Psychoneuroendocrinology of depression. Hypothalamic-pituitary-adrenal axis

We present a new approach to cardiovascular analysis based on a well-known signal processing technique, namely, the frequency subband decomposition. The subbands are chosen in accordance with physiological standards: (1) 0-0.04 Hz, (2) 0.04-0.15 Hz, (3) 0.15-0.4 Hz. It is shown that such a pre-processing drastically improves the accuracy of the analysis and introduces a new direction in the understanding of the relationships between cardiovascular signals.     

Hypothalamic-pituitary-adrenal axis activity in depressive illness. Its relationship to classification

Serum cortisol response to the 1-mg overnight dexamethasone suppression test was studied in 221 depressed patients and 109 nondepressed psychiatric controls. Nonsuppression distinguished patients with primary unipolar depression (65/146) from patients with secondary unipolar depression (0/42) and nondepressed controls (0/109). Furthermore, nonsuppression distinguished the three familial subtypes of primary unipolar depressive illness: familial pure depressive disease (FPDD; 38/50 patients), sporadic depressive disease (SDD; 24/55 patients), and depression spectrum disease (3/41 patients). Moderate elevations in baseline serum cortisol levels were found in FPDD, SDD, and bipolar depression. Medication did not affect the results. The data suggest that the depressive syndrome is composed of separate illnesses, each of which has a distinctive pattern of hypothalamic-pituitary-adrenal axis activity during the depressed state as well as a specific clinical and familial psychiatric history.     

Hypothalamic-pituitary-adrenal axis activity in the inbred Brown Norway and Fischer 344 rat strains

We have examined the basal and the stress-induced secretion of corticosterone in relation to the expression of adrenal steroid receptors in the pituitary, hypothalamus and hippocampus of the inbred Brown Norway and Fischer 344 rat strains. Our data indicated that plasma transcortin and integrated plasma corticosterone levels were significantly higher in Fischer 344 compared to Brown Norway rats. Fischer 344 hypersecrete corticosterone during the dark phase of the diurnal cycle and during the phase of recovery following a 20 min period of restraint stress compared to Brown Norway rats. This hypersecretion of corticosterone was negatively correlated with the size of the adrenal gland but might be related to the higher density of mineralocorticoid receptors in the hippocampus of Fischer 344 rats.     

Hypothalamic-pituitary-adrenal axis suppression and inhaled corticosteroid therapy. 1. General principles

The safety of long-term inhaled corticosteroid therapy at commonly prescribed doses is an issue of growing concern to physicians and international regulatory bodies. This is so because long-term use of these drugs has become the mainstay of chronic asthma management and their introduction now is widely recommended in official treatment guidelines at the 'mild persistent' stage of asthma, where regular daily therapy is first begun. In addition to more frequent use of inhaled corticosteroids, there is a further trend to use higher doses of existing inhaler therapies and to use the newer and more potent compounds that have recently become available. At the same time as these developments have been taking place, there has not been a concurrent move to a more rigorous examination of the safety profile of these inhaled corticosteroid treatments - especially to assess their effects on the hypothalamic-pituitary-adrenal (HPA) axis. Most safety data with respect to HPA axis effects have been derived from testing methods that are limited in their ability to detect HPA system impairment and, more seriously, that can give the impression of functional integrity in the HPA axis when there may be moderate (or even greater) impairment. In this first part of a two-part review of the HPA axis effects of inhaled corticosteroids and of how these effects should be assessed, we examine the currently used and the currently available testing methodologies and also review the present state of knowledge concerning the structure and function of the HPA axis and the effects of its suppression. It is clear that there are state-of-the-art tests to assess in a discriminating manner the safety profile of inhaled corticosteroids. These tests have been insufficiently employed, including during the drug development process, yet they are readily available, relatively inexpensive and can detect adrenal suppression before the appearance of clinical effects. In part 2 of this review we examine what can be learned about the effects of inhaled corticosteroid therapy on the HPA axis from the limited amount of reliable published information from clinical and pharmacological studies describing their use and safety.     

Hypothalamic-pituitary-adrenal axis function and platelet serotonin concentrations in depressed patients

Plasma cortisol and platelet serotonin (5-hydroxytryptamine, 5-HT) concentrations were determined in 39 male psychotic and 39 male non-psychotic depressed inpatients, and in 69 male healthy control subjects. Psychotic or non-psychotic depressed patients had higher predexamethasone plasma cortisol levels than found in the control group. After the dexamethasone suppression test (DST), psychotic and non-psychotic depressed patients were subdivided into suppressors and non-suppressors. Psychotic and non-psychotic patients had significantly different platelet 5-HT concentrations among themselves and compared with the control group. However, there was no significant correlation between plasma cortisol levels and platelet 5-HT concentrations. Dexamethasone administration did not affect platelet 5-HT concentrations within subtypes of depressed patients. Abnormal cortisol suppression after the DST occurred more frequently in psychotic than in non-psychotic patients. Platelet 5-HT and plasma cortisol concentrations were decreased in patients with pronounced suicidal behaviour. Our results suggest that plasma cortisol and platelet 5-HT concentrations might serve as independent biological markers for different subtypes of depression.     

Hypothalamic-pituitary-adrenal axis function and prolactin secretion in systemic lupus erythematosus

Continued improvement in the computer price-to-performance ratio and the adoption of international standards have enhanced the feasibility of completely digital echocardiographic laboratories that were initially described more than a decade ago. Digital archival has distinct advantages over analog recording, including improved laboratory efficiency, capability of side-by-side comparison of current and historical studies, streamlined image storage, and enhanced interinstitution image transfer. Studies have demonstrated that clinical and electronic image compression allows efficient storage of data, without affecting diagnostic accuracy. Finally, digital echocardiography has important telemedicine applications.     

Hypothalamic-pituitary-adrenal axis in abdominal obesity: effects of dexfenfluramine

BACKGROUND AND OBJECTIVE: Minimal conization with carbon dioxide laser (CO2) for safe diagnosis and treatment of cervical intraepithelial neoplasia (CIN) 1-3 has been utilized for 15 years. To evaluate the results of 15 years' follow-up. STUDY DESIGN/MATERIALS AND METHODS: Clinical prospective study: 2,903 non-pregnant women whose cervicovaginal smear revealed CIN 1-3, confirmed by colposcopy, were referred for minimal conization treatment (LMC). This outpatient free-hand excision is performed under local anesthesia with a 60-W continuous laser beam focused to a 0.1-mm spot size, giving a power density of 165,000 W/cm2. Adjuvant cervical curettage is done routinely. RESULTS: Complications after the procedure were insignificant. Histopathological investigations revealed invasive carcinoma in 1.2% of the minicones. The primary cure rate was 96.1%. In the life table analysis of the patients the cumulative risk of recurrence for all forms of CIN was 0.89% at year 5, 1.36% at year 10, and 3.02% at year 15. There was no sudden onset carcinoma during the follow-up period. CONCLUSION: Minimal conization is a safe, effective treatment for CIN and early forms of microinvasive carcinoma. Invasive carcinoma can be detected early and should be treated without delay. The cumulative risk of developing new CIN is 3.02% at year 15 and there is no risk of sudden-onset invasive carcinoma following this procedure.     

Three- to 5-year prospective follow-up of outcome in major depression

STUDY OBJECTIVES: Recurrent chylothorax as a complication of lymphoma has had unsatisfactory outcomes. Serial thoracentesis, tube thoracostomy, and pleurodesis via chest tube have been ineffective and compromise the nutritional and immune status of the patient. Medical thoracoscopic talc pleurodesis has been safe and effective in the treatment of some other varieties of recurrent pleural effusions. Our objective was to investigate the safety and efficacy of medical thoracoscopic talc pleurodesis in the palliation of chylothorax related to lymphoma. DESIGN: This is a report of 24 hemithoraces treated in 19 consecutive patients with lymphoma-related chylothorax, failing chemotherapy or radiation therapy. The average patient age was 55 years. INTERVENTIONS: Medical thoracoscopy was performed under local anesthesia and conscious sedation in a bronchoscopy suite. Sedation included midazolam (mean dose, 6 mg; range, 2-14 mg) with either meperidine (mean dose, 94 mg; range 25-140 mg), or morphine (mean dose, 18 mg; range 4-40 mg). Pleurodesis was performed with insufflation of sterile asbestos-free talc, (4-8 g). After pleurodesis, chest tubes were placed, with the mean duration of chest tube placement being 4 days, range 3 to 10 days. RESULTS: One patient died a few days after the procedure due to causes related to the primary disease process. Follow-up was for at least 90 days following the procedure. Patients were assessed at 30, 60, and 90 days following the procedure. At each of these endpoints, all patients remaining alive were without recurrence of pleural effusions, which was confirmed by chest radiography. Eight patients in the series died of the effects of their malignancy during the 90-day evaluation interval. Complications included medication reactions in two patients (8.3%) and ARDS in one patient (4.1%). CONCLUSION: Many patients with lymphoma-related chylothorax are refractory to chemotherapy and/or radiation therapy. In this group, medical thoracoscopic talc pleurodesis has an acceptable complication rate and a 100% success rate in the prevention of recurrence of pleural effusions at 30, 60, and 90 days following the procedure.     

Hypothalamic-pituitary-adrenal axis suppression and inhaled corticosteroid therapy. 2. Review of the literature

In order to overcome the need for secondary intervention to remove metallic osteosynthesis devices after fracture healing, endeavours have been directed towards developing resorbable osteosynthesis materials during the last decade. The resorbable material must fulfil a number of basic demands. For example, an adequate holding strength of these materials is essential for undisturbed fracture union, complete resorption after bone healing, good histocompatibility without any damage to the surrounding tissues and without detrimental distant effects within the organism. Suggested materials are primarily high-polymerlactic acid or glycolic acid compounds. In particular, research was concentrated on the enhancement of the mechanical properties and biodegradation of polylactides. Debris high in crystallin was found to be responsible for late soft tissue reactions. To achieve disintegration products with lower crystallin content stereocopolymeres of lactic acids are preferred nowadays. Based on our experimental work, another osteosynthesis system manufactured from autoclaved allogenic bone tissue was developed as an alternative. This has osteoconductive properties and converts by creeping substitution into bone. In contrast to metallic plates and screws, the modulus of elasticity is quite similar to vital bone tissue. The initial strength enables its use in the field of maxillofacial surgery.     

Biological markers, treatment outcome, and 1-year follow-up in endogenous depression: Electroencephalographic sleep studies and response to cognitive therapy.

Although there are now considerable data attesting to the efficacy of several forms of treatment for depression, there is surprisingly little information to guide the selection of the treatment most likely to benefit a given patient. Biologic markers of depression have received much attention for their potential to provide theoretically and clinically meaningful subgroups for specific treatments. The relationship between EEG sleep disturbances, treatment outcome, and 1-yr follow-up was examined for a sample of 53 patients with endogenous major depression receiving cognitive-behavioral therapy. Overall, there was little support for the prediction of a difference in short- or long-term outcome between patients with and without EEG sleep disturbances. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The hypothalamic-pituitary-thyroid axis in major depression

We investigated the capacity of several thyroid-axis measures to distinguish between depressed and control subjects and determined whether these variables were related to antidepressant treatment response. We studied 105 subjects who fulfilled the DSM-III-R criteria for a current major depressive episode and 41 volunteers with no current mental disorder. The following thyroid-axis variables were measured: difference between T4 levels at 09.00 hours and 13.00 hours; baseline TSH; maximal TSH response to 400 micrograms TRH (delta max TSH); and presence of a blunted delta max TSH. The T4 difference variable alone distinguished between depressed and control subjects. In multivariate analyses, T4 difference and delta max TSH were independently related to antidepressant-treatment outcome, and predicted a modest proportion (14%) of the variance in outcome. The relationship between these two variables and treatment outcome was particularly strong in depressed male subjects who were receiving desipramine, for whom they accounted for 36% of the variance in treatment outcome. The T4 difference variable both distinguished between depressed and control subjects and was related to treatment outcome. Although this finding requires replication, it is consistent with other reports of the usefulness of thyroid-axis indices measured at different times of day in depressed patients.     

Neuropsychological outcome at 1-year post head injury.

Neuropsychological outcome at 1 year postinjury was examined prospectively in representative groups of 4–6 adult head-injured participants and 121 general-trauma control participants. A comprehensive battery of neuropsychological measures was administered. The head-injured group performed significantly worse than the trauma controls on most measures (p?     

Social support predict 5-year outcome in 1st-episode schizophrenia.

Investigations of social support in schizophrenia have been relatively sparse. In this research, patients with 1st-episode schizophrenia or affective psychosis were asked to describe supportive social relationships immediately prior to their 1st lifetime treatment contact and were interviewed 18 months and 5 years later for assessment of their social and occupational functioning. The results indicated that 18-month adaptive functioning was lower than in the year prior to 1st treatment contact but at 5 years rose above that seen both at baseline and 18 months. Moreover, social support from nonfamily members of the social network predicted 5-year adaptive functioning in the schizophrenia (n?=?54) group but not in the affective psychosis (n?=?55) group. Support from family did not predict 5-year outcome in either group. Together, these findings replicate and extend earlier findings that social support predicts outcome in 1st-episode schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychoneuroendocrinology of depression. Hypothalamic-pituitary-gonadal axis

Women are more susceptible than men to depression, particularly during periods of rapid fluctuation of gonadal hormones, such as premenstrually, postpartum, and during the climacteric. This review summarizes the evidence for the association of depression with abnormalities in reproductive hormones. Although there are similarities in stress hormones changes between depressed women and women with stress-related amenorrhea, no abnormalities in LH activity have been documented in depression. Similarly no abnormalities in LH, estradiol, or progesterone have been documented in premenstrual syndrome (PMS), although complete elimination of monthly cycling with leuprolide improves mood. Some studies have suggested beneficial effects of estrogen on mood in postmenopausal women but as yet there have been no adequately controlled studies of estrogen treatment of either premenopausal or postmenopausal women.     

Hypothalamic-pituitary-adrenal axis function in patients with active rheumatoid arthritis: a controlled study using insulin hypoglycemia stress test and prolactin stimulation

OBJECTIVE: To study the response of cortisol and of prolactin (PRL) to specific stimuli in rheumatoid arthritis (RA). METHODS: We measured the response of cortisol to insulin induced hypoglycemia and of PRL to thyrotropin releasing hormone (TRH) in 10 patients with active RA and in 10 paired control subjects. All were women with regular menstrual cycles. They had never received corticosteroids before the study. The PRL concentration was assessed by chemiluminescence immune assay and the cortisol concentration by radioimmunoassay. RESULTS: The basal serum levels of cortisol (14.47+/-2.5 microg/dl) and PRL (10.1+/-1.3 ng/ml) in the RA group were not significantly different from those of the control group (12.3+/-1.1 microg/dl and 13.7+/-2.4 ng/ml, respectively). The peak value of cortisol after hypoglycemia was comparable in both groups (25.5+/-2.4 microg/dl in RA vs. 26.0+/-1.5 ng/ml in controls). The integrated cortisol response to hypoglycemia expressed as area under the response curve (AUC) did not differ significantly in either group (1927+/-196 in RA vs. 1828+/-84 in controls). The interval-specific "delta" cortisol response was significantly higher for the 30 to 45 min interval in controls compared to patients with RA (9.8+/-0.9 microg/dl vs. 6.1+/-1.1 microg/dl; p = 0.02). The peak of PRL after TRH did not differ significantly in both groups (56.4+/-6.4 ng/ml in RA vs. 66.3+/-7.7 ng/ml in controls) and the AUC of PRL secretion after TRH was comparable in both groups (3245+/-321 vs. 4128+/-541). CONCLUSION: Our findings suggest that active RA is associated with subtle dysfunction of the hypothalamic-pituitary-adrenal glucocorticoid function and normal PRL secretion.     

The impact of posttraumatic seizures on 1-year neuropsychological and psychosocial outcome of head injury

This study examined the relationship of posttraumatic seizures and head injury severity to neuropsychological performance and psychosocial functioning in 210 adults who were prospectively followed and assessed 1 year after moderate to severe traumatic head injury. Eighteen percent (n = 38) of the patients experienced 1 or more late seizures (i.e., seizures occurring 8 or more days posttrauma) by the time of the 1-year followup. As expected, the head injured patients who experienced late posttraumatic seizures were those with the most severe head injuries, and they were significantly more impaired on the neuropsychological and psychosocial measures compared to those who remained seizure free. However, after the effects of head injury severity were controlled, there were no significant differences in neuropsychological and psychosocial outcome at 1 year as a function of having seizures. These findings suggest that worse outcomes in patients who develop posttraumatic seizures up to 1 year posttrauma largely reflect the effects of the brain injuries that cause seizures, rather than the effect of seizures.     

Tumour progression and survival in patients with T1G3 bladder tumours: 15-year outcome

OBJECTIVE: To evaluate tumour progression and survival of patients with T1G3 bladder tumours who were followed for 15 years. PATIENTS AND METHODS: A subset of 48 patients with T1G3 bladder tumours was entered into a randomized trial of transurethral resection (TUR) or TUR plus bacille Calmette-Guèrin (BCG) therapy and followed for a minimum of 15 years. Thirty-nine (81%) patients received one or more courses of BCG. The endpoints of the study were stage progression (defined as muscle invasion of metastasis) and disease-specific survival. RESULTS: Of the 48 patients, 25 (52%) progressed and 15 (31%) died from the disease; 33 patients (69%) survived, including 24 (50%) with an intact bladder. The median progression-free survival time was 151 months. Tumour progression occurred in 35% of the patients within the first 5 years, in 16% after 5-10 years and in 12% of those followed for 10-15 years. Deaths from cancer occurred in 25% of the patients in the first 5 years and in 10% of patients at risk from 5 to 15 years. CONCLUSIONS: Patients with T1G3 bladder tumours who are treated conservatively are at life-long risk of having a muscle-invasive tumour and dying from bladder cancer.     

Co-morbid depression and drinking outcome in those with alcohol dependence

We report the efficacy of oral clarithromycin and inhaled beclomethasone against severe bronchorrhea in a patient with alveolar cell carcinoma. A 54-year-old man produced about 500 to 900 ml of clear and egg-white-like sputum each day. Anti-cancer chemotherapy and erythromycin therapy did not reduce the volume of sputum. After administration of clarithromycin and inhaled beclomethasone, sputum volume decreased to about 300 nl each day and the patient's ability to perform daily activities improved. Two months later, clarithromycin was stopped and the patient was treated with inhaled beclomethasone alone. Sputum volume did not increase for 6 months, although the chestroentgenographic findings gradually worsened. Then the sputum volume gradually increased. Five months after the sputum volume began to increase, he was producing about 2 liters of sputum each day and died of respiratory failure. Although the levels of CA 19-9, SLX, and CEA in serum were all within the normal range, the sputum contained high levels of CA 19-9 (1,133,620 U/ml), SLX (3,000 U/ml), and CEA (283 ng/ml). In patients with bronchorrhea, measurement of tumor markers in sputum may be useful for the diagnosis of alveolar cell carcinoma.     

Hyperactivity of hypothalamic pituitary axis in neonatal clomipramine model of depression

This study examined the integrity of hypothalamic-pituitary-adrenal (HPA) axis in clomipramine model of depression. Male rat pups were treated twice daily from postnatal day 5 to 21 with clomipramine (15 mg/kg, s.c.). At three months of age, serum corticosterone level was estimated before and after dexamethasone (100 microg/kg, s.c.) administration and after subjected to REM sleep deprivation (RSD) for 4 days consecutively. Data indicated enhanced baseline corticosterone levels and nonsuppression to dexamethasone in clomipramine treated rats. The corticosterone levels however, reversed to the levels of control group in rats subjected to RSD. These findings thus indicated for the first time an HPA hyperactivity in rats treated with clomipramine during neonatal period and are in harmony with cholinergic hypersensitivity reported earlier in this model of depression.     

Coping style and depression level influence outcome in in vitro fertilization

OBJECTIVE: To examine the influence of depression levels and coping on IVF outcome in women, taking into account the cause of infertility. DESIGN: Prospective clinical study. SETTING: A university hospital. PATIENT(S): Ninety-eight women undergoing IVF treatment. INTERVENTION(S): Psychometric tests were administered at the first visit (day 3) of the investigated treatment cycle. MAIN OUTCOME MEASURE(S): Achievement of pregnancy. RESULTS: The nonpregnant group reported increased expression of negative emotions. In the subgroup with a female indication for IVF, increased depressive symptomatology (correlated with increased expression of negative emotions) was associated with lower pregnancy rates (PRs), whereas in the subgroup with a male indication for IVF, increased depressive symptomatology (correlated with decreased expression of negative emotions) was associated with higher PRs. CONCLUSION(S): Expression of negative emotions predicts depression levels and outcome in IVF. The cause of infertility should be taken into account when investigating the relation between psychologic functioning and outcome in IVF.