The impact of transvaginal, mesh-augmented level one apical repair on anorectal dysfunction due to pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the symptom prevalence of anorectal dysfunction (AD) in women with pelvic organ prolapse (POP) and whether symptom improvement can be achieved by pelvic floor surgery. METHODS: Secondary analysis of the Propel Study data from 277 women with POP stage II-IV regarding bothersome AD symptoms, which were assessed using the Pelvic Floor Distress Inventory (PFDI) questionnaire preoperatively, and 6, 12, and 24 months after transvaginal prolapse repair with Elevate anterior and posterior. RESULTS: Prevalence of AD was high in the study cohort (14.4-56.3%) and could be reduced significantly throughout a 2-year follow-up (cure rates 44.3-83.1%). AD symptoms decreased in a similar manner after posterior/apical fixation to the way they did after anterior/apical fixation (e.g., feeling of incomplete bowel emptying 66.7% to 25.5% vs 46.5% to 10.7% respectively). Hemorrhoids and loss of loose stool decreased even more after anterior/apical fixation than after posterior/apical fixation. Even though AD symptoms decreased significantly more in patients with POP stage III-IV, there was still a considerable improvement in patients with POP stage II (e.g., pain when passing stool 31.1 to 7.7% vs 21.4 to 0% respectively). Notably, even symptoms of hemorrhoids and rectal prolapse improved substantially (cure rates 44.2% and 70.1% respectively). CONCLUSIONS: Symptoms of AD were frequent in our study cohort, and they significantly improved after vaginal mesh-augmented sacrospinous prolapse repair with Elevate anterior and posterior throughout the follow-up period. Anterior/apical fixation showed results that were almost as good as those after posterior/apical fixation. Patients with POP stage II experienced considerable symptom improvement, but cure rates were significantly higher in patients with POP stage III-IV. Vaginal mesh-augmented prolapse repair with good apical fixation is efficacious in resolving AD symptoms with low de novo rates in women suffering of POP.

The renin secretion profile under the influence of sleep deprivation and the neuropeptides CRH and GHRH.

It is already known that during normal sleep plasma renin activity (PRA) shows oscillations with decreases during rapid-eye-movement (REM) sleep and increases during non-REM (NREM) sleep. We also know that renin correlates positively with slow-wave sleep (SWS). Sleep deprivation is known to enhance significantly SWS and slow wave activity (SWA, known as δ power). Based on these findings we addressed the question whether and to which extent sleep deprivation may affect the synchronization found between PRA and REM sleep during normal sleep and whether this synchronization is affected by other sleep regulating factors. To investigate these questions we compared sleep EEG and sleep-related free renin levels in 48 normal women and men 19-69 years old between nights before and after 40 h of sleep deprivation. During the recovery night, four bolus injections of either GHRH, CRH or placebo were injected via long catheter around sleep onset. When compared to baseline after each of the treatments SWS, SWA and renin levels increased. The characteristical oscillation profiles of renin during normal sleep were also preserved after sleep deprivation. Similar to normal sleep our data support also a distinct link between nocturnal renin secretion and SWS after sleep deprivation and that independent of the applied treatments.

Sleep after intranasal progesterone vs. zolpidem and placebo in postmenopausal women - A randomized, double-blind cross over study.

CONTEXT: The loss of progesterone during menopause is linked to sleep complaints of the affected women. Previously we demonstrated sleep promoting effects of oral progesterone replacement in postmenopausal women. The oral administration of progesterone, however, is compromised by individual differences in bioavailability and metabolism of the steroid. OBJECTIVE: We compared the sleep-endocrine effects after intranasal progesterone (MPP22), zolpidem and placebo in healthy postmenopausal women. DESIGN: This was a randomized double-blind cross-over study. SETTING: German monocentric study PARTICIPANTS: Participants were 12 healthy postmenopausal women. INTERVENTIONS: Subjects received in randomized order four treatments, 2 doses of intranasal progesterone (4.5 mg and 9 mg of MPP22), 10 mg of zolpidem and placebo. OUTCOME MEASURES: Main outcome were conventional and quantitative sleep-EEG variables. Secondary outcomes were the subjective sleep variables and the sleep related concentrations of cortisol, growth hormone (GH), melatonin and progesterone. RESULTS: Sleep promoting effects were found after the higher dosage of MPP22 and after zolpidem. Zolpidem prompted benzodiazepine-like effects on quantitative sleep EEG as expected, whereas no such changes were found after the two dosages of MP22. Nocturnal progesterone levels increased after 9.0 mg MPP22. No other changes of hormone secretion were found. CONCLUSIONS: Our study shows sleep promoting effects after intranasal progesterone. The spectral signature of intranasal progesterone did not resemble the sleep-EEG alterations induced by GABA active compounds. Progesterone levels were elevated after 9.0 mg MPP22. No other endocrine effects were observed.

Corticotropin-releasing hormone induces depression-like changes of sleep electroencephalogram in healthy women.

We reported previously that repetitive intravenous injections of corticotropin-releasing hormone (CRH) around sleep onset prompt depression-like changes in certain sleep and endocrine activity parameters (e.g. decrease of slow-wave sleep during the second half of the night, blunted growth hormone peak, elevated cortisol concentration during the first half of the night). Furthermore a sexual dimorphism of the sleep-endocrine effects of the hormones growth hormone-releasing hormone and ghrelin was observed. In the present placebo-controlled study we investigated the effect of pulsatile administration of 4×50µg CRH on sleep electroencephalogram (EEG) and nocturnal cortisol and GH concentration in young healthy women. After CRH compared to placebo, intermittent wakefulness increased during the total night and the sleep efficiency index decreased. During the first third of the night, REM sleep and stage 2 sleep increased and sleep stage 3 decreased. Cortisol concentration was elevated throughout the night and during the first and second third of the night. GH secretion remained unchanged. Our data suggest that after CRH some sleep and endocrine activity parameters show also depression-like changes in healthy women. These changes are more distinct in women than in men.

Does Pregnenolone Enhance Exposure Therapy in Obsessive-Compulsive Disorder? - A Pilot, Interim Report of a Randomized, Placebo-Controlled, Double-Blind Study.

Exposure therapy is an effective cognitive-behavioral treatment for patients with obsessive-compulsive disorder (OCD). However, a further amelioration of symptoms by additional drugs that enhance extinction learning is desirable. An interesting candidate is pregnenolone, which positively modulates NMDA and GABAA receptors in preclinical studies and influences amygdala and prefrontal activity in humans. We present pilot data showing high acceptance and good tolerability of pregnenolone given 2 h before exposure sessions in OCD patients. As per our interim analyses, exposure treatment resulted in significantly improved main outcome parameters, but no effects of pregnenolone vs. placebo pretreatment were detectable thus far.

Interferon ß-1a reduces increased interleukin-16 levels in multiple sclerosis patients.

OBJECTIVES: There is convergent evidence for an important role of interleukin-16 (IL-16) in the pathogenesis of multiple sclerosis (MS). IL-16 serves as a chemoattractant for different immune cells that are involved in developing lesions. Here, we compared IL-16 levels of MS patients and controls and addressed the long-term effect of IFN-ß, the most common immunomodulatory MS therapy, on IL-16 serum levels in MS patients over 2 years. Beyond this, we analysed the expression of IL-16 in two CD4(+) T-cell subsets, Th1 and Th17 cells, which are important autoimmune mediators and affected by IFN-ß treatment, derived from myelin-specific T-cell transgenic mice. MATERIALS AND METHODS: IL-16 serum levels of 17 controls and of 16 MS patients before therapy and at months 1, 2, 3, 6, 9, 12 and 24 during IFN-ß1a therapy were determined by ELISA. MRI was performed before therapy, at months 12 and 24. IL-16 expression of in vitro differentiated murine myelin oligodendrocyte glycoprotein (MOG)-specific Th1 and Th17 cells was quantified by real-time PCR. RESULTS: Before therapy, MS patients showed significantly elevated IL-16 levels compared with controls irrespective of disease activity determined by MRI. Therapy with IFN-ß1a led to a significant linear decrease in IL-16 serum levels beginning after 2 months. MOG-specific Th17 cells expressed more IL-16 than Th1 cells. CONCLUSIONS: Reduction in increased IL-16 levels may be of relevance for the therapeutic effect of IFN-ß1a in MS. Easily accessible IL-16 serum levels hold a potential as biomarker of treatment efficacy in MS.

Polymorphisms of the drug transporter gene ABCB1 predict side effects of treatment with cabergoline in patients with PRL adenomas.

INTRODUCTION: Treatment with dopamine agonists in patients with prolactin (PRL) adenomas and Parkinson's disease is associated with central side effects. Central side effects may depend on a substance's ability to pass the blood-brain barrier, which can be actively controlled by transporter molecules such as the P-glycoprotein (P-gp) encoded by the ABCB1 gene. MATERIALS AND METHODS: We aimed to determine whether cabergoline is transported by the P-gp and whether polymorphisms of its encoding ABCB1 gene predict central side effects of cabergoline therapy in patients with PRL adenomas. i) In an experimental mouse model lacking the homologues of the human ABCB1 gene (Abcb1ab double knockout mouse model), we examined whether cabergoline is a substrate of the P-gp using eight mutant and eight wild-type mice. ii) In a human case-control study including 79 patients with PRL adenomas treated with cabergoline at the Max Planck Institute of Psychiatry in Munich, we investigated the association of four selected ABCB1 gene single nucleotide polymorphisms (SNPs) (rs1045642, rs2032582, rs2032583 and rs2235015), with the occurrence of central side effects under cabergoline therapy. RESULTS: i) In the experimental mouse model, we observed that brain concentrations of cabergoline were tenfold higher in the mutant mice compared with their wild-type littermates, implying that cabergoline is indeed a substrate of the transporter P-gp at the blood-brain barrier level. ii) In the human study, we observed significant negative associations under cabergoline for the C-carriers and heterozygous CT individuals of SNP rs1045642 with two central side effects (frequency of fatigue and sleep disorders) and for the G-carriers of SNP rs2032582 with the enhancement of dizziness. For the SNPs rs2235015 and rs2032583, no associations with central side effects under cabergoline were found. DISCUSSION: This is the first study demonstrating that individual ABCB1 gene polymorphisms, reflecting a different expression and function of the P-gp, could predict the occurrence of central side effects under cabergoline. Our findings can be viewed as a step into personalised therapy in PRL adenoma patients.

Endocannabinoids render exploratory behaviour largely independent of the test aversiveness: role of glutamatergic transmission.

To investigate the impact of averseness, controllability and familiarity of a test situation on the involvement of the endocannabinoid system in the regulation of exploratory behaviour, we tested conventional and conditional cannabinoid receptor type 1 (CB1)-deficient mice in behavioural paradigms with different emotional load, which depended on the strength of illumination and the ability of the animals to avoid the light stimulus. Complete CB1 null-mutant mice (Total-CB1-KO) showed an anxiogenic-like phenotype under circumstances where they were able to avoid the bright light such as the elevated plus-maze and the light/dark avoidance task. Conditional mutant mice lacking CB1 expression specifically in cortical glutamatergic neurons (Glu-CB1-KO), in contrast, failed to show a similar phenotype under the same experimental conditions. However, both mutant lines showed increased avoidance of open arm exploration during a second exposure to the elevated plus-maze. If tested in situations where the fear eliciting light could not be avoided, Total-CB1-KO mice showed increased thigmotaxis in an open field, decreased social investigation and decreased novel object exploration under aversive light conditions, but not under non-aversive low light. This time, Glu-CB1-KO also showed decreased exploratory behaviour towards objects and conspecific juveniles and increased thigmotaxis in the open field. Taking into consideration that the behavioural performance of wild-type mice was only marginally affected by changes in light intensities, these data indicate that the endocannabinoid system renders exploratory behaviour largely independent of the test averseness. This process differentially involves endocannabinoid-controlled glutamatergic transmission, depending on the controllability of the test situation.

Progesterone reduces wakefulness in sleep EEG and has no effect on cognition in healthy postmenopausal women.

Sleep is frequently impaired in postmenopausal women. Progesterone prompted benzodiazepine-like effects on sleep EEG in young normal male subjects. Aim of this study was to test if treatment with progesterone improves sleep after menopause. A randomised double blind crossover design study with 2 treatment intervals of 21 days duration separated by a 2 weeks washout was performed. An oral dose of 300 mg micronized progesterone was given each for 21 days. At the beginning and the end of the two intervals a sleep EEG was recorded and cognitive performance was assessed in 10 healthy postmenopausal women (age: 54-70 years). Progesterone treatment led to a decrease of intermittent time spent awake. During the first third of the night rapid eye movement (REM) sleep increased. The spectral analysis of the EEG resulted in no significant differences of the power spectra. Progesterone did not affect cognitive performance. In summary progesterone demonstrated a distinct sleep promoting effect by reduction of time of wake without impairing cognitive functions during daytime. As possible mechanisms of progesterone a GABA-agonistic effect and the regulation of gene expression via the progesterone receptor are discussed. Progesterone might be useful in the treatment of sleep disturbances of postmenopausal women.

Predictors of anterior pituitary insufficiency after traumatic brain injury.

BACKGROUND: Several studies have reported a high prevalence of hypopituitarism after traumatic brain injury (TBI). Risk stratification is a prerequisite for cost-effective hormonal screening of these patients. However, it is still unclear which risk factors predispose patients to develop anterior hypopituitarism after TBI. OBJECTIVE: To assess clinical and radiological risk factors for post-traumatic hypopituitarism. PATIENTS AND METHODS: Seventy-eight consecutive patients (52 men, 26 women; mean age 36.0 years, range 18-65 years) with mild, moderate or severe TBI were studied. Endocrine and clinical parameters were assessed 3 and 12 months after TBI. RESULTS: We found diffuse axonal injury, basal skull fracture and older age to be major risk factors of post-traumatic hypopituitarism. CONCLUSIONS: We have defined specific risk factors for the development of post-traumatic hypopituitarism that are consistent with pathophysiological considerations. These findings might help to identify at-risk patients.

Time of interferon-beta 1a injection and duration of treatment affect clinical side effects and acute changes of plasma hormone and cytokine levels in multiple sclerosis patients.

During initiation of interferon-beta (IFN-beta) therapy, many multiple sclerosis (MS) patients experience systemic side effects which may depend on the time point of IFN-beta injection. We investigated the time course of plasma hormone-, cytokine- and cytokine-receptor concentrations after the first injection of IFN-beta either at 8.00 a.m. (group A) or at 6.00 p.m. (group B) and quantified clinical side effects within the first 9 h in 16 medication free patients with relapsing-remitting MS. This investigation was repeated after 6-month IFN-beta therapy. Plasma ACTH and cortisol concentrations followed their physiological rhythms, with lower levels in the evening compared to the morning, but raised earlier and stronger in group B after IFN-beta administration. IFN-beta injection in the evening led to a prompter increase of plasma IL-6 concentrations and temperature during the first hours and correlated to more intense clinical side effects compared to group A. Plasma IL-10 concentrations increased more in group A compared to group B, but sTNF-RI and sTNF-RII concentrations raised 7 h after IFN-beta injection only in group B. Acute effects on plasma hormone and cytokine concentrations adapted after 6-month IFN-beta treatment, while diurnal variations were still present. Baseline sTNF-RII concentrations were elevated after 6-month IFN-beta therapy only in group A. Our results show that time point of IFN-beta injection has differential effects on acute changes of plasma hormone and cytokine concentrations and is related to systemic side effects. This may have implications on the tolerability and effectiveness of IFN-beta therapy.

Growth hormone-releasing hormone and corticotropin-releasing hormone enhance non-rapid-eye-movement sleep after sleep deprivation.

The neuropeptides growth hormone (GH)-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) regulate sleep and nocturnal hormone secretion in a reciprocal fashion, at least in males. GHRH promotes sleep and GH and inhibits hypothalamo-pituitary-adrenocortical (HPA) hormones. CRH exerts opposite effects. In women, a sexual dimorphism was found because GHRH impairs sleep and stimulates HPA hormones. Sleep deprivation (SD) is the most powerful stimulus for inducing sleep. Studies in rodents show a key role of GHRH in sleep promotion after SD. The effects of GHRH and CRH on sleep-endocrine activity during the recovery night after SD are unknown. We compared sleep EEG, GH, and cortisol secretion between nights before and after 40 h of SD in 48 normal women and men aged 19-67 yr. During the recovery night, GHRH, CRH, or placebo were injected repetitively. After placebo during the recovery night, non-rapid-eye-movement sleep (NREMS) and rapid-eye-movement sleep (REMS) increased and wakefulness decreased compared with the baseline night. After GHRH, the increase of NREMS and the decrease of wakefulness were more distinct than after placebo. Also, after CRH, NREMS increased higher than after placebo, and a positive correlation was found between age and the baseline-related increase of slow-wave sleep. REMS increased after placebo and after GHRH, but not after CRH. EEG spectral analysis showed increases in the lower frequencies and decreases in the higher frequencies during NREMS after each of the treatments. Cortisol and GH did not differ between baseline and recovery nights after placebo. After GHRH, GH increased and cortisol decreased. Cortisol increased after CRH. No sex differences were found in these changes. Our data suggest that GHRH and CRH augment NREMS promotion after SD. Marked differences appear to exist in peptidergic sleep regulation between spontaneous and recovery sleep.

Clinical outcome after trimipramine in patients with delusional depression - a pilot study.

The treatment of delusional depression is a major challenge in psychopharmacology. Hypothalamic-pituitary-adrenocortical (HPA) overdrive may contribute, via increased dopaminergic activity, to the pathophysiology of the disorder. Trimipramine appears to be an interesting potential candidate, since it is an atypical antidepressant that is known to inhibit HPA activity. In a four-week open trial we investigated its effects in 15 inpatients with delusional depression. The dosage was increased within 7 days up to 300 - 400 mg/d and was then maintained for three weeks. Psychometric assessments and safety monitoring were conducted weekly. Assessment of the HPA activity was achieved by a combined dexamethasone suppression/corticotropin-releasing hormone stimulation (Dex/CRH) test before and after four weeks of treatment. Therapeutic response was defined as a decrease in the HAMD-score of at least 50 %. Eight out of 13 completers were rated as responders. Therapeutic response was associated with L, D-trimipramine concentrations higher than 160 ng/ml. Intent-to-treat analysis showed significant improvement in psychometric variables. Despite the high dosage, the substance was generally well tolerated, with the exception of one patient who suffered from a hypotensive reaction. Mean +/- SD concentration of L-trimipramine and D-trimipramine were 138 +/- 61 ng/ml and 119 +/- 50 ng/ml at a final dose of 346 +/- 50 mg/d. The ACTH and cortisol area under the curve in the Dex/CRH tests decreased significantly, reflecting a decrease of activity in the HPA system. We suggest that the clinical use of high-dose trimipramine in delusional depression seems to be a promising treatment strategy.

[Deglutition disorders in neurological patients. A prospective study of diagnosis, pattern of impairment, therapy and outcome]. / Schluckstörungen bei neurologischen Patienten. Eine prospektive Studie zu Diagnostik, Störungsmustern, Therapie und Outcome.

We performed a prospective study on 208 patients with neurogenic dysphagia who were consecutively admitted for swallowing therapy over a 3-year period. The most frequent etiology was stroke (48%). Videofluoroscopic and/or fiber optic endoscopic evaluation of swallowing were performed in 204 patients. Swallowing therapy was comprised of restitution methods, compensation, and adaptation, each of which was applied in more than 80% of the patients. Mean duration of swallowing therapy was 2 months (full oral patients 1 month, patients dependent on tube feeding or tracheostomy 2.5 and 3.5 months, respectively). Fifty-five percent of the patients initially dependent on tube feeding were full oral feeders after swallowing therapy. A target variable reflecting functional feeding status showed significant improvement after swallowing therapy, also in patients with a disease duration of more than half a year, ruling out spontaneous recovery as a sole explanation of amelioration. The following variables were the main contributors to outcome prediction: functional feeding status, Barthel index, duration of disease, and degree of aspiration as shown by endoscopy.

Intravenous C-type natriuretic peptide augments behavioral and endocrine effects of cholecystokinin tetrapeptide in healthy men.

Given the anxiogenic effects of the type-B natriuretic peptide receptor agonist C-type natriuretic peptide (CNP) in rodents, we investigated the influence of CNP pretreatment upon the behavioral and endocrine action of the panicogen cholecystokinin tetrapeptide (CCK-4) in healthy men. In a randomized double-blind balanced design, 20 male volunteers were given an intravenous infusion of 300 microg of CNP vs. placebo followed by 25 microg of CCK-4. The behavior was assessed using panic, anxiety, and dissociation questionaires before the infusion and after the CCK-4 stimulus. Furthermore, the stress-sensitive hormones adrenocorticotropic hormone (ACTH), cortisol, and prolactin were measured. CNP pretreatment enhanced the anxiogenic and prodissociative effects of CCK-4 and significantly augmented the ACTH surge after CCK-4. However, no effect of CNP was seen upon panic symptoms. Our preliminary data support a role of type-B natriuretic peptide receptors in anxiety modulation in normal man.

Increased alpha activity in REM sleep in de novo patients with Parkinson's disease.

We compared the sleep structure including a quantitative electroencephalographic (EEG) analysis and the frequency of periodic limb movements (PLM) in 17 patients with Parkinson's disease (PD; 10 men, seven women, mean age 65.9 years, mean Hoehn and Yahr stage 1.8) who had never been treated with dopaminergic agents (de novo), and 10 healthy controls (six men, four women, mean age 64.5 years). The REM sleep EEG of the PD patients was characterized by a sustained increase in the high-theta/alpha (7.8-10.5 Hz) frequency range during the first one-third (i.e., 11.00 p.m. to 01.40 a.m.) of the night. There was no significant difference in the sleep continuity and sleep architecture as well as in the PLM index between both groups. The analysis of the temporal dynamics of the observed changes suggests a dysregulation of the REM sleep homeostasis in the patients with PD.

Treatment of multiple sclerosis with Copaxone (COP): Elispot assay detects COP-induced interleukin-4 and interferon-gamma response in blood cells.

Copolymer-1 (Copaxone or COP) inhibits experimental allergic encephalomyelitis and has beneficial effects in multiple sclerosis. There is presently no practical in vitro assay for monitoring the immunological effects of COP. We used an automated, computer-assisted enzyme-linked immunoadsorbent spot assay for detecting COP-induced interferon-gamma (IFN-gamma)- and interleukin-4 (IL-4)-producing cells and a standard proliferation assay to assess the immunological response to COP in peripheral blood mononuclear cells from 20 healthy donors, 20 untreated multiple sclerosis patients and 20 COP-treated multiple sclerosis patients. Compared with untreated and healthy controls, COP-treated patients showed (i) a significant reduction of COP-induced proliferation; (ii) a positive IL-4 Elispot response mediated predominantly by CD4 cells after stimulation with a wide range of COP concentrations; and (iii) an elevated IFN-gamma response partially mediated by CD8 cells after stimulation with high COP concentrations. All three effects were COP-specific as they were not observed with the control antigens, tuberculin-purified protein or tetanus toxoid. The COP-induced changes were consistent over time and allowed correct identification of COP-treated and untreated donors in most cases. We propose that these criteria may be helpful to monitor the immunological response to COP in future clinical trials.

Anxiolyticlike effects of atrial natriuretic peptide on cholecystokinin tetrapeptide-induced panic attacks: preliminary findings.

BACKGROUND: Panic attacks induced by administration of cholecystokinin tetrapeptide (CCK-4) have been evaluated as a valuable tool to investigate the neurobiological mechanisms involved in panic anxiety. The rationale to study the effects of natriuretic peptides on the CCK-4 response is derived from observations that atrial natriuretic peptide (ANP) is released during panic attacks in humans and has anxiolyticlike actions in various animal models. METHODS: A double-blind, placebo-controlled design was conducted in 9 patients with panic disorder and 9 similar healthy control subjects. After pretreatment with an infusion of 150 microg of ANP or placebo in random order, each subject received 50 microg of CCK-4. Psychopathological parameters as well as physiological measures were sampled before and after CCK-4 administration. RESULTS: After pretreatment with ANP, the number of CCK-4-induced panic attacks decreased from 8 to 6 in patients and from 5 to 2 in controls. Acute Panic Inventory ratings were significantly reduced in patients after ANP vs placebo pretreatment. Infusion of ANP significantly curtailed the CCK-4-induced release of corticotropin in patients. Heart rate variability analysis indicated a sympathetic stimulation by CCK-4 that was inhibited by ANP in patients and controls. CONCLUSIONS: The present study indicates that ANP exerts anxiolyticlike effects on CCK-4-stimulated anxiety attacks in patients with panic disorder. In addition, ANP produced an inhibition of the hypothalamopituitary-adrenocortical system and sympatholytic effects.

Neither major depression nor glucocorticoid treatment affects the cellular integrity of the human hippocampus.

In major depression, decreased hippocampal volume has been attributed to hypercortisolemia, a frequent sign of the disorder, because in animals an excess of corticosteroids has led to dendritic atrophy, astrogliosis and loss of neurons in this brain region. The present study is the first to investigate the structural integrity of the human hippocampus in major depression and following glucocorticoid treatment. Post-mortem hippocampal tissue from 15 patients who had had major depression or bipolar affective disorder, 10 patients who had been treated with glucocorticoids and 16 controls was assessed using haematoxylin-eosin, Nissl and Bodian staining. The patterns of reactive astrogliosis (glial fibrillary acidic protein, GFAP), synaptic density (synaptophysin), synaptic reorganization (growth-associated protein B-50) and early signs of Alzheimer's disease (Alz-50) were examined immunocytochemically. Multivariate analysis, with the patients' age, tissue fixation time and postmortem delay as covariates, was performed. There was no evidence of neuronal cell loss or other major morphological alterations in any of the groups, nor was there a significant change in the distribution pattern of synaptophysin or Alz-50. Changes in B-50 and GFAP staining were observed in the steroid-treated and depressed patients in areas CA1 and CA2 only. The human hippocampus in major depression and after glucocorticoid treatment does not reveal any major morphological changes or signs of neuronal cell death, but does show subtle alterations in B-50 and GFAP expression in selected parts of the pyramidal cell layer.