MORRIS MC,COMPAS BE,GARBERJ.Relations among posttraumatic stress disorder,comorbid major depression,and HPA function: a systematic review and meta-analysis[J].Clin Psychol Rev,2012,32(4):301-315.
Exposure to traumatic stress is associated with increased risk for posttraumatic stress disorder (PTSD) and alterations of hypothalamic-pituitary-adrenocortical (HPA) function. Research linking traumatic stress with HPA function in PTSD has been inconsistent, however, in part due to (a) the inclusion of trauma-exposed individuals without PTSD (TE) in control groups and (b) a failure to consider comorbid major depressive disorder (MDD) and moderating variables. This meta-analysis of 47 studies (123 effect sizes, N=6008 individuals) revealed that daily cortisol output was lower for PTSD (d=-.36, SE=.15, p=.008) and PTSD+MDD (d=-.65, SE=.25, p=.008) groups relative to no trauma controls (NTC); TE and NTC groups did not differ significantly from each other. Afternoon/evening cortisol was lower in TE (d=-.25, SE=.09, p=.007) and PTSD (d=-.27, SE=.12, p=.021) groups and higher in PTSD+MDD groups (d=.49, SE=.24, p=.041) relative to NTC. Post-DST cortisol levels were lower in PTSD (d=-.40, SE=.12, p<.001), PTSD+MDD (d=-.65, SE=.14, p<.001), and TE groups (d=-.53, SE=.14, p<.001) relative to NTC. HPA effect sizes were moderated by age, sex, time since index event, and developmental timing of trauma exposure. These findings suggest that enhanced HPA feedback function may be a marker of trauma-exposure rather than a specific mechanism of vulnerability for PTSD, whereas lower daily cortisol output may be associated with PTSD in particular.
O'KEANEV,FRODL T,DINAN T G.A review of atypical depression in relation to the course of depression and changes in HPA axis organization[J].Psychoneuroendocrinology,2012,37(10):1589-1599.
Abstract Depression is a clinically heterogenous condition defined by sub-types that can have diametrically opposed features, such as sleep and appetite. Within the same individual these features may change over time, and different symptom clusters may respond selectively to different treatments. It has been hypothesized that different pathophysiological processes may be operating in the different sub-types of depression and specifically that Melancholic depression may be associated with relative overactivity, and Atypical depression with relative hypoactivity, of the hypothalamic drive of the HPA axis. A consistent finding that emerges from the literature is that the experience of depression alters over the course of the illness with the features of Atypical depression dominating a more chronic clinical picture. This suggests that different stress states characterize the different profiles of depression as the illness becomes more chronic. There is evidence that the corticotropin-releasing hormone (CRH) control of HPA axis output is reduced in Atypical, compared to Melancholic, sub-types, but there is no convincing evidence that overall HPA activity, i.e., cortisol output, reduces. We suggest that there is a "switch" in the regulation of the HPA system from CRH to arginine vasopressin (AVP) control as stress becomes more sustained or repeated; resulting in an altered homeostasis within the HPA system. Cortisol, and the neuropeptides CRH and AVP, have different neurobiological, behavioural and experiental effects. The "switch" process should result in different neuropeptide/cortisol combinations and ratios and may explain the changing profile of depression over time. The heuristic merit in making a distinction between the different clinical states of depression will be discussed. Copyright 漏 2012 Elsevier Ltd. All rights reserved.
TOUMAC,BUNCKM,GLASLL,et al.Mice selected for high versus low stress reactivity: a new animal model for affective disorders[J].Psychoneuroendocrinology,2008,33(6):839-862.
Taken together, our results suggest that distinct mechanisms influencing the function and regulation of the HPA axis are involved in the respective behavioral and neurobiological endophenotypes. Thus, the generated HR/IR/LR mouse lines can be a valuable model to elucidate molecular genetic, neuroendocrine, and behavioral parameters associated with altered stress reactivity, thereby improving our understanding of affective disorders, presumably including the symptomatology and pathophysiology of specific subtypes of major depression.
BELVEDERE MR,PARIANTEC,MONDELLIV,et al.HPA axis and aging in depression: systematic review and meta-analysis[J].Psychoneuroendocrinology,2014,41:46-62.
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[5]
CHENF,ZHOU LB,BAI YY.Hypothalamic-pituitary-adrenal axis hyperactivity accounts for anxiety-and depression-like behaviors in rats perinatally exposed to bisphenol A[J].J Biomed Res,2015,29(3):250-258.
BSCHORT,ISINGM,ERBES,et al.Impact of citalopram on the HPA system.a study of the combined DEX/CRH test in 30 unipolar depressed patients[J].Psychiatr Res,2012,46(1):111-117.
Abstract BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system is one of the best replicated pathophysiological findings in depression. However, studies on the influence of treatment on the HPA system have partly yielded inconsistent results. OBJECTIVE: To assess the effects of citalopram monotherapy on the HPA system of mainly drug na07ve patients with major depression by means of the combined DEX/CRH test. METHODS: The DEX/CRH test was conducted twice in 30 patients (25 drug na07ve for the index episode) with major depression (single episode or unipolar recurrent; SCID I- and II-confirmed): directly before the start of a citalopram monotherapy (day 0) and four weeks thereafter (day 28). RESULTS: Twenty-three patients responded (≥50% reduction in the HDRS(21)-score), and 17 of them also reached criteria of remission (HDRS02≤027). Baseline (dexamethasone-suppressed) and CRH-stimulated ACTH concentrations significantly decreased from day 0 to day 28. CRH-stimulated cortisol concentrations also fell, although not significantly, but baseline cortisol concentrations exhibited a significant increase from day 0 to day 28. CONCLUSIONS: The blunting of the ACTH response in the DEX/CRH test under citalopram is in line with what has been observed in most studies with antidepressants. However, the partial rise in cortisol concentrations indicates an increase in the sensitivity of the adrenal cortex to ACTH. State-dependent alterations in the volume and the ACTH responsiveness of the adrenal gland have repeatedly been reported in depressed subjects, which indicates the possibility that SSRIs such as citalopram might exhibit a direct or indirect effect on the adrenal cortex. Copyright 08 2011 Elsevier Ltd. All rights reserved.
NIKISCHG, MATHE AA,CZERNIKA,et al.Long-term citalopram administration reduces responsiveness of HPA axis in patients with major depression: relationship with S-citalopram concentrations in plasma and cerebrospinal fluid (CSF) and clinical response[J].Psychopharmacology,2005,181(4):751-760.
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[9]
MARTISOVAE,AISAB,TORDERA RM,et al.Venlafaxine reverses decreased proliferation in the subventricular zone in a rat model of early life stress[J].Behav Brain Res,2015,292:79-82.
It is believed that glucocorticoids control the proliferation of neural progenitor cells, and this process is highly involved in mood disorders and cognitive processes. Using the maternal separation model of chronic neonatal stress, it has been found that stress induced depressive-like behavior, cognitive deficits and a decrease in proliferation in the subventricular zone (SVZ). Venlafaxine reversed all deleterious effects of chronic stress by modulating HPA activity. These outcomes suggest modulation of stress-mediated glucocorticoid secretion as a target for the treatment of mood disorders and neurodegenerative processes.
KUNZEL HE,BINDER EB,NICKELT,et al.Pharmacological and nonpharmacological factors influencing hypothalamic-pituitary-adrenocortical axis reactivity in acutely depressed psychiatric in-patients,measured by the Dex-CRH test[J].Neuropsychopharmacology,2003,28(12):2169-2178.
[本文引用:1]
[11]
MARCUSI, SONJAH, STEFANK.Combined dexamethasone/corticotropin releasing hormone test predicts treatment response in major depression- a potential biomarker?[J].Biolog Psych,2006,62(1):47-54.
[本文引用:1]
[12]
UYS JD,MARISL,FAUREJ.Developmental trauma is associated with behavioral hyperarousal,altered HPA axis activity,and decreasedhippocampal neurotrophin expression in the adult rat[J].Ann N Y Acad Sci,2006,1071(1):542-546.
Abstract Abstract:鈥 Effects of early-life trauma on adult behavioral responses, corticosterone (CORT) concentration, and levels of nerve growth factor (NGF), brain-derived neutrophic factor (BDNF), and neurotrophin-3 (NT-3) in hippocampus and frontal cortex were investigated. Traumatized animals showed an increase in rearing in both the elevated plus maze and open field after adult restress, higher basal levels of CORT, lower levels of BDNF in dorsal hippocampus, and lower levels of NT-3 in dorsal and ventral hippocampus. Trauma-related behavioral hyperarousal and altered hypothalamic-pituitary-adrenal (HPA) axis activity may be mediated by decreases in hippocampal neurotrophin expression.
GEORGN.Involvement and role of antidepressant drugs of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor function[J].Neuroendocrinol Lett,2009,30(1):11-16.
ABSTRACT Changes in the hypothalamic-pituitary-adrenal (HPA) axis are characteristic of major depression. Because the effects of glucocorticoids are mediated by intracellular receptors including, most notably, the glucocorticoid receptor (GR), several studies have examined the number and/or function of GR's in depressed patients. Review scientific evidences have consistently demonstrated that GR function is impaired in major depression, resulting in reduced GR-mediated negative feedback on the HPA axis and increased production and secretion of corticotropin-releasing hormone (CRH) in various brain regions postulated to be involved in the causality of major depression. Hyperactivity of HPA axis is the main biochemical change, besides disturbed monoaminergic neurotransmission, observed in the patients suffering from a major depression. High incidence of depression in Cushing's syndrome as well as antidepressant effects of adrenocortical enzyme inhibitors in major depression support hypothesis that hyperactivity of HPA axis may be involved in pathogenesis of depression. Major alterations of the HPA axis that can be reversed by successful antidepressant therapy are often seen in depressed patients. A possible explanation for this is that the antidepressant-induced increase in GR's renders the HPA axis more sensitive to glucocorticoid feedback. This new insight into antidepressant drug action suggests a novel approach to the development of antidepressant drugs.
WANGS, NIY, GUOF,et al.Differential expression of hypothalamic fear- and stress-related genes in broiler chickens showing short or long tonic immobility[J].Domest Anim Endocrinol,2014,47:65-72.
The serotonin system and the hypothalamic-pituitary-adrenal axis play important roles in modulating fear and stress-coping characteristics. Tonic immobility (TI) is a fear-related phenotype, and previously we have shown that broiler chickens showing short TI (STI) duration experience better growth performance and higher adaptability to stress. Here, we sought to further elucidate the central mechanisms underlying the phenotypic differences between chickens showing STI and long TI duration, by comparing the hypothalamic expression of genes in the serotonergic system and the hypothalamic-pituitary-adrenal axis under basal and corticosterone-exposed situations. The STI broilers had significantly lower ( P < 0.01) hypothalamic expression of serotonin reuptake transporter and serotonin receptor 1A. Moreover, 11尾-hydroxysteroid dehydrogenase type 2 was expressed significantly lower in STI chickens at the level of both mRNA ( P < 0.01) and protein ( P < 0.05). Hypothalamic expression of glucocorticoid receptor (GR) mRNA tended to be higher ( P < 0.059) in long TI chickens, but the protein content was approximately 2 times higher ( P < 0.01) in STI chickens. The uncoupled expression of GR mRNA and protein was associated with significantly lower ( P < 0.05) expression of gga-miR-181a, gga-miR-211, and gga-miR-22 , which are predicted to target GR , in STI chickens. Corticosterone administration reduced the mRNA expression of postsynaptic serotonin receptors, 5-hydroxytryptamine receptor 1B ( P = 0.059) and 5-hydroxytryptamine receptor 7 ( P < 0.05), yet significantly increased the protein content of 11尾-hydroxysteroid dehydrogenase type 2 ( P < 0.05). These results suggest that broilers of different TI phenotypes have a distinct pattern of hypothalamic expression of fear- and stress-related genes.
VENTURA-JUNCAR,SYMONA,LOPEZP,et al.Relationship of cortisol levels and genetic polymorphisms to antidepressant response to placebo and fluoxetine in patients with major depressive disorder: a prospective study[J].BMC Psychiatry,2014,14:220.
Background Increased cortisol levels and genetic polymorphisms have been related to both major depressive disorder and antidepressant treatment outcome. The aim of this study is to evaluate the relationship between circadian salivary cortisol levels, cortisol suppression by dexamethasone and genetic polymorphisms in some HPA axis-related genes to the response to placebo and fluoxetine in depressed patients. Methods The diagnosis and severity of depression were performed using the Mini International Neuropsychiatric Interview (M.I.N.I.) and Hamilton depression scale (HAM-D17), respectively. Euthyroid patients were treated with placebo (one week) followed by fluoxetine (20聽mg) (two months). Severity of depression was re-evaluated after placebo, three weeks and two months of fluoxetine treatments. Placebo response was defined as HAM-D17 score reductions of at least 25% and to???<???15. Early response and response were reductions of at least 50% after three weeks and two months, and remission with?????????7 after two months. Plasma TSH, free-T4, circadian salivary cortisol levels and cortisol suppression by dexamethasone were evaluated. Seven genetic polymorphisms located in the Corticotrophin-releasing-hormone-receptor-1 (rs242939, rs242941, rs1876828), Corticotrophin-releasing-hormone-receptor-2 (rs2270007), Glucocorticoid-receptor (rs41423247), FK506-binding-protein-5 (rs1360780), and Arginine-vasopressin (rs3729965) genes were determined. Association analyses between response to placebo/fluoxetine and polymorphism were performed by chi-square or Fisher exact test. Cortisol levels were compared by t-test, ANOVA and the general linear model for repeated measures. Results 208 depressed patients were recruited, 187 of whom were euthyroid. Placebo responders, fluoxetine responders and remitters exhibited significantly lower circadian cortisol levels than those who did not respond (p-values of 0.014, 0.008 and 0.021 respectively). Patients who abandoned treatment before the third week also exhibited a trend to low cortisol levels (p???=???0.057). The polymorphisms rs242939 (CRHR1) and rs2270007 (CRHR2) were not in Hardy-Weinberg equilibrium. Only the rs242939 polymorphism (CRHR1) exhibited association with early response (three weeks) to fluoxetine (p-value???=???0.043). No other association between outcomes and polymorphisms was observed. Conclusions These results support the clinical relevance of low salivary cortisol levels as a predictor of antidepressant response, either to placebo or to fluoxetine. Only one polymorphism in the CRHR1 gene was associated with the early response. Other factors may be involved in antidepressant response, although further studies are needed to identify them.
MANTHEYL,GILTAY EJ,VAN VEENT,et al.Long-term benzodiazepine use and salivary cortisol: the Netherlands Study of Depression and Anxiety (NESDA)[J].J Clin Psychopharmacol,2010,30(2):160-168.
Abstract BACKGROUND: As benzodiazepines (BZDs) have anxiolytic effects, it is expected that they influence the stress system. During short-term treatment, BZD use was found to suppress cortisol levels. However, little research has been done on the effects of long-term BZD administration on the hypothalamic-pituitary-adrenal (HPA) axis. METHODS: The association between long-term BZD use and cortisol levels was investigated in subjects of the Netherlands Study of Depression and Anxiety with a lifetime diagnosis of anxiety or depression (n = 1531). The subjects were categorized as "daily BZD users" (n = 96), "infrequent BZD users" (n = 172), and "nonusers" (n = 1263). Possible associations between characteristics of BZD use (dose, duration, and dependence) and salivary cortisol levels were analyzed. MAIN OUTCOME MEASURE: Subjects provided 7 saliva samples, from which 4 cortisol indicators were calculated: the cortisol awakening response, diurnal slope, evening cortisol, and cortisol suppression after ingestion of 0.5 mg of dexamethasone. RESULTS: Daily users used BZDs for a median duration of 26.5 months and had a median daily dosage of 6.0 mg as measured in diazepam equivalents. Evening cortisol levels were significantly lower in daily users (P = 0.004; effect size: d = 0.24) and infrequent users (P = 0.04; effect size: d = 0.12) compared to nonusers. We did not find significant differences in the cortisol awakening response, diurnal slope, or in the dexamethasone suppression test. CONCLUSIONS: Despite the finding of slightly lower evening cortisol levels in daily and infrequent BZD users compared to nonusers, results indicate that long-term BZD use is not convincingly associated with HPA axis alterations.
BINDER EB,KUNZEL HE,NICKELT,et al.HPA-axis regulation at in-patient admission is associated with antidepressant therapy outcome in male but not in female depressed patients[J].Psychoneuroendocrinology,2009,34(1):99-109.
A concatenation of data implicates a hyperactivity of the hypothalamus pituitary adrenal ()-axis in the of and its normalization as a necessary predecessor of clinical response to . In addition, regulation of the -axis has been shown to be dependent on sex hormones. We therefore investigated gender differences in -axis regulation in and its normalization during remission of clinical symptoms. We used the combined suppression/stimulation (-) test to evaluate the degree of -axis dysregulation in 194 in-patients with from the Munich Antidepressant Response Signature () study at both admission and discharge. The Hamilton (HAM-D) Rating Scale was used to monitor clinical response to antidepressant treatment. For both genders, we observed a normalization of -axis dysregulation in remitters but not in non-remitters, both after 5 weeks of treatment and at discharge. The pattern of -axis normalization with remission of depressive symptoms, however, showed gender-specific differences. In male patients, remission after 5 weeks of in-patient treatment was associated with a significantly higher response in the -test at admission. In female patients, 5-week remitters and non-remitters had a comparable response at admission. response at admission was not correlated with gonadal steroid levels at this time point and the results were similar for pre-menopausal women vs. post-menopausal women. Gender-associated biological characteristics, likely independent of circulating gonadal steroids, thus seem to influence -axis regulation in . In male patients, a single measure of -axis dysregulation at admission may serve as a predictor of response to antidepressant treatment in addition to the previously reported repeated measure of the -test.
RUHE HG,KHOENKHOEN SJ,OTTENHOF KW,et al.Longitudinal effects of the SSRI paroxetine on salivary cortisol in major depressive disorder[J].Psychoneuroendocrinology,2015,52:261-271.
In conclusion, paroxetine seems to interfere with HPA-axis dysregulation, reflected in significant overall decreases in BCL and AUC during treatment. Paroxetine appears to decrease HPA-axis set-point in MDD, which might result in increased HPA-axis activity over time, which is further improved when patients achieve remission (ISRCTN register nr. ISRCTN44111488).
SALARI AA,FATEHI-GHAREHLARL,MOTAYAGHENIN,et al.Fluoxetine normalizes the effects of prenatal maternal stress on depression-and anxiety-like behaviors in mouse dams and male offspring[J].Behav Brain Res,2016,311:354-367.
Maternal depression during pregnancy and the postpartum period (lactation) is a common debilitating condition affecting mother-fetus/-infant interactions, which can be a risk factor for cognitive and affective disorders in mothers and their children. Selective-serotonin-reuptake-inhibitor-(SSRI) pharmacotherapy is known as the first-line treatment of maternal depression. However, its use during pregnancy and lactation is a topic of concern. The present study aimed to investigate the effects of prenatal stress alone or in combination with fluoxetine (FLX) on hypothalamic鈥損ituitary鈥揳drenal axis (HPA) activity, anxiety-/depression-like behaviors in dams and in offspring. To do this, gestationally-stressed and non-stressed mouse dams were orally treated with FLX-(8/mg/kg/day) from gestational day 10 to lactation day 20. The behavioral outcomes of prenatal stress and FLX treatment in dams and male offspring were assessed using the sucrose preference, forced swim, zero maze, and light-dark box tests. Stress-induced corticosterone levels were also evaluated as indicative of abnormal HPA-axis function. Our findings indicated that maternal stress resulted in increased depression-like behavior and HPA axis hyperactivity in dams during pregnancy and lactation which were reversed by FLX. Furthermore, prenatal stress increased anxiety/depression-like behaviors and HPA-axis reactivity in male offspring. These effects were reversed by maternal FLX treatment. Developmental FLX exposure, without prenatal stress, did not have any adverse effects on the above measured parameters. Our results suggest that prenatal stress induces maternal depression-like behavior which affects the development of affective symptoms in male offspring, and that remediation of maternal depression-like behavior coincidences with the normalization of anxiety-and depression-like symptoms in male offspring.
KASCKOW JW,BAKERD,GERACIOTI TD.Corticotropin-releasing hormone in depression and post-traumatic disorder[J].Peptides, 2001,22(5): 845-851.
Corticotropin-releasing hormone (CRH) has been implicated in the regulation of a wide range of behaviors including arousal, motor function, feeding, and reproduction. Because depressed patients are often hypercortisolemic and intracerebroventricular administration of CRH to experimental animals produces a syndrome reminiscent of depression, dysregulation of this compound has been suggested to be involved in the pathogenesis of depressive and anxiety disorders. Studies of cerebrospinal fluid CRH levels and clinical neuroendocrine tests in patients with anxiety and affective disorders have supported this hypothesis. This review discusses these neuroendocrine findings in melancholic and atypical depression as well as post-traumatic stress disorder (PTSD). Overall, the data suggest that melancholic depression is characterized by hyperactive central CRH systems with overactivity of the pituitary-adrenal (HPA) axis. On the other hand, atypical depression is characterized by hypoactive central CRH systems and accompanying underactivity of the hypothalamic-pituitary-adrenal axis. Furthermore, the neuroendocrinology of PTSD appears to be unique, in that patients have hyperactive central CRH systems with underactivity of the pituitary-adrenal axis.
HOLSBOERF.Stress,hypercortisolism and corti-costeroid receptors in depression: implications for therapy[J].J Affect Disord,2001,62(1/2): 77-91.
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WATSONS,GALLAGHERP,RITCHIE JC,et al.Hypothalamic-pituitary-adrenal axis function in patients with bipolar disorder[J].Br J Psychiatry,2004,184:496-502.
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[23]
WATSONS,GALLAGHERP,SMITH MS,et al.The dex /CRH test is it better than the DST?[J].Psychoneuroendocrinology,2006,31(7): 889-894.
The dexamethasone suppression test (DST), frequently abnormal in mood disorder patients, is considered to measure glucocorticoid receptor-mediated negative feedback. We examined the hypothesis that the, apparently more sensitive, dexamethasone/corticotrophin-releasing-hormone (dex/CRH) test unveils subtle hypothalamic–pituitary–adrenal axis disturbance not detected by the DST in 82 patients with mood disorders and 28 controls. There was a close correlation between the cortisol responses on the two tests ( r s=0.73, p<0.0005). However, ROC analysis revealed that the dex/CRH test had better diagnostic performance than the DST ( p=0.031). The sensitivity of delta cortisol (from the dex/CRH) was 61.9% and the specificity 71.4%. The sensitivity of 1500 h cortisol (the DST) was 66.6% and the specificity was 47.6%. This suggests that the two tests measure common pathology but that the dex/CRH test has better diagnostic utility.
HATZINGERM,HEMMETER UM,BAUMANNK.The combined DEX-CRH test in treatment course and long-term outcome of major depression[J].J Psychiatr Res,2002,36(5):287-297.
Neuroendocrine studies strongly suggest that the hypothalamic鈥損ituitary鈥揳drenocortical (HPA) system plays a crucial role in the development and course of depression. The interaction between the disease process and HPA system function in long-term course, however, is unclear. Since improvement of HPA system deterioration has been demonstrated to be associated with treatment response, the question has arisen whether the course of therapy response as reflected by, for example, early improvement or response (after 1 or 2 weeks of therapy) is also based on HPA system dysfunction and whether the course of HPA regulation during treatment is only a state marker or has additional predictive implications for long-term outcome. In order to elucidate these questions a long-term study was carried out to investigate whether HPA system disturbance is associated (1) with the course of treatment response, predominantly early treatment response, during acute depression and (2) with the long-term course of depression, i.e. number of episodes. Twenty patients with affective disorders who participated in earlier controlled antidepressant treatment studies over 6 weeks were enrolled in an exploratory follow-up study. Using the combined DEX/CRH test it was demonstrated that (1) early improvement, early treatment response and beneficial treatment outcome after 6 weeks were associated with a lower HPA system activity and that (2) in long-term course of depression the HPA system deterioration increases in parallel with the number of previous episodes. These findings suggest that HPA system alterations are closely related to treatment response and long-term outcome of depression.
CARPENTER LL,TYRKA AR,LEE JK,et al.A placebo-controlled study of sertraline's effect on cortisol response to the dexamethasone/corticotropin-releasing hormone test in healthy adults[J].Psychopharmacology (Berl),2011,218(2):371-379.
The dexamethasone/corticotropin-releasing hormone (Dex/CRH) test is a neuroendocrine probe involving serial blood sampling of cortisol during a standardized pharmacological challenge without inducing psychological distress in humans. Some past studies in depressed patients have shown a "normalization" or decrease in cortisol response to the Dex/CRH test following successful treatment with an antidepressant. Studies in nondepressed healthy adult samples have also shown aberrant cortisol reactivity to be associated with depression risk factors. These findings prompted research into the use of the Dex/CRH test as a tool for developing antidepressant drugs.In this study, the Dex/CRH test was evaluated with regard to its potential utility for drug development in nonclinical samples.The Dex/CRH test was administered before and after 6 weeks of blinded treatment with either sertraline 100 mg/day or matching placebo in 22 healthy adults (13 women, nine men).Cortisol response to the Dex/CRH test increased following treatment with standard doses of sertraline, compared to placebo, after controlling for age and sex.The observed pattern of change contrasts with results from published studies in depressed patients and with our initial hypothesis.
PASLAKISG,HEUSERI,SCHWEIGERU,et al.A single DEX/CRH test in male drug-free depressed patients is associated with the clinical response to treatment with fluoxetine[J].J Psychiatr Res,2010,44(16):1154-1157.
The DEX/CRH test has been proposed to be suitable as a biomarker for the prediction of treatment response in depression.We performed the DEX/CRH test in 10 severely depressed male patients with melancholic features before initiation of antidepressant treatment with 20 mg fluoxetine.We found a low cortisol response (as measured by cortisol AUC) to a single DEX/CRH test to be associated with clinical response to treatment.A strength of this study lies in the inclusion of patients after a drug wash-out phase. Despite a certain inconsistency described in the literature, several studies support the notion that it might be of importance to measure baseline HPA system activity before choice of treatment. Further systematic studies are warranted.
HORSTMANNS,DOSET,LUCAES,et al.Suppressive effect of mirtazapine on the HPA system in acutely depressed women seems to be transient and not related to antidepressant action[J].Psychoneuroendocrinology,2009,34(2):238-248.
Abstract Impaired regulation of the hypothalamus-pituitary-adrenocortical (HPA) system is a consistent finding among patients with depression, which can be most sensitively detected with the combined dexamethasone (dex)/corticotrophin releasing hormone (CRH) test. The majority of patients with acute depression shows an exaggerated plasma corticotrophin (ACTH) and cortisol response to this test that normalizes gradually during successful antidepressant therapy. In contrast, persistently high HPA-responses to this challenge are prognostically less favorable. It has been recently questioned, whether this observation applies also to treatment with the atypical antidepressant mirtazapine, as patients treated with this drug showed a distinct attenuation of the endocrine response to the dex/CRH test already after 1 week of treatment. In the present study, we investigated whether the attenuating effect of mirtazapine on the HPA system is an acute pharmacological reaction disappearing after physiological adaptation or whether this effect is related to the antidepressant action of the drug. We examined plasma ACTH and cortisol responses to the dex/CRH test in acutely depressed inpatients treated either with mirtazapine (n=55) or a monoamine reuptake inhibitor (n=105) according to doctor's choice and compared the test results with healthy controls (n=40). Patients treated with monoamine reuptake inhibitors received either selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (TCA) or the combined serotonin and noradrenalin reuptake inhibitor venlafaxine. We found increased plasma ACTH and cortisol responses to the dex/CRH test in depressed patients compared with healthy controls, but also significantly (p=.017) attenuated plasma cortisol secretion in the mirtazapine group compared to the group of monoamine reuptake inhibitor treated patients. This effect was not significant in male patients. Furthermore this effect was independent of the psychopathological state, but depended on treatment duration. Patient treatment with mirtazapine for up to 7 days resulted in dex/CRH test outcome that was indistinguishable from controls. This effect, however waned as it was not observable in patients treated for a longer period. These results suggest that short-term administration of mirtazapine has immediate but only transient suppressive effects on the HPA system predominantly in women. Our results confirm that dex/CRH tests can be used as predictors of clinical course also under mirtazapine treatment.
GEORGIOSP,BERTRAMK,MARIAG,et al.Discrimination between patients with melancholic depression and healthy controls: comparison between 24 h cortisol profiles,the DST and the Dex/CRH test[J].Psychoneuroendocrinology,2010,36(5):691-698.
Diurnal (24-h) cortisol profiles were compared to DST and Dex/CRH test outcomes with regard to their discriminative power in depressive disorder. With regard to several statistical measures (effect sizes, area under the curve) we found 24-h cortisol profiles to better discriminate between healthy controls and inpatients with the melancholic subtype of depression compared to the DST and Dex/CRH test. In search of a shortened time interval we found the 2-h time window 1000-1200 h of the cortisol profile to be the one with the highest sensitivity (83.3%) and specificity (87.9%). The specificity of the DST was 93.3% and somewhat higher than that of the cortisol profiles and the Dex/CRH test (87.9% and 78.8.%, respectively). However, the sensitivity of the DST was very low (30.8%), in fact similar to that of the Dex/CRH test (30.8%), but much lower than that of the 1000-1200 h interval (83.3%). The assessment of cortisol in plasma is an easy to perform, cost-saving method for the evaluation of the HPA system activity, which may have a series of clinical and scientific implications for the depressive disorder.
SARUBINN,NOTHDURFTERC,SCHMOTZC.Impact on cortisol and antidepressant efficacy of quetiapine and escitalopram in depression[J].Psychoneuroendocrinology,2014,39:141-151.
NOTHDURFTERC,SCHMOTZC,SARUBINN,et al.Effects of escitalopram/quetiapine combination therapy versus escitalopram monotherapy on hypothalamic-pituitary-adrenal-axis activity in relation to antidepressant effectiveness[J].J Psychiatr Res,2014,52:15-20.
The hypothalamic-pituitary-adrenocortical (HPA) system is believed to play an important role in the pathophysiology of major depressive disorder. In this context, the atypical antipsychotic quetiapine (QUE) has been shown to inhibit HPA system activity in healthy subjects. In this study we investigated whether the putative inhibitory effects of QUE on HPA system activity may contribute to its antidepressant efficacy. We analyzed the effects of QUE as an augmentation to the selective serotonin reuptake inhibitor (SSRI) escitalopram (ESC) on HPA system activity in comparison to a monotherapy with ESC in relation to the antidepressant effectiveness. HPA axis activity (cortisol and ACTH) was measured by means of the dexamethasone/corticotropin-releasing hormone (DEX/CRH) test which was performed before (week 0) and during (week 1, week 5) antidepressant psychopharmacotherapy. The combination therapy, but not the ESC monotherapy showed significantly inhibiting effects on HPA system activity leading to stepwise down-regulation. ACTH concentrations were reduced in the ESC/QUE group during five weeks of treatment. The inhibitory effect of QUE maybe involved in its antidepressant effects as an augmentation strategy.
KUNZEL HE,ACKLN,HATZINGERM,et al.Outcome in delusional depression comparing trimipramine monotherapy with a combination of amitriptyline and haloperidol-a double-blind multicenter trial[J].J Psychiatr Res,2009,43(7):702-710.
BACKGROUND: Patients with delusional depression are difficult to treat. The atypical antidepressant trimipramine was effective in a previous 4-week open label pilot study in patients with this disorder. The major neurobiological effect of trimipramine is the inhibition of the hypothalamic-pituitary-adrenocortical (HPA) system. In delusional depression HPA overactivity is more distinct than in other subtypes of depression. HPA suppression is thought to contribute to the action of trimipramine. METHODS: In a double-blind, randomized, placebo controlled multicenter trial we compared the effects of trimipramine monotherapy versus a combination of amitriptyline and haloperidol. Dosage was increased stepwise from 100mg up to 400mg trimipramine and from 100mg up to 200mg amitriptyline combined with 2mg up to 7.5mg haloperidol. The average dose of trimipramine was higher than that of amitriptyline throughout the trial. During sixth week mean dosage (+/-standard deviation) were 356.1+/-61.2mg trimipramine, 184.0+/-23.6 mg amitriptyline and 6.3+/-1.8 mg haloperidol. During six weeks psychometric assessments were performed weekly. For HPA monitoring a dexamethasone/corticotropin-releasing hormone (Dex/CRH) test was performed before active medication and at the end of treatment. Additionally tolerability was monitored by ECG, EEG assessment of extrapyramidal symptoms and akathisia, clinical laboratory routine and recording of blood pressure and heart rate. Adverse events were documented. RESULTS: 94 patients were enclosed into the study. The per protocol sample consisted of 33 patients of the trimipramine group and of 24 patients of the amitriptyline/haloperidol group. The decrease of the Hamilton depression (HAMD) score (24 items) showed non-inferiority of trimipramine compared to amitriptyline/haloperidol. Twenty-eight patients (84.84%) in the trimipramine arm and 17 patients (70.83%) in the amitriptyline/haloperidol arm were responders (HAMD <or=50%). Remission (HAMD<8
HENNINGS JM,OWASHIT,BINDER EB.Clinical characteristics and treatment outcome in a representative sample of depressed inpatients-findings from the munich antidepressant response signature (MARS) project[J].J Psychiatr Res,2009,43(3):215-229.
<h2 class="secHeading" id="section_abstract">Abstract</h2><p id="simple-para0050">Depression is a common and often difficult-to-treat clinical condition with a high rate of patients showing insufficient treatment response and persistence of symptoms. We report the characteristics of a representative sample of depressed inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Eight hundred and forty-two inpatients admitted to a psychiatric hospital for treatment of a major depressive episode, recurrent or bipolar depression were thoroughly characterized with respect to demographic factors, clinical history, and the degree of HPA-axis dysregulation evaluated by means of combined dex/CRH tests, and the predictive value of these factors for treatment outcome is investigated. 80.8% of patients responded to treatment (i.e., improvement in symptom severity of at least 50%) and 57.9% reached remission (i.e., near absence of residual depressive symptoms) at discharge after a mean treatment period of 11.8 weeks. Regression analysis identified early partial response (within 2 weeks) as the most important positive predictor for achieving remission. Previous ineffective treatment trials in the current episode and presence of a migration background are potent negative predictors for treatment outcome. In addition, remitters were characterized by a more pronounced normalization of an initially dysregulated HPA-axis. We could show that a large majority of inpatients suffering from depression benefits from antidepressant treatment during hospitalization. However, a considerable number of patients failed to achieve remission. We demonstrated that this subgroup can be characterized by a set of demographic, clinical and neuroendocrine variables allowing to predict unfavorable outcome at an early stage of treatment.</p>
ISINGM,HORSTMANNS,KLOIBERS,et al.Combined dexamethasone/corticotropin releasing hormone test predicts treatment response in major depression-a potential biomarker?[J].Biol Psychiatry,2007,62(1):47-54.
[本文引用:1]
[34]
LOZANO-ORTIZR,MARIN-LACASAR,PASCUAL-GARCIAA,et al.Therapeutic monitoring of escitalopram by dexamethasone suppression test[J].Actas Esp Psiquiatr,2012,40(5):275-280.
INTRODUCTION: is associated with a dysfunction of regulation of the hypothalamic-pituitary-adrenal, HPA, which is reflected in the alteration of the suppression test, . and other SSRIs decrease the HPA axis response to the , beeing the aim of this study validate the as a surrogate marker of central serotonergic activity in the treatment with and its application to the calculation of the dosage regimens.: Prospective observational study on 29 patients, upon whom was performed the -test with 0.25 mg of and subsequent genetic analysis of by Progenika PHARMAchip test.: The range of plasma levels post-associated with each phenotypic group were: PM phenotype= 0.6 to 1.7 mcg/dl, IM phenotype= 1.2 to 3.5 mcg/dl and EM phenotype = 4.8 to 13.2 mcg/dl, being carried out the dose titration and correspondng, respectively, the following dose regimens: 3-4 mg/day, 5-8 mg/day and 10-31 mg/day.: It has been shown that the test can be used as a surrogate marker of drug response to and as a tool for dose adjustment, providing significant data on different phenotypes of metabolizers.
HATZINGERM,HEMMETER UM,BAUMANNK,et al.The combined DEX-CRH test in treatment course and long-term outcome of major depression[J].J Psychiatr Res,2002,36(5):287-297.
Neuroendocrine studies strongly suggest that the hypothalamic鈥損ituitary鈥揳drenocortical (HPA) system plays a crucial role in the development and course of depression. The interaction between the disease process and HPA system function in long-term course, however, is unclear. Since improvement of HPA system deterioration has been demonstrated to be associated with treatment response, the question has arisen whether the course of therapy response as reflected by, for example, early improvement or response (after 1 or 2 weeks of therapy) is also based on HPA system dysfunction and whether the course of HPA regulation during treatment is only a state marker or has additional predictive implications for long-term outcome. In order to elucidate these questions a long-term study was carried out to investigate whether HPA system disturbance is associated (1) with the course of treatment response, predominantly early treatment response, during acute depression and (2) with the long-term course of depression, i.e. number of episodes. Twenty patients with affective disorders who participated in earlier controlled antidepressant treatment studies over 6 weeks were enrolled in an exploratory follow-up study. Using the combined DEX/CRH test it was demonstrated that (1) early improvement, early treatment response and beneficial treatment outcome after 6 weeks were associated with a lower HPA system activity and that (2) in long-term course of depression the HPA system deterioration increases in parallel with the number of previous episodes. These findings suggest that HPA system alterations are closely related to treatment response and long-term outcome of depression.
VREEBURG SA,HOOGENDIJK WJ,DERIJK RH,et al.Salivary cortisol levels and the 2-year course of depressive and anxiety disorders[J].Psychoneuroendocrinology,2013,38(9):1494-1502.
Depression and anxiety disorders have been associated with hyperactivity of the hypothalamic-pituitary adrenal (HPA) axis. However, lower cortisol levels have also been observed in depressed patients. Whether cortisol level predicts the course of these disorders has not been examined in detail. We examined whether salivary cortisol indicators predict the 2-year course of depression and anxiety disorders.Longitudinal data are obtained from 837 participants of the Netherlands Study of Depression and Anxiety, with a DSM-IV based depressive and/or anxiety disorder at baseline. At baseline, seven saliva samples were obtained, including the 1-h cortisol awakening response, evening cortisol level and a 0.5mg dexamethasone suppression test. At follow-up, DSM-IV based diagnostic interviews and Life Chart Interview integrating diagnostic and symptom trajectories over 2 years were administered to determine an unfavorable course.41.5% of the respondents had a 2-year unfavorable course trajectory without remission longer than 3 months. Adjusted analyses showed that a lower awakening response was associated with an unfavorable course (RR=0.83, p=0.03). No associations were found between evening cortisol or cortisol suppression after dexamethasone ingestion and an unfavorable course trajectory.Among patients with depressive or anxiety disorders, a lower cortisol awakening response - which may be indicative of underlying exhaustion of the HPA axis - predicted an unfavorable course trajectory.
HARDEVELDF,SPIJKERJ,VREEBURG SA,et al.Increased cortisol awakening response was associated with time to recurrence of major depressive disorder[J].Psychoneuroendocrinology,2014,50:62-71.
Our data support previous studies reporting that subjects with a higher CAR are more vulnerable to recurrence of MDD.
OWASHIT,OTSUBOT,OSHIMAA.Longitudinal neuroendocrine changes assessed by dexamethasone/CRH and growth hormone releasing hormone tests in psychotic depression[J].Psychoneuroendocrinology,2007,33(2):152-161.
Although psychotic depression has been reported to exhibit a greater degree of dysregulation of hypothalamic-pituitary-adrenocortical (HPA) function than non-psychotic depression, little is known concerning hypothalamic-pituitary-somatotropic (HPS) function in psychotic depression and how neuroendocrine function changes after treatment. To investigate the longitudinal changes in HPA and HPS system function in psychotic depression, we performed repeated dexamethasone/corticotropin releasing hormone (DEX/CRH) tests and growth hormone (GH) releasing hormone (GHRH) tests in inpatients with major depressive disorder. The psychotic depression group exhibited greater elevation of ACTH responses to the DEX/CRH test and stronger decreases in GH responses to the GHRH test than the non-psychotic depression group at admission. At discharge, the neuroendocrine responses to the DEX/CRH test of the psychotic depression group were still stronger than those of the non-psychotic depression group, though there were no significant differences in severity of depression between the groups. There were significant longitudinal changes in neuroendocrine responses to the DEX/CRH test between admission and discharge. The psychotic depression group exhibited increased GH responses to GHRH at discharge compared with those at admission, whereas no significant longitudinal change in GH response was found in the non-psychotic depression group. Consequently, there were no significant differences in GH responses to GHRH between the psychotic and non-psychotic depression groups at discharge. The results of GHRH test showed no significant relationships with severity of depression except psychotic features and the results of the DEX/CRH test. Our findings suggest that the HPS axis may be associated with psychotic features rather than general severity of depression. Further longitudinal studies are needed to clarify the role of HPS function in psychotic depression and whether sustained dysregulation of HPA function in psychotic depression is associated with a poor outcome after discharge.
SORBERA LA,CASTANERJ,BAYES M,at al.Aprepitant and L758298[J].Drugs Fut,2002,27:211-222.
[本文引用:1]
[40]
HOLSBOERF,ISINGM.Central CRH system in depression and anxiety-evidence from clinical studies with CRH1 receptor antagonists[J].Eur J Pharmacol,2008,583(2/3): 350-357.
Basic and clinical studies provide convincing evidence that altered stress hormone regulation frequently observed in depression and anxiety are caused by elevated secretion of the hypothalamic neuropeptides corticotrophin releasing hormone (CRH) and vasopressin. CRH predominantly acts through CRH 1 receptors to produce a number of anxiety- and depression-like symptoms, which resulted in extensive validation of CRH 1 receptors as potential drug target. A number of orally available nonpeptidergic small molecules capable to pass the blood-brain barrier have been discovered; only some of these compounds entered clinical development. Here, we summarize results from clinical studies of two CRH 1 receptor antagonists. In the first study originally designed as a safety and tolerability trial in major depression, it was observed that the CRH 1 receptor antagonist NBI-30775/R121919 has a clinical profile comparable to the antidepressant paroxetine. In a second study the effect of another CRH 1 receptor antagonist, NBI-34041, upon stress hormone secretion in response to a psychosocial stressor was investigated. Administration of this compound reduced the stress-elicited secretion of cortisol. Both compounds, however, did not impair the CRH-induced release of ACTH and cortisol rejecting the possibility that the peripheral stress hormone system is impaired by CRH 1 receptor antagonists. From these studies we conclude that both CRH 1 receptor antagonists have psychotropic effects unrelated to their neuroendocrine action, which is in line with behavioral data obtained from transgenic mice. The results of the clinical studies underscore that CRH 1 receptor antagonists represent promising novel therapeutics in the psychopharmacology of depression and anxiety.
TRINGALI TG,LISIL,DE SIMONE M L,et al.Effects of olanzapine and quetiapine on corticotropin-releasing hormone release in the rat brain[J].Prog Neuropsychopharmacol Biol Psychiatry,2009,33(6):1017-1021.
An altered regulation of the corticotropin-releasing hormone (CRH) system in the CNS is consistently associated with anxiety and depression; several drugs used to treat CNS disorders modulate--usually in a negative manner--CRH turnover in the brain, and it can be postulated that their effectiveness may be at least in part related to their effects on CRH. This study was aimed to investigate the effects of two atypical antipsychotics also employed in the treatment of bipolar disorders, i.e. quetiapine (QTP) and olanzapine (OLZ), on CRH release from isolated rat brain regions. Acute rat hypothalamic and hippocampal explants were exposed for 1 h to plain medium or medium containing the test drugs, either under baseline conditions or after stimulation of CRH release by veratridine or 56 mM KCl. CRH immunoreactivity present in the incubation medium and in the tissues was assessed by radioimmunoassay. QTP 10 microM but not OLZ inhibited baseline CRH secretion from the hypothalamus; neither drug affected basal CRH release from the hippocampus. Both QTP and OLZ, 1 and 10 microM, inhibited veratridine- or K(+)-stimulated CRH release from the hypothalamus, whereas OLZ only, when given at 10 microM, was able to inhibit stimulated CRH release from the hippocampus. In conclusion, two widely used atypical antipsychotics, QTP and OLZ are able to acutely reduce the release of CRH from isolated rat hypothalami and hippocampi.
... 20世纪50年代,第一个开发的抗抑郁药是单胺氧化酶抑制药(inhibitors of the monoaminooxidase,MAOIs),因严重不良反应而被三环类抗抑郁药(TCAs)取代,后者成为20世纪50年代至80年代世界范围抑郁症治疗一线用药,被称为典型(传统)抗抑郁药.20世纪90年代以后,世界各国陆续开发一些新品种,按其作用机制分类,有选择性5-羟色胺(5-HT)再摄取抑制药(selective serotonin reuptake inhibitors,SSRI)、选择性5-HT和肾上腺素(noradrenaline ,NE)再摄取抑制药(selective serotonin and noradrenaline reuptake inhibitors,SNRIs)、NE及5-HT抗抑郁药(noradrenergic and specific serotonergic antidepressants,NaSSAs),NE和DA再摄取抑制药(norepinephrine and dopamine reuptake inhibitors,NDRIs)、NE再摄取抑制药(noradrenerine reuptake inhibitor,NaRI ),5-HT拮抗药和再摄取抑制药(serotonin antagonist /reuptake inhibitor,SARI)等[6].BSCHOR等[7]研究发现,伴有单相抑郁30例抑郁症患者,口服抗抑郁药物西酞普兰20 mg·d-1,治疗4周后, DST阳性率下降及CRH刺激促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)明显下降.NIKISCH等[8]研究也发现,无论治疗效果如何,抗抑郁药物艾司西酞普兰都可以降低地塞米松或CRH试验反应阳性率,即刺激后ACTH以及皮质醇水平都显著降低,并且具有时间依赖性.动物实验也提示,首先给予动物一定程度的慢性刺激导致出现抑郁样症状,而后给予抗抑郁药物文拉法辛不仅可以逆转由慢性刺激导致的动物HPA功能调节失调,伴随的抑郁症状也得以改善[9].这些研究提示,抗抑郁药物有可能降低刺激DST阳性率,实际上就是恢复HPA 轴的调节功能.有意义的是有些研究虽然不赞同这样的研究结论,但是治疗效果却显示同样结果.KUNZEL等[10]研究发现,在235例抑郁症患者中,无论使用抗抑郁药物与否,也不论使用哪一类抗抑郁药物,只要没有治疗效果,DST/CRH试验都没有变化,相反抗癫痫间药物卡马西平以及有效的药物干预可显著改善DST/CRH试验阳性率,提示抗抑郁药物的有效治疗可改善HPA 轴的调节功能. ...
Impact of citalopram on the HPA system.a study of the combined DEX/CRH test in 30 unipolar depressed patients
1
2012
... 20世纪50年代,第一个开发的抗抑郁药是单胺氧化酶抑制药(inhibitors of the monoaminooxidase,MAOIs),因严重不良反应而被三环类抗抑郁药(TCAs)取代,后者成为20世纪50年代至80年代世界范围抑郁症治疗一线用药,被称为典型(传统)抗抑郁药.20世纪90年代以后,世界各国陆续开发一些新品种,按其作用机制分类,有选择性5-羟色胺(5-HT)再摄取抑制药(selective serotonin reuptake inhibitors,SSRI)、选择性5-HT和肾上腺素(noradrenaline ,NE)再摄取抑制药(selective serotonin and noradrenaline reuptake inhibitors,SNRIs)、NE及5-HT抗抑郁药(noradrenergic and specific serotonergic antidepressants,NaSSAs),NE和DA再摄取抑制药(norepinephrine and dopamine reuptake inhibitors,NDRIs)、NE再摄取抑制药(noradrenerine reuptake inhibitor,NaRI ),5-HT拮抗药和再摄取抑制药(serotonin antagonist /reuptake inhibitor,SARI)等[6].BSCHOR等[7]研究发现,伴有单相抑郁30例抑郁症患者,口服抗抑郁药物西酞普兰20 mg·d-1,治疗4周后, DST阳性率下降及CRH刺激促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)明显下降.NIKISCH等[8]研究也发现,无论治疗效果如何,抗抑郁药物艾司西酞普兰都可以降低地塞米松或CRH试验反应阳性率,即刺激后ACTH以及皮质醇水平都显著降低,并且具有时间依赖性.动物实验也提示,首先给予动物一定程度的慢性刺激导致出现抑郁样症状,而后给予抗抑郁药物文拉法辛不仅可以逆转由慢性刺激导致的动物HPA功能调节失调,伴随的抑郁症状也得以改善[9].这些研究提示,抗抑郁药物有可能降低刺激DST阳性率,实际上就是恢复HPA 轴的调节功能.有意义的是有些研究虽然不赞同这样的研究结论,但是治疗效果却显示同样结果.KUNZEL等[10]研究发现,在235例抑郁症患者中,无论使用抗抑郁药物与否,也不论使用哪一类抗抑郁药物,只要没有治疗效果,DST/CRH试验都没有变化,相反抗癫痫间药物卡马西平以及有效的药物干预可显著改善DST/CRH试验阳性率,提示抗抑郁药物的有效治疗可改善HPA 轴的调节功能. ...
Long-term citalopram administration reduces responsiveness of HPA axis in patients with major depression: relationship with S-citalopram concentrations in plasma and cerebrospinal fluid (CSF) and clinical response
2
2005
... 20世纪50年代,第一个开发的抗抑郁药是单胺氧化酶抑制药(inhibitors of the monoaminooxidase,MAOIs),因严重不良反应而被三环类抗抑郁药(TCAs)取代,后者成为20世纪50年代至80年代世界范围抑郁症治疗一线用药,被称为典型(传统)抗抑郁药.20世纪90年代以后,世界各国陆续开发一些新品种,按其作用机制分类,有选择性5-羟色胺(5-HT)再摄取抑制药(selective serotonin reuptake inhibitors,SSRI)、选择性5-HT和肾上腺素(noradrenaline ,NE)再摄取抑制药(selective serotonin and noradrenaline reuptake inhibitors,SNRIs)、NE及5-HT抗抑郁药(noradrenergic and specific serotonergic antidepressants,NaSSAs),NE和DA再摄取抑制药(norepinephrine and dopamine reuptake inhibitors,NDRIs)、NE再摄取抑制药(noradrenerine reuptake inhibitor,NaRI ),5-HT拮抗药和再摄取抑制药(serotonin antagonist /reuptake inhibitor,SARI)等[6].BSCHOR等[7]研究发现,伴有单相抑郁30例抑郁症患者,口服抗抑郁药物西酞普兰20 mg·d-1,治疗4周后, DST阳性率下降及CRH刺激促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)明显下降.NIKISCH等[8]研究也发现,无论治疗效果如何,抗抑郁药物艾司西酞普兰都可以降低地塞米松或CRH试验反应阳性率,即刺激后ACTH以及皮质醇水平都显著降低,并且具有时间依赖性.动物实验也提示,首先给予动物一定程度的慢性刺激导致出现抑郁样症状,而后给予抗抑郁药物文拉法辛不仅可以逆转由慢性刺激导致的动物HPA功能调节失调,伴随的抑郁症状也得以改善[9].这些研究提示,抗抑郁药物有可能降低刺激DST阳性率,实际上就是恢复HPA 轴的调节功能.有意义的是有些研究虽然不赞同这样的研究结论,但是治疗效果却显示同样结果.KUNZEL等[10]研究发现,在235例抑郁症患者中,无论使用抗抑郁药物与否,也不论使用哪一类抗抑郁药物,只要没有治疗效果,DST/CRH试验都没有变化,相反抗癫痫间药物卡马西平以及有效的药物干预可显著改善DST/CRH试验阳性率,提示抗抑郁药物的有效治疗可改善HPA 轴的调节功能. ...
Venlafaxine reverses decreased proliferation in the subventricular zone in a rat model of early life stress
1
2015
... 20世纪50年代,第一个开发的抗抑郁药是单胺氧化酶抑制药(inhibitors of the monoaminooxidase,MAOIs),因严重不良反应而被三环类抗抑郁药(TCAs)取代,后者成为20世纪50年代至80年代世界范围抑郁症治疗一线用药,被称为典型(传统)抗抑郁药.20世纪90年代以后,世界各国陆续开发一些新品种,按其作用机制分类,有选择性5-羟色胺(5-HT)再摄取抑制药(selective serotonin reuptake inhibitors,SSRI)、选择性5-HT和肾上腺素(noradrenaline ,NE)再摄取抑制药(selective serotonin and noradrenaline reuptake inhibitors,SNRIs)、NE及5-HT抗抑郁药(noradrenergic and specific serotonergic antidepressants,NaSSAs),NE和DA再摄取抑制药(norepinephrine and dopamine reuptake inhibitors,NDRIs)、NE再摄取抑制药(noradrenerine reuptake inhibitor,NaRI ),5-HT拮抗药和再摄取抑制药(serotonin antagonist /reuptake inhibitor,SARI)等[6].BSCHOR等[7]研究发现,伴有单相抑郁30例抑郁症患者,口服抗抑郁药物西酞普兰20 mg·d-1,治疗4周后, DST阳性率下降及CRH刺激促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)明显下降.NIKISCH等[8]研究也发现,无论治疗效果如何,抗抑郁药物艾司西酞普兰都可以降低地塞米松或CRH试验反应阳性率,即刺激后ACTH以及皮质醇水平都显著降低,并且具有时间依赖性.动物实验也提示,首先给予动物一定程度的慢性刺激导致出现抑郁样症状,而后给予抗抑郁药物文拉法辛不仅可以逆转由慢性刺激导致的动物HPA功能调节失调,伴随的抑郁症状也得以改善[9].这些研究提示,抗抑郁药物有可能降低刺激DST阳性率,实际上就是恢复HPA 轴的调节功能.有意义的是有些研究虽然不赞同这样的研究结论,但是治疗效果却显示同样结果.KUNZEL等[10]研究发现,在235例抑郁症患者中,无论使用抗抑郁药物与否,也不论使用哪一类抗抑郁药物,只要没有治疗效果,DST/CRH试验都没有变化,相反抗癫痫间药物卡马西平以及有效的药物干预可显著改善DST/CRH试验阳性率,提示抗抑郁药物的有效治疗可改善HPA 轴的调节功能. ...
Pharmacological and nonpharmacological factors influencing hypothalamic-pituitary-adrenocortical axis reactivity in acutely depressed psychiatric in-patients,measured by the Dex-CRH test
1
2003
... 20世纪50年代,第一个开发的抗抑郁药是单胺氧化酶抑制药(inhibitors of the monoaminooxidase,MAOIs),因严重不良反应而被三环类抗抑郁药(TCAs)取代,后者成为20世纪50年代至80年代世界范围抑郁症治疗一线用药,被称为典型(传统)抗抑郁药.20世纪90年代以后,世界各国陆续开发一些新品种,按其作用机制分类,有选择性5-羟色胺(5-HT)再摄取抑制药(selective serotonin reuptake inhibitors,SSRI)、选择性5-HT和肾上腺素(noradrenaline ,NE)再摄取抑制药(selective serotonin and noradrenaline reuptake inhibitors,SNRIs)、NE及5-HT抗抑郁药(noradrenergic and specific serotonergic antidepressants,NaSSAs),NE和DA再摄取抑制药(norepinephrine and dopamine reuptake inhibitors,NDRIs)、NE再摄取抑制药(noradrenerine reuptake inhibitor,NaRI ),5-HT拮抗药和再摄取抑制药(serotonin antagonist /reuptake inhibitor,SARI)等[6].BSCHOR等[7]研究发现,伴有单相抑郁30例抑郁症患者,口服抗抑郁药物西酞普兰20 mg·d-1,治疗4周后, DST阳性率下降及CRH刺激促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)明显下降.NIKISCH等[8]研究也发现,无论治疗效果如何,抗抑郁药物艾司西酞普兰都可以降低地塞米松或CRH试验反应阳性率,即刺激后ACTH以及皮质醇水平都显著降低,并且具有时间依赖性.动物实验也提示,首先给予动物一定程度的慢性刺激导致出现抑郁样症状,而后给予抗抑郁药物文拉法辛不仅可以逆转由慢性刺激导致的动物HPA功能调节失调,伴随的抑郁症状也得以改善[9].这些研究提示,抗抑郁药物有可能降低刺激DST阳性率,实际上就是恢复HPA 轴的调节功能.有意义的是有些研究虽然不赞同这样的研究结论,但是治疗效果却显示同样结果.KUNZEL等[10]研究发现,在235例抑郁症患者中,无论使用抗抑郁药物与否,也不论使用哪一类抗抑郁药物,只要没有治疗效果,DST/CRH试验都没有变化,相反抗癫痫间药物卡马西平以及有效的药物干预可显著改善DST/CRH试验阳性率,提示抗抑郁药物的有效治疗可改善HPA 轴的调节功能. ...
Combined dexamethasone/corticotropin releasing hormone test predicts treatment response in major depression- a potential biomarker?
Developmental trauma is associated with behavioral hyperarousal,altered HPA axis activity,and decreasedhippocampal neurotrophin expression in the adult rat
Relationship of cortisol levels and genetic polymorphisms to antidepressant response to placebo and fluoxetine in patients with major depressive disorder: a prospective study
Discrimination between patients with melancholic depression and healthy controls: comparison between 24 h cortisol profiles,the DST and the Dex/CRH test
Effects of escitalopram/quetiapine combination therapy versus escitalopram monotherapy on hypothalamic-pituitary-adrenal-axis activity in relation to antidepressant effectiveness
Outcome in delusional depression comparing trimipramine monotherapy with a combination of amitriptyline and haloperidol-a double-blind multicenter trial
Clinical characteristics and treatment outcome in a representative sample of depressed inpatients-findings from the munich antidepressant response signature (MARS) project
, 金卫东
