Young adult Swedish patients with autoimmune Addison's disease report difficulties with executive functions in daily life despite overall good cognitive performance.

OBJECTIVES: Sub-optimal replacement of glucocorticoids (GC) in autoimmune Addison's disease (AAD) may affect cognitive functioning. The present study therefore sought to investigate cognitive performance and self-reported problems with executive functions in a cohort of young adult patients with AAD. DESIGN AND METHODS: 67 patients with AAD (39 females), mean age 32 yrs. (range 19-41), and 80 control participants (43 females), mean age 29 yrs. (range 19-43), completed neuropsychological tests estimating verbal and non-verbal intellectual ability, learning, memory and executive functioning, in addition to self-report scales assessing problems with executive functions, fatigue and symptoms of anxiety and depression. RESULTS: Patients performed within the average range on all cognitive tests compared to population norms. However, female AAD patients reported more problems than controls with both hot (emotion regulation) and cold (cognitive regulation) executive functions in daily life. Moreover, experienced problems with executive functions in both male and female patients were associated with increased mental fatigue and lower GC replacement doses. CONCLUSIONS: Despite average performance in neuropsychological tests by both sexes, young adult female patients with AAD experience problems with executive functions in daily life. Coping with mental fatigue and optimization of pharmacotherapy may be important factors to be addressed in order to provide timely support for patients. Future research is needed to further determine other risk factors for experiencing executive function impairments in AAD.

Targeting excessive worry with internet-based extinction therapy: a randomised controlled trial with mediation analysis and economical evaluation.

BACKGROUND: Excessive worry is a common phenomenon. Our research group has previously developed an online intervention for excessive worry based on operant principles of extinction (IbET; internet-based extinction therapy) and tested it against a waiting-list. The aim of this study was to evaluate IbET against an active control comparator (CTRL). METHODS: A 10-week parallel participant blind randomised controlled trial with health-economical evaluation and mediation analyses. Participants (N = 311) were randomised (ratio 4.5:4.5:1) to IbET, to CTRL (an internet-based stress-management training program) or to waiting-list. The nation-wide trial included self-referred adults with excessive worry. The primary outcome was change in worry assessed with the Penn State Worry Questionnaire from baseline to 10 weeks. RESULTS: IbET had greater reductions in worry compared to CTRL [-3.6 point difference, (95% CI -2.4 to -4.9)] and also a significantly larger degree of treatment responders [63% v. 51%; risk ratio = 1.24 (95% CI 1.01-1.53)]. Both IbET and CTRL made large reductions in worry compared to waiting-list and effects were sustained up to 1 year. Treatment credibility, therapist attention, compliance and working alliance were equal between IbET and CTRL. Data attrition was 4% at the primary endpoint. The effects of IbET were mediated by the hypothesized causal mechanism (reduced thought suppression) but not by competing mediators. Health-economical evaluation indicated that IbET had a 99% chance of being cost-effective compared to CTRL given societal willingness to pay of 1000€. CONCLUSIONS: IbET is more effective than active comparator to treat excessive worry. Replication and extensions to real-world setting are warranted.

Evaluation of behavioral problems after prenatal dexamethasone treatment in Swedish children and adolescents at risk of congenital adrenal hyperplasia.

Prenatal dexamethasone (DEX) treatment in congenital adrenal hyperplasia (CAH) is effective in reducing virilization in affected girls, but potential long-term adverse effects are largely unknown. In this report we intended to explore potential side effects of DEX therapy to enhance the adequacy of future risk benefit analyses of DEX treatment. We investigated the long-term effects of first trimester prenatal DEX treatment on behavioral problems and temperament in children and adolescents aged 7-17 years. The study included 34 children and adolescents, without CAH, who had been exposed to DEX during the first trimester and 67 untreated controls. Standardized parent-completed questionnaires were used to evaluate adaptive functioning and behavioral/emotional problems (CBCL), social anxiety (SPAI-C-P), and temperament (EAS) in the child. Self-reports were used to assess the children's perception of social anxiety (SASC-R). No statistically significant differences were found between DEX-treated and control children and adolescents, suggesting that, in general, healthy children treated with DEX during early fetal life are well adjusted.

Cognitive impairment in adolescents and adults with congenital adrenal hyperplasia.

OBJECTIVE: Impaired cognition has been reported in patients with congenital adrenal hyperplasia (CAH), although the findings have been conflicting. It has been hypothesized that the major causes of the deficits are prenatal hormonal imbalances and/or excessive glucocorticoid treatment. DESIGN: An observational study investigating cognition in patients with CAH. PATIENTS: A total of 55 patients with CAH and 58 control subjects from the general population, aged 16-33 years. Nine CAH subjects had been treated prenatally with dexamethasone. SETTING: Singel research institute. MEASUREMENTS: Standardized neuropsychological tests (Wechsler Scales and Stroop Interference Test) and questionnaires (Barkley Deficit in Executive Functioning Scale) were used. RESULTS: Compared to controls, patients with CAH had impaired performance in tests measuring verbal working memory (P = .024), visual-spatial working memory (P = .005 and P = .003) and inhibition (P = .002). In measures of fluid intelligence/nonverbal logical reasoning, males with CAH performed poorer than control males (P = .033). Patients with salt-wasting CAH performed equally compared to patients with simple virilizing CAH. However, patients with a null genotype performed poorer than patients with a non-null genotype and significantly worse on fluid intelligence/nonverbal logical reasoning (P = .042). Prenatally-treated women performed worse on most cognitive measures than women with CAH not treated prenatally. CONCLUSIONS: Patients with CAH had normal psychometric intelligence but impaired executive functions compared with population controls. A null CAH genotype was associated with poorer general cognitive capacity.

Sex-Dimorphic Effects of Prenatal Treatment With Dexamethasone.

CONTEXT: Dexamethasone (DEX) is used to prevent virilization in female fetuses at risk of congenital adrenal hyperplasia (CAH). Given that treatment has to be started before the genotype is known, 7 out of 8 fetuses will be exposed to DEX without benefit. OBJECTIVE: To evaluate long-term cognitive effects of prenatal DEX therapy in healthy (non-CAH) DEX-treated children. DESIGN AND SETTING: Observational study with patient and control groups from a single research institute. PARTICIPANTS: Healthy (non-CAH) DEX-treated subjects (n = 34) and untreated population controls (n = 66) from Sweden, aged 7-17 years. INTERVENTION: DEX-treatment used in unborn children at risk of CAH, during first trimester of fetal life. MAIN OUTCOME MEASURES: Standardized neuropsychological tests and questionnaires were used. RESULTS: DEX treatment has widespread negative effects in girls. In Wechsler Intelligence Scales for Children-III scale subtests, we observed significant interactions between DEX and GENDER (coding, P = .044; block design, P = .013; vocabulary, P = .025) and a trend for the subtest digit span (P = .074). All interactions were driven by DEX effects in girls, but not boys, with DEX-treated females showing lower scores than female untreated controls (coding, P = .068, d = 0.66; block design, P = .021, d = 0.81; vocabulary, P = .014, d = 0.84; digit span, P = .001, d = 1.0). Likewise, DEX-treated girls tend to have poorer visual spatial working memory performance than controls (span board test forward: P = .065, d = .80). We observed no effects on long-term memory, handedness, speed of processing, nor self-perceived or parentally reported scholastic performance. CONCLUSIONS: Early prenatal DEX exposure affects cognitive functions in healthy girls, ie, children who do not benefit from the treatment. It can therefore not be considered safe to use this therapy in the context of CAH.

RETRACTED: Evaluation of behavioral problems after prenatal dexamethasone treatment in Swedish adolescents at risk of CAH.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the authors due to technical errors that have called into question the reliability of the data used to inform the author's conclusions. All data on cognitive and behavioral outcomes in CAH and non­CAH cases, treated or not treated with DEX prenatally, were put into a single Excel database. The authors had in total four different patient groups for each age group (5­6 y, 7­17 y and 18-35 y). The database consisted of 237 cases in total and there were multiple columns for the different outcome measures. When the behavioral data for the sub-cohort described in this paper (first trimester treated non-CAH cases and healthy population controls, age 7­17 y) were copied to another sheet and compressed/modified in preparation for statistical analysis in SPSS, an error occurred. This technological issue caused rows to shift and the data from the different groups got mixed up. In particular, the non­CAH group versus the control group were "contaminated" with cases from the wrong patient group. The authors discovered this mistake when they started to analyse the data from the other sub­groups of patients, the CAH cases and the adult cohort, which was after their original results had already been published in Hormones and Behavior in this manuscript "Evaluation of behavioral problems after prenatal dexamethasone treatment in Swedish adolescents at risk of CAH". It then became apparent that the entire data set was unreliable and needed to be re­analysed which is what has motivated the retraction of this article. The authors have recently completed this re­analysis and the results have been published here: https://www.sciencedirect.com/science/article/pii/S0018506X17300752