***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 
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    ***EXAMPLES*** 
    Input: An altered function of the hypothalamic-pituitary-adrenal axis is assumed to be characteristic for Posttraumatic Stress Disorder ( PTSD ) , although there is inconsistent empirical evidence . Only few studies examined the awakening cortisol response and a daytime profile in PTSD .  Salivary cortisol levels were measured at seven intervals from awakening until 8 PM in trauma-exposed subjects with ( N=29 ) and without PTSD ( N=19 ) and in 15 non-exposed controls . While the three groups did not differ with respect to their first cortisol level immediately after awakening , the expected cortisol increase to awakening 15 - 60 min later was significantly lower in PTSD patients compared to non-PTSD subjects and healthy controls . This effect remained stable when trauma-exposed subjects with comorbid major depression were excluded from the analysis . A significant negative correlation between the overall cortisol secretion ( AUC(G ) ) and overall PTSD symptomatology and hyper-arousal symptoms was found . The findings are discussed in light of the hypothesis of a counterregulation of hyper-arousal symptoms and chronic stress in PTSD Subjects at their first psychotic episode show an enlarged volume of the pituitary gl and , but whether this is due to hypothalamic – pituitary – adrenal ( HPA ) axis hyperactivity , or to stimulation of the prolactin-secreting cells by antipsychotic treatment , is unclear . We measured pituitary volume , using 1.5-mm , coronal , 1.5 T , high-resolution MRI images , in 78 patients at the first psychotic episode and 78 age- and gender-matched healthy controls . In all , 18 patients were antipsychotic-free ( 12 of these were antipsychotic-naïve ) , 26 were receiving atypical antipsychotics , and 33 were receiving typical antipsychotics .  As hypothesized , patients had a larger pituitary volume than controls ( + 22 % , p<0.001 ) . When divided by antipsychotic treatment , and compared to controls , the pituitary volume was 15 % larger in antipsychotic-free patients ( p=0.028 ) , 17 % larger in patients receiving atypicals ( p=0.01 ) , and 30 % larger in patients receiving typicals ( p<0.001 ) . Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together ( + 11 % , p=0.08 ) . When divided by diagnosis , and compared to controls , the pituitary volume was 24 % larger in patients with schizophrenia/schizophreniform disorder ( n=40 , p<0.001 ) , 19 % larger in depressed patients ( n=13 , p=0.022 ) , 16 % larger in bipolar patients ( n=16 , p=0.037 ) , and 12 % larger in those with other psychoses ( n=9 , p=0.2 ) . In conclusion , the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presence of antipsychotic treatment , and this could be due to activation of the HPA axis . Typical antipsychotics exert an additional enlarging effect on pituitary volume , likely to be related to activation of prolactin-secreting cells . This activation of the hormonal stress response could participate to the important metabolic abnormalities observed in patients with psychosis OBJECTIVES Higher rates of dexamethasone test ( DST ) nonsuppression in schizophrenia have been attributed to depressive symptoms , suicidality and negative symptoms . No study concerning first-episode schizophrenia has yet been published . DESIGN In patients hospitalised for the first time with first-episode schizophrenia the DST has been performed before , at the end of the acute treatment and after one year . At the same time the clinical evaluation with PANSS was performed . A cortisol value > 5 microgram/dl in either of the postdexamethasone sample s indicated nonsuppression of cortisol . RESULTS A total of 56 males were included . 18 % of pts were DST nonsuppressors at medication-free baseline , 5 % and 16 % after acute treatment and after one year respectively . After 1 year 42/56 of patients fulfilled the criteria of remission . The rate of nonsuppression was 21.4 % , 5 % and 16.4 % in remitters and 7 % , 7 % and 14.3 % in nonremitters . Significant differences in the whole group were found between postdexamethasone cortisolemia at discharge on the one h and and on admission and at the one-year follow-up on the other . Significant correlations were observed between postdexamethasone cortisolemia and negative symptoms at the end of acute treatment . MAIN FINDINGS In first-episode schizophrenia the short-term treatment led to a decrease in cortisolemia and rates of nonsuppression and an increase at a one-year follow-up . CONCLUSIONS Rates of DST nonsuppression in schizophrenia including first-episode schizophrenia are influenced by the stage of illness and medication status . The impairment of feedback regulation of cortisol secretion may be related to different biopathogenetic mechanisms depending on the phase of the illness Rationale Increased activity of the hypothalamic – pituitary – adrenal ( HPA ) axis is an important aspect of the pathophysiology of major depression and schizophrenia . Despite the usefulness of atypical antipsychotics in the treatment of depression and their positive influence on cognitive functioning possibly related to their impact on cortisol , little is known about their effect on HPA axis function . Objective Therefore , this double-blind , placebo-controlled , r and omized cross-over study investigated the influence of the atypical antipsychotics quetiapine and olanzapine in comparison with haloperidol and placebo on plasma adrenocorticotropic hormone ( ACTH ) , cortisol , and prolactin levels .  Eleven healthy male volunteers were studied during four sessions one week apart , orally receiving placebo , quetiapine ( 50 mg ) , olanzapine ( 5 mg ) , or haloperidol ( 3 mg ) . Blood sample s were taken at hourly intervals from 0900 until 1700 hours . For ACTH , cortisol , and prolactin a significant effect of treatment condition ( p≤0.005 ; p≤0.035 ; p≤0.0001 , respectively ) for area under the curve ( AUC ) was found . In comparison to placebo , quetiapine and olanzapine significantly reduced ACTH ( p≤0.002 ; p≤0.05 , respectively ) and cortisol ( p≤0.005 ; p≤0.03 , respectively ) . No effect of haloperidol on AUC of ACTH or cortisol levels was observed . In comparison with placebo , haloperidol ( p≤0.0001 ) and olanzapine ( p≤0.0001 ) elevated AUC of prolactin plasma levels , whereas no significant effect was observed for quetiapine as a main effect of treatment condition . The atypical antipsychotics ’ strong influence on HPA-function with pronounced ACTH and cortisol lowering is possibly related to the atypicals ’ blockade of serotonergic receptors , but blockade of adrenergic or histaminergic receptors may play a role as well . The observed HPA-axis down-regulation may be clinical ly important for the atypicals ’ effects on depressive symptomatology and cognitive functioning BACKGROUND An early response to antipsychotic treatment in patients with psychosis has been associated with a better course and outcome . However , factors that predict treatment response are not well understood . The onset of schizophrenia and related disorders has been associated with increased levels of stress and hyper-activation of the hypothalamic-pituitary-adrenal ( HPA ) axis . This study examined whether pituitary volume at the onset of psychosis may be a potential predictor of early treatment response in first-episode psychosis ( FEP ) patients . METHODS We investigated the relationship between baseline pituitary volume and symptomatic treatment response over 12 weeks using mixed model analysis in a sample of 42 drug-naïve or early treated FEP patients who participated in a controlled dose-finding study of quetiapine fumarate . Logistic regression was used to examine predictors of treatment response . Pituitary volume was measured from magnetic resonance imaging scans that were obtained upon entry into the trial . RESULTS Larger pituitary volume was associated with less improvement in overall psychotic symptoms ( Brief Psychiatric Rating Scale ( BPRS ) P=0.031 ) and positive symptoms ( BPRS positive symptom subscale P=0.010 ) . Regardless of gender , patients with a pituitary volume at the 25th percentile ( 413 mm(3 ) ) were approximately three times more likely to respond to treatment by week 12 than those at the 75th percentile ( 635 mm(3 ) ) ( odds ratio=3.07 , CI : 0.90 - 10.48 ) . CONCLUSION The association of baseline pituitary volumes with early treatment response highlights the importance of the HPA axis in emerging psychosis . Potential implication s for treatment strategies in early psychosis are discussed The bilateral communication between the immune and neuroendocrine systems plays an essential role in modulating the adequate response of the hypothalamic – pituitary – adrenal ( HPA ) axis to the stimulatory influence of cytokines and stress-related mediators . Growing evidence suggests that neuro-immune-endocrine crosstalk may be impaired in schizophrenia . We determined the relationship between cortisol , cytokines interleukin-2 ( IL-2 ) and interleukin-6 ( IL-6 ) , and symptoms in schizophrenia during treatment with typical and atypical antipsychotic drugs . Subjects included 30 healthy controls ( HC ) and 78 schizophrenic ( SCH ) in- patients . SCH were r and omly assigned to 12-week treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol using a double-blind design . Clinical efficacy was determined using the Positive and Negative Syndrome Scale ( PANSS ) . Serum cortisol and IL-2 levels were assayed by radioimmunometric assay , and serum IL-6 levels by quantitative enzyme-linked immunosorbent assay . Following a 2-week washout period , serum levels of cortisol , IL-2 , and IL-6 were increased in patients with schizophrenia compared to HC . Elevations in cortisol were associated with increase in both IL-2 and IL-6 in SCH . Moreover , elevations in cortisol were associated with negative symptoms and IL-2 with positive symptoms . In all , 12 weeks of risperidone treatment significantly decreased elevated cortisol and improved negative symptoms , but produced similar effects on IL-2 and IL-6 as well as on positive symptoms compared to haloperidol . The improvement of negative symptoms was related to the change in cortisol . Our results suggest that the imbalance in the HPA axis and cytokine system in patients with SCH is implicated in clinical symptoms , and is improved with atypical antipsychotic treatment Dynamic testing of the hypothalamic-pituitary-adrenal axis in schizophrenia has yielded conflicting results , which may be related to patient selection and previous exposure to psychotropic medication . The objective of this study was to determine the pattern of corticotropin ( ACTH ) and cortisol release in response to metoclopramide ( a dopamine antagonist ) , which appears to be unique in its ability to release vasopressin ( AVP ) , in drug naive patients with schizophrenia experiencing their first episode of psychosis . In this study , we examined AVP , ACTH and cortisol release in response to metoclopramide in 10 drug-naive , first-episode male patients with a DSM IV diagnosis of paranoid schizophrenia and compared them to healthy control subjects matched for age , sex and smoking status . Patients , as compared to controls had higher levels of baseline plasma cortisol ( 375.5+/-47.4/l vs. 273.8+/-42.2 nmol/l , respectively ; t=2.48 , df=9 , p < 0.02 ) and plasma ACTH ( 14.9+/-0.85 vs. 11.3+/-0.57 pg/ml , respectively ; t=4.29 , df=9 , p<0.001 ) . AVP levels were lower in patients though this did not reach statistical significance ( 0.89+/-0.09 vs. 1.3+/-0.08 pmol/l , respectively ; t=1.97 , df=9 , p<0.07 ) . A repeated measures 2-way ANOVA to compare responses to metoclopramide over time between the two groups yielded a significant group by time interaction for cortisol ( F=11.3 , df=6 , 108 , p<0.001 ) and ACTH ( F=15.65 , df=6 , 108 , p<0.002 ) . Post hoc Tukey 's test revealed significant differences between the two groups at + 30 , + 45 , + 60 , + 90 and + 120 min for cortisol ( p<0.01 ) and at + 30 , + 45 , + 60 and + 90 min for ACTH ( 
    Output:
    
Findings from these studies support the presence of HPA axis hyperactivity and a blunted HPA axis response to stress at the onset of psychosis .