Exploring neurocognitive features in adolescents and young adults with anorexia nervosa: Evidence from a longitudinal study.

OBJECTIVE: We aimed to evaluate longitudinal changes in set-shifting and central coherence in a predominantly adolescent cohort with anorexia nervosa (AN) and to explore whether these factors predict long-term eating disorder outcomes. METHOD: Ninety-two female patients with AN (mean age: 16.2, range: 13-21 years) completed neurocognitive tests (Rey Complex Figure Test, Adapted Version of the Wisconsin Card Sorting Test) before and after 12 months of psychotherapeutic treatment (n = 45 Maudsley AN Treatment, MANTRa; n = 47 standard psychotherapy; groups not randomised). Eating disorder severity was assessed at baseline, after 6, 12 and 18 months. RESULTS: Central coherence (indicated by an increase in the Rey Figure Style Index) and set-shifting (indicated by a reduction in the percentage of perseverative errors) significantly improved over the course of treatment, with similar outcomes across groups. Lower central coherence was associated with higher eating disorder severity. Individuals with lower baseline set-shifting ability tended to have worse eating disorder outcomes in the long-term. However, this trend did not reach statistical significance in a multilevel linear mixed model. CONCLUSIONS: Neurocognitive difficulties in adolescents and young adults with AN can improve after treatment. Interventions specifically addressing flexibility in thinking and behaviour may contribute to treatment success.

Comprehensive analysis of two hotspot codons in the TUBB4B gene and associated phenotypes.

Our purpose was to elucidate the genotype and ophthalmological and audiological phenotype in TUBB4B-associated inherited retinal dystrophy (IRD) and sensorineural hearing loss (SNHL), and to model the effects of all possible amino acid substitutions at the hotspot codons Arg390 and Arg391. Six patients from five families with heterozygous missense variants in TUBB4B were included in this observational study. Ophthalmological testing included best-corrected visual acuity, fundus examination, optical coherence tomography, fundus autofluorescence imaging, and full-field electroretinography (ERG). Audiological examination included pure-tone and speech audiometry in adult patients and auditory brainstem response testing in a child. Genetic testing was performed by disease gene panel analysis based on genome sequencing. The molecular consequences of the substitutions of residues 390 and 391 on TUBB4B and its interaction with α-tubulin were predicted in silico on its three-dimensional structure obtained by homology modelling. Two independent patients had amino acid exchanges at position 391 (p.(Arg391His) or p.(Arg391Cys)) of the TUBB4B protein. Both had a distinct IRD phenotype with peripheral round yellowish lesions with pigmented spots and mild or moderate SNHL, respectively. Yet the phenotype was milder with a sectorial pattern of bone spicules in one patient, likely due to a genetically confirmed mosaicism for p.(Arg391His). Three patients were heterozygous for an amino acid exchange at position 390 (p.(Arg390Gln) or p.(Arg390Trp)) and presented with another distinct retinal phenotype with well demarcated pericentral retinitis pigmentosa. All showed SNHL ranging from mild to severe. One additional patient showed a variant distinct from codon 390 or 391 (p.(Tyr310His)), and presented with congenital profound hearing loss and reduced responses in ERG. Variants at codon positions 390 and 391 were predicted to decrease the structural stability of TUBB4B and its complex with α-tubulin, as well as the complex affinity. In conclusion, the twofold larger reduction in heterodimer affinity exhibited by Arg391 substitutions suggested an association with the more severe retinal phenotype, compared to the substitution at Arg390.

Acceptability and feasibility of SUCCEAT, an intervention for parents of adolescents with anorexia nervosa.

OBJECTIVE: "Supporting Carers of Children and Adolescents with Eating Disorders in Austria" (SUCCEAT), a skills training for parents, delivered via workshops (WS) or online modules (ONL), has been proven to be effective in terms of parental distress, caregiver skills, and adolescents' outcome. This study examined the adherence to and the acceptability and feasibility of SUCCEAT. METHOD: One-hundred parents (86% mothers) of adolescents with anorexia nervosa participated in the 8-week training. Parents were assigned to the WS (n = 50) or ONL (n = 50) format using a quasi-randomised design. Adherence, acceptability, and feasibility were assessed using self-report questionnaires. RESULTS: Adherence to the sessions was high (66%-98%) for both groups. The usage of the material was comparable between the groups. However, in the WS group, participants actively approached the coaches (71.8% vs. 48.9% often/very often) or other parents (63% vs. 4.4% often/very often) more often. Perceived helpfulness was high in both groups, overall satisfaction and practicability were higher in the WS group. CONCLUSIONS: Good adherence, acceptability, and feasibility were confirmed for both formats of SUCCEAT, with minimal advantages of the WS regarding satisfaction and contact with other parents and coaches. Thus, both formats can be recommended for implementation in clinical routine.

Therapeutic drug monitoring in adolescents with anorexia nervosa for safe treatment with adjunct olanzapine.

OBJECTIVE: Medication is commonly used in anorexia nervosa (AN) despite largely missing high grade evidence. Olanzapine (OLZ) is the best-evidenced substance used off-label in this group, with conflicting outcome regarding BMI, clinical and safety parameters. Therefore, it is important to strictly assure quality of treatment with OLZ in AN by using 'Therapeutic Drug Monitoring' according to AGNP-guidelines, including serum levels and adverse drug reactions (ADRs) to support safety for adolescents with AN and attempt to generate an initial age- and disorder-specific therapeutic reference range. METHOD: Sixty-five adolescents with AN (aged 10-18) treated with OLZ (98% female; 97.5% AN-restricting-type) were prospectively observed, ADRs reported, and correlations between dosage and serum levels measured at trough level were calculated, a preliminary therapeutic range defined. RESULTS: Mean dosage of OLZ was 8.15 (SD: 2.91) mg and 0.19 (SD: 0.07) mg/kg respectively, average concentration was 26.57 (SD: 13.46) ng/mL. Correlation between daily dosage/dosage per kg and serum level was 0.72 (**p < 0.001)/0.65 (**p < 0.001), respectively. ADRs with impairment were rare (6.3%). 75% improved clinically (CGI). BMI increased significantly by 1.5 kg/m2 (t = 10.6, p < 0.001). A preliminary therapeutic reference range is 11.9 and 39.9 ng/mL. CONCLUSIONS: OLZ in the hands of specialists is a well-tolerated and safe treatment adjunct for adolescents with AN.

Fathers in the spotlight: parental burden and the effectiveness of a parental skills training for anorexia nervosa in mother-father dyads.

PURPOSE: Research on the engagement of fathers in the treatment of childhood psychiatric disorders is scarce. This study aims to investigate differences between mothers and fathers of adolescents with anorexia nervosa regarding parental burden and effectiveness of a parental skills training. METHODS: Ninety-one mother-father dyads caring for a child with anorexia nervosa participated in an 8-week parental skills training and completed a set of questionnaires assessing parental psychopathology, eating disorder related burden, caregiver skills and expressed emotion at baseline and post-intervention. RESULTS: Fathers showed lower levels of general psychological distress, depression, anxiety and eating disorder related burden as well as lower emotional overinvolvement compared to mothers. The skills training was effective in reducing parental psychopathology, eating disorder-related burden and emotional overinvolvement as well as in increasing caregiver skills with no differences between mothers and fathers. However, session adherence and the willingness to practice skills between the sessions were slightly lower in fathers. CONCLUSIONS: These findings show that fathers are a great resource for the child's eating disorder treatment as they may counterbalance maternal emotional overinvolvement and over-protection. Furthermore, this is the first study demonstrating that fathers can profit from a parental skills training for anorexia nervosa in a similar way as mothers. LEVEL III: Evidence obtained from well-designed cohort or case-control analytic studies.

The Maudsley model of anorexia nervosa treatment for adolescents and emerging adults: A multi-centre cohort study.

OBJECTIVE: The aim of this study was examining the efficacy of the Maudsley Model of Anorexia Nervosa Treatment for Adolescents and Young Adults (MANTRa) compared to individual psychotherapy that can be considered as standard in Austria (TAU-O). METHOD: In this cohort study, 92 patients between 13 and 21 years suffering from full-syndrome, atypical or weight-restored anorexia nervosa (AN) received either 24-34 individual MANTRa sessions (n = 45) or TAU-O (n = 47). Outcome variables were age- and sex-related BMI, eating disorder and comorbid psychopathology at 6-, 12- and 18-month post baseline as well as acceptability of treatment and therapeutic alliance. RESULTS: Both treatments resulted in significant improvements in age- and sex related BMI and reductions in eating disorder and comorbid psychopathology over time with significant differences between groups in favour of MANTRa. The percentage of participants with fully remitted AN was significantly higher in the MANTRa group compared to TAU-O at 18-month follow-up (MANTRa: 46% vs. TAU-O: 16%, p = 0.006). Satisfaction with both treatments was high. CONCLUSIONS: MANTRa is an effective treatment programme for adolescents and young adults with AN. Randomised controlled trials comparing MANTRa with existing treatments are necessary. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (Identifier: NCT03535714).

Isoform-specific translational control is evolutionarily conserved in primates.

Alternative splicing (AS) alters messenger RNA (mRNA) coding capacity, localization, stability, and translation. Here we use comparative transcriptomics to identify cis-acting elements coupling AS to translational control (AS-TC). We sequenced total cytosolic and polyribosome-associated mRNA from human, chimpanzee, and orangutan induced pluripotent stem cells (iPSCs), revealing thousands of transcripts with splicing differences between subcellular fractions. We found both conserved and species-specific polyribosome association patterns for orthologous splicing events. Intriguingly, alternative exons with similar polyribosome profiles between species have stronger sequence conservation than exons with lineage-specific ribosome association. These data suggest that sequence variation underlies differences in the polyribosome association. Accordingly, single nucleotide substitutions in luciferase reporters designed to model exons with divergent polyribosome profiles are sufficient to regulate translational efficiency. We used position specific weight matrices to interpret exons with species-specific polyribosome association profiles, finding that polymorphic sites frequently alter recognition motifs for trans-acting RNA binding proteins. Together, our results show that AS can regulate translation by remodeling the cis-regulatory landscape of mRNA isoforms.

Mental Health and Health-Related Quality of Life in Austrian Adolescents with Chronic Physical Health Conditions: Results from the MHAT Study.

Chronic physical health conditions (CPHC) are on the rise in younger age groups and might have a negative impact on children and adolescents. In a representative sample of Austrian adolescents aged 10-18 years, internalizing, externalizing, and behavioral problems were assessed cross-sectionally using the Youth Self-Report and health-related quality of life (HrQoL) using the KIDSCREEN questionnaire. Sociodemographic variables, life events, and chronic illness specific parameters were considered as associated variables with mental health problems in individuals with CPHC. Of 3469 adolescents, 9.4% of girls and 7.1% of boys suffered from a chronic pediatric illness. Of these individuals, 31.7% and 11.9% had clinically relevant levels of internalizing and externalizing mental health problems, respectively, compared to 16.3% and 7.1% adolescents without a CPHC. Anxiety, depression, and social problems were twice as high in this population. Medication intake due to CPHC and any traumatic life-event were related to mental health problems. All HrQoL domains were deteriorated in adolescents with a double burden of mental and CPHC, whereas adolescents with a CPHC without mental health problems did not differ significantly from adolescents without a chronic illness. Targeted prevention programs for adolescents with a CPHC are urgently needed to prevent mental health problems in the long term.

Psychological distress and caregiving experience during the first two years of the COVID-19 pandemic among parents of an offspring with anorexia nervosa.

OBJECTIVE: To compare different aspects of caregiving distress and experience in parents of patients with anorexia nervosa (AN) before and during the COVID-19 pandemic. METHODS: Three cohorts of parents of AN patients (cohort 1-pre-pandemic: N = 78, cohort 2-first pandemic year: N = 51, cohort 3-second pandemic year: N = 119) were recruited from child and adolescent psychiatry wards and cross-sectionally assessed as part of the clinical routine. Quantitative measures of psychological distress, psychopathology, eating disorder (ED)-related burden, expressed emotion and caregiver skills were obtained at the beginning of the child's inpatient or outpatient treatment. RESULTS: Cohort 2 showed lower levels of anxiety and a tendency of lower emotional overinvolvement and higher caregiving skills compared to the pre-pandemic cohort. In contrast, the levels of general psychological distress, depression, ED-related burden and criticism observed in cohort 3 significantly exceeded pre-pandemic levels. The prevalence of clinically relevant depression was higher in cohort 3 (41.5%) compared to cohorts 1 (24.4%) and 2 (21.6%). DISCUSSION: The pandemic effects on parents seem to be time-specific. Lower distress in the early phase of the pandemic may be associated with improvements in parent-child-relationships reported in previous studies. However, the pandemic may has negative consequences in the long-term emphasising the need of ongoing parental support.

An investigation of the factor structure of a German version of the Eating Disorder Symptom Impact Scale (EDSIS) among parents of adolescents and young adults with anorexia nervosa.

The aim of this study was to explore the factor structure, scale characteristics and convergent validity of a German version of the Eating Disorder Symptom Impact Scale (EDSIS). A total of 335 parents of adolescents and young adults with anorexia nervosa in inpatient or outpatient treatment completed the 24-item German translation of the EDSIS and other measures of caregiving burden and psychological distress. We tested a 4 vs. 6-factor model of the EDSIS using confirmatory factor analyses. The 6-factor model treating items as ordinal variables showed the best fit to the data (CFI = 0.949, RMSEA = 0.064). Strong invariance of this model was shown between the sample of mothers and fathers. Internal consistencies of the EDSIS scales were in the acceptable-to-good range. Bottom effects were observed for the 'Binge-Purge-Impacts' subscale only. Mothers had significantly higher EDSIS scores compared to fathers. The EDSIS total score and most of the subscores showed substantial positive correlations with caregivers' psychological distress, level of depression, anxiety and expressed emotion as well as negative associations with the level of perceived caregiving skills. The German version of the EDSIS is a useful tool to assess caregiving burden in mothers and fathers of patients with anorexia nervosa.