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

Neuropeptide S receptor gene - converging evidence for a role in panic disorder

Animal studies have suggested neuropeptide S (NPS) and its receptor (NPSR) to be involved in the pathogenesis of anxiety-related behavior. In this study, a multilevel approach was applied to further elucidate the role of NPS in the etiology of human anxiety. The functional NPSR A/T (Asn¹⁰⁷Ile) variant (rs324981) was investigated for association with (1) panic disorder with and without agoraphobia in two large, independent case-control studies, (2) dimensional anxiety traits, (3) autonomic arousal level during a behavioral avoidance test and (4) brain activation correlates of anxiety-related emotional processing in panic disorder. The more active NPSR rs324981 T allele was found to be associated with panic disorder in the female subgroup of patients in both samples as well as in a meta-analytic approach. The T risk allele was further related to elevated anxiety sensitivity, increased heart rate and higher symptom reports during a behavioral avoidance test as well as decreased activity in the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate cortex during processing of fearful faces in patients with panic disorder. The present results provide converging evidence for a female-dominant role of NPSR gene variation in panic disorder potentially through heightened autonomic arousal and distorted processing of anxiety-relevant emotional stimuli

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

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

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

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).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.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.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

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

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