Andrea H. Meyer

Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF ) after acute psychosocial stress

Environmentally induced epigenetic alterations are related to mental health. We investigated quantitative DNA methylation status before and after an acute psychosocial stressor in two stress-related genes: oxytocin receptor (OXTR) and brain-derived neurotrophic factor (BDNF ). The cross sectional study took place at the Division of Theoretical and Clinical Psychobiology, University of Trier, Germany and was conducted from February to August 2009. We included 83 participants aged 61–67 years. Thereof, 76 participants completed the full study procedure consisting of blood sampling before (pre-stress), 10 min after (post-stress) and 90 min after (follow-up) the Trier social stress test. We assessed quantitative DNA methylation of whole-blood cells using Sequenom EpiTYPER. Methylation status differed between sampling times in one target sequence of OXTR (P<0.001): methylation increased from pre- to post-stress (P=0.009) and decreased from post-stress to follow-up (P<0.001). This decrease was also found in a second target sequence of OXTR (P=0.034), where it lost statistical significance when blood cell count was statistically controlled. We did not detect any time-associated differences in methylation status of the examined BDNF region. The results suggest a dynamic regulation of DNA methylation in OXTR—which may in part reflect changes in blood cell composition—but not BDNF after acute psychosocial stress. This may enhance the understanding of how psychosocial events alter DNA methylation and could provide new insights into the etiology of mental disorders.

Binge eating in binge eating disorder: A breakdown of emotion regulatory process?

Current explanatory models for binge eating in binge eating disorder (BED) mostly rely on models for bulimia nervosa (BN), although research indicates different antecedents for binge eating in BED. This study investigates antecedents and maintaining factors in terms of positive mood, negative mood and tension in a sample of 22 women with BED using ecological momentary assessment over a 1-week. Values for negative mood were higher and those for positive mood lower during binge days compared with non-binge days. During binge days, negative mood and tension both strongly and significantly increased and positive mood strongly and significantly decreased at the first binge episode, followed by a slight though significant, and longer lasting decrease (negative mood, tension) or increase (positive mood) during a 4-h observation period following binge eating. Binge eating in BED seems to be triggered by an immediate breakdown of emotion regulation. There are no indications of an accumulation of negative mood triggering binge eating followed by immediate reinforcing mechanisms in terms of substantial and stable improvement of mood as observed in BN. These differences implicate a further specification of etiological models and could serve as a basis for developing new treatment approaches for BED.

Maternal psychosocial adversity during pregnancy is associated with length of gestation and offspring size at birth: evidence from a population-based cohort study.

Objective: To study in a large-scale cohort with prospective data the associations of psychosocial adversities during pregnancy with length of gestation and offspring size at birth. Methods: We defined a priori two types of psychosocial adversity during pregnancy: life stress (perceived burdens in major areas of life) and emotional symptoms (e.g. anxiety). Measures of offspring size at birth, including body weight, body length, abdominal and head circumference, were obtained from a national medical birth registry. We included in the analyses gestational age and offspring size at birth controlled for length of gestation; the latter was calculated by gestational-age-specific z scores (ZS) reported in 10−3. We conducted multiple regression analyses adjusted for potential confounders to estimate the association between exposures and birth outcomes (n = 78017 pregnancies). Results: Life stress (per score increase by 1; range, 0-18) was associated with shorter length of gestation (days; B, −0.14; 95% confidence interval (CI), −0.19, −0.10), increased offspring body weight (ZS; B, 9.14; 95% CI, 4.99, 13.28), body length (ZS; B, 6.58; 95% CI, 2.39, 10.77), abdominal circumference (ZS; B, 9.96; 95% CI, 5.77, 14.16), and head circumference (ZS; B, 6.13; 95% CI, 1.95, 10.30). Emotional symptoms were associated with shorter length of gestation (days; B, −0.04; 95% CI, −0.07, −0.004) and decreased body length (ZS; B, −4.44; 95% CI, −7.57, −1.32) only. Conclusions: Life stress and emotional symptoms both predicted a shorter length of gestation, while only life stress predicted an increased offspring size at birth controlled for length of gestation; yet, the associations were rather small. The fetoplacental-maternal unit may regulate fetal growth according to the type of psychosocial adversity and even increase fetal growth in response to maternal stress in major areas of life. This potentially reflects a basic principle of intrauterine human development in response to stress. BMI = body mass index; DNBC = Danish National Birth Cohort;IL1B = interleukin 1, beta.

Randomized controlled comparison of two cognitive behavioral therapies for obese children : mother versus mother-child cognitive behavioral therapy

Background: Parent-child treatments have been shown to be superior to child-focused treatments of childhood obesity. Yet until now, the comparative effectiveness of parent-only and parent-child approaches has been little studied. Method: Fifty-six obese children and their families were randomly assigned to a 16-session cognitive behavioral therapy (CBT) for the parents only or for a combined treatment of parents and children. Children’s percent overweight, the body mass index of their mothers, and behavioral and psychological problems of children and mothers were assessed. Results: Both treatments reduced children’s percent overweight significantly and equally by 6-month follow-up. Also both treatments provided similar results in reducing general behavior problems (externalizing and internalizing behavior problems), global and social anxiety, and depression. Conclusions: Our results point to a comparable efficacy of the two treatments. Further, psychological well-being of both mothers and children can be improved in a CBT for obese children and their parents. Future studies should focus on finding ways to improve the adherence of families to long-term treatment of obesity in childhood.

Childhood maternal care is associated with DNA methylation of the genes for brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) in peripheral blood cells in adult men and women

Abstract In adults, reporting low and high maternal care in childhood, we compared DNA methylation in two stress-associated genes (two target sequences in the oxytocin receptor gene, OXTR; one in the brain-derived neurotrophic factor gene, BDNF) in peripheral whole blood, in a cross-sectional study (University of Basel, Switzerland) during 2007–2008. We recruited 89 participants scoring < 27 (n = 47, 36 women) or > 33 (n = 42, 35 women) on the maternal care subscale of the Parental Bonding Instrument (PBI) at a previous assessment of a larger group (N = 709, range PBI maternal care = 0–36, age range = 19–66 years; median 24 years). 85 participants gave blood for DNA methylation analyses (SequenomR EpiTYPER, San Diego, CA) and cell count (Sysmex PocH-100i™, Kobe, Japan). Mixed model statistical analysis showed greater DNA methylation in the low versus high maternal care group, in the BDNF target sequence [Likelihood-Ratio (1) = 4.47; p = 0.035] and in one OXTR target sequence Likelihood-Ratio (1) = 4.33; p = 0.037], but not the second OXTR target sequence [Likelihood-Ratio (1) < 0.001; p = 0.995). Mediation analyses indicated that differential blood cell count did not explain associations between low maternal care and BDNF (estimate = −0.005, 95% CI = −0.025 to 0.015; p = 0.626) or OXTR DNA methylation (estimate = −0.015, 95% CI = −0.038 to 0.008; p = 0.192). Hence, low maternal care in childhood was associated with greater DNA methylation in an OXTR and a BDNF target sequence in blood cells in adulthood. Although the study has limitations (cross-sectional, a wide age range, only three target sequences in two genes studied, small effects, uncertain relevance of changes in blood cells to gene methylation in brain), the findings may indicate components of the epiphenotype from early life stress.

The efficacy of a short version of a cognitive-behavioral treatment followed by booster sessions for binge eating disorder.

This waitlist-controlled study evaluated the efficacy of a short version of a group CBT for BED followed by booster sessions after the active treatment phase. Thirty-six females with BED were randomly assigned to CBT (eight weekly sessions during active treatment plus five booster sessions during follow-up) or a waitlist condition. At the end of the active treatment, binge eating was significantly reduced relative to waitlist. Furthermore, at 12-month follow-up short-term CBT produced significant improvements in binge eating symptoms relative to baseline. Findings suggest that the short-term CBT followed by booster sessions may provide a valuable treatment option for patients with BED.

Maternal Psychosocial Stress during Pregnancy and Placenta Weight: Evidence from a National Cohort Study

Background To study in a large-scale cohort with prospective data the associations between psychosocial stress during pregnancy and placenta weight at birth. Animal data suggest that the placenta is involved in stress-related fetal programming. Methodology/Principal Findings We defined a priori two types of psychosocial stress during pregnancy, life stress (perceived burdens in major areas of life) and emotional symptoms (e.g. anxiety). We estimated the associations of maternal stress during pregnancy with placenta weight at birth, controlled for length of gestation, by predicting gestational age- and sex-specific z-scores of placenta weight through multiple regression analysis, adjusted for potential confounders (N = 78017 singleton pregnancies). Life stress (per increase in stress score by 1, range: 0–18) during pregnancy was associated with increased placenta weight at birth (z-score, reported in 10−3; B, 14.33; CI, 10.12–18.54). In contrast, emotional symptoms during pregnancy were not associated with placenta weight at birth. Conclusions/Significance Maternal life stress but not emotional symptoms during pregnancy was associated with increased placenta weight at birth; yet, the association-estimate was rather small. Our results may contribute to a better understanding of the role of the placenta in the regulation of intrauterine processes in response to maternal stress.

Increasing the motivation for physical activity in obese patients

OBJECTIVE In this randomized controlled study, a standardized motivation intervention was compared with a relaxation intervention with regard to its effectiveness in decreasing dropout rates and increasing physical activity in a sample of obese patients. METHOD Thirty-eight obese participants were randomly assigned to a one-session motivation or relaxation intervention. Thereafter, both groups participated in an 8-week aerobic program. Adherence, physical activity, motivational stage of change, and body mass index (BMI) were assessed during intervention and at 3- and 6-month follow-ups. RESULTS During the aerobic program, the motivation group showed significantly fewer dropouts but comparable adherence if only completers were considered. Moreover, their weekly minutes of physical activity increased over time before leveling off, whereas steady decreases were observed in the relaxation group. For motivational stage of change and BMI, no significant group differences were observed. DISCUSSION The importance and efficacy of motivational interventions in enhancing the high dropout rates in obesity treatment is underlined.

Efficacy and predictors of long-term treatment success for cognitive-behavioral treatment and behavioral weight-loss-treatment in overweight individuals with binge eating disorder

OBJECTIVE The aim of the study was to assess the long-term efficacy of Cognitive-Behavioral Treatment (CBT) and Behavioral Weight-Loss-Treatment (BWLT) in patients with binge eating disorder (BED) and to identify potential predictors of long-term treatment success. METHOD In a sample of overweight to obese BED patients from a randomized comparative trial we evaluated the efficacy of four months of CBT or BWLT, followed by 12 months extended care, and a final follow-up assessment 6 years after the end of active treatment. Outcomes included binge eating, eating disorder pathology, depressive feelings, and body mass index. RESULTS After a strong improvement during active treatment, outcomes worsened during follow-up, yet remained improved at 6-year follow-up relative to pretreatment values. Long-term effects between CBT and BWLT were comparable. Rapid response during the early treatment phase was the only characteristic that was predictive of favorable treatment outcome in the long term. CONCLUSIONS Both CBT and BWLT can be considered to be comparably efficacious in the long-term. Patients not responding strongly enough during the first four therapy sessions might be in need of tailored interventions early during the treatment phase.

Treating Treatment-Resistant Patients with Panic Disorder and Agoraphobia Using Psychotherapy: A Randomized Controlled Switching Trial

Background: Nonresponsiveness to therapy is generally acknowledged, but only a few studies have tested switching to psychotherapy. This study is one of the first to examine the malleability of treatment-resistant patients using acceptance and commitment therapy (ACT). Methods: This was a randomized controlled trial that included 43 patients diagnosed with primary panic disorder and/or agoraphobia (PD/A) with prior unsuccessful state-of-the-art treatment (mean number of previous sessions = 42.2). Patients were treated with an ACT manual administered by novice therapists and followed up for 6 months. They were randomized to immediate treatment (n = 33) or a 4-week waiting list (n = 10) with delayed treatment (n = 8). Treatment consisted of eight sessions, implemented twice weekly over 4 weeks. Primary outcomes were measured with the Panic and Agoraphobia Scale (PAS), the Clinical Global Impression (CGI), and the Mobility Inventory (MI). Results: At post-treatment, patients who received ACT reported significantly more improvements on the PAS and CGI (d = 0.72 and 0.89, respectively) than those who were on the waiting list, while improvement on the MI (d = 0.50) was nearly significant. Secondary outcomes were consistent with ACT theory. Follow-up assessments indicated a stable and continued improvement after treatment. The dropout rate was low (9%). Conclusions: Despite a clinically challenging sample and brief treatment administered by novice therapists, patients who received ACT reported significantly greater changes in functioning and symptomatology than those on the waiting list, with medium-to-large effect sizes that were maintained for at least 6 months. These proof-of-principle data suggest that ACT is a viable treatment option for treatment-resistant PD/A patients. Further work on switching to psychotherapy for nonresponders is clearly needed.