***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The dexamethasone suppression test ( DST ) and the depressive attributional style question naire ( ASQ ) were administered to 105 depressed patients prior to participation in a double-blind outpatient study and to 29 normal controls . The depressed patients were classified into three groups ( 1 ) met criteria for both research diagnostic criteria for definite endogenous depression and DSM III melancholia ; ( 2 ) met criteria for neither , and ( 3 ) met criteria for one but not both . The group that met criteria for both RDC endogenous depression and DSM-III melancholia had a statistically greater frequency of abnormal DST versus the group that met neither criteria and the normal controls . With regard to ASQ , patients who met both criteria had statistically higher bad event internality scores but statistically lower bad event stability and globality scores as opposed to the group that met neither criteria . In general , normal controls had significantly lower bad event ASQ scores than the three depressive groups . There was no correlation between ASQ and DST , as both DST suppressors and nonsuppressors had similar ASQ scores and there was no correlation between ASQ bad event attributions and initial severity of depression BACKGROUND People with severe depressive illness have raised levels of cortisol and reduced glucocorticoid receptor function . AIMS To obtain a physiological assessment of hypothalamic-pituitary-adrenal ( HPA ) axis feedback status in an in-patient sample with depression and to relate this to prospect ively determined severe treatment resistance . METHOD The prednisolone suppression test was administered to 45 in- patients with depression assessed as resistant to two or more antidepressants and to 46 controls , prior to intensive multimodal in-patient treatment . RESULTS The patient group had higher cortisol levels than controls , although the percentage suppression of cortisol output after prednisolone in comparison with placebo did not differ . Non-response to in-patient treatment was predicted by a more dysfunctional HPA axis ( higher cortisol levels post-prednisolone and lower percentage suppression ) . CONCLUSIONS In patients with severe depression , HPA axis activity is reset at a higher level , although feedback remains intact . However , prospect ively determined severe treatment resistance is associated with an impaired feedback response to combined glucocorticoid and mineralocorticoid receptor activation by prednisolone Depressed patients have reduced glucocorticoid receptor ( GR ) function , as demonstrated by resistance to the suppressive effects of the synthetic glucocorticoid hormone , and GR agonist , dexamethasone . We have developed a suppressive test with prednisolone , a synthetic glucocorticoid that is similar to cortisol in its pharmacodynamics and pharmacokinetics , and binds to both the GR and the mineralocorticoid receptor ( MR ) . We have found that depressed patients suppress normally to prednisolone , unless they are particularly non-responsive to treatment . In the present study , we evaluated 28 in patients with treatment-resistant depression ( TRD ) , and compared salivary cortisol secretion ( at 0900 h , 1200 h and 1700 h ) after placebo or after prednisolone ( 5 mg ) , before and after an inpatient treatment admission . Half of the patients ( n=14 ) reached treatment response . When comparing the assessment between admission and discharge , cortisol output after placebo fell ( -26 % of area under the curve ; p=0.024 ) while the output after prednisolone did not change . Moreover , there was no change in the response to prednisolone ( percentage suppression ) between admission at discharge , and this was not influenced by treatment response . Finally , we could confirm and extend our previously published data with prednisolone ( 5 mg ) , showing that depressed patients ( n=12 ) and controls ( n=12 ) suppressed equally to both 5 and 10 mg doses of prednisolone . This study suggests that the response to prednisolone  is similar in depressed patients and controls at different doses of prednisolone , and does not change with symptomatic improvement . This is in contrast with findings , from us and others , using other measures of hypothalamic-pituitary-adrenal axis function , such as basal cortisol levels or the response to dexamethasone . Thus , we propose that the prednisolone suppression test may offer specific biological and clinical information , related to its action at both the GR and the MR INTRODUCTION The serotonin-1A ( 5-HT1A ) receptor subtypes are considered as targets of a variety of antidepressant drugs . Previous studies have suggested different adaptive changes in pre- and post-synaptic 5-HT receptors in the brain after treatment with non-selective tricyclic antidepressants ( TCA ) and selective 5-HT re-uptake inhibitors ( SSRIs ) . The present study aim ed to investigate the adaptive effect of the TCA imipramine on the post-synaptic 5-HT1A receptor function in the hypothalamus . METHODS A longitudinal design was used in 14 patients with major depressive disorder ( DSM-IV ) with endogenous features ( Newcastle Scale ) in order to assess the functional status of post-synaptic 5-HT1A receptors before and after successful antidepressant treatment with imipramine . The effect of the 5-HT1A receptor agonist , buspirone , on ACTH , cortisol , and prolactine ( PRL ) plasma levels was used to assess the functional status of hypothalamic 5-HT1A receptors . A group of 15 concurrent normal subjects were used as control . RESULTS Endogenous depressed patients in remission and currently receiving treatment with imipramine ( mean length of treatment 145 days , SD=27 ) presented significantly lower buspirone responses to ACTH and cortisol than in the pre-treatment condition ( Deltamax p < or = .05 ; AUC p<.001 ) and to ACTH in comparison with healthy controls ( Deltamax p<.01 ; AUC p<.05 ) . No significant differences were found between the post-treatment and pre-treatment PRL responses , or between patients in both conditions and controls ; nevertheless , the PRL response in patients in remission and receiving treatment almost reached the values seen in controls . CONCLUSIONS This study extends previous findings from our group using the SSRI citalopram as an antidepressant . Imipramine and citalopram induce similar changes in the endocrine response to buspirone in depressed patients . As the direction of change in ACTH-cortisol and PRL responses after treatment is the opposite , we can not substantiate increases or decreases in the sensitivity of post-synaptic 5-HT1A receptors in the hypothalamus by long-term imipramine treatment and /or resolution of illness . Therefore , the hormonal changes may result from different or multiples unknown mechanisms Both stress-system activation and melancholic depression are characterized by fear , constricted affect , stereotyped thinking , and similar changes in autonomic and neuroendocrine function . Because norepinephrine ( NE ) and corticotropin-releasing hormone ( CRH ) can produce these physiological and behavioral changes , we measured the cerebrospinal fluid ( CSF ) levels each hour for 30 consecutive hours in controls and in patients with melancholic depression .  Plasma adrenocorticotropic hormone ( ACTH ) and cortisol levels were obtained every 30 min . Depressed patients had significantly higher CSF NE and plasma cortisol levels that were increased around the clock . Diurnal variations in CSF NE and plasma cortisol levels were virtually superimposable and positively correlated with each other in both patients and controls . Despite their hypercortisolism , depressed patients had normal levels of plasma ACTH and CSF CRH . However , plasma ACTH and CSF CRH levels in depressed patients were inappropriately high , considering the degree of their hypercortisolism . In contrast to the significant negative correlation between plasma cortisol and CSF CRH levels seen in controls , patients with depression showed no statistical relationship between these parameters . These data indicate that persistent stress-system dysfunction in melancholic depression is independent of the conscious stress of the disorder . These data also suggest mutually reinforcing bidirectional links between a central hypernoradrenergic state and the hyperfunctioning of specific central CRH pathways that each are driven and sustained by hypercortisolism . We postulate that alpha-noradrenergic blockade , CRH antagonists , and treatment with antiglucocorticoids  may act at different loci , alone or in combination , in the treatment of major depression with melancholic features Rationale Patients with major depression show hypothalamic – pituitary – adrenal ( HPA ) axis hyperactivity , but the mechanisms underlying this abnormality are still unclear . Objectives We have compared two synthetic glucorticoids , dexamethasone and prednisolone , in their ability to suppress the hypothalamic – pituitary – adrenal ( HPA ) axis in depressed patients .  Dexamethasone probes glucocorticoid receptor ( GR ) function , while prednisolone probes both GR and mineralocorticoid receptor ( MR ) function . Material s and methods We used a single-blind , repeated-measure design . We administered placebo , prednisolone ( 5 mg ) or dexamethasone ( 0.5 mg ) , at 22:00 , to 18 severe , treatment-resistant depressed in patients ( 15 of them with a history of childhood trauma ) and 14 healthy volunteers . On the following days , we collected salivary cortisol from 9:00 to 22:00 . Results Depressed patients had higher salivary cortisol levels compared with controls , at baseline and after both prednisolone and dexamethasone ( p<0.001 ) . Consistent with previous studies , depressed in patients showed impaired suppression by dexamethasone :  based on the analysis of the areas under the curve ( AUCs ) , suppression by  dexamethasone ( 0.5 mg ) was −85 % in controls vs −46 % in depressed patients ( p=0.018 ) . However , the same depressed patients showed normal suppression  by prednisolone ( 5 mg ) : suppression was −41 % in controls and −36 % in depressed patients ( p=0.6 ) . Conclusions We suggest that the additional effects of prednisolone on the MR explain the different responses to these glucocorticoids in the same depressed patients BACKGROUND Depression , a clinical ly heterogeneous syndrome , may also be etiologically heterogeneous . Using a prospect i ve , epidemiologic , and genetically informative sample of adult female twins , we identify and vali date a typology of depressive syndromes . METHODS Latent class analysis was applied to 14 disaggregated DSM-III-R symptoms for major depression reported over the last year by members of 1029 female-female twin pairs . RESULTS Seven classes were identified , of which 3 represented clinical ly significant depressive syndromes : ( 1 ) mild typical depression , ( 2 ) atypical depression , and ( 3 ) severe typical depression . Severe typical depression was characterized by comorbid anxiety and panic , long episodes , impairment , and help seeking . Atypical depression was similar in severity to mild typical depression , but was characterized by increased eating , hypersomnia , frequent , relatively short episodes , and a proclivity to obesity . Individuals with recurrent episodes tended to have the same syndrome on each occasion . The members of twin pairs concordant for depression had the same depressive syndrome more often than expected by chance and this resemblance was greater in monozygotic than in dizygotic pairs . CONCLUSION In an epidemiologic sample of female twins , depression is not etiologically homogeneous , but is instead made up of several syndromes that are at least partially distinct from a clinical , longitudinal , and familial/genetic perspective We summarise a series of studies using a MAOI to help establish the validity of a subgroup of depressives referred to as atypical depressives . Patients with reactive mood meeting DSM-III criteria for depressive illness who had associated atypical features ( which include hyperphagia , hypersomnolence , leaden paralysis , and rejection sensitivity ) were r and omised to imipramine , phenelzine and placebo . Non-responders were crossed over , and in all there were over 400 patient trials .  Phenelzine consistently was found to be superior to imipramine . Only in trials which included patients lacking atypical ,  vegetative symptoms  was imipramine found to equal phenelzine . We conclude that the research er and the clinician should consider the relevance of the atypical depressive syndrome Depression may be associated with a hypofunction of central serotonergic systems . The prolactin response to fenfluramine , an indicator of serotonergic activity , has been reported to be blunted in depressed patients compared to controls . It has also been suggested that blunting is more likely in melancholic depression . Baseline cortisol , prolactin and tryptophan availability have also been suggested to affect this response . Forty-eight men and 61 women with a major depressive episode , and who were drug free , and 20 healthy control men underwent clinical evaluation and fenfluramine challenge with dl-fenfluramine 1 mg/kg . When baseline variables were covaried , there was no difference in prolactin response to fenfluramine between males with depression and age-matched controls . Amongst all the depressed patients , body mass index showed a significant association with prolactin response to fenfluramine . There was an interaction between baseline cortisol and DSM-III-R melancholic subtype of depression whereby non-melancholic patients appeared more likely to increase prolactin response to fenfl 
    Output:
    
Detailed analysis of the method ologies used in the studies revealed significant variability especially regarding the sample s ' definition comparing the HPA axis activity of melancholic patients to atypical depression , including healthy controls .
While the majority of studies did confirm the association between melancholic depression and increased post-challenge cortisol levels , the association with increases in basal cortisol and basal ACTH were less consistent .
In conclusion , our findings indicate that there is a difference in the activity of the HPA-axis between melancholic and atypical depressive subtypes .
However , these are more likely explained by hypercortisolism in melancholia ; and most often normal than decreased function in atypical depression .