Eating disorder treatment in routine clinical care: A descriptive study examining treatment characteristics and short-term treatment outcomes among patients with anorexia nervosa and bulimia nervosa in Germany and Switzerland.

This descriptive study examined patient characteristics, treatment characteristics, and short-term outcomes among patients with Anorexia Nervosa (AN) and Bulimia Nervosa (BN) in routine clinical care. Results for patients receiving full-time treatment were contrasted with results for patients receiving ambulatory treatment. Data of a clinical trial including 116 female patients (18-35 years) diagnosed with AN or BN were subjected to secondary analyses. Patients were voluntarily admitted to one of nine treatment facilities in Germany and Switzerland. Patients received cognitive-behavioral interventions in accordance with the national clinical practice guidelines for the treatment of EDs under routine clinical care conditions, either as full-time treatment or ambulatory treatment. Assessments were conducted after admission and three months later. Assessments included a clinician-administered diagnostic interview (DIPS), body-mass-index (BMI), ED pathology (EDE-Q), depressive symptoms (BDI-II), symptoms of anxiety (BAI), and somatic symptoms (SOMS). Findings showed that treatment intensity differed largely by setting and site, partly due to national health insurance policies. Patients with AN in full-time treatment received on average 65 psychotherapeutic sessions and patients with BN in full-time treatment received on average 38 sessions within three months. In comparison, patients with AN or BN in ambulatory treatment received 8-9 sessions within the same time. Full-time treatment was associated with substantial improvements on all measured variables for both women with AN (d = .48-.83) and BN (d = .48-.81). Despite the relatively small amount of psychotherapeutic sessions, ambulatory treatment was associated with small increases in BMI (d = .37) among women with AN and small improvements on all measured variables among women with BN (d = .27-.43). For women with AN, reduction in ED pathology were positively related to the number of psychotherapeutic sessions received. Regardless of diagnosis and treatment setting, full recovery of symptoms was rarely achieved within three months (recovery rates ranged between 0 and 4.4%). The present study shows that a considerable amount of patients with EDs improved after CBT-based ED treatment in routine clinical care within three months after admission. Intensive full-time treatment may be particularly effective in quickly improving ED-related pathology, although full remission of symptoms is typically not achieved. A small amount of ambulatory sessions may already produce considerable improvements in BN pathology and weight gain among women with AN. As patient characteristics and treatment intensity differed largely between settings, results should not be interpreted as superiority of one treatment setting over another. Furthermore, this study shows that treatment intensity is quite heterogeneous, indicating the possibility for increasing effectiveness in the treatment of EDs in routine clinical care.

Consequences of exposure to the thin ideal in mass media depend on moderators in young women: An experimental study.

This study examined the consequences of media exposure to thin ideals compared to pictures of landscapes in healthy young women and women with eating and mixed mental disorders and investigated whether appearance-related cognitive factors and cognitive distortions moderate the effects. Two hundred seventy-five women in a multisite laboratory trial (174 in- or outpatients and 101 healthy women; Mage 22.87 years, SD = 3.94) were exposed to either thin ideals or to landscape pictures and guided through a vivid imagery of these pictures thereafter. Changes in body image dissatisfaction, mood, eating behavior, and physiological markers were assessed. After thin ideal exposure and even more after guided imagery, women's body image dissatisfaction increased and mood declined. The effect on mood was most pronounced in women with eating disorders, less in women with mixed disorders, and smallest in healthy controls. No effects were found on physiological measures. Higher values of appearance-related cognitive factors moderated the effect of thin ideal exposure and guided imagery on all psychological outcomes. Cognitive distortions moderated the effect of thin ideal exposure and guided imagery on mood. Findings indicate an overall susceptibility to viewing thin ideal pictures in magazines in young and especially in women with eating disorders. Though exposure in the laboratory resulted in psychological effects, it did not lead to a physiological stress response. The impact of thin ideal exposure on mood is in line with affect-regulation models in eating disorders, with appearance-related cognitive factors and cognitive distortions potentially accelerating such effects. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The role of stigma during the course of inpatient psychotherapeutic treatment in a German sample.

The current study intends to investigate whether the therapeutic process is impeded by stigma and how stigma develops over the course of cognitive behavioural psychotherapy treatment. Sixty German psychotherapy inpatients were asked on a weekly basis about two facets of stigma: self-stigma and perceived public stigma. That information was linked to additional process as well as outcome variables (therapeutic engagement, working alliance, depressive, and general psychological symptoms). Both facets of stigma decreased over the course of psychotherapy, but only the decrease in self-stigma was significant. In a weekly interval, low (high) self-stigma predicted high (low) levels of working alliance and therapeutic engagement and vice versa. The current study shows that self-stigma is especially subject to change during the course of an inpatient psychotherapeutic treatment. In addition, our results point to the interrelation between self-stigma and other process variables contributing to the effectiveness and success of psychotherapy.

Facial Emotion Recognition Abilities in Women Experiencing Eating Disorders.

OBJECTIVE: Impairments in facial emotion recognition are an underlying factor of deficits in emotion regulation and interpersonal difficulties in mental disorders and are evident in eating disorders (EDs). METHODS: We used a computerized psychophysical paradigm to manipulate parametrically the quantity of signal in facial expressions of emotion (QUEST threshold seeking algorithm). This was used to measure emotion recognition in 308 adult women (anorexia nervosa [n = 61], bulimia nervosa [n = 58], healthy controls [n = 130], and mixed mental disorders [mixed, n = 59]). The M (SD) age was 22.84 (3.90) years. The aims were to establish recognition thresholds defining how much information a person needs to recognize a facial emotion expression and to identify deficits in EDs compared with healthy and clinical controls. The stimuli included six basic emotion expressions (fear, anger, disgust, happiness, sadness, surprise), plus a neutral expression. RESULTS: Happiness was discriminated at the lowest, fear at the highest threshold by all groups. There were no differences regarding thresholds between groups, except for the mixed and the bulimia nervosa group with respect to the expression of disgust (F(3,302) = 5.97, p = .001, η = .056). Emotional clarity, ED pathology, and depressive symptoms did not predict performance (RChange ≤ .010, F(1,305) ≤ 5.74, p ≥ .079). The confusion matrix did not reveal specific biases in either group. CONCLUSIONS: Overall, within-subject effects were as expected, whereas between-subject effects were marginal and psychopathology did not influence emotion recognition. Facial emotion recognition abilities in women experiencing EDs compared with women experiencing mixed mental disorders and healthy controls were similar. Although basic facial emotion recognition processes seems to be intact, dysfunctional aspects such as misinterpretation might be important in emotion regulation problems. CLINICAL TRIAL REGISTRATION NUMBER: DRKS-ID: DRKS00005709.

Self-reported emotion regulation difficulties are associated with mood but not with the biological stress response to thin ideal exposure.

BACKGROUND: Difficulties in emotion regulation have been related to psychological and physiological stress responses such as lower mood and lower parasympathetic activation (HF-HRV) under resting condition, but evidence on the potential link to the hypothalamic-pituitary-adrenal (HPA) axis functioning and to physiological stress responses during a stress task is still scarce. The aim of the study was to investigate stress responses in young women when confronted to a daily stressor such as exposure to thin ideals and to understand the role of correlates of self-reported trait-like emotion regulation difficulties (ERD). METHODS: Heart rate variability (HRV) and salivary cortisol data were collected in a sample of 273 young women aged 18-35 with and without mental disorders during a vivid imagination of thin ideals (experimental condition) or landscapes (control condition). Changes in mood states were measured on a visual analogue scale (0-100). Correlates of trait-like ERD were self-reported using the Difficulties in Emotion Regulation Scale (DERS). RESULTS: Participants with higher ERD showed a stronger decline in self-reported mood after vivid imagination of thin ideals compared to participants with lower ERD in the experimental condition but also a stronger increase of positive mood with increasing ERD in the control condition. ERD were not related to baseline HF-HRV or baseline salivary cortisol levels nor to any physiological response during and after the imagination of thin ideals. DISCUSSION AND CONCLUSION: The results corroborate the role of ERD regarding the immediate psychological impact of daily stressors. Exposition to daily stressors in the laboratory results in discrepant psychological and physiological reactivity. Future studies should investigate under what conditions the complex interrelations between immediate and long-term ERD and biological activation are amenable to assessment in a laboratory setting. The additive effects of multiple exposition to stressors, such as thin ideals in daily life, also need to be addressed.

RGS2 ggenetic variation: association analysis with panic disorder and dimensional as well as intermediate phenotypes of anxiety.

Accumulating evidence from mouse models points to the G protein-coupled receptor RGS2 (regulator of G-protein signaling 2) as a promising candidate gene for anxiety in humans. Recently, RGS2 polymorphisms were found to be associated with various anxiety disorders, e.g., rs4606 with panic disorder (PD), but other findings have been negative or inconsistent concerning the respective risk allele. To further examine the role of RGS2 polymorphisms in the pathogenesis of PD, we genotyped rs4606 and five additional RGS2 tag single nucleotide polymorphisms (SNPs; rs16834831, rs10801153, rs16829458, rs1342809, rs1890397) in two independent PD samples, comprising 531 matched case/control pairs. The functional SNP rs4606 was nominally associated with PD when both samples were combined. The upstream SNP rs10801153 displayed a Bonferroni-resistant significant association with PD in the second and the combined sample (P = 0.006 and P = 0.017). We furthermore investigated the effect of rs10801153 on dimensional anxiety traits, a behavioral avoidance test (BAT), and an index for emotional processing in the respective subsets of the total sample. In line with categorical results, homozygous risk (G) allele carriers displayed higher scores on the Agoraphobic Cognitions Questionnaire (ACQ; P = 0.015) and showed significantly more defensive behavior during fear provoking situations (P = 0.001). Furthermore, significant effects on brain activation in response to angry (P = 0.013), happy (P = 0.042) and neutral faces (P = 0.032) were detected. Taken together, these findings provide further evidence for the potential role of RGS2 as a candidate gene for PD.

[Experience of loss and complicated grief in depressive inpatients]. / Verlusterleben und prolongierte Trauer bei depressiven Patienten.

OBJECTIVE: Inpatients diagnosed with major depression that had lost a loved person were asked about loss-related variables and symptoms of complicated grief (CG). METHODS AND RESULTS: CG was assessed by the Inventory of Complicated Grief (ICG-R). 14.2% of n = 127 individuals with unipolar depression met the criteria for CG. Depressive patients with CG compared to those without CG had a lower educational level; reported a higher loss-related burden at the time of loss, during the survey and the year after the loss; had significant different closeness within the relationships to the deceased; and time of loss was more recently. CONCLUSIONS: An adequate differential diagnostic is essential for the treatment of major depression. Therefore loss-related factors and symptoms of complicated grief must be investigated regularly.

Neuropeptide S receptor gene (NPSR) and life events: G × E effects on anxiety sensitivity and its subdimensions.

OBJECTIVES: The pathogenesis of anxiety is assumed to be interactively influenced by genetic and environmental factors. Thus, a gene-environment interaction (G × E) study of the neuropeptide S receptor gene (NPSR) A/T polymorphism (rs324981) and life events was conducted with respect to anxiety sensitivity (AS) as an intermediate phenotype of anxiety disorders. METHODS: A sample of 475 healthy German subjects was genotyped for NPSR and assessed for AS, childhood maltreatment (CTQ) and recent life events (LTE). Influences on AS and its subdimensions were determined by a step-wise hierarchical regression and a multiple indicator multiple cause (MIMIC) model. RESULTS: Significant main effects of NPSR and CTQ as well as significant G × E were observed, with T/T homozygosity and a high CTQ score resulting in increased anxiety sensitivity. MIMIC modelling yielded association of AS subfactor "concern about mental/cognitive incapacitation" and the basal somatic subdimension "concern about physical sensations" to be associated with CTQ and its interaction with NPSR, while the acute somatic subfactor "concern about heart/lung failure" was associated with NPSR and its interaction with LTE. CONCLUSIONS: Results indicate G × E effects of the more active NPSR rs324981 T allele and life events on AS with differential effects of temporally proximal and distal factors on specific AS subdimensions.

Epigenetic signature of panic disorder: a role of glutamate decarboxylase 1 (GAD1) DNA hypomethylation?

Glutamate decarboxylases (GAD67/65; GAD1/GAD2) are crucially involved in gamma-aminobutyric acid (GABA) synthesis and thus were repeatedly suggested to play an important role in the pathogenesis of anxiety disorders. In the present study, DNA methylation patterns in the GAD1 and GAD2 promoter and GAD1 intron 2 regions were investigated for association with panic disorder, with particular attention to possible effects of environmental factors. Sixty-five patients with panic disorder (f=44, m=21) and 65 matched healthy controls were analyzed for DNA methylation status at 38 GAD1 promoter/intron2 and 10 GAD2 promoter CpG sites via direct sequencing of sodium bisulfate treated DNA extracted from blood cells. Recent positive and negative life events were ascertained. Patients and controls were genotyped for GAD1 rs3762556, rs3791878 and rs3762555, all of which are located in the analyzed promoter region. Patients with panic disorder exhibited significantly lower average GAD1 methylation than healthy controls (p<0.001), particularly at three CpG sites in the promoter as well as in intron 2. The occurrence of negative life events was correlated with relatively decreased average methylation mainly in the female subsample (p=0.01). GAD1 SNP rs3762555 conferred a significantly lower methylation at three GAD1 intron 2 CpG sites (p<0.001). No differential methylation was observed in the GAD2 gene. The present pilot data suggest a potentially compensatory role of GAD1 gene hypomethylation in panic disorder possibly mediating the influence of negative life events and depending on genetic variation. Future studies are warranted to replicate the present finding in independent samples, preferably in a longitudinal design.

Meta-analysis argues for a female-specific role of MAOA-uVNTR in panic disorder in four European populations.

Panic disorder (PD) is a common mental disorder, ranking highest among the anxiety disorders in terms of disease burden. The pathogenesis of PD is multifactorial with significant heritability, however only a few convincing risk genes have been reported thus far. One of the most promising candidates is the gene encoding monoamine oxidase A (MAOA), due to its key role in monoaminergic neurotransmission, established validity of animal models, and the efficacy of MAO inhibitors in the treatment of PD. A promoter repeat polymorphism in MAOA (MAOA-uVNTR) impacts on gene expression; high-expression alleles have been reported to increase the risk for PD. To further scrutinize the role of this polymorphism, we performed a formal meta-analysis on MAOA-uVNTR and PD using original data from four published European (Estonian, German, Italian, and Polish) samples and genotypes from three hitherto unpublished German PD samples, resulting in the largest (n = 1,115 patients and n = 1,260 controls) genetic study on PD reported to date. In the unpublished samples, evidence for association of MAOA-uVNTR with PD was obtained in one of the three samples. Results of the meta-analysis revealed a significant and female-specific association when calculating an allelic model (OR = 1.23, P = 0.006). This sex-specific effect might be explained by a gene-dose effect causing higher MAOA expression in females. Taken together, our meta-analysis therefore argues that high-expression MAOA-uVNTR alleles significantly increase the risk towards PD in women. However, epigenetic mechanisms might obfuscate the genetic association, calling for ascertainment in larger samples as well as assessment of the MAOA promoter methylation status therein.

Gender differences in associations of glutamate decarboxylase 1 gene (GAD1) variants with panic disorder.

BACKGROUND: Panic disorder is common (5% prevalence) and females are twice as likely to be affected as males. The heritable component of panic disorder is estimated at 48%. Glutamic acid dehydrogenase GAD1, the key enzyme for the synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to influence various mental disorders, including mood and anxiety disorders. In a recent association study in depression, which is highly comorbid with panic disorder, GAD1 risk allele associations were restricted to females. METHODOLOGY/PRINCIPAL FINDINGS: Nineteen single nucleotide polymorphisms (SNPs) tagging the common variation in GAD1 were genotyped in two independent gender and age matched case-control samples (discovery sample n = 478; replication sample n = 584). Thirteen SNPs passed quality control and were examined for gender-specific enrichment of risk alleles associated with panic disorder by using logistic regression including a genotype×gender interaction term. The latter was found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034, rs2241165) in the discovery sample; of note, the respective minor/risk alleles were associated with panic disorder only in females. These findings were not confirmed in the replication sample; however, the genotype×gender interaction of rs3749034 remained significant in the combined sample. Furthermore, this polymorphism showed a nominally significant association with the Agoraphobic Cognitions Questionnaire sum score. CONCLUSIONS/SIGNIFICANCE: The present study represents the first systematic evaluation of gender-specific enrichment of risk alleles of the common SNP variation in the panic disorder candidate gene GAD1. Our tentative results provide a possible explanation for the higher susceptibility of females to panic disorder.

Affect-modulated startle: interactive influence of catechol-O-methyltransferase Val158Met genotype and childhood trauma.

The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system--partly conferred by catechol-O-methyltransferase (COMT) gene variation--for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.

Modification of caffeine effects on the affect-modulated startle by neuropeptide S receptor gene variation.

RATIONALE/OBJECTIVES: Both the neuropeptide S (NPS) system and antagonism at the adenosine A2A receptor (e.g., by caffeine) were found to play a crucial role in the mediation of arousal and anxiety/panic in animal and human studies. Furthermore, a complex interaction of the neuropeptide S and the adenosinergic system has been suggested with administration of the adenosine A2A receptor antagonist caffeine downregulating NPS levels (Lage et al., 2006) and attenuating the stimulatory effects of NPS in rodents (Boeck et al., 2010). METHODS: Thus, in the present study, the impact of the functional neuropeptide S receptor (NPSR) A/T (Asn(107)Ile; rs324981) variant on affect-modulated (neutral, unpleasant, and pleasant IAPS pictures) startle response depending on the administration of 300 mg caffeine citrate was investigated in a sample of 124 (m = 58, f = 66) healthy probands using a double-blind, placebo-controlled design. RESULTS: ANOVA revealed a significant interaction between NPSR genotype, challenge condition, and picture valence. Comparing startle magnitudes upon stimulation with neutral or emotional pictures between the placebo and caffeine condition, in AA/AT non-risk genotype carriers no significant difference was discerned, while TT risk genotype carriers showed a significantly increased startle magnitude in response to neutral stimuli (p = .02) and a significantly decreased startle magnitude in response to unpleasant stimuli (p = .02) in the caffeine condition as compared to the placebo condition. CONCLUSIONS: In summary, the present findings - extending previous evidence from rodent studies - for the first time provide support for a complex, non-linear interaction of the neuropeptide S and adenosinergic systems affecting the affect-modulated startle response as an intermediate phenotype of anxiety in humans.

Monoamine oxidase A gene DNA hypomethylation - a risk factor for panic disorder?

The monoamine oxidase A (MAOA) gene has been suggested as a prime candidate in the pathogenesis of panic disorder. In the present study, DNA methylation patterns in the MAOA regulatory and exon 1/intron 1 region were investigated for association with panic disorder with particular attention to possible effects of gender and environmental factors. Sixty-five patients with panic disorder (44 females, 21 males) and 65 healthy controls were analysed for DNA methylation status at 42 MAOA CpG sites via direct sequencing of sodium bisulfate treated DNA extracted from blood cells. The occurrence of recent positive and negative life events was ascertained. Male subjects showed no or only very minor methylation with some evidence for relative hypomethylation at one CpG site in intron 1 in patients compared to controls. Female patients exhibited significantly lower methylation than healthy controls at 10 MAOA CpG sites in the promoter as well as in exon/intron 1, with significance surviving correction for multiple testing at four CpG sites (p≤0.001). Furthermore, in female subjects the occurrence of negative life events was associated with relatively decreased methylation, while positive life events were associated with increased methylation. The present pilot data suggest a potential role of MAOA gene hypomethylation in the pathogenesis of panic disorder particularly in female patients, possibly mediating a detrimental influence of negative life events. Future studies are warranted to replicate the present finding in independent samples, preferably in a longitudinal design.

Serotonin transporter gene and childhood trauma--a G × E effect on anxiety sensitivity.

BACKGROUND: Genetic factors and environmental factors are assumed to interactively influence the pathogenesis of anxiety disorders. Thus, a gene-environment interaction (G × E) study was conducted with respect to anxiety sensitivity (AS) as a promising intermediate phenotype of anxiety disorders. METHOD: Healthy subjects (N = 363) were assessed for AS, childhood maltreatment (Childhood Trauma Questionnaire), and genotyped for functional serotonin transporter gene variants (5-HTTLPR/5-HTT rs25531). The influence of genetic and environmental variables on AS and its subdimensions was determined by a step-wise hierarchical regression and a multiple indicator multiple cause (MIMIC) model. RESULTS: A significant G × E effect of the more active 5-HTT genotypes and childhood maltreatment on AS was observed. Furthermore, genotype (LL)-childhood trauma interaction particularly influenced somatic AS subdimensions, whereas cognitive subdimensions were affected by childhood maltreatment only. CONCLUSIONS: Results indicate a G × E effect of the more active 5-HTT genotypes and childhood maltreatment on AS, with particular impact on its somatic subcomponent.

Life events in panic disorder-an update on "candidate stressors".

Studies on gene-environment interactions in mental disorders are characterized by powerful genetic techniques and well defined "candidate genes," whereas a definition of "candidate stressors," in most cases assessed in the form of life events (LEs), is inconsistent or not even provided. This review addresses this problem, with particular attention to the clinical phenotype of panic disorder (PD), by providing an overview and critical discussion for which life events are known to contribute to the etiology of the disease and how they may be conceptualized. There is converging evidence for a significant impact of cumulative as well as specific life events, such as threat, interpersonal and health-related events in adulthood, and abuse or loss/separation experiences in childhood, respectively, on the pathogenesis of panic disorder with some overlapping effect across the anxiety disorder spectrum as well as on comorbid major depression. Besides genetic vulnerability factors, personality and behavioral characteristics, such as anxiety sensitivity, neuroticism, and cognitive appraisal might moderate the influence of LEs on the development of panic disorder. The present state of knowledge regarding the specification and conceptualization of LEs in PD within a more complex multifactorial model, involving mediating and moderating factors in between genes and the clinical phenotype, is hoped to aid in informing future gene-environment interaction studies in panic disorder.

New names for known things: on the association of novel word forms with existing semantic information.

The plasticity of the adult memory network for integrating novel word forms (lexemes) was investigated with whole-head magnetoencephalography (MEG). We showed that spoken word forms of an (artificial) foreign language are integrated rapidly and successfully into existing lexical and conceptual memory networks. The new lexemes were learned in an untutored way, by pairing them frequently with one particular object (and thus meaning), and infrequently with 10 other objects (learned set). Other novel word forms were encountered just as often, but paired with many different objects (nonlearned set). Their impact on semantic memory was assessed with cross-modal priming, with novel word forms as primes and object pictures as targets. The MEG counterpart of the N400 (N400m) served as an indicator of a semantic (mis)match between words and pictures. Prior to learning, all novel words induced a pronounced N400m mismatch effect to the pictures. This component was strongly reduced after training for the learned novel lexemes only, and now closely resembled the brain's response to semantically related native-language words. This result cannot be explained by mere stimulus repetition or stimulus-stimulus association. Thus, learned novel words rapidly gained access to existing conceptual representations, as effectively as related native-language words. This association of novel lexemes and conceptual information happened fast and almost without effort. Neural networks mediating these integration processes were found within left temporal lobe, an area typically described as one of the main generators of the N400 response.