Chapter 7 Biological Markers and Genetic Factors of Major Depressive Disorder
Hwa-Young Lee and Yong-Ku Kim
Additional information is available at the end of the chapter
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1. Introduction
Major depressive disorder (MDD) is very prevalent and severe psychiatric disorder with prevalence estimates ranging 5% to 20% [1, 2] and has been a growing public health concern due to its recurrent, deliberate, and lethal nature. According to projections, MDD will be‐come the second leading cause of disability worldwide by the year 2020. [3]
MDD is considered to be a clinically heterogeneous disorder which result from multiple genes interacting with environmental factors such as early stressful life events [4] and the diagnosis is based on a patient’s symptoms, not on laboratory test.
Although recent decades have witnessed a tremendous revolution in the development of an‐tidepressant drugs, the neurochemical effects that underlie the therapeutic action of these agents remain largely unknown. Antidepressant drugs acutely increase levels of monoa‐mines, but it takes 2–3 weeks to show a clinical response after the administration of an anti‐depressant drug, [5] and the initial response rate in patients with major depressive disorders is about 70%. [6]
For the further understanding of the pathogenesis or the prediction of treatment response of MDD, biological approach for depression is needed.
The term ‘biological marker’ means biological change associated with depression that could be used to indicate the presence and severity of the condition and predict drug or other treatments’ response as well as the clinical prognosis. So, the research for biological markers of depressive disorders is helpful for finding diagnostic method and useful to distinguish the effectiveness and early improvement after antidepressant administration.
Although work in this area has been inconclusive, many animal, post-mortem, clinical, and genetic studies have produced results implicating at least 3 neurobiological systems in the
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pathogenesis in major depression: dysfunction in the serotonergic system, hyperactivity of the hypothalamic-pituitary-adrenal axis, and decreased neuroplasticity. Additionally, other neurotransmitters, biochemical factors including inflammatory markers, neurophysiologic markers and neuroimaging markers may be associated with MDD.
In this chapter, we discuss biological markers involved in the pathogenesis of major depres‐sive disorder.
2. Biological marker and genetic factor
2.1. Neurotransmitters
2.1.1. Serotonergic system
It has been hypothesized that a deficit in serotonin may be a crucial determinant in the path‐ophysiology of major depression. The serotonin system has been widely investigated in studies of major depression. The innervations of the serotonin system project from the dor‐sal raphe nucleus to all of the regions of the brain, including the cerebral cortex and hippo‐campus. Decreased function and activity of the serotonergic system in patients with major depression have been also confirmed in postmortem, serotonin transporter and serotonin re‐ceptor studies.
In suicide victims with major depression, enhanced radioligand binding of an agonist to in‐hibitory serotonin-1A autoreceptors in the human dorsal raphe nucleus provides pharmaco‐logical evidence to support the hypothesis of diminished activity of serotonin neurons. [7]
A trend of decreased 5-HT1A receptor expression appears to be a robust finding in ma‐jor depression. A functional genetic variant of the 5-HT1A receptor, the C-1019G pro‐moter polymorphism (rs6295), has been investigated in major depression. The G allele was more frequent in major depression. [8] By contrast, polymorphisms of HTR1A showed no association in Caucasians, while a significant association was observed in several studies of Asians. [9]
Imipramine binds to the serotonin transporter (5-HTT) on platelets, and it has been suggest‐ed that decreased platelet imipramine binding may be a putative biological marker of de‐pressive disorder. A meta-analysis has shown that imipramine binding to platelets is indeed a robust biological marker of depression. [10]
Tryptophan hydroxylase (TPH), which has two isoforms (TPH1 and TPH2), is one of the rate limiting factors in serotonin synthesis, Postmortem studies have reported significantly higher numbers and higher densities of TPH immunoreactive neurons in the dorsal raphe nuclei of alcohol dependent, depressed suicide victims [11] when compared to controls. We have found that the TPH2 -703G/T SNP may have an important effect on susceptibility to suicidal behavior in those with major depressive disorder. Additionally, an increased fre‐quency of the G allele of the TPH2 SNP is associated with elevated risk of suicidal behavior itself rather than with the diagnosis of major depression. [12]
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Collectively, serotonin receptor, TPH and 5-HTT studies suggest that deficient or impaired serotonin activity is involved in major depression.
2.1.2. Noradrenergic and dopaminergic systems
The mechanism of action of tricyclic and monoamine oxidase inhibitor antidepressants in‐volves the monoaminergic neurobiology. Recently, dual-acting antidepressants such as sero‐tonin norepinephrine reuptake inhibitors (SNRIs) are introduced and have presented clinicians with a wider range of antidepressants. The action of the antidepressants is based on alterations in the functions of neurotransmitter systems and changes in the monoamine systems. [13, 14] Catecholamine metabolites, particularly 3-methoxy-4-hydroxy phenylgly‐col (MHPG), did not sufficiently distinguish depressed from other groups. Work in this area then underwent a subtle but significant shift toward the use of catecholamine metabolites to predict the response to tricyclic antidepressants. [15, 16] Nonetheless, research into the lev‐els of monoamine transmitters and their metabolites have not found convincing evidence of a primary dysfunction into a particular transmitter system in depression, or a critical role in helping predict antidepressant response. [17]
The norepinephrine (NE) system has been studied in depression, particularly the action of NE reuptake inhibitors and SNRIs, which act at the NE transporter. Although polymor‐phisms the NET gene have not shown consistent association regarding susceptibility to de‐pression, [18-20] but it cannot be denied that it may be an important candidate.
The Antidepressant effect of mirtazapine appears to be related to the dual enhancement of central noradrenergic and serotonergic neurotransmission via the blockade of adrenergic α2receptors. [21-23] Previous studies have outlined the functional aspects of α2 receptors in depression, reporting reduced α2 inhibition of platelet adenylate cyclase activity [24] and in‐creased adrenergic α2 agonist-induced platelet aggregation in depressed patients. [25] Three genes that encode human adrenergic α2 receptors have been cloned: α2a, α2B, and α2C. [26]The adrenergic α2a receptor (ADRA2A) subtype is expressed in the central nervous system and peripheral tissues. [27] According to this classification, the classic α2 receptor studied in mood disorders is the α2a receptor.
Previous study didn’t show any association between this polymorphism and mood dis‐orders, including depressive and bipolar disorders. [28] Regarding the prediction of anti‐depressant treatment, the ADRA2A ?1291C/G genotypes did not show consistent results.
[29, 30]
The dopamine (DA) system is also highly asssocitated with the symptomatology of depres‐sion, with the proposed pathophysiology of melancholic depression involving decreased DA transmission. [31] A VNTR in exon 15 of the DA transporter gene (SLC6A3), which af‐fects the expression levels of the transporter, [32] is associated with a faster onset of antide‐pressant-treatment response. [33] The DA receptors have also been involved in pharmacogenetic studies of antidepressants in depression. The exon 3 VNTR of the DRD4gene was also investigated in antidepressant drug response, with some studies finding no
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association, [34, 35] and one study finding a significant modulation of this polymorphism on various antidepressant drugs. [36]
2.2. Hypothalamic-pituitary- adrenal axis (HPA axis)
Hyperactivity of the hypothalamic-pituitaryadrenal (HPA) axis is one of the most consistent neuroendocrine abnormalities in major depressive disorder. [37] Specifically, patients with MDD show increased concentrations of cortisol in the plasma, urine and cerebrospinal fluid (CSF) and an exaggerated cortisol response to adrenocorticotrophic hormone (ACTH).[38-40] The corticosteroid receptor hypothesis has been proposed for the pathogenesis of MDD, which focuses on impaired corticosteroid receptor signalling, leading to a reduced negative feedback of cortisol, an increased production of corticotropin-releasing hormone (CRH) and hypercortisolism. [38]
Interestingly, cortisol and CRH affect the serotonin (5-HT) system. [39, 41] During the stress response, glucocorticoids (GCs) stimulate all these features of 5-HT transmission.[42] Conversely, 5-HT transmission is impaired and noradrenergic transmission in the hippocampus is suppressed during chronic psychosocial stress and hypercortisolism,which is similar to the series of events evident during depression. [43] It is reported HPA axis dysregulation could be a trait genetically determined which contributes to an increased risk for depression. From the fact that this trait is found both in affected sub‐jects and in healthy relatives with a high familial risk, HPA axis is an interesting candi‐date endophenotype for affective disorders. [44, 45]
Studies investigating the hypothetical causes of an impaired regulation of HPA axis in de‐pression have mainly focused on two elements: i) glucocorticoid receptor (GR) feedback mechanisms and ii) CRH signaling system.
Reduced GR function has been pointed out as the responsible of diminished sensitivity to cortisol which would lead to an inefficient feedback mechanism. [46] On the other hand,CRH peptide mediates the regulation of HPA axis as well as autonomic and behavioral re‐sponses in front of stress. [47] Moreover, dysregulation of HPA axis has also been suggested to play a central role in the mechanisms of action of antidepressants. [38, 48] Normalization of disturbances at HPA axis has been considered a prerequisite of a proper clinical response to antidepressant treatment. [39, 49]
It was reported that Bcl1 polymorphism was associated with the susceptibility to MDD, not the prediction of treatment response. [50] Genetic association studies have yielded prelimi‐nary evidence for a role of GR genetic variations in the genetic vulnerability for MDD. Tak‐en together, the evidence for a role of GR and the GR gene in the neurobiology of MDD is building rapidly. [51]
2.3. Neuroplasticity
A time-lag in clinical response after the administration of an antidepressant drug sug‐gests that alterations in monoamine metabolism alone cannot explain the entire antide‐
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pressant effect. In this respect, it was suggested that the mechanism of action might be associated with intracellular signal transduction pathways that are linked to the expres‐sion of specific genes. [52]
The neural plasticity hypothesis proposes that depression results from an inability to make ap‐propriate adaptive responses to stress. [53] By stimulating intracellular pathways, antidepres‐sants lead to upregulation of cAMP response element-binding (CREB) protein and an increase in the expression of neurotrophic factors, particularly BDNF. Brain-derived neurotrophic fac‐tor (BDNF), an important member of the neurotrophin family, affects the survival and function of neurons in the central nervous system and is abundant in the brain and peripheral nervous system. BDNF is the neurotrophic factor in the focus of intense research for the last years. BDNF acts on neurons at both presynaptic and postsynaptic sites by binding to its tyrosine kinase re‐ceptor TrkB, and internalization of the BDNF TrkB complex-signalling endosome. [54]
It has many effects on the nervous system, such as neuronal growth, differentiation, and re‐pair. [55] It has been shown that stress decreases the synthesis of hippocampal BDNF in adult animals [33, 56] and induces atrophy of the apical dendrites of CA3 neurons. [57-59]Growing evidence suggests that BDNF may play a crucial role in depression. [60-63] So far,considerable work on the involvement of neurotrophic factors in the pathophysiology of de‐pression has been carried out. Direct infusion of BDNF into the rat midbrain has antidepres‐sant effects in the learned helplessness and forced swim behavioral models of depression in rodents. [62] In addition, long-term antidepressant drug treatment and electroconvulsive therapy can increase BDNF expression. [64]
BDNF and serotonin (5-hydroxytryptamine, 5-HT) are known to regulate synaptic plasticity,neurogenesis and neuronal survival in the adult brain. These two signals co-regulate one an‐other such that 5-HT stimulates the expression of BDNF, and BDNF enhances the growth and survival of 5-HT neurons. [65]
Several lines of research show that the BDNF molecule is probably the ‘‘final common path‐way’’ for different antidepressant approaches. These include antidepressants [64], electro‐convulsive therapy, [64, 66] exercise [67, 68] and repetitive transcranial magnetic stimulation. [69] A large body of evidence, in humans, shows the similar result with direct measurements of BDNF in the bloodstream. [70-72] Treatment of depressed patients with antidepressants increases the serum BDNF levels close to the levels of normal controls.[73-75] In addition, they support the possibility that the enhancement of BDNF expression may be an important element in the clinical response to antidepressant treatment. [76]
Measurements of BDNF levels in sera or plasma in previous studies have been chal‐lenged. Our research group has also examined plasma BDNF levels among patients with major depression who both have and have not attempted suicide. One study found that plasma BDNF levels were significantly lower among depressed patients than among nor‐mal controls. [77]
The BDNF gene has several polymorphic markers, including an intronic microsatellite (GT)n dinucleotide repeat [78] and a functional coding region single-nucleotide polymorphism (SNP) at position 196/758, which results in a valine (Val) to methionine (Met) amino acid
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change at codon 66 (rs6265). Because this codon lies in region of the BDNF precursor protein that is cleaved away, it is not apparent in the mature BDNF protein. On pharmacogenetic study of BDNF, it was suggested that the Val66Met polymorphism of BDNF is associated with citalopram efficacy, with Met allele carriers responding better to citalopram treatment.[79] However, other studies suggested that BDNF polymorphism does not affect the clinical outcome of antidepressant administration. [80, 81]
2.4. Neuroimaging marker
Positron emission tomography (PET) imaging studies have revealed multiple abnormalities of regional cerebral blood flow (CBF) and glucose metabolism in brain regions. In PET imag‐ing of unmedicated subjects with major depression, regional CBF and metabolism are con‐sistently increased in the amygdala, orbital cortex, and medial thalamus, and decreased in the dorsomedial/dorsal anterolateral PFC and anterior cingulate cortex ventral to the genu of the corpus callosum (subgenual PFC) relative to healthy controls. [82, 83] These circuits have also been implicated more generally in emotional behavior.
Recent neuroimaging studies have focused on the neurobiological abnormalities that are as‐sociated with MDD, such as dysfunctional or structural differences in cerebral regions, in‐cluding the prefrontal cortex, amygdala, anterior cingulate cortex (ACC), and hippocampus,in patients with MDD compared with healthy controls. [84-87]
Reductions in hippocampal volume may not antedate illness onset, but volume may de‐crease at the greatest rate in the early years after illness onset. [87] In the absence of a signifi‐cant correlation between hippocampal volume and age in either post-depressive or control subjects, a significant correlation with total lifetime duration of depression was found. This suggest that repeated stress during recurrent depressive episodes may result in cumulative hippocampal injury as reflected in volume loss. [88]
Previous structural magnetic resonance imaging (MRI) studies using region-of-interest (ROI) analyses have shown a variety of findings. [89, 90] These inconsistencies can be ex‐plained by the variability in the ROI criteria among studies and an inconsistency in ROI vali‐dation. [89, 91, 92] Consequently, voxel-based morphometry (VBM) [93] is being increasingly used as a viable alternative methodology for detecting structural abnormalities in patients with neuropsychiatric disorders, including MDD. [94-97] Previous MDD VBM studies have also shown reduced gray matter density in the hippocampus. [95, 96, 98] Re‐cently, it is reported that gray matter density of several regions associated with emotion reg‐ulation, particularly dorsal raphe nucleus, was lower in MDD patients. [99]
Findings to directly compare unipolar depressed and bipolar depressed individuals, [100]more widespread abnormalities in white matter connectivity and white matter hyperintensi‐ties in bipolar depression than unipolar depression, habenula volume reductions in bipolar but not unipolar depression, and differential patterns of functional abnormalities in emotion regulation and attentional control neural circuitry in the two depression types.
Neuroimaging technology has provided unprecedented opportunities for elucidating the anatomical correlates of major depression. [82] Nowadays, researches that combine brain
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imaging and genetics have been emerging. The first imaging genetics research reported that carriers of the short allele of the serotonin transporter promoter polymorphism exhibit greater amygdala neuronal activity, as assessed by functional magnetic resonance imaging,in response to fearful stimuli compared with individuals homozygous for the long allele.[101] Since then, however, it has been reported that homozygosity for the l or s allele is asso‐ciated with decreased hippocampal volumes in patients with major depression. [102, 103]Even though these results inconsistent, future direction for imaging genetics is promising.
3. Conclusions
Major depressive disorder is considered to be a clinically heterogeneous disorder and the diag‐nosis is based on a patient’s symptoms, not on laboratory test. So, the pathogenesis of major de‐pressive disorder is not clear. MDD results from multiple genes interacting with environmental factors such as early stressful life events. Although recent decades have wit‐nessed a tremendous revolution in the development of antidepressant drugs, the neurochemi‐cal effects that underlie the therapeutic action of these agents remain largely unknown.Antidepressants alter the levels of neurotransmitters such as serotonin in the synaptic cleft sev‐eral minutes after their administration, and this alters the activity of the neurotransmission system. Nevertheless, an improvement in the symptoms of depression takes 2–6 weeks of treatment, during which time the neuronal response and morphology of cells change.
The research results for the monoamine system, hyperactivity of the hypothalamic-pituitary-adrenal axis, decreased neuroplasticity, and neuroimaging will be helpful to understand the pathogenesis of major depressvie disorder. To find biological markers for diagnosing MDD and predicting the individual responses to antidepressants, genetic case-control association studies are used widely because they are relatively easy to conduct and can discover genetic variants with small influences on phenotype.
Researchers have searched for biological markers of diagnosis and treatment response, and will try to understand the pathogenesis of depression and the mechanisms underlying the delayed response to antidepressant treatment.
Author details
Hwa-Young Lee 1 and Yong-Ku Kim 2*
*Address all correspondence to: yonkgu@korea.ac.kr
1 Department of Psychiatry, College of Medicine, Soonchunhyang University, Republic of Korea
2 Department of Psychiatry, College of Medicine, Korea University, Republic of Korea
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References
[1]Bierut, L.J., et al., Major depressive disorder in a community-based twin sample: are there different genetic and environmental contributions for men and women? Arch Gen Psychiatry, 1999. 56(6): p. 557-63.
[2]Hamet, P. and J. Tremblay, Genetics and genomics of depression. Metabolism, 2005.54(5 Suppl 1): p. 10-5.
[3]Murray, C.J. and A.D. Lopez, Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet, 1997. 349(9063): p. 1436-42.
[4]Caspi, A., et al., Influence of life stress on depression: moderation by a polymor‐phism in the 5-HTT gene. Science, 2003. 301(5631): p. 386-9.
[5]Hindmarch, I., Expanding the horizons of depression: beyond the monoamine hy‐pothesis. Hum Psychopharmacol, 2001. 16(3): p. 203-218.
[6]Nemeroff, C.B., Psychopharmacology of affective disorders in the 21st century. Biol Psychiatry, 1998. 44(7): p. 517-25.
[7]Stockmeier, C.A., et al., Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity. J Neurosci, 1998. 18(18): p. 7394-401.
[8]Lemonde, S., et al., Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. J Neurosci, 2003.23(25): p. 8788-99.
[9]Horstmann, S. and E.B. Binder, Pharmacogenomics of antidepressant drugs. Pharma‐col Ther, 2009. 124(1): p. 57-73.
[10]Ellis, P.M. and C. Salmond, Is platelet imipramine binding reduced in depression? A meta-analysis. Biol Psychiatry, 1994. 36(5): p. 292-9.
[11]Bonkale, W.L., G. Turecki, and M.C. Austin, Increased tryptophan hydroxylase im‐munoreactivity in the dorsal raphe nucleus of alcohol-dependent, depressed suicide subjects is restricted to the dorsal subnucleus. Synapse, 2006. 60(1): p. 81-5.
[12]Yoon, H.K. and Y.K. Kim, TPH2 -703G/T SNP may have important effect on suscepti‐bility to suicidal behavior in major depression. Prog Neuropsychopharmacol Biol Psychiatry, 2009. 33(3): p. 403-9.
[13]Blier, P. and C. de Montigny, Current advances and trends in the treatment of de‐pression. Trends Pharmacol Sci, 1994. 15(7): p. 220-6.
[14]Delgado, P.L., et al., Monoamines and the mechanism of antidepressant action: ef‐fects of catecholamine depletion on mood of patients treated with antidepressants.Psychopharmacol Bull, 1993. 29(3): p. 389-96.
Mood Disorders
188
[15]Schildkraut, J.J., The catecholamine hypothesis of affective disorders: a review of supporting evidence. 1965. J Neuropsychiatry Clin Neurosci, 1995. 7(4): p. 524-33;discussion 523-4.
[16]Mooney, J.J., et al., Urinary 3-methoxy-4-hydroxyphenylglycol and the depression-type score as predictors of differential responses to antidepressants. J Clin Psycho‐pharmacol, 1991. 11(6): p. 339-43.
[17]Delgado, P.L., Depression: the case for a monoamine deficiency. J Clin Psychiatry,2000. 61 Suppl 6: p. 7-11.
[18]Ryu, S.H., et al., Association between norepinephrine transporter gene polymor‐phism and major depression. Neuropsychobiology, 2004. 49(4): p. 174-7.
[19]Chang, C.C., et al., Lack of association between the norepinephrine transporter gene and major depression in a Han Chinese population. J Psychiatry Neurosci, 2007.32(2): p. 121-8.
[20]Zill, P., et al., Identification of a naturally occurring polymorphism in the promoter region of the norepinephrine transporter and analysis in major depression. Neuro‐psychopharmacology, 2002. 26(4): p. 489-93.
[21]Herman, G.M., Pharmacology of Antidepressant: Selectivity or Multiplicity? J Clin Psychiatry 1999. 60 suppl 17: p. 4-8.
[22]Kasper, S., Efficacy of antidepressants in the treatment of severe depression: the place of mirtazapine. J Clin Psychopharmacol, 1997. 17 Suppl 1: p. 19S-28S.
[23]Preskorn, S.H., Selection of an antidepressant: mirtazapine. J Clin Psychiatry, 1997.58 Suppl 6: p. 3-8.
[24]Siever, L.J., et al., Platelet alpha-adrenergic binding and biochemical responsiveness in depressed patients and controls. Psychiatry Res, 1984. 11(4): p. 287-302.
[25]Garcia-Sevilla, J.A., et al., Alpha 2-adrenoceptor-mediated inhibition of platelet ade‐nylate cyclase and induction of aggregation in major depression. Effect of long-term cyclic antidepressant drug treatment. Arch Gen Psychiatry, 1990. 47(2): p. 125-32.
[26]Bylund, D.B., et al., International Union of Pharmacology nomenclature of adreno‐ceptors. Pharmacol Rev, 1994. 46(2): p. 121-36.
[27]Lorenz, W., et al., Expression of three alpha 2-adrenergic receptor subtypes in rat tis‐sues: implications for alpha 2 receptor classification. Mol Pharmacol, 1990. 38(5): p.599-603.
[28]Ohara, K., et al., Polymorphism in the promoter region of the alpha 2A adrenergic receptor gene and mood disorders. Neuroreport, 1998. 9(7): p. 1291-4.
[29]Lee, H.Y., et al., Association of the adrenergic alpha 2a receptor--1291C/G polymor‐phism with weight change and treatment response to mirtazapine in patients with major depressive disorder. Brain Res, 2009. 1262: p. 1-6.
Biological Markers and Genetic Factors of Major Depressive Disorder
https://www.doczj.com/doc/8417533240.html,/10.5772/54388189
[30]Wakeno, M., et al., The alpha 2A-adrenergic receptor gene polymorphism modifies antidepressant responses to milnacipran. J Clin Psychopharmacol, 2008. 28(5): p.518-24.
[31]Geracitano, R., et al., On the effects of psychostimulants, antidepressants, and the an‐tiparkinsonian drug levodopa on dopamine neurons. Ann N Y Acad Sci, 2006. 1074:p. 320-9.
[32]Fuke, S., et al., The VNTR polymorphism of the human dopamine transporter (DAT1) gene affects gene expression. Pharmacogenomics J, 2001. 1(2): p. 152-6.
[33]Smith, M.A., et al., Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci,1995. 15(3 Pt 1): p. 1768-77.
[34]Serretti, A., et al., No association between dopamine D(2) and D(4) receptor gene var‐iants and antidepressant activity of two selective serotonin reuptake inhibitors. Psy‐chiatry Res, 2001. 104(3): p. 195-203.
[35]Serretti, A., et al., Dopamine receptor D4 is not associated with antidepressant activi‐ty of sleep deprivation. Psychiatry Res, 1999. 89(2): p. 107-14.
[36]Garriock, H.A., et al., Number of risk genotypes is a risk factor for major depressive disorder: a case control study. Behav Brain Funct, 2006. 2: p. 24.
[37]Holsboer, F., The rationale for corticotropin-releasing hormone receptor (CRH-R) an‐tagonists to treat depression and anxiety. J Psychiatr Res, 1999. 33(3): p. 181-214.
[38]Holsboer, F., The corticosteroid receptor hypothesis of depression. Neuropsycho‐pharmacology, 2000. 23(5): p. 477-501.
[39]Holsboer, F. and N. Barden, Antidepressants and hypothalamic-pituitary-adreno‐cortical regulation. Endocr Rev, 1996. 17(2): p. 187-205.
[40]Nemeroff, C.B., The corticotropin-releasing factor (CRF) hypothesis of depression:new findings and new directions. Mol Psychiatry, 1996. 1(4): p. 336-42.
[41]De Kloet, E.R., et al., Brain corticosteroid receptor balance in health and disease. En‐docr Rev, 1998. 19(3): p. 269-301.
[42]Meijer, O.C. and E.R. de Kloet, Corticosterone and serotonergic neurotransmission in the hippocampus: functional implications of central corticosteroid receptor diversity.Crit Rev Neurobiol, 1998. 12(1-2): p. 1-20.
[43]Wolkowitz, O.M., et al., Ketoconazole administration in hypercortisolemic depres‐sion. Am J Psychiatry, 1993. 150(5): p. 810-2.
[44]Holsboer, F., et al., Altered hypothalamic-pituitary-adrenocortical regulation in healthy subjects at high familial risk for affective disorders. Neuroendocrinology,1995. 62(4): p. 340-7.
Mood Disorders
190
[45]Modell, S., et al., Hormonal response pattern in the combined DEX-CRH test is stable over time in subjects at high familial risk for affective disorders. Neuropsychophar‐macology, 1998. 18(4): p. 253-62.
[46]Pariante, C.M. and A.H. Miller, Glucocorticoid receptors in major depression: rele‐vance to pathophysiology and treatment. Biol Psychiatry, 2001. 49(5): p. 391-404.
[47]Arborelius, L., et al., The role of corticotropin-releasing factor in depression and anxi‐ety disorders. J Endocrinol, 1999. 160(1): p. 1-12.
[48]Nemeroff, C.B. and M.J. Owens, Treatment of mood disorders. Nat Neurosci, 2002. 5Suppl: p. 1068-70.
[49]Nemeroff, C.B., The role of corticotropin-releasing factor in the pathogenesis of major depression. Pharmacopsychiatry, 1988. 21(2): p. 76-82.
[50]Lee, H., et al., Association of glucocorticoid receptor polymorphisms with the sus‐ceptibility to major depressive disorder and treatment responses in Korean depres‐sive patients. Acta Neuropsychiatrica, 2009. 21(1): p. 11-17.
[51]Claes, S., Glucocorticoid receptor polymorphisms in major depression. Ann N Y Acad Sci, 2009. 1179: p. 216-28.
[52]Duman, R.S., et al., Neuronal plasticity and survival in mood disorders. Biol Psychia‐try, 2000. 48(8): p. 732-9.
[53]Popoli, M., M. Gennarelli, and G. Racagni, Modulation of synaptic plasticity by stress and antidepressants. Bipolar Disord, 2002. 4(3): p. 166-82.
[54]Lu, B., BDNF and activity-dependent synaptic modulation. Learn Mem, 2003. 10(2):p. 86-98.
[55]Lewin, G.R. and Y.A. Barde, Physiology of the neurotrophins. Annu Rev Neurosci,1996. 19: p. 289-317.
[56]Nibuya, M., et al., Repeated stress increases catalytic TrkB mRNA in rat hippocam‐pus. Neurosci Lett, 1999. 267(2): p. 81-4.
[57]Gould, E., et al., Neurogenesis in the dentate gyrus of the adult tree shrew is regulat‐ed by psychosocial stress and NMDA receptor activation. J Neurosci, 1997. 17(7): p.2492-8.
[58]Gould, E., et al., Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress. Proc Natl Acad Sci U S A, 1998. 95(6): p. 3168-71.
[59]Magarinos, A.M. and B.S. McEwen, Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: involvement of glucocorticoid secretion and excitatory amino acid receptors. Neuroscience, 1995. 69(1): p. 89-98.
[60]Duman, R.S., G.R. Heninger, and E.J. Nestler, A molecular and cellular theory of de‐pression. Arch Gen Psychiatry, 1997. 54(7): p. 597-606.
Biological Markers and Genetic Factors of Major Depressive Disorder
https://www.doczj.com/doc/8417533240.html,/10.5772/54388191
[61]Altar, C.A., Neurotrophins and depression. Trends Pharmacol Sci, 1999. 20(2): p.
59-61.
[62]Siuciak, J.A., et al., Antidepressant-like effect of brain-derived neurotrophic factor
(BDNF). Pharmacol Biochem Behav, 1997. 56(1): p. 131-7.
[63]Chen, B., et al., Increased hippocampal BDNF immunoreactivity in subjects treated
with antidepressant medication. Biol Psychiatry, 2001. 50(4): p. 260-5.
[64]Nibuya, M., S. Morinobu, and R.S. Duman, Regulation of BDNF and trkB mRNA in
rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci, 1995. 15(11): p. 7539-47.
[65]Mattson, M.P., S. Maudsley, and B. Martin, BDNF and 5-HT: a dynamic duo in age-
related neuronal plasticity and neurodegenerative disorders. Trends Neurosci, 2004.27(10): p. 589-94.
[66]Altar, C.A., et al., Effects of electroconvulsive seizures and antidepressant drugs on
brain-derived neurotrophic factor protein in rat brain. Biol Psychiatry, 2003. 54(7): p.703-9.
[67]Oliff, H.S., et al., Exercise-induced regulation of brain-derived neurotrophic factor
(BDNF) transcripts in the rat hippocampus. Brain Res Mol Brain Res, 1998. 61(1-2): p.147-53.
[68]Garcia, C., et al., The influence of specific noradrenergic and serotonergic lesions on
the expression of hippocampal brain-derived neurotrophic factor transcripts follow‐ing voluntary physical activity. Neuroscience, 2003. 119(3): p. 721-32.
[69]Muller, M.B., et al., Long-term repetitive transcranial magnetic stimulation increases
the expression of brain-derived neurotrophic factor and cholecystokinin mRNA, but not neuropeptide tyrosine mRNA in specific areas of rat brain. Neuropsychopharma‐cology, 2000. 23(2): p. 205-15.
[70]Karege, F., et al., Decreased serum brain-derived neurotrophic factor levels in major
depressed patients. Psychiatry Res, 2002. 109(2): p. 143-8.
[71]Karege, F., et al., Low brain-derived neurotrophic factor (BDNF) levels in serum of
depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity. Biol Psychiatry, 2005. 57(9): p. 1068-72.
[72]Shimizu, E., et al., Alterations of serum levels of brain-derived neurotrophic factor
(BDNF) in depressed patients with or without antidepressants. Biol Psychiatry, 2003.54(1): p. 70-5.
[73]Aydemir, O., A. Deveci, and F. Taneli, The effect of chronic antidepressant treatment
on serum brain-derived neurotrophic factor levels in depressed patients: a prelimina‐ry study. Prog Neuropsychopharmacol Biol Psychiatry, 2005. 29(2): p. 261-5.
Mood Disorders
192
[74]Gervasoni, N., et al., Partial normalization of serum brain-derived neurotrophic fac‐tor in remitted patients after a major depressive episode. Neuropsychobiology, 2005.51(4): p. 234-8.
[75]Gonul, A.S., et al., Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients. Eur Arch Psychiatry Clin Neurosci, 2005. 255(6): p.381-6.
[76]Russo-Neustadt, A., et al., Physical activity-antidepressant treatment combination:impact on brain-derived neurotrophic factor and behavior in an animal model. Behav Brain Res, 2001. 120(1): p. 87-95.
[77]Lee, B.H., et al., Decreased plasma BDNF level in depressive patients. J Affect Disord,2007. 101(1-3): p. 239-44.
[78]Proschel, M., et al., Dinucleotide repeat polymorphism at the human gene for the brain-derived neurotrophic factor (BDNF). Hum Mol Genet, 1992. 1(5): p. 353.
[79]Choi, M.J., et al., Brain-derived neurotrophic factor gene polymorphism (Val66Met)and citalopram response in major depressive disorder. Brain Res, 2006. 1118(1): p.176-82.
[80]Kang, R.H., et al., Brain-derived neurotrophic factor gene polymorphisms and mirta‐zapine responses in Koreans with major depression. J Psychopharmacol, 2010. 24(12):p. 1755-63.
[81]Tsai, S.J., et al., Association study of a brain-derived neurotrophic-factor genetic polymorphism and major depressive disorders, symptomatology, and antidepres‐sant response. Am J Med Genet B Neuropsychiatr Genet, 2003. 123B(1): p. 19-22.
[82]Drevets, W.C., Neuroimaging and neuropathological studies of depression: implica‐tions for the cognitive-emotional features of mood disorders. Curr Opin Neurobiol,2001. 11(2): p. 240-9.
[83]Manji, H.K., W.C. Drevets, and D.S. Charney, The cellular neurobiology of depres‐sion. Nat Med, 2001. 7(5): p. 541-7.
[84]Canli, T., et al., Brain activation to emotional words in depressed vs healthy subjects.Neuroreport, 2004. 15(17): p. 2585-8.
[85]Frodl, T., et al., Hippocampal and amygdala changes in patients with major depres‐sive disorder and healthy controls during a 1-year follow-up. J Clin Psychiatry, 2004.65(4): p. 492-9.
[86]Henriques, J.B., Davidson, R.J., Decreased responsiveness to reward in depression.COGNITION AND EMOTION, 2000. 15(5): p. 711-724.
[87]MacQueen, G.M., et al., Course of illness, hippocampal function, and hippocampal volume in major depression. Proc Natl Acad Sci U S A, 2003. 100(3): p. 1387-92.
Biological Markers and Genetic Factors of Major Depressive Disorder
https://www.doczj.com/doc/8417533240.html,/10.5772/54388193
[88]Sheline, Y.I., et al., Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci, 1999.19(12): p. 5034-43.
[89]Konarski, J.Z., et al., Volumetric neuroimaging investigations in mood disorders: bi‐polar disorder versus major depressive disorder. Bipolar Disord, 2008. 10(1): p. 1-37.
[90]Lorenzetti, V., et al., Structural brain abnormalities in major depressive disorder: a selective review of recent MRI studies. J Affect Disord, 2009. 117(1-2): p. 1-17.
[91]Goldstein, J.M., et al., Cortical abnormalities in schizophrenia identified by structural magnetic resonance imaging. Arch Gen Psychiatry, 1999. 56(6): p. 537-47.
[92]Wolkin, A., et al., Structural magnetic resonance image averaging in schizophrenia.Am J Psychiatry, 1998. 155(8): p. 1064-73.
[93]Ashburner, J. and K.J. Friston, Voxel-based morphometry--the methods. Neuro‐image, 2000. 11(6 Pt 1): p. 805-21.
[94]Leung, K.K., et al., Neural correlates of attention biases of people with major depres‐sive disorder: a voxel-based morphometric study. Psychol Med, 2009. 39(7): p.1097-106.
[95]Shah, P.J., et al., Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression. Controlled magnetic resonance imaging study. Br J Psy‐chiatry, 1998. 172: p. 527-32.
[96]Vasic, N., et al., Gray matter reduction associated with psychopathology and cogni‐tive dysfunction in unipolar depression: a voxel-based morphometry study. J Affect Disord, 2008. 109(1-2): p. 107-16.
[97]Cheng, Y.Q., et al., Brain volume alteration and the correlations with the clinical characteristics in drug-naive first-episode MDD patients: a voxel-based morphome‐try study. Neurosci Lett, 2010. 480(1): p. 30-4.
[98]Bergouignan, L., et al., Can voxel based morphometry, manual segmentation and au‐tomated segmentation equally detect hippocampal volume differences in acute de‐pression? Neuroimage, 2009. 45(1): p. 29-37.
[99]Lee, H.Y., et al., Demonstration of decreased gray matter concentration in the mid‐brain encompassing the dorsal raphe nucleus and the limbic subcortical regions in major depressive disorder: an optimized voxel-based morphometry study. J Affect Disord, 2011. 133(1-2): p. 128-36.
[100]Almeida, J.R. and M.L. Phillips, Distinguishing between Unipolar Depression and Bi‐polar Depression: Current and Future Clinical and Neuroimaging Perspectives. Biol Psychiatry, 2012.
[101]Hariri, A.R., et al., Serotonin transporter genetic variation and the response of the hu‐man amygdala. Science, 2002. 297(5580): p. 400-3.
Mood Disorders
194
[102]Frodl, T., et al., Reduced hippocampal volumes associated with the long variant of
the tri- and diallelic serotonin transporter polymorphism in major depression. Am J Med Genet B Neuropsychiatr Genet, 2008. 147B(7): p. 1003-7.
[103]Eker, M.C., et al., Smaller hippocampus volume is associated with short variant of 5-
HTTLPR polymorphism in medication-free major depressive disorder patients. Neu‐ropsychobiology, 2011. 63(1): p. 22-8.
Biological Markers and Genetic Factors of Major Depressive Disorder
https://www.doczj.com/doc/8417533240.html,/10.5772/54388195
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 文章目录*一、抑郁的概述*二、抑郁的原因及发病机制*三、抑郁的检查诊断鉴别方法*四、抑郁的危害*五、抑郁的防治方法抑郁的概述 1、定义抑郁情绪与抑郁症不同,正常人的抑郁情绪是基于一定的客观事物,事出有因。而抑郁症则是病理情绪抑郁,通常无缘无故地产生,缺乏客观精神应激的条件,或者虽有不良因素,但是“小题大做”,不足以真正解释病理性抑郁征象。 2、症状部位全身 3、症状科室精神科 4、常见病因生物、心理、社会(文化)因素相互作用的结果 抑郁的原因及发病机制迄今为止,抑郁症病因与发病机制还不明确,也无明显的体征和实验室指标异常, 概括的说是生物、心理、社会(文化)因素相互作用的结果。也正因为抑郁症当前病因不明,有关假说很多,比较常见公认的病因假设包括: 遗传因素:大样本人群遗传流行病学调查显示,与患病者血缘关系愈近,患病概率越高。一级亲属患病的概率远高于其他亲
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 Jeff Simmons and Jean-Francois Pittet 脓毒症，被定义为存在感染和宿主炎症，是一种全球范围内死亡率增加的致死性的临床综合征。严重的病例，其凝血系广泛地被激活，伴随多种凝血因子消耗，从而导致播散性血管内凝血（DIC）。DIC出现预示着死亡率更高。了解炎症和弥漫性血栓的机制将允许治疗干预获得进展。急性脓毒症凝血病是一个动态的过程，既花费时间，又特别消耗财力。与传统的检验相比，全血凝血方面的检验可提供更多临床有用的信息。在脓毒症中，调整血栓的天然的抗凝剂是下调的。当全身炎症和高凝存在时，患者可能对从凝血系统的调解中获得益处。合适时机的抗凝治疗可能最终导致多器官功能不全发生率降低。 近期的发现 脓毒症凝血病的发病机制是，由致凝血机制上调且同时天然的抗凝剂下调共同作用而引起。由侵袭性微生物所致的炎症是治疗过程中不能被消除的一种自然的宿主防御。预防多器官功能不全的成功的策略集中在DIC高危患者分层识别，以及恢复炎症和凝血之间的平衡。 总结 对于脓毒症患者，预防DIC是预防多器官功能不全导致死亡的关键治疗靶点。为了治疗，应用血栓弹力图、DIC的特异性指标、以及复合评分系统对于患者进行分层，是一个有研究前景的领域。 关键词：凝血病，炎症，脓毒症，血栓 关键点 ●炎症和凝血紊乱是不可分割地联系在一起，两者互为激活对方的正反馈因子 ●凝血异常在脓毒症患者中几乎普遍存在，且在多器官功能不全可能发挥关键的作用 ●脓毒症凝血病可能是由针对单一媒介的多条途径紊乱造成的，这样解释了为什么多种单 一治疗策略并不能改善预后的原因 ●针对急性脓毒症凝血病理想化的治疗应是恢复炎症和凝血间的平衡，对于感染的宿主反 应不要有负面的影响。 ●治疗策略是处于敏感时期、且应针对正处于进展为DIC的高危患者。 前言 脓毒症已经被用于描述为动态的且经常是威胁生命的对于感染的全身宿主反应。几个世纪以来，医生们一直在寻找一些控制该疾病的负担的线索。1841年，奥地利内科医生Ignaz Semmelweiss观察发现，“学生们和医生们近期解剖污染的手和手指，会把处理尸体的污染药传递给正在分娩的母体生殖器官中。通过这一敏锐的观察，在他当地的产科病房开展合适的手卫生策略，因脓毒症死亡的胎儿，从16%下降到3%[1]。 今天，脓毒症仍然是全球范围内首位的的死亡原因，其发生率在（75-300）/10万[2,3]。在美国，脓毒症的经济负担是惊人的。每年脓毒症患者花费接近240亿美元，且该数字呈增加趋势[4]。单一的脓毒症死亡率为25%，但是当合并器官功能不全，其死亡率成倍增加[3]。目前，更多注意力集中在对脓毒症的炎症宿主反应方面。事实上，脓毒症患者展示出一些炎症生物标志物，往往先于器官功能衰竭出现，这些标志物和器官衰竭之间呈一种因果关系。 [5]。对感染的炎症反应，可能最终作为抵御微生物入侵的一种保护机制；然而，当这种反应过分夸大时，炎症可导致多器官功能不全（MODS）。炎症和凝血紊乱密不可分地联系在
土壤 (Soils), 2004, 36 (1): 12~15 湖泊沉积物中磷释放的研究进展 高 丽 杨 浩 周健民 （土壤与农业可持续发展国家重点实验室(中国科学院南京土壤研究所) 南京 210008） 摘 要沉积物是湖泊营养物质的重要蓄积库，也是湖泊内源性P的主要来源。沉积物中部分固定的P 可通过分解或溶解作用而释放磷酸盐到沉积物间隙水中，然后通过扩散作用或表层沉积物的再悬浮作用而释放到上覆水体中。本文就目前对沉积物P释放的影响因素及释放机制的研究进展作一简要概述。 关键词湖泊沉积物；释放；间隙水扩散；释放机制 中图分类号 X524 沉积物是湖泊营养物质的重要蓄积库，也是湖泊内源性P的主要来源。不少湖泊调查资料表明，当入湖营养盐减少或完全截污后，沉积物营养盐的释放作用仍会使水质继续处于富营养化状态，甚至出现“水华”[1、2]。P是造成湖泊水质富营养化的关键性的限制性因素之一[3]，沉积物中营养盐的释放对水体的营养水平有着不可忽视的影响，研究富营养化湖泊沉积物P的释放行为对于湖泊水质的治理和预测具有非常重要的指导意义。 湖泊沉积物-水界面是水体和沉积物之间物质交换和输送的重要途径，对于浅水湖泊而言，来自各种途径的营养物，经过一系列物理、化学及生物释放作用，其中一部分沉积于湖泊底部，成为湖体营养物的内负荷。在一定条件下，由于风力和湖流引起湖泊底部沉积物的扰动使沉积物处于再悬浮状态，这种再悬浮状态会强烈的影响P在沉积物-水界面间的再分配，部分营养元素可从沉积物中向上层水体释放，使水体营养负荷增加[4]。P在沉积物-水界面循环受溶解释放以及间隙水扩散两个过程的控制。 １ Ｐ的释放 沉积物P的释放涉及到的过程有解吸附、分解、配位体交换以及酶水解作用。当沉积物中P以可溶无机P形式存在时，可通过扩散、风引起的沉积物再悬浮、生物扰动以及平流（如气体沸腾）等方式进入上覆水体[5]。影响沉积物P释放的因子很多，现概括如下： １．１ 沉积物中Ｐ含量和形态 沉积物中P的结合态及形态之间的相互转化是控制沉积物P迁移和释放的一个主要因子，这也是目前国内外研究P释放的一个热点。P释放量是由不同的迁移和转化过程决定的。控制沉积物P迁移（释放和形态转化）的环境参数的相对重要性首先取决于沉积物中P的化学形态[6]。沉积物释P量的多少并不与沉积物中的总P量成比例关系，释放进入间隙水中的P大部分是无机可溶性P[7、8]。在厌氧释放过程中，存在着有机P向无机P转化，Fe-P、Al-P向Ca-P、O-P转化的趋势，沉积物中总P浓度不断减少，就是P形态迁移转化动态平衡的结果[9]。１．２ 沉积物组成 非石灰性湖泊沉积物中Fe、P、TOC含量高于石灰性沉积物，前者在好氧状态下P释放受铁氧化物吸附作用的抑制。在石灰性湖泊沉积物中，Ca2+浓度是影响沉积物释P的不容忽视的因素，在不同pH下磷灰石的溶解平衡影响着湖泊水体中P的含量。沉积物中释放的P与Fe-P关系密切相关，曾有人提出用沉积物中P：Fe比例作为表层沉积物P释放能力的一个参数，两者呈负相关关系[10]。此外沉积物中硫酸盐含量、P矿物的类型也是控制P释放的极其重要的变量[11]。在氧化条件下红磷铁矿是稳定存在的；而在还原条件下尤其在酸性环境中，大量P和Fe从矿物中溶解出来。在Fe为主的系统中，氧化条件下Fe2+和Fe3+的羟磷灰石是最稳定的矿物形式，而在还原条件下蓝铁矿是主要的存在形式[12]。１．３ 环境因子 １．３．１ 氧化还原电位 对非石灰性湖泊沉积物而言，P释放对表层沉积物的氧化还原电位（Eh）的变化非常敏感。当表层沉积物Eh较高时（>350mv），Fe3+与磷酸盐结合成不溶的磷酸铁，可
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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 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！ 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（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
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.doczj.com/doc/8417533240.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 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 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）
J. Lake Sci.(湖泊科学), 2008, 20(3): 263-270 https://www.doczj.com/doc/8417533240.html,. E-mail: jlakes@https://www.doczj.com/doc/8417533240.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.doczj.com/doc/8417533240.html,.
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 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。