Cross-sectional associations of self-perceived stress and hair cortisol with metabolic outcomes and microvascular complications in type 2 diabetes.

Introduction: Increasing evidence supports chronic psychological stress as a risk factor for the development of type 2 diabetes. Much less is known, however, about the role of chronic stress in established diabetes. Methods: The aim of the current study was to comprehensively assess chronic stress in a sample of 73 patients with type 2 diabetes and 48 non-diabetic control participants, and to investigate associations with indicators of glycemic control (HbA1c), insulin resistance (HOMA-IR), ß-cell functioning (C-peptide), illness duration, and the presence of microvascular complications. Chronic stress was measured using questionnaires [the Perceived Stress Scale (PSS), the Screening Scale of the Trier Inventory of Chronic Stress (SSCS), the Perceived Health Questionnaire (PHQ) as well as the Questionnaire on Stress in Patients with Diabetes-Revised (QSD-R)]; hair cortisol was used as a biological indicator. Results: We found that patients with type 2 diabetes had higher levels of hair cortisol in comparison to the control group (F(1,112) = 5.3; p = 0.023). Within the diabetic group, higher hair cortisol was associated with a longer duration of the illness (r = 0.25, p = 0.04). General perceived stress did not show significant associations with metabolic outcomes in type 2 diabetes patients. In contrast, higher diabetes-related distress, as measured with the QSD-R, was associated with lower glycemic control (r = 0.28, p = 0.02), higher insulin resistance (r = 0.26, p = 0.03) and a longer duration of the illness (r = 0.30, p = 0.01). Discussion: Our results corroborate the importance of chronic psychological stress in type 2 diabetes. It appears, however, that once type 2 diabetes has developed, diabetes-specific distress gains in importance over general subjective stress. On a biological level, increased cortisol production could be linked to the course of the illness.

Time course and reaction types of serum IGF-1 and its relationship to BMI and leptin regarding inpatients with anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) is a severe mental disorder that is characterized by restriction of energy intake, low weight, and endocrine abnormalities. One of the known endocrine changes in relation to underweight is in the GH/IGF-I axis. The aim of the study was (a) to investigate longitudinal characteristics of the IGF-I-change during therapy and weight gain in adult AN, (b) to determine relationships between IGF-I and leptin, (c) to characterize patients with weak and pronounced hormonal reactions to underweight. DESIGN: Data was assessed from 19 AN patients. Over the first two months, serum IGF-I concentrations were assessed on a weekly basis; thereafter on a monthly basis. The trend of IGF-I values over time was analyzed using individual growth models. RESULTS: In total, n = 177 IGF-I measurements were analyzed. IGF-I increased significantly dependent on BMI (slope = 20.81, p < 0.001), not modulated by duration of disease. The increase in IGF-I was significantly related to the increase in leptin concentrations over time (slope = 15.57, p < 0.001). Patients with a weaker hormonal reaction to underweight were significantly older compared to patients with a pronounced hormonal reaction (t(17) = 3.07, p = 0.007). CONCLUSIONS: During treatment, IGF-I change is clearly related to BMI as well as to leptin. Age appears to be associated with the IGF-I response to underweight.

The cardiac autonomic response to acute psychological stress in type 2 diabetes.

BACKGROUND: Impaired cardiac autonomic control is common among people with type 2 diabetes. The autonomic nervous system and its regulatory influence on the cardiovascular system also play a key role in the physiological response to psychosocial stressors. It is unclear whether the disease-related impairment of cardiac autonomic control in people with type 2 diabetes affects the stress response. The aim of this study was therefore to examine the cardiac autonomic and the psychological stress response of people with type 2 diabetes compared to healthy control participants. METHODS: We used the trier social stress test to induce stress in n = 51 participants with type 2 diabetes and n = 47 healthy controls. We assessed heart rate (HR) and heart rate variability (HRV) using six ECG samples before, during and after the stress test. We measured participants' psychological stress response using visual analogue scales. RESULTS: Longitudinal multilevel models showed an attenuated HR increase in response to the stress test combined with a slower HR recovery after the stress test, in people with type 2 diabetes. This pattern was accompanied by significantly lower low frequency HRV but no differences in high frequency HRV between the groups. Additionally, people with type 2 diabetes showed an increased level of self-reported psychological tension 45 minutes after the stress test. CONCLUSIONS: The impairment of the autonomic nervous system found in people with type 2 diabetes is reflected in the HR response to stress-but not in the HRV response-and partially mirrored in the psychological stress response. Our results underline the importance of considering the interplay of psychosocial stress and disease-related changes in the physiological stress response system in research and treatment of type 2 diabetes.

Associations of Childhood Neglect With the ACTH and Plasma Cortisol Stress Response in Patients With Type 2 Diabetes.

Background: Cross-sectional as well as longitudinal studies have linked childhood maltreatment to type 2 diabetes in adulthood with childhood neglect showing the strongest effect on type 2 diabetes risk. However, the mechanisms that link childhood maltreatment to type 2 diabetes are still unclear. Alterations in the psychological and physiological stress response system, specifically the hypothalamus-pituitary-adrenal (HPA) axis are a common finding in samples with a background of childhood neglect and are associated with type 2 diabetes. In the present study, we investigated the association between childhood neglect and the physiological and psychological stress response in patients with type 2 diabetes and healthy control participants. Method: We assessed emotional and physical childhood neglect in a sample of n = 74 patients with type 2 diabetes and n = 50 healthy control participants. We used the trier social stress test (TSST) to induce a stress response. Blood ACTH and cortisol levels were measured before (T0), directly after (T1) as well as 30 (T2) and 60 (T3) min after the TSST. Participants' subjective experience was assessed via visual analog scales before, directly after as well as at 45 min after the TSST. We used multiple regression analyses to predict the change in self-reported tension between T0 and T1. Multilevel models were applied to predict cortisol and ACTH levels across all measurement points. Results: We found a significant association between moderate to severe childhood neglect and a stronger psychological stress response in patients with type 2 diabetes, that was not present in healthy controls. In type 2 diabetes patients, but not in healthy controls, higher ACTH levels across all measurement points were significantly associated with higher severity of emotional neglect and higher severity of physical neglect was significantly associated with a stronger increase in plasma cortisol from T0 to T1. Conclusions: This is the first study to investigate whether childhood maltreatment in patients with type 2 diabetes could be associated with a dysregulated stress response. Our results show a link between the psychological and physiological stress response and childhood neglect in type 2 diabetes patients. This pathway is thus a possible mechanism connecting type 2 diabetes and childhood neglect.

Acupuncture in persons with an increased stress level-Results from a randomized-controlled pilot trial.

BACKGROUND: In today's Western societies a high percentage of people experience increased or chronic stress. Acupuncture could serve as treatment for persons affected adversely by the increased stress. METHODS: The AkuRest study was a two-centre randomized controlled pilot study in adult persons with increased stress levels. Participants were randomly allocated to one of three groups: verum acupuncture treatment, sham acupuncture, and a waiting control group. The feasibility of the study was assessed. In addition, effects on stress level (measured by the Perceived Stress Questionnaire (PSQ-20)) and other variables were assessed at the end of treatment and a 3-month follow-up. RESULTS: Altogether, N = 70 persons were included in the study. At the end of the treatment 15.7% were lost to follow-up. The adherence to the protocol was good: 82.9% of the participants completed 100% of their treatment. The stress level of the participants was high at baseline (mean PSQ-20 score 75.5, SD = 8.2). Effect sizes (ES) at T1 showed that verum and sham acupuncture were superior to the waiting condition in reducing stress (ES (verum) = -1.39, 95%-CI = [-2.11; -0.67]: ES (sham) = -1.12, CI = [-1.78;-0.44]). At follow-up, effect sizes were in favour of the verum group (as compared to sham). However, confidence intervals and t-tests showed that these differences were not significant. CONCLUSION: The pilot study demonstrated the feasibility of the acupuncture RCT in persons with increased stress levels. Estimated parameters can be used to design a larger RCT to prove the-here indicated-efficacy of verum acupuncture to decrease stress. TRIAL REGISTRATION NUMBER: ISRCTN15259166.

Time course of adiponectin and its relationship to psychological aspects in patients with anorexia nervosa during inpatient treatment.

OBJECTIVE: The protein hormone adiponectin promotes metabolic and psychological health. The aim of the study was to track changes in adiponectin levels in response to weight gain and to assess associations between adiponectin and psychological aspects in patients with anorexia nervosa (AN). METHODS: To investigate if adiponectin levels depend on AN severity, data were assessed from 11 inpatients with a very low body mass index (BMI) and a high chronicity (high severity group; HSS), and nine with less severe symptoms (LSS). During the course of treatment, serum adiponectin concentrations were assessed on a weekly basis along with BMI. Psychological variables (i.e., depression, anxiety, stress, and AN-specific symptoms) were obtained by means of electronic diaries. Longitudinal regressions and correlations were calculated to evaluate the temporal course of adiponectin and its relationship with psychological self-ratings. RESULTS: At the beginning adiponectin was not increased in HSS patients (p = .56), and only marginally elevated in LSS patients (p = 0.07) compared with controls. In HSS patients, adiponectin increased along with BMI during the first treatment phase (i.e., when the BMI of patients was below 16 kg/m2) and thereafter decreased with further weight gain. In LSS patients, adiponectin was not associated with BMI increase. Furthermore, adiponectin was strongly negatively correlated with psychological self-ratings when the BMI of patients was above 16 kg/m2, i.e., higher levels of adiponectin were related to lower ratings of depression, anxiety, and AN-specific symptoms. DISCUSSION: The study connects previous varying results by indicating that the course of adiponectin is dependent on BMI and symptom severity. Similarly, associations of adiponectin and psychological health depended on BMI.

Time Course of Leptin in Patients with Anorexia Nervosa during Inpatient Treatment: Longitudinal Relationships to BMI and Psychological Factors.

BACKGROUND: Leptin, a hormone secreted by adipose tissue, appears to play a major role in the homeostasis of body weight and psychobiological processes associated with anorexia nervosa (AN). However, there is scarce data on its exact influence on this disorder, in particular data over time. OBJECTIVE: The present study addresses whether leptin changes during inpatient treatment play a role for treatment outcome and psychological factors in underweight AN patients. METHODS: In order to understand whether leptin's role differs in relation to AN severity, data were assessed from 11 patients with a very low BMI and a higher chronicity (high severity group; HSS; mean BMI at the beginning of the study = 13.6; mean duration of illness = 5.1 years) vs. nine with less severe symptoms (LSS; mean BMI = 16.2; mean duration of illness = 3.7 years). During the course of treatment, serum leptin concentrations were assessed weekly while weight (BMI) was assessed twice per week. Concomitantly, psychological variables were obtained by means of electronic diaries. Unconditional linear growth models were calculated to evaluate the temporal course of leptin in relation to BMI. For HSS patients, two phases of treatment (BMI < 16 and BMI ≥ 16 kg/m2) were investigated. RESULTS: Leptin increased significantly with BMI in both groups of patients. For HSS patients, the increase of leptin in the first treatment phase did not predict later increases in BMI. Furthermore, the relationship of leptin and psychological factors was modulated by symptom severity. In HSS patients, higher leptin levels were associated with greater feelings of depression, anxiety, and stress whereas in LSS patients a higher leptin level showed the trend to be associated with lower psychological symptom burden. CONCLUSIONS: Our results suggest that leptin changes are differently associated with weight gain and psychological symptoms depending on the severity of starvation.

Acute stress affects risk taking but not ambiguity aversion.

Economic decisions are often made in stressful situations (e.g., at the trading floor), but the effects of stress on economic decision making have not been systematically investigated so far. The present study examines how acute stress influences economic decision making under uncertainty (risk and ambiguity) using financially incentivized lotteries. We varied the domain of decision making as well as the expected value of the risky prospect. Importantly, no feedback was provided to investigate risk taking and ambiguity aversion independent from learning processes. In a sample of 75 healthy young participants, 55 of whom underwent a stress induction protocol (Trier Social Stress Test for Groups), we observed more risk seeking for gains. This effect was restricted to a subgroup of participants that showed a robust cortisol response to acute stress (n = 26). Gambling under ambiguity, in contrast to gambling under risk, was not influenced by the cortisol response to stress. These results show that acute psychosocial stress affects economic decision making under risk, independent of learning processes. Our results further point to the importance of cortisol as a mediator of this effect.

The COMT Val158Met polymorphism modulates working memory performance under acute stress.

BACKGROUND: One of the most widely studied genetic polymorphisms regarding cognitive and emotional phenotypes is the COMT Val158Met polymorphism that influences dopamine availability in the prefrontal cortex (PFC). The PFC is the key brain structure for higher cognitive functions such as working memory, as well as an important regulatory site and target of the psychoendocrine stress response. Dopamine is thought to influence PFC functions in an inverted u-shaped manner. Thus, a stress-related increase in prefrontal dopamine is hypothesized to exert differential effects on working memory performance depending on the genetically determined baseline dopamine level in the PFC. METHOD: Thirty-three healthy young subjects homozygous for the COMT Val158Met polymorphism were selected from a larger pre-genotyped sample. They performed an n-back working memory task after exposure to a laboratory psychosocial stress induction paradigm (The Trier Social Stress Test for Groups; TSST-G). RESULTS: Under stress, working memory performance of Met homozygotes was significantly worse than working memory performance of Val homozygotes. Importantly, this genotype effect was restricted to the medium difficulty level of the n-back task. CONCLUSION: Our results demonstrate that working memory performance under stress is influenced by genetic variation in prefrontal dopamine levels. More generally, our results point to the importance of considering the complex interaction of genes, environment, and task variables.

Association between a serotonin transporter length polymorphism and primary insomnia.

STUDY OBJECTIVE: To test the hypothesis that a 44-base-pair insertion/deletion polymorphism in the 5' regulatory region of the serotonin transporter gene (5-HTTLPR) is associated with primary insomnia. DESIGN: Association study. SETTING: Sleep laboratory at the Central Institute of Mental Health, Mannheim, Germany. PATIENTS: 157 patients with primary insomnia and 827 healthy controls. INTERVENTIONS: N/A. MEASUREMENT AND RESULTS: We found the short (s-) allele of the 5-HTTLPR to be significantly more frequent in patients suffering from insomnia than in control individuals (47.1% vs. 39.9%: OR = 1.34). CONCLUSIONS: This finding contributes to the understanding of the pathophysiology of primary insomnia and suggests a biological basis between the prevalent comorbidity of primary insomnia and other psychiatric disorders.