***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: Alterations in basal cortisol secretion and feedback sensitivity are reported in aging . However , it is not known whether these hypothalamus-pituitary-adrenal ( HPA ) axis alterations are related to structural brain changes . This study was design ed to investigate these relationships in the human . Nine young ( 24.0 ± 1.2 years ; mean ± SE ; range : 19–30 ) and 11 older ( 69.0 ± 1.8 years ; range : 59–76 ) men , in addition to having st and ardized magnetic resonance imaging of their brains , were given 0.5 mg/kg cortisol or placebo intravenously in a double-blind , crossover study . As expected , older men had significantly smaller volumes for all brain regions . Although the groups did not differ in baseline HPA axis activity , there were significant and specific relationships between the brain volumes and the baseline measures of HPA activity . Namely , for young and older subjects combined and after controlling for age and cerebral vault size , hippocampal volumes were inversely associated with 24-hour urinary cortisol and basal corticotropin ( ACTH ) levels , and the anterior cingulate gyrus volume was negatively correlated with baseline ACTH . Elderly subjects had a slower decrease in ACTH levels ( percent of baseline level ) during the first 30 min after cortisol administration . However , no associations were observed between the ACTH feedback indices and any brain measure . This report , although based on a small number of subjects , supports previous studies showing a blunted ACTH fast feedback during normal aging . Hippocampal atrophy appears to be related to increased basal measures of HPA axis activity , but not to fast ACTH feedback . It remains possible that age-associated changes in fast feedback may be related to changes to other brain sites , such as hypothalamus or pituitary 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 Background In this study the predictive value of the combined dexamethasone/CRH test ( DEX/CRH test ) for acute antidepressant response was investigated . Methodology /Principal Findings In 114 depressed in patients suffering from unipolar or bipolar depression ( sample 1 ) the DEX/CRH test was performed at admission and shortly before discharge . During their stay in the hospital patients received different antidepressant treatment regimens . At admission , the rate of nonsuppression ( basal cortisol levels > 75.3 nmol/l ) was 24.6 % and was not related to the later therapeutic response . Moreover , 45 out of 114 ( 39.5 % ) patients showed an enhancement of HPA axis function at discharge in spite of clinical improvement . In a second sample , 40 depressed patients were treated either with reboxetine or mirtazapine for 5 weeks . The DEX/CRH test was performed before , after 1 week , and after 5 weeks of pharmacotherapy . Attenuation of HPA axis activity after 1 week was associated with a more pronounced alleviation of depressive symptoms after 5-week mirtazapine treatment , whereas downregulation of HPA system activity after 5 weeks was related to clinical response to reboxetine . However , early improvement of HPA axis dysregulation was not necessarily followed by a beneficial treatment outcome . Conclusions / Significance Taken together , performance of a single DEX/CRH test does not predict the therapeutic response . The best predictor for response seems to be an early attenuation of HPA axis activity within 1 or 2 weeks . However , early improvement of HPA system dysfunction is not a sufficient condition for a favourable response . Since a substantial part of depressive patients display a persistence of HPA axis hyperactivity at discharge , downregulation of HPA system function is not a necessary condition for acute clinical improvement either . Our data underline the importance of HPA axis dysregulation for treatment outcome in major depression , although restoration of HPA system dysfunction seems to be neither a necessary nor a sufficient determinant for acute treatment response CONTEXT Results of experimental studies suggest that neuroplastic changes may occur during depressive episodes . These effects have not been confirmed in patients with depression , to our knowledge . OBJECTIVE To examine changes in the brains of patients with major depression vs those of healthy control subjects . DESIGN Prospect i ve longitudinal 3-year study . SETTING In patients with major depression were recruited from the Department of Psychiatry and Psychotherapy , Ludwig Maximilians University of Munich , Munich , Germany , and controls were recruited from the local community . PARTICIPANTS The study included 38 patients with major depression and 30 healthy controls . MAIN OUTCOME MEASURES High-resolution magnetic resonance imaging was performed at baseline and 3 years later . Voxel-based morphometric measurements were estimated from magnetic resonance images , and psychopathologic findings were assessed at baseline , weekly during the inpatient phase , and then after 1 , 2 , and 3 years . RESULTS Compared with controls , patients showed significantly more decline in gray matter density of the hippocampus , anterior cingulum , left amygdala , and right dorsomedial prefrontal cortex . Patients who remitted during the 3-year period had less volume decline than nonremitted patients in the left hippocampus , left anterior cingulum , left dorsomedial prefrontal cortex , and bilaterally in the dorsolateral prefrontal cortex . CONCLUSION This study supports findings from animal studies of neuroplastic stress-related processes that occur in the hippocampus , amygdala , dorsomedial prefrontal cortex , dorsolateral prefrontal cortex , and anterior cingulum during depressive episodes BACKGROUND A proposed explanation for memory impairments in posttraumatic stress disorder ( PTSD ) is stress-induced hippocampal damage due to elevated cortisol levels . We have previously reported smaller hippocampi in police officers with PTSD . In this study , we examined changes in and associations between cortisol , learning , memory , attention , and hippocampal volume in PTSD . METHODS In a case-matched control study , 12 police officers with PTSD and 12 traumatized police officers without lifetime PTSD were examined with magnetic resonance imaging ( for hippocampal volume ) , salivary cortisol tests , and neurocognitive assessment s. RESULTS Significantly smaller hippocampi and higher early morning salivary cortisol levels were found in PTSD . Subjects with PTSD performed worse on a delayed visual memory recall task at trend level , and made more perseverations and intrusions on a verbal memory task . Negative correlations were found between PTSD symptom severity and immediate recall function , and between re-experiencing symptoms and left hippocampal volume . A positive correlation was found between salivary cortisol level in early morning and right hippocampal volume ; however , hippocampal volume did not correlate with memory . CONCLUSIONS Smaller hippocampi , higher cortisol levels , and memory impairments were associated with PTSD but were not directly correlated to one another . Memory impairments in PTSD do not seem to be a direct consequence of hippocampal size BACKGROUND The hippocampal formation is damaged early in Alzheimer 's disease ( AD ) . An association between temporal lobe volume and cognitive function has been shown in several studies . Increased limbic-hypothalamic-pituitary-adrenal ( LHPA ) axis function has been suggested to be related to hippocampal atrophy and cognitive impairment . Our hypothesis was that there is a clear link between hippocampal volume -- notably of the CA1 region -- memory ( episodic and visuospatial ) and decreased feedback sensitivity in the LHPA axis in AD . METHODS Sixteen medication-free out patients with mild to moderate AD were included .  Hippocampal  volume was measured with magnetic resonance imaging . Dexamethasone suppression tests were performed using .5 mg and .25 mg dexamethasone . Three different components in the neuropsychological battery -- Rey 15 item memory test , Alzheimer 's Disease Assessment Scale ( ADAS ) word recall and spatial span from Wechsler Adult Intelligence Scale - Revised neuropsychological instrument ( WAIS-R NI ) -- were found to represent episodic and visuospatial memory . RESULTS Low hippocampal CA1 volume and high post-dexamethasone cortisol levels in combination were significantly associated with Rey 15 item memory and spatial span test outcomes . No association was found between LHPA feedback and hippocampal volume . CONCLUSIONS Low hippocampal volume and a disturbed negative feedback in the LHPA axis link to specific cognitive impairments in Alzheimer 's disease Abstract Rationale : Corticosteroids are elevated in certain neuropsychiatric disorders and this may contribute to the neuropsychological impairments reported in these disorders . Objective : To examine the effects of hydrocortisone on learning , memory and executive function . Methods : Hydrocortisone 20 mg was administered twice daily for 10 days to normal male volunteers in a r and omized , placebo control , crossover , within-subject design . Learning , memory and executive function were measured using selected subtests from the Cambridge Neuropsychological Test Automated Battery . Results : Hydrocortisone caused impairments of visuo-spatial memory . These included increased within search errors and impaired use of strategies on the spatial working memory subtest . In addition , administration of hydrocortisone was associated with more errors in the paired associate learning subtest , although no effect was found on the Tower of London .  Hydrocortisone  speeded response latencies in certain tests ( pattern and spatial recognition memory ) . Conclusion : These results indicate that chronic administration of hydrocortisone leads to deficits in certain tests of cognitive function sensitive to frontal lobe dysfunction and may contribute to the cognitive impairment reported in certain neuropsychiatric disorders BACKGROUND Depression has been linked to stress , memory deficits , and hypercortisolemia . However , the relationships between depression , hippocampal structure and function , and cortisol levels are unclear and the effects of antidepressant treatment on the measures are not well studied . METHODS Whole hippocampal volume , performance on verbal and visual declarative memory function and cortisol status was evaluated in 38 subjects with major depressive disorder ( MDD ) and 33 healthy subjects . All measures were repeated in a subgroup ( n = 22 ) of depressed patients after successful selective serotonin reuptake inhibitor ( SSRI ) treatment . RESULTS Hippocampal volume was not significantly different between patients with untreated MMD and healthy subjects , after controlling for whole brain volume , age and gender . However , depressed subjects had significantly greater deficits in delayed memory and percent retention on the verbal portion of the Wechsler Memory Scale-Revised ( WMS-R ) compared with healthy subjects , without significant differences in visual memory , attention , vigilance , or distractibility . Baseline plasma or urinary free cortisol ( UFC ) was not related to either hippocampal volume or memory deficits . Successful treatment with antidepressants did not change hippocampal volume but did result in a significant improvement in memory function and a reduction in UFC excretion . CONCLUSIONS Medication-free nonelderly depressed out patients without alcohol dependence or adverse experiences in childhood had normal hippocampal volume . Focal declarative memory deficits in depression supported localized hippocampal dysfunction in depressed patients . Treatment with antidepressants significantly improved memory and depression but did not alter hippocampal volume , suggesting that antidepressants may improve hippocampal function in the absence of detectable structural changes In the present article , we report on two studies performed in young human population s which tested the cognitive impact of glucocorticoids ( GC ) in situations of decreased or increased ratio of mineralocorticoid ( MR ) and glucocorticoid ( GR ) receptor occupation . In the first study , we used a hormone replacement protocol in which we pharmacologically decreased cortisol levels by administration of metyrapone and then restored baseline cortisol levels by a subsequent hydrocortisone replacement treatment .  Memory function was tested after each pharmacological manipulation . We observed that metyrapone treatment significantly impaired delayed recall , while hydrocortisone replacement restored performance at placebo level . In the second study , we took advantage of the circadian variation of circulating levels in cortisol and tested the impact of a bolus injection of 35 mg of hydrocortisone in the late afternoon , at a time of very low cortisol concentrations . In a previous study with young normal controls , we injected a similar dose of hydrocortisone in the morning , at the time of the circadian peak , and reported detrimental effects of GC on cognitive function . Here , when we injected a similar dose of hydrocort 
    Output:
    
There is evidence that prenatal stress and childhood maltreatment is associated with an abnormally developing HPA system , as well as hippocampal volume reduction .
Smaller hippocampal volumes are associated with increased cortisol secretion during the day .
While there is evidence that early life maltreatment results in structural hippocampal changes and these are in turn more prominent in subjects with higher continuous cortisol secretion it is less clear which role early life maltreatment plays in HPA axis alteration