Unexpected identification of obesity-associated mutations in LEP and MC4R genes in patients with anorexia nervosa.

Mutations leading to a reduced or loss of function in genes of the leptin-melanocortin system confer a risk for monogenic forms of obesity. Yet, gain of function variants in the melanocortin-4-receptor (MC4R) gene predispose to a lower BMI. In individuals with reduced body weight, we thus expected mutations leading to an enhanced function in the respective genes, like leptin (LEP) and MC4R. Therefore, we have Sanger sequenced the coding regions of LEP and MC4R in 462 female patients with anorexia nervosa (AN), and 445 healthy-lean controls. In total, we have observed four and eight variants in LEP and MC4R, respectively. Previous studies showed different functional in vitro effects for the detected frameshift and non-synonymous variants: (1) LEP: reduced/loss of function (p.Val94Met), (2) MC4R: gain of function (p.Val103Ile, p.Ile251Leu), reduced or loss of function (p.Thr112Met, p.Ser127Leu, p.Leu211fsX) and without functional in vitro data (p.Val50Leut). In LEP, the variant p.Val94Met was detected in one patient with AN. For MC4R variants, one patient with AN carried the frameshift variant p.Leu211fsX. One patient with AN was heterozygous for two variants at the MC4R (p.Val103Ile and p.Ser127Leu). All other functionally relevant variants were detected in similar frequencies in patients with AN and lean individuals.

Postoperative Dumping Syndrome, Health-Related Quality of Life, Anxiety, Depression, and Eating Disturbances: Results of a Longitudinal Obesity Surgery Study.

INTRODUCTION: Given the lack of research on the relationship of post-surgery dumping syndrome and eating disturbances, the purpose of the present longitudinal study was to investigate whether dumping after obesity surgery is associated with pre-/postoperative eating disorder symptoms or addiction-like eating beyond the type of surgery, gender, health-realted quality of life (HRQoL) and anxiety/depressive symptoms. METHODS: The study included 220 patients (76% women) before (t0) and 6 months after (t1) obesity surgery (sleeve gastrectomy [n = 152], Roux-en-Y gastric bypass [n = 53], omega loop gastric bypass [n = 15]). The Sigstad Dumping Score was used to assess post-surgery dumping syndrome. Participants further answered the Eating Disorder Examination Questionnaire (EDE-Q), Yale Food Addiction Scale 2.0 (YFAS 2.0), Short-Form Health Survey (SF-12), and Hospital Anxiety and Depression Scale (HADS) at t0 and t1. RESULTS: The point prevalence of symptoms suggestive of post-surgery dumping syndrome was 33%. Regression analyses indicate an association of dumping with surgical procedure (bypass), female gender, reduced HRQoL, more anxiety/depressive symptoms, and potentially with binge eating but not with eating disorder symptoms in general or with addiction-like eating. CONCLUSION: The current study failed to show a close relationship between the presence of self-reported dumping syndrome and eating disorder symptoms or addiction-like eating following obesity surgery. Further studies with longer follow-up periods should make use of clinical interviews to assess psychosocial variables and of objective measures to diagnose dumping in addition to standardized self-ratings.

Cutoff scores of the Eating Disorder Examination-Questionnaire for the German population.

OBJECTIVE: The Eating Disorder Examination-Questionnaire (EDE-Q) is one of the most widely used self-report measures for the assessment of eating disorder (ED) symptomatology. However, proposed cutoff scores that may indicate the presence of an ED have been heterogeneous. Therefore, the current study derived cutoff scores from two large samples: one representative for the German population and one composed of persons with EDs at admission to inpatient treatment. METHOD: Receiver operating characteristic analysis was used with the EDE-Q global score as independent variable and group (controls: n = 2519, patients: n = 2038) as dependent variable. These analyses were also conducted separately with the patient group divided into persons with anorexia nervosa (AN; n = 1456), bulimia nervosa (BN; n = 370), and other EDs (n = 212) and after matching groups for age and sex distribution. RESULTS: The EDE-Q global score discriminated well between controls and patients (AUC >91%, sensitivity >.84, specificity >.79). A score of 1.6 discriminated best between controls and patients in general and persons with AN in particular. Optimal thresholds for discriminating between controls and persons with BN and other EDs ranged between scores of 1.8 and 2.4. DISCUSSION: In the German population, cutoff scores between 1.6 and 2.4 may be used to screen for the presence or absence of an ED or evaluate treatment outcome, with slightly higher cutoff scores for persons with BN and other EDs than for persons with AN. PUBLIC SIGNIFICANCE: Questionnaire scores have little value when it is unclear which scores indicate the likely presence of an ED, as such scores can be used to estimate the prevalence of or screen for EDs in the general population and evaluate outcome at the end of ED treatment. The current study indicates a score around 2 on the EDE-Q as an optimal threshold for this.

Blood T cell phenotypes correlate with fatigue severity in post-acute sequelae of COVID-19.

PURPOSE: Post-acute sequelae of COVID-19 (PASC) affect approximately 10% of convalescent patients. The spectrum of symptoms is broad and heterogeneous with fatigue being the most often reported sequela. Easily accessible blood biomarkers to determine PASC severity are lacking. Thus, our study aimed to correlate immune phenotypes with PASC across the severity spectrum of COVID-19. METHODS: A total of 176 originally immunonaïve, convalescent COVID-19 patients from a prospective cohort during the first pandemic phase were stratified by initial disease severity and underwent clinical, psychosocial, and immune phenotyping around 10 weeks after first COVID-19 symptoms. COVID-19-associated fatigue dynamics were assessed and related to clinical and immune phenotypes. RESULTS: Fatigue and severe fatigue were commonly reported irrespective of initial COVID-19 severity or organ-specific PASC. A clinically relevant increase in fatigue severity after COVID-19 was detected in all groups. Neutralizing antibody titers were higher in patients with severe acute disease, but no association was found between antibody titers and PASC. While absolute peripheral blood immune cell counts in originally immunonaïve PASC patients did not differ from unexposed controls, peripheral CD3+CD4+ T cell counts were independently correlated with fatigue severity across all strata in multivariable analysis. CONCLUSIONS: Patients were at similar risk of self-reported PASC irrespective of initial disease severity. The independent correlation between fatigue severity and blood T cell phenotypes indicates a possible role of CD4+ T cells in the pathogenesis of post-COVID-19 fatigue, which might serve as a blood biomarker.

Effect of the addition of a mental health specialist for evaluation of undiagnosed patients in centres for rare diseases (ZSE-DUO): a prospective, controlled trial with a two-phase cohort design.

Background: People with complex symptomatology but unclear diagnosis presenting to a centre for rare diseases (CRD) may present with mental (co-)morbidity. We hypothesised that combining an expert in somatic medicine with a mental health specialist working in tandem will improve the diagnostic outcome. Methods: Patients aged 12 years and older who presented to one of the 11 participating German CRDs with an unknown diagnosis were recruited into this prospective cohort trial with a two-phase cohort design. From October 1, 2018 to September 30, 2019, participants were allocated to standard care (SC, N = 684), and from October 1, 2019 to January 31, 2021 to innovative care (IC, N = 695). The cohorts consisted mainly of adult participants with only a minority of children included (N = 67). IC included the involvement of a mental health specialist in all aspects of care (e.g., assessing medical records, clinic visits, telehealth care, and case conferences). Clinicaltrials.gov identifier: NCT03563677. Findings: The proportion of patients with diagnoses established within 12 months after the first visit to the CRD explaining the entire symptomatology (primary outcome) was 19% (N = 131 of 672) in the SC and 42% (N = 286 of 686) in the IC cohort (OR adjusted for centre effects 3.45 [95% CrI: 1.99-5.65]). The difference was mainly due to a higher prevalence of mental disorders and non-rare somatic diseases in the IC cohort. The median time to explaining diagnoses was one month shorter with IC (95% CrI: 1-2), and significantly more patients could be referred to local regular care in the IC (27.5%; N = 181 of 659) compared to the SC (12.3%; N = 81 of 658) cohort (OR adjusted for centre effects 2.70 [95% CrI: 2.02-3.60]). At 12-month follow-up, patient satisfaction with care was significantly higher in the IC compared to the SC cohort, while quality of life was not different between cohorts. Interpretation: Our findings suggested that including a mental health specialist in the entire evaluation process of CRDs for undiagnosed adolescents and adults should become an integral part of the assessment of individuals with a suspected rare disease. Funding: The study was funded by the Global Innovation Fund from the Joint Federal Committee in Germany (Innovationsfonds des Gemeinsamen Bundesausschusses), grant number 01NVF17031.

Words count in psychotherapy: Differentiating language characteristics of cognitive behavioral therapy and focal psychodynamic therapy for anorexia nervosa.

It is generally assumed that psychodynamic therapy and cognitive behavioral therapy (CBT) differ in terms of applied techniques and processes. To date, however, little is known about whether and how such differences can actually be observed at a basic linguistic level and in what the two treatment approaches differ most strongly (i.e., how psychodynamic and CBT therapists differ in what they actually say word-by-word in therapy sessions). Building on theoretical models and previous research that used observer ratings, we formulated specific hypotheses regarding which word categories psychodynamic and CBT therapists who treat patients with an eating disorder should differ in. To investigate these hypotheses, we used verbatim transcripts from 297 therapy sessions of a randomized controlled trial in which patients with anorexia nervosa (n = 88) received either focal psychodynamic therapy (FPT) or CBT. These transcripts were then examined using computerized quantitative text analysis. In line with our hypotheses, we found that CBT therapists overall spoke more than their FPT counterparts and that they used more words related to eating. Also in line with our hypotheses, FPT therapists used more words related to social processes. Contrary to our expectations, CBT therapists did not show a stronger focus on the future but talked more about emotions than FPT therapists. The latter effect, however, appears to be driven by a stronger focus on positive emotions. These findings suggest that computerized quantitative text analysis can differentiate meaningful language characteristics of CBT and FPT on spoken-word level and that it holds potential as a tool for researchers and therapists. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Prevalence and Correlates of Dry Eye in a German Population Sample.

PURPOSE: In this cross-sectional survey, we assessed the prevalence of dry eye disease (DED) in a representative German population sample. In addition, we examined the associations between DED, health-related quality of life (HRQoL), and level of fatigue. Finally, we further validated the German version of the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire and present norm data of the German population. METHODS: A random sample of German residents aged 16 years and older was recruited between October and December 2021. All participants completed the SPEED, Short Form 36, and Multidimensional Fatigue Inventory 20 questionnaires. RESULTS: Of the 2495 participants who completed the survey, 450 (21.6%; 95% confidence intervals 20.0-23.1) reported a SPEED total score of ≥4, indicating a positive screening for DED. DED was significantly more common in women and older age. Participants who screened positive for DED reported significantly higher levels of fatigue and lower values in all domains of HRQoL. A receiver operating characteristic curve of the SPEED was generated using an ophthalmologist's diagnosis. The area under the curve was estimated to be 0.886 (95% confidence intervals 0.858-0.913). A cutoff score ≥4 seemed to be appropriate as an indicator of DED. Cronbach's α was excellent (0.95). CONCLUSIONS: DED is common in the German population. We confirmed associations with sex, age, HRQoL, and fatigue level, indicating a high burden of DED. The German version of the SPEED is a valid instrument for the assessment of DED symptoms.

The multicenter effectiveness study of inpatient and day hospital treatment in departments of psychosomatic medicine and psychotherapy in Germany.

Background: Reliable outcome data of psychosomatic inpatient and day hospital treatment with a focus on psychotherapy are important to strengthen ecological validity by assessing the reality of mental health care in the field. This study aims to evaluate the effectiveness of inpatient and day hospital treatment in German university departments of Psychosomatic Medicine and Psychotherapy in a prospective, naturalistic, multicenter design including structured assessments. Methods: Structured interviews were used to diagnose mental disorders according to ICD-10 and DSM-IV at baseline. Depression, anxiety, somatization, eating disorder and posttraumatic stress disorder (PTSD) symptoms, as well as personality functioning were assessed by means of questionnaires on admission and at discharge. Results: 2,094 patients recruited by 19 participating university hospitals consented to participation in the study. Effect sizes for each of the outcome criteria were calculated for 4-5 sub-groups per outcome domain with differing severity at baseline. Pre-post effect sizes for patients with moderate and high symptom severity at baseline ranged from d = 0.78 to d = 3.61 with symptoms of PTSD, depression, and anxiety showing the largest and somatization as well as personality functioning showing somewhat smaller effects. Conclusions: Inpatient and day hospital treatment in German university departments of Psychosomatic Medicine and Psychotherapy is effective under field conditions. Clinical trial registration: https://drks.de/search/de/trial/DRKS00016412, identifier: DRKS00016412.

Comprehensive Questionnaire in Postpartum Women to Assess Women's Knowledge of the Current Weight Gain Guidelines during Pregnancy in Lower Saxony.

INTRODUCTION: Maternal body mass index and gestational weight gain (GWG) are important factors for maternal and neonatal health. The objective of this study was to assess women's knowledge and examine adherence to the Institute of Medicine (IOM) criteria for weight gain during pregnancy by evaluating the information received from obstetricians and women's knowledge about GWG. METHODS: This is an analytical semi-longitudinal observational study. Weight data from a nonconsecutive convenience sample of 389 women who gave birth at the Hannover Medical School in the period from August 2020 to July 2021 were taken from their maternal records. Immediately after giving birth, the whole collective (n = 389) was asked to participate in a questionnaire study including questions that were taken from the EMat Health Survey inquiring about their knowledge and received information about GWG and about their eating behavior. Here, a subset of 202 women participated. RESULTS: Sixty-five percent of the participants who answered the questionnaire reported that they had not been informed by their obstetrician about GWG recommendations. Additionally, a minority of women knew the correct IOM GWG category based on their pre-pregnancy weight. Meeting the IOM GWG guidelines did not depend on whether or not women received GWG recommendations or knew about the correct GWG category. The majority of women were not concerned about gaining too much weight during pregnancy. 20.7% of all women participating in the study were affected by obesity pre-pregnancy. According to the IOM criteria for GWG, 50.4% gained too much weight. The proportion of women exceeding IOM recommendations was highest in women with pre-pregnancy overweight and obesity (67%). DISCUSSION: Weight gain outside of the IOM recommendations is widespread in our survey. Information received and knowledge about GWG recommendations were inadequate in our sample. Considering the fact that GWG outside recommended ranges can contribute to short- and long-term health complications, especially when a woman enters pregnancy already with overweight or obesity, identifying ways of achieving a healthier GWG is warranted.

Cognitive-behavioral and dietary weight loss intervention in adult kidney transplant recipients with overweight and obesity: Results of a pilot RCT study (Adi-KTx).

The obesity epidemic and its health consequences have not spared the population of kidney transplant (KTx) candidates and recipients. In addition, KTx recipients are susceptible to weight gain after transplantation. Overweight and obesity after KTx are strongly associated with adverse outcomes. Therefore, we designed a randomized controlled, mono-center study to specifically test the effectiveness of a primarily cognitive-behavioral approach supplemented by nutritional counseling for weight reduction following KTx as the intervention group (IG) in comparison to a brief self-guided intervention as control group (CG). The study was registered in the German Clinical Trials Register (DRKS-ID: DRKS00017226). Fifty-six KTx patients with a BMI from 27 to 40 kg/m2 were included in this study and randomized to the IG or CG. Main outcome was the number of participants achieving a 5% weight loss during the treatment phase. Additionally, participants were assessed 6 and 12 months after the end of the 6-month treatment phase. Participants significantly lost weight without group differences. 32.0% (n = 8) of the patients in the IG and 16.7% (n = 4) of the patients in the CG achieved a weight loss of 5% or more. Weight loss was largely maintained during follow-up. Retention and acceptance rate in the IG was high, with 25 (out of 28) patients completing all 12 sessions and one patient completing 11 sessions. Short-term, cognitive-behaviorally oriented weight loss treatment seems to be feasible and acceptable for patients after KTx who suffer from overweight or obesity. This clinical trial was ongoing at the onset of the COVID-19 pandemic which might have influenced study conduct and results. Clinical Trial Registration: https://clinicaltrials.gov/ DRKS-ID: DRKS00017226.

Genetic variants in genes involved in creatine biosynthesis in patients with severe obesity or anorexia nervosa.

Increased thermogenesis in brown adipose tissue might have an obesity-reducing effect in humans. In transgenic mice, depletion of genes involved in creatine metabolism results in disrupted thermogenic capacity and altered effects of high-fat feeding on body weight. Data analyses of a sex-stratified genome-wide association study (GWAS) for body mass index (BMI) within the genomic regions of genes of this pathway (CKB, CKMT1B, and GATM) revealed one sex-dimorphic BMI-associated SNP in CKB (rs1136165). The effect size was larger in females than in males. A mutation screen of the coding regions of these three candidate genes in a screening group (192 children and adolescents with severe obesity, 192 female patients with anorexia nervosa, and 192 healthy-lean controls) identified five variants in each, CKB and GATM, and nine variants in the coding sequence of CKMT1B. Non-synonymous variants identified in CKB and CKMT1B were genotyped in an independent confirmation study group (781 families with severe obesity (trios), 320 children and adolescents with severe obesity, and 253 healthy-lean controls). In silico tools predicted mainly benign yet protein-destabilizing potentials. A transmission disequilibrium test in trios with severe obesity indicated an obesity-protective effect of the infrequent allele at rs149544188 located in CKMT1B. Subsequent correlation analyses in 1,479 individuals of the Leipzig Obesity BioBank revealed distinct correlations of CKB with the other two genes in omental visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT). Furthermore, between-subject comparisons of gene expression levels showed generally higher expressions of all three genes of interest in VAT than in SAT. Future in vitro analyses are needed to assess the functional implications of these findings.

Lipocalin 2 - mutation screen and serum levels in patients with anorexia nervosa or obesity and in lean individuals.

Context: The bone-derived adipokine lipocalin-2 is relevant for body weight regulation by stimulating the leptin-melanocortin pathway. Objective: We aimed to (i) detect variants in the lipocalin-2 gene (LCN2) which are relevant for body weight regulation and/or anorexia nervosa (AN); (ii) describe and characterize the impact of LCN2 and MC4R variants on circulating lipocalin-2 level. Methods: Sanger sequencing of the coding region of LCN2 in 284 children and adolescents with severe obesity or 287 patients with anorexia nervosa. In-silico analyses to evaluate functional implications of detected LCN2 variants. TaqMan assays for rare non-synonymous variants (NSVs) in additional independent study groups. Serum levels of lipocalin-2 were measured by ELISA in 35 females with NSVs in either LCN2 or MC4R, and 33 matched controls without NSVs in the two genes. Results: Fourteen LCN2-variants (five NSVs) were detected. LCN2-p.Leu6Pro and p.Gly9Val located in the highly conserved signal peptide region may induce functional consequences. The secondary structure change of lipocalin-2 due to LCN2-p.Val89Ile may decrease solubility and results in a low lipocalin-2 level in a heterozygotes carrier (female recovered from AN). Lean individuals had lower lipocalin-2 levels compared to patients with obesity (p = 0.033). Conclusion: Lipocalin-2 levels are positively associated with body mass index (BMI). Single LCN2-variants might have a profound effect on lipocalin-2 levels.

Live Donor Assessment Tool (LDAT): Reliability and Validity of the German Version in Living Kidney Donor Candidates.

BACKGROUND: The Live Donor Assessment Tool (LDAT) is a semi-structured psychosocial assessment tool for evaluating potential organ donors. It enables standardization of the psychosocial evaluation across institutions and allows the quantification of the evaluation result. OBJECTIVE: To evaluate the validity and reliability of the German version of the LDAT in living kidney donors. METHODS: We assessed the internal consistency and convergent validity (using known groups) of the German version of the LDAT in donor candidates who were evaluated at Hannover Medical School from May 2017 to December 2021. RESULTS: One hundred fifty-two donor candidates were evaluated. The mean age was 50.9 (standard deviation, 12.0), 99 were female (65.1%) and 53 (34.9%) were male candidates. LDAT scores ranged from 39 to 78 (possible maximum score = 82). The mean and median LDAT scores in the entire sample were 69 (standard deviation, 6.4) and 71 (95% confidence interval, 68; 70), respectively. The LDAT items demonstrated good internal consistency (α = 0.737). LDAT scores were significantly lower in high and moderate risk donors compared to a low/no risk group as determined by clinical evaluation. We found a significant positive association of the LDAT total score with age and a negative correlation with levels of depression and anxiety. The best cutoff score in our sample was 66.5 with an area under the curve of 93%. CONCLUSIONS: The German version of the LDAT was found to be a reliable and valid tool, which seems suitable to support psychosocial donor evaluation.

The role of general change mechanisms in sudden gains in the treatment of anorexia nervosa.

Previous research has shown a robust association between sudden gains (SGs) and treatment outcome in psychotherapy for various mental disorders including anorexia nervosa (AN). However, little is known about factors contributing to SGs. This study investigated the role of general change mechanisms in body-weight related SGs in AN. Data were drawn from a randomized-controlled trial on cognitive-behavioral therapy (CBT) and focal psychodynamic therapy (FPT) for adult outpatients with AN. Session-level data on the general change mechanisms 'clarification' (insight), 'mastery' (coping), and 'therapeutic relationship' were analyzed. Pre-gain sessions were compared with control (pre-pre-gain) sessions in 99 patients with a SG in body weight. Additionally, propensity score matching was used to compare data from pre-gain sessions from 44 patients with SG and data from the corresponding session from 44 patients without SG. In the pre-gain session, patients experienced higher levels of clarification and mastery but not therapeutic relationship. Compared to patients without a SG, patients with a SG likewise experienced more clarification and mastery but not a better therapeutic relationship in the pre-gain/corresponding session. CBT and FPT did not differ regarding these effects. The findings suggest that general change mechanisms contribute to SGs in CBT and FPT for AN.

What Kind of Patients Receive Inpatient and Day-Hospital Treatment in Departments of Psychosomatic Medicine and Psychotherapy in Germany?

INTRODUCTION: Germany is one of the few countries with a medical specialty of psychosomatic medicine and psychotherapy and many treatment resources of this kind. OBJECTIVE: This observational study describes the psychosomatic treatment programs as well as a large sample of day-hospital and inpatients in great detail using structured diagnostic interviews. METHODS: Mental disorders were diagnosed according to ICD-10 and DSM-IV by means of Mini-DIPS and SCID-II. In addition to the case records, a modified version of the CSSRI was employed to collect demographic data and service use. The PHQ-D was used to assess depression, anxiety, and somatization. RESULTS: 2,094 patients from 19 departments participated in the study after giving informed consent. The sample consisted of a high proportion of "complex patients" with high comorbidity of mental and somatic diseases, severe psychopathology, and considerable social and occupational dysfunction including more than 50 days of sick leave per year in half of the sample. The most frequent diagnoses were depression, somatoform and anxiety disorders, eating disorders, personality disorders, and somato-psychic conditions. CONCLUSIONS: Inpatient and day-hospital treatment in German university departments of psychosomatic medicine and psychotherapy is an intensive multimodal treatment for complex patients with high comorbidity and social as well as occupational dysfunction.

Assessment of health-related quality of life in individuals with depressive symptoms: validity and responsiveness of the EQ-5D-3L and the SF-6D.

BACKGROUND: The EQ-5D and the SF-6D are examples of commonly used generic preference-based instruments for assessing health-related quality of life (HRQoL). However, their suitability for mental disorders has been repeatedly questioned. OBJECTIVE: To assess the responsiveness and convergent validity of the EQ-5D-3L and SF-6D in patients with depressive symptoms. METHODS: The data analyzed were from cardiac patients with depressive symptoms and were collected as part of the SPIRR-CAD (Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease) trial. The EQ-5D-3L and SF-6D were compared with the HADS (Hospital Anxiety and Depression Scale) and PHQ-9 (Patient Health Questionnaire) as disease-specific instruments. Convergent validity was assessed using Spearman's rank correlation. Effect sizes were calculated and ROC analysis was performed to determine responsiveness. RESULTS: Data from 566 patients were analysed. The SF-6D correlated considerably better with the disease-specific instruments (|rs|= 0.63-0.68) than the EQ-5D-3L (|rs|= 0.51-0.56). The internal responsiveness of the SF-6D was in the upper range of a small effect (ES: - 0.44 and - 0.47), while no effect could be determined for the EQ-5D-3L. Neither the SF-6D nor the EQ-5D-3L showed acceptable external responsiveness for classifying patients' depressive symptoms as improved or not improved. The ability to detect patients whose condition has deteriorated was only acceptable for the EQ-5D-3L. CONCLUSION: Overall, both the convergent validity and responsiveness of the SF-6D are better than those of the EQ-5D-3L in patients with depressive symptoms. The SF-6D appears, therefore, more recommendable for use in studies to evaluate interventions for this population.

Mentalization-enhancing therapeutic interventions in the psychotherapy of anorexia nervosa: An analysis of use and influence on patients' mentalizing capacity.

OBJECTIVE: Improvement in patients' mentalizing capacities is considered a possible mechanism of change in psychotherapy. This improvement might take place via mentalization-enhancing interventions (MEIs) performed by psychotherapists. The study aimed to explore the use of MEIs in two evidence-based psychotherapeutic treatments for patients with anorexia nervosa (enhanced cognitive-behavior therapy, focal psychodynamic therapy) and their association with the patients' capacity to mentalize in sessions ("in-session reflective functioning" / in-session RF). Additionally, it was explored, if the amount of MEIs used could either predict change in in-session RF or outcome (end of treatment, one year follow-up). METHOD: 84 audiotapes from psychotherapy sessions of 28 patients of the ANTOP-study (three sessions per patient) were transcribed and rated with both the MEI Rating Scale and the In-Session RF Scale by trained raters. RESULTS: MEIs were applied in both treatments. A moderate correlation between the amount of MEIs and patients' in-session RF as well as its change over the course of treatment was found, but no relation to change in BMI or eating disorder symptoms. CONCLUSION: A greater use of MEIs was related to patients' in-session-mentalizing. However, there seems to be no simple relation between RF as shown in sessions and symptom change.

Prevalence and clinical correlates of misophonia symptoms in the general population of Germany.

Introduction: Misophonia refers to a phenomenon in which affected individuals have a selective intolerance to sounds of mostly oral or nasal origin. This intolerance is typically associated with strong emotional reactions such as anger, irritation, and disgust. The aim of this study was to conduct the first large epidemiological survey to determine the prevalence of misophonia symptoms in the adult population in Germany. Methods: We conducted a large-scale representative population survey between December 2020 and March 2021. For this purpose, a sample of 2,519 people were visited in their households and assessed with the Misophonia Questionnaire (MQ) and the Amsterdam Misophonia Questionnaire (AMISOS-R) to document misophonic symptoms. The primary estimate of clinical misophonia symptoms prevalence was based on the MQ Severity Scale and a secondary estimate was based on the AMISOS-R. The survey further included self-ratings to measure perfectionism, not-just-right experience (NJRE), autonomous sensory meridian response (ASMR) and general health as well as demographic data. Results: Five percent of the sample scored equal or above the MQ Severity Scale threshold for clinical misophonia symptoms (5.9% based on AMISOS-R). Individuals with clinical misophonia symptoms had a higher rate of perfectionism, a higher occurrence of NJRE, higher susceptibility to ASMR, and a worse general health status than those scoring below the cut-off-score. All those factors also independently predicted the severity of misophonia symptoms in a multiple regression model. Conclusion: Misophonia is a frequent condition and should further be examined as an independent diagnostic entity.

Common Genetic Variation and Age of Onset of Anorexia Nervosa.

Background: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche. Methods: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (<13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses. Results: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h 2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early- and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early-onset AN. Conclusions: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.