抑郁症流行病学的相关信息。抑郁现在是世界第四大健康问题，而至2020年，抑郁将成为第二大健康负担，影响全球的健康问题。抑郁症具有三高的特点：发病率高，危险性高，复发率高。（图表） 说到底什么才是抑郁呢？ 1.抑郁症的概念： 抑郁障碍是以情绪低落，思维迟缓并伴有减低，主动性下降等精神运动迟滞症状为主要表现的一类心境障碍综合症。这张图表现的是抑郁和抑郁症的区别。大家也可以看一下（图片） 2.病因（接下来我们了解一下病因，主要有两类，一类是个人性格上不同特质：如孤独自闭，完美主义，容易焦虑恐惧；一类则是现实生活中的诱因：如情感挫折，生活挫折，紧张与压力。）（ppt上体现出病因内容）
长江中下游湖泊沉积物氮磷形态与释放风险关系_张路
J. Lake Sci.(湖泊科学), 2008, 20(3): 263-270 https://www.wendangku.net/doc/f514085680.html,. E-mail: jlakes@https://www.wendangku.net/doc/f514085680.html, ?2008 by Journal of Lake Sciences 长江中下游湖泊沉积物氮磷形态与释放风险关系* 张路, 范成新, 王建军, 陈宇炜, 姜加虎 (中国科学院南京地理与湖泊研究所湖泊与环境国家重点实验室, 南京 210008) 摘 要: 运用聚类分析、主成分分析和相关矩阵的统计分析手段, 对长江中下游湖群共18个湖泊的沉积物氮磷释放风险以及湖泊沉积物、间隙水和上覆水中氮磷形态以及其他相关地球化学参数进行分析. 草型和藻型湖泊的环境差异是造成氮磷释放风险的主要原因. 氮磷释放风险与铁磷、藻类可利用磷、总氮、总磷、上覆水氮磷含量、间隙水氮含量、孔隙度和有机质含量间的关系最为密切. 决定磷酸盐释放风险的主要形态磷是藻类可利用磷和铁磷, 其他形态磷或者含量较低或者不易被转化释放, 对磷酸盐释放风险影响较小. 有机磷含量对磷的释放风险没有直接决定作用, 但它与有机质含量间呈显著正相关. 关键词: 沉积物; 氮磷; 营养盐形态; 释放风险; 湖泊 Nitrogen and phosphorus forms and release risks of lake sediments from the middle and lower reaches of the Yangtze River ZHANG Lu, FAN Chengxin, WANG Jianjun, CHEN Yuwei & JIANG Jiahu (State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008, P.R.China) Abstract: Cluster analysis, principal component analysis and correlation matrix analysis were used to analysis the nitrogen and phosphorus release risks from sediments in 18 lakes located in the middle and lower reaches of the Yangtze River, as well as the nitrogen and phosphorus forms and related geochemical parameters from sediments, pore waters and overlying waters. The ecological difference of macrophyte and algae dominated lakes was the main reason of the difference of nitrogen and phosphorus release. The release risks were well correlated with the iron-bound phosphorus (FeP), algae available phosphorus (AAP), total nitrogen (TN), total phosphorus (TP) in sediment, the content of nitrogen and phosphorus in overlying and pore waters, porosity and organic matter content of surficial sediment. The AAP and FeP was the main phosphorus forms deciding the phosphorus release risk and other forms were in less effect on it due to the lower contents or lower transformation ability. The sediment organic phosphorus was not directly related to the phosphorus release risks but remarkably positively correlated to organic matter contents in sediment. Keywords: Sediment; nitrogen and phosphorus; nutrients form; release risk; lake 沉积物是湖泊及其流域中营养盐及其他污染物的重要归宿和蓄积库. 沉积物中蕴藏的营养盐可以在一定的环境条件下向上覆水体释放. 这种潜在释放能力的大小主要取决于湖泊沉积物及其上覆水体的物理化学和生物特性的改变. 在湖泊底泥营养盐释放风险的研究中, 沉积物的物理和化学的特性(包括其含量和地球化学形态)是影响沉积物中氮磷营养要素迁移、转化以及生态效应的重要参数. 长江中下游有许多由长江洪泛和自然演化形成的湖泊, 其中大于1km2的650多个湖泊中大部分属于浅水湖泊. 这些湖泊目前普遍受到了湖泊水质恶化, 富营养化程度加重的影响, 其生态环境和社会经济效益严重受损. 对浅水湖泊而言, 由于其更复杂的生态类型, 更加频繁的水土界面营养盐交换以及更易受动力作用的影响, 沉积物中营养盐含量和形态的差异对与水土界面交换和上覆水的营养盐含量影响机制更加复杂[1-2]. 虽然湖泊沉积物氮磷形态, 间隙水氮磷含量与潜在释放之间的关系已有一些研究[3-7], 但仍然缺乏较 *科技部基础性工作专项(2006FY110600)和国家自然科学基金项目(40501064, 40730528)联合资助. 2006-10-26收稿; 2007-12-24收修改稿. 张路, 男, 1975年生, 博士, 副研究员; E-mail: luzhang@https://www.wendangku.net/doc/f514085680.html,.
抑郁症案例
标准化病人专科病例 1.编制的要求 选择编制的病例应为具有实际应用价值的常见病例或者是早期诊断和干预都具有重要意义的病例。临床问题应适当覆盖主要器官系统。多数病例应当是需要分析鉴别的，诊断不完全清楚，具有多种可能需进一步检查确诊的，而不应是经过几个病史提问就能作出诊断的过于简单的病例。 如果通过病史收集就能作出鉴别诊断，那就不需要包括体检部分。如果体检能提供对诊断有用的信息，就应有体检部分，体检的阳性发现可为病人的真正体征，也可为模拟的体征。一般来说，如有体检部分，应排出直肠或生殖器检查。 病例也可以包括交流技能，例如简单的病人教育、咨询，严重病情的说明等，如告知病人或家属严重病情、患有癌症等坏消息，教育病人戒除不良嗜好，说服病人遵守医嘱、服从治疗，以及与不合作、持敌意的病人接触等。病例中涉及的交流技能应是普通的和常见的情形，也可以是用真病人难以练习的情形，这使得考生会很珍惜用标准化病人来练习此技能的机会（如：要求尸检）。 病例应尽可能反映真实的病人与医生相遇的情景，尽可能在每个病例合适之处表述所有三个部分（病史、体检及交流技能）。病例应具有真实、可信、合乎逻辑的特点，其难易程度可视教学的对象及目的确定。 2.编制的内容及技巧 1）主诉 2）病例概述 这部分应提供对病例的良好的概括。应包括对病史和体检的概述（如有阳性体征，也应包括在内），最可能的诊断和适当的初始检查和处理计划。 3）场景 急诊，门诊，病房，时间（如果与疾病的情况有关）。 4）病人行为、情感、秉性的描述 描述病人行为、情感，与医生接触过程中的反应及病人最关心的问题等，以便规范SP的扮演及保持扮演的一致性。描述应尽可能详细。提供病人对问诊态度的信息（他或她在积极寻求帮助，不情愿，或反感），以及检查者的哪些问题或行为会激发病人行为的改变。
浅水湖泊沉积物中磷的地球化学特征
浅水湖泊沉积物中磷的地球化学特征 朱广伟,高 光,秦伯强,张 路,罗潋葱 (中国科学院南京地理与湖泊研究所,江苏南京 210008) 摘要:对太湖不同污染状况和生态系统状况的湖区沉积物中磷的地球化学形态及其分布进行了研究。结果发现,沉 积物的理化性质和磷的化学形态一般都在表层下深5～15cm 发生明显的转折;草型湖区、藻型湖区、开阔湖面的 大湖区沉积物的理化性质、间隙水中的磷浓度及沉积物中磷的形态存在较大的差异。东太湖沉积物间隙水磷浓度 和交换态磷含量都显著低于其他湖区;风浪扰动相对剧烈的开阔湖面湖区沉积物中磷的沉积规律也不同于梅梁湾 藻型湖区和东太湖草型湖区。研究表明,浅水湖泊中水生生物状况、风浪扰动状况对沉积物中磷的地球化学行为有 至关重要的影响。 关 键 词:浅水湖泊;沉积物;磷;地球化学形态;富营养化;太湖 中图分类号:X142 文献标识码:A 文章编号:100126791(2003)062714206 收稿日期:2002209211;修订日期:2002212230 基金项目:中国科学院知识创新项目(KZCX12SW 2122II 202;KZCX22311);国家自然科学基金资助项目(40203007);中国 博士后科学基金资助项目(2002031226) 作者简介:朱广伟(1972-),男,河南中牟人,中国科学院南京地理与湖泊研究所助理研究员,博士,主要从事湖泊水环 境治理研究。E 2mail :gwzhu @niglas 1ac 1cn 深水湖泊沉积物中磷的释放比较有规律,主要随季节变化呈现周期性的变化,浅水湖泊中磷的释放、沉积等地球化学行为则较为复杂。浅水湖泊中,一方面,由于水浅,温度等理化性质分层不明显,风浪作用对沉积物2水界面的干扰大,表层沉积物的氧化比较充分,铁锰氧化物等胶体通过吸附作用对磷的迁移控制作用也较大,有利于沉积物中磷的固定;另一方面,与深水湖泊相比,浅水湖泊单位体积的水拥有更大面积的沉积物表面,风浪作用更容易扰动沉积物2水界面,沉积物与水体的接触机会大大增加,沉积物与水之间磷的交换作用更加充分,沉积物对水体磷的影响也更为直接和频繁[1],尤其是在湖面开阔、风的吹程长的大型湖泊中。研究浅水湖泊沉积物中磷的地球化学规律,对正确认识浅水湖泊的内源负荷特点及揭示水华爆发机制都有重要意义。本文以太湖为例,研究了不同水文状况、水质特征和生态类型的湖区沉积物中磷的地球化学特征及其与浅水湖泊中磷的内源负荷之间的联系,为湖泊富营养化治理提供依据。 1 研究区域概况 太湖水面面积为2338km 2,平均水深为1189m ,是一个典型的大型浅水湖泊[2]。由于湖面开阔,又位于典型的季风气候区,太湖风浪的发生频繁,5m/s 以上的风速在太湖地区很常见,比如在2000年至2001年的731d 中,有119d 的日平均风速在5m/s 以上,平均每611d 就有1d 的日平均风速超过5m/s ,还不包括许多短时间的大风天气[3,4]。湖面风速在5m/s 以上时风浪对沉积物的扰动作用已经相当强烈,可引起上覆水悬浮物浓度的显著增高[5],风浪作用对太湖沉积物2水界面的交换过程的干扰相当强烈,而这种风浪频繁扰动下沉积物中磷的地球化学特征并不清楚。 太湖的主要入湖河道集中在西岸,自北向南主要有梁溪河、直湖港、 太 运河、大浦港(宜溧河)、东西苕溪等,其中大浦港和东西苕溪是太湖的主要水源,70%以上的太湖水都来自这两条河。东部河网地区是太湖的 出水河道,经东太湖而入淀山湖以及经望虞河入长江是太湖的两个主要出口。 太湖的富营养化问题自1988年以来就比较突出,20世纪90年代以来水华频繁爆发。水华爆发主要集中第14卷第6期 2003年11月 水科学进展ADVANCES IN WA TER SCIENCE Vol 114,No 16 Nov.,2003
抑郁症的案例分析作业
抑郁性神经症的治疗方案 定义和概述 抑郁性神经症又称神经症性抑郁，是由社会心理因素引起的一种以持久的心境低落状态为特征的神经症，常伴有焦虑、躯体不适感和睡眠障碍，患者有治疗要求，但无明显的运动性抑制或精神病情症状，生活不受严重影响。是一种以持久的心境低落状态为特征的神经症，常伴有焦虑、躯体不适感和睡眠障碍。患者有治疗要求，而无明显的运动性抑郁或精神病性症状，生活能力不受严重影响。本症国际上通称为“心境恶劣”。 咨询方案的制定 .遵循神经症防治原则，以心理治疗为主，辅以抗郁剂治疗。消除致病的各种不良心理社会因素至关重要，如正确解决择业、进步、家庭、工作、恋爱、婚姻等心理矛盾。 （一）主要治疗方法和适用原理 由于这种心理疾病以抑郁心境为主，并伴有焦虑、空虚感、疲惫、食欲不振和睡眠障碍等神经症症状，但人格仍较完整，日常生活不受显著影响，感到痛苦，且有求治愿望。发病前大多数有比较明显的心理—社会因素，所以咨询师认为应以心理治疗为主，综合运用支持疗法、认知治法和行为疗法等对来访者进行系统治疗。 咨询方法：认知行为疗法，运动治疗，厌恶疗法，身心减压治疗，催眠治疗疗法中的放松训练。 咨询原理：认知心理学认为，认知是指一个对某件事的认识、看法，包括对过去事情的评价，对当前事件的解释，以及对未来发生事件的预期。认知是行为和情感的基础，错误认知和不合理信念是导致行为与情绪问题的根源，而一旦对这种信念和认知过程加以纠正，就可以改变不良的情绪与行为。认知行为治疗就是通过改变来访者关于
自身的错误的思维方式和观念，教会来访者一些适应环境的技能，以帮助纠正导致不良情绪与行为的信念的认知过程。 1、合理情绪疗法 ABC理论是合理情绪疗法的核心理论——A表示诱发性事件，B 表示个体针对此诱发性事件产生的一些信念，即对这件事的一些看法、解释，C表示自己产生的情绪和行为的结果。该理论强调情绪困扰和行为不良并非由外部诱发事件本身所引起的，而是由个体对事件的评价和解释所造成的。这种疗法旨在通过理性的分析和逻辑思辨的途径，改变来访者的非理性观念，以帮助他解决情绪和行为上的问题。 2、厌恶疗法 依据经典条件反射理论，通过附加某种刺激的方法，使来访者在进行不适行为时，同时产生令人厌恶的心理或生理反应。 在来访者者手臂上缚上一圈粗橡皮筋，松紧适宜，要求来访者每当回忆那些不愉快的事情时，立即拉开橡皮筋，弹击手臂造成疼痛，提醒自己不再去想那些导致自己情绪低落的内容，使注意力集中到工作上或当前所做的事情上，思维不转换弹击不止。 3、放松训练 依据交互抑制原理，教来访者做放松训练。每晚睡前一次，30 分钟左右。 4、运动疗法 让来访者者坚持每日进行一定强度的体育运动，一方面用以帮助来访者宣泄抑郁情绪，另一方面可使其兴奋起来，调节内分泌，使体内多巴胺分泌趋于正常。