Kai Österberg

High incidence of mental disorders, reduced mental well-being and cognitive function in hypopituitary women with GH deficiency treated for pituitary disease

objective Previous studies have shown possible neuroendocrine effects of GH. In the present study we investigated the incidence of mental disorders and the prevalence of mental distress and cognitive dysfunction in hypopituitary women with untreated GH deficiency compared to population‐based controls.

Cognitive performance in patients with burnout, in relation to diurnal salivary cortisol.

This study investigated cognitive performance in patients with burnout, in relation to the flexibility of the hypothalamic–pituitary–adrenal (HPA) axis. Clinical cases with work stress-induced burnout (n = 65), and demographically matched, healthy reference subjects (n = 65), were given six neuropsychological tests and a self-rating scale for cognitive problems. Diurnal salivary cortisol was measured among burnout cases and an external reference group (n = 174), including a dexamethasone suppression test (DST) among burnout cases. Compared with referents, the burnout group under-performed in a cognitive speed test (Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol), but not in any other test of sustained attention, episodic memory, or vocabulary. Burnout cases had considerably more subjective cognitive problems, but ratings were unrelated to test performance. Compared with referents, burnout cases had similar morning salivary cortisol levels and similar awakening response, but lower evening cortisol. Among burnout cases, lower diurnal cortisol variability was related to slower performance in several tests. The DST response showed no consistent relationship with any cognitive parameter. Hence, despite considerable subjective cognitive problems, the burnout group showed only a partial, mild deviation in cognitive performance. A flatter diurnal cortisol profile was related to lower cognitive processing speed, but diurnal cortisol pattern and DST response were normal, suggesting a maintained HPA axis flexibility.

Cardiovascular and cortisol reactivity and habituation to a virtual reality version of the Trier Social Stress Test: A pilot study

The Trier Social Stress Test (TSST) is a widely used protocol to induce stress in laboratory settings. Briefly, in the TSST, the test participant is asked to hold a speech and to do an arithmetic task in front of an audience. In the present pilot study, we examined endocrine and autonomic reactivity and habituation to repeated stress provocations using a virtual reality (VR) version of TSST. The VR system was a CAVE™ system with three rear projected walls (4 m×3 m), and one floor projection. The system also included a head tracking system and passive stereoscopy. The virtual audience consisted of one woman, and two men. Ten healthy men, mean age 28.3 years (24-38 years), were confronted with the test twice (1 week between sessions), during which salivary cortisol, heart rate (HR), high frequency heart rate variability (HF-HRV, parasympathetic activity), and T-wave amplitude (TWA, suggested to be related to sympathetic influence on myocardial performance) were assessed. Cortisol secretion showed a marked increase (88% vs. baseline) during the first stress provocation, but habituated in the second session. The magnitude of HR and TWA reactivity during stress provocation was approximately the same at both sessions, implying a stable increase in sympathetic activity. Heart rate showed a maximum increase of 40% at the first session, and 32% at the second. TWA showed a maximum decrease of 42% at the first session, and 39% at the second. The results resemble those obtained in prior studies using the real-life TSST. If these results can be replicated with larger samples, VR technology may be used as a simple and standardized tool for social stress induction in experimental settings.

Seasonal Variation in Human Salivary Cortisol Concentration

Measurement of cortisol concentration can contribute important information about an individuals ability to adjust to various environmental demands of both physical and psychosocial origin. However, one uncertainty that affects the possibilities of correctly interpreting and designing field studies is the lack of observations of the impact of seasonal changes on cortisol excretion. For this reason, the month‐to‐month changes in diurnal cortisol concentration, the awakening cortisol response (ACR), maximum morning concentration, and fall during the day were studied in a group of 24 healthy men and women 32 to 61 yrs of age engaged in active work. On one workday for 12 consecutive months, participants collected saliva at four time points for determination of cortisol: at awakening, +30 min, +8 h, and at 21:00 h. Data were analyzed by a repeated measures design with month (12 levels) and time‐of‐day (4 levels) as categorical predictors. Cortisol concentrations were analyzed on a log scale. The diurnal pattern of cortisol was similar across months (interaction between month and time of day: p>0.4). The main effects of month and time‐of‐day were statistically significant (p <0.001). Highest concentrations were observed in February, March, and April, and lowest concentrations were observed in July and August. There were no statistically significant effects in any of the other measures, or between men and women. In conclusion, a seasonal variation in salivary cortisol concentrations was detected in an occupationally active population. Thus, seasonal variation needs to be taken into account when designing and evaluating field studies and interventions and when making comparisons across studies.

Return to work after a workplace-oriented intervention for patients on sick-leave for burnout - a prospective controlled study

BackgroundIn the present study the effect of a workplace-oriented intervention for persons on long-term sick leave for clinical burnout, aimed at facilitating return to work (RTW) by job-person match through patient-supervisor communication, was evaluated. We hypothesised that the intervention group would show a more successful RTW than a control group.MethodsIn a prospective controlled study, subjects were identified by the regional social insurance office 2-6 months after the first day on sick leave. The intervention group (n = 74) was compared to a control group who had declined participation, being matched by length of sick leave (n = 74). The RTW was followed up, using sick-listing register data, until 1.5 years after the time of intervention.ResultsThere was a linear increase of RTW in the intervention group during the 1.5-year follow-up period, and 89% of subjects had returned to work to some extent at the end of the follow-up period. The increase in RTW in the control group came to a halt after six months, and only 73% had returned to work to some extent at the end of the 1.5-year follow-up.ConclusionsWe conclude that the present study demonstrated an improvement of long-term RTW after a workplace-oriented intervention for patients on long-term sick leave due to burnout.Trial registrationCurrent Controlled Trials NCT01039168.

Personality, mental distress, and subjective health complaints among persons with environmental annoyance

The aim of this study was to assess possible early determinants of idiopathic environmental intolerance (IEI), contributing to an integrated model for the development of IEI. Questionnaires concerning personality traits, current mental distress, subjective health complaints, work load and satisfaction, and options for recovery, were given to 84 persons from the general population attributing annoyance to (i) chemicals/smells (smell-annoyed (SA) n= 29); (ii) electrical equipment (electrically annoyed (EA) n= 16); and (iii) both smells and electricity (generally annoyed (GA) n= 39), but otherwise healthy and in active work. Compared to referents (n= 54), the EA and GA groups showed strongly elevated scores on 5/6 scales within the trait anxiety/neuroticism personality dimension, while the SA group had a slight elevation on only one anxiety scale. Current mental distress and subjective health complaints scores were generally elevated in the EA and GA groups, but only partially in the SA group. Higher proportions of the EA, GA, and SA groups reported low satisfaction with their work situation, including more frequent fatigue after work and a higher, and often unfulfilled, need for recovery. The findings suggest that trait anxiety is prominent already at prodromal stages of IEI, possibly indicating that trait anxiety facilitates the acquisition of attribution of health complaints to environmental factors.

EUROQUEST—A Questionnaire for Solvent Related Symptoms: Factor Structure, Item Analysis and Predictive Validity

The study evaluates the factor structure and predictive validity of the symptom questionnaire EUROQUEST (EQ) that had been developed with the goal of simplifying the evaluation of health effects associated with long-term solvent exposure. The EQ was added to the normal evaluation procedures for 118 male patients with suspected solvent-induced toxic encephalopathy (TE) referred to seven Swedish clinics of occupational medicine during an 18-month period. EQ was also completed by 239 males from a random sample of 400 Swedish males aged 25-64 years selected from the general population and a sample of 559 occupationally active male spray painters aged 25-64 years. Factor and item analyses of EQ responses were performed. Ordinary least square regression analysis was used to evaluate sensitivity and correlation to evaluate the specificity of EQ and the separate components. Questions concerning memory and concentration symptoms alone showed better sensitivity than the other five EQ dimensions singly or combined for the entire EQ and for a subset of questions approximating Q16, a widely used organic solvent symptom screening questionnaire. However, the diagnosis of TE required information in addition to exposure and responses to EQ and Q16-like questions. The results indicate that the subset of EQ questions concerning memory and concentration might replace the more cumbersome EQ and less sensitive Q16 in screening for TE, although none of the screening instruments alone replaces current clinical diagnostic procedures.

Cardiovascular Risk, Cardiac Function, Physical Activity, and Quality of Life with and without Long-Term Growth Hormone Therapy in Adult Survivors of Childhood Acute Lymphoblastic Leukemia

CONTEXT Long-term data are missing in GH-treated acute lymphoblastic leukemia (ALL) patients. GH therapy may result in poorer outcome regarding cardiovascular (CV) and particularly cardiac effects than in patients with hypothalamic-pituitary disease. OBJECTIVE Our objective was to evaluate GH therapy on CV risk, cardiac function, physical activity, and quality of life in ALL patients treated with cranial radiotherapy (18-24 Gy) and chemotherapy (anthracycline dose 120 mg/m2). DESIGN AND SETTING We conducted a 5- and 8-yr open nonrandomized prospective study in a university hospital clinic. STUDY PARTICIPANTS Two groups of GH-deficient ALL patients (aged 25 yr; range 19-32 yr) and matched population controls participated. INTERVENTIONS One ALL group (n=16) received GH for 5 yr, and the other ALL group (n=13) did not receive GH therapy. MAIN OUTCOME MEASURES We evaluated the prevalence of CV risk factors and metabolic syndrome (International Diabetes Federation consensus), cardiac function (echocardiography), and quality of life and physical activity questionnaires. RESULTS In comparison with 8 yr without, 5 yr with GH therapy resulted in significant positive changes in plasma glucose (-0.5 vs. 0.6 mmol/liter, P=0.002), apolipoprotein B/apolipoprotein A1 ratio (-0.1 vs. 0.0, P=0.03), and high-density lipoprotein-cholesterol (0.20 vs.-0.01 mmol/liter, P=0.008) and a significant reduction in the prevalence of metabolic syndrome (P=0.008). No significant difference in the left-ventricular systolic function or in physical activity and quality of life was recorded before and after 5 or 8 yr, respectively (all P>0.3). CONCLUSION GH therapy reduced the CV risk in this young ALL population but resulted in no clear benefit or deterioration in cardiac function.

Hypothalamic Involvement Predicts Cognitive Performance and Psychosocial Health in Long-term Survivors of Childhood Craniopharyngioma

CONTEXT Hypothalamic damage caused by craniopharyngioma (CP) is associated with poor functional outcome. OBJECTIVE To assess cognitive function and quality of life in childhood-onset CP on hormonal replacement, including GH treatment. DESIGN A cross-sectional study with a median follow-up time of 20 years (1-40). SETTING Patients were recruited from the South Medical Region of Sweden. PARTICIPANTS The study included 42 patients (20 women) surgically treated for a childhood-onset CP between 1958 and 2000. Patients were aged ≥17 years. Equally many controls, matched for age, sex, residence, and smoking habits, were included. Tumor growth into the third ventricle was found in 25 patients. MAIN OUTCOME MEASURES All subjects were examined with a battery of cognitive tests and the following questionnaires: Symptom Checklist-90, the Interview Schedule for Social Interaction, and the Social Network concept. RESULTS The CP patients had lower cognitive performance, reaching statistical significance in 12 of 20 test variables, including executive function and memory. Comparison of patients with tumor growth into the third ventricle to controls revealed a significant lower mean total score (P = .006). A significant negative correlation was recorded between mean z-score of cognitive performance and years since operation (r = -0.407; P = .014). No statistically significant group differences were observed across any of the 9 Symptom Checklist-90 subscales. CONCLUSIONS Adults with childhood-onset CP, on hormone replacement, including GH treatment, have memory defects, disturbed attention, and impaired processing speed. Patients with hypothalamic involvement are more affected. Patients rated their quality of life as good as their matched controls.

Effects of lifestyle factors on concentrations of salivary cortisol in healthy individuals

Objective. Salivary cortisol is widely used in occupational health research. However, many ordinary daily activities can influence the concentrations of cortisol and the interpretation of field studies. The aim of the present study was to evaluate the effect of lifestyle factors on salivary cortisol in everyday settings. Material and methods. Healthy employees participated in one or more sub‐studies on the effect of eating a vegetable salad versus protein‐rich mid‐day meal (n = 40), drinking coffee and smoking (n = 12), drinking alcohol (n = 32), awakening at different times (n = 29) and exercising (n = 21). Cortisol in saliva was measured by radioimmunoassay (RIA). Results. When eating a mid‐day meal, salivary cortisol was increased by 10 % (CI −1 % to 24 %) 1 h after eating compared to before eating in the case of both types of meal. Salivary cortisol increased by 80 % (CI 9 % to 199 %) after exercising compared to before exercise. The relative awakening response was approximately 100 % when using an alarm clock on both work‐days and days off. However, the awakening response was 39 % (CI 10 % to 75 %) on a day off with spontaneous awakening. No effects of alcohol, coffee or smoking were observed. Discussion. In field studies, the biological variation in salivary cortisol may be reduced by restricting physical exercise and in collecting pre‐meal samples. However, the protein content of food and moderate consumption of alcohol had no effect on concentrations of cortisol. Differences in relative awakening responses on work‐days and days off are related to time and mode of awakening.