Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression.

Panic disorder (PD) has a lifetime prevalence of 2-4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0-34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10-4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10-7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD.

[Interactive Health Literacy, Sociodemographic Characteristics and the Uptake of Psychotherapeutic or Pharmacological Interventions - are there Social Inequalities in the Treatment of Social Anxiety Disorder?] / Interaktive Gesundheitskompetenz, soziodemografische Faktoren und der Zeitraum bis zur Inanspruchnahme psychotherapeutischer oder medikamentöser Behandlung ­ gibt es Hinweise auf soziale Ungleichheiten in der Therapie der Sozialen Angststörung?

AIM: The aim is to investigate the association between sociodemographic characteristics and the interactive health literacy and the time to treatment of social anxiety disorder. METHODS: An online survey of N = 311 patients was carried out (response rate 54.1 %). Descriptive statistical analysis and a logistic regression analysis were carried out. RESULTS: The respondents are on average 46 years old (20-81), 59 % are women. Older age (OR 2,579), not living in partnership (OR 1,963), fear of personal contact (OR 5,716) and low (OR 3,585) or moderate (OR 3,144) interactive health literacy were significantly associated with the time to treatment. CONCLUSION: The data suggest that social inequalities exist regarding the use of psychotherapeutic or pharmacological interventions in people with social anxiety disorder.

Childhood adversities, bonding, and personality in social anxiety disorder with alcohol use disorder.

Social anxiety disorder (SAD) is frequently associated with alcohol use disorders (abuse/dependence). However, there has been little research on the characteristics of this subgroup so far. In the current study we investigated individuals with SAD and comorbid alcohol use disorder (AUD) with regard to socialization experiences and personality. The sample comprised 410 individuals diagnosed with SAD by the Structured Clinical Interview of DSM-IV. 108 participants with comorbid AUD were compared to 302 participants without comorbid AUD concerning traumatic experiences during childhood and adolescence (Adverse Childhood Experiences Questionnaire; ACE), parental bonding (Parental Bonding Instrument; PBI), and personality (Temperament and Character Inventory; TCI). MANCOVA with covariates sex and depression displayed that individuals with SAD plus AUD reported significantly more traumatic events during childhood and adolescence, lower levels of maternal care, as well as lower cooperativeness. Our results highlight that adverse childhood experiences and unfavourable maternal bonding characterize individuals suffering from SAD plus AUD. These experiences might be reflected in a personality-based tendency to distance themselves from others, which corresponds to low scores on the character dimension cooperativeness. A deeper understanding of personality and specific socialization experiences is necessary to develop new treatment options in this clinically challenging subgroup.

Further evidence for genetic variation at the serotonin transporter gene SLC6A4 contributing toward anxiety.

OBJECTIVES: Social anxiety disorder (SAD) is a common and heritable psychiatric disorder. However, genetic studies in SAD are rare and only a few candidate genes have been implicated so far. In the present study, we investigated whether single-nucleotide polymorphisms (SNPs) associated with other psychiatric disorders also contribute toward the development of SAD and followed up variants associated with SAD on the phenotypic level. PATIENTS AND METHODS: We genotyped a total of 24 SNPs in a German sample of 321 SAD patients and 804 controls. We carried out single-marker analyses as well as quantitative association analyses of SAD severity and harm avoidance. RESULTS: None of the variants investigated showed an association with SAD in our case-control sample after Bonferroni correction. Two SNPs reached nominal significance (rs818702, P=0.032; rs140701, P=0.048). Of these, only rs140701 showed an association in the same allelic direction as reported previously. This SNP is located within the serotonin transporter gene SLC6A4, which is the primary target of selective-serotonin reuptake inhibitors used for the treatment of depressive and anxiety disorders. The quantitative association analysis of all cases with available data on symptom severity showed four SNPs with a nominal significant association. Among these SNPs, rs10994359 showed the strongest association (P=0.001) and was located near the ANK3 gene. In addition, rs10994359 was nominally associated with harm avoidance scores (P=0.001). CONCLUSION: Our results provide further evidence for an involvement of the serotonin transporter gene SLC6A4 in the etiology of anxiety-related traits. Furthermore, our study implicates that genetic variation at the genome-wide associated bipolar disorder locus ANK3 might influence anxiety-related personality traits.

Suicidality in patients with somatoform disorder - the speechless expression of anger?

OBJECTIVE: To identify emotion-associated risk factors for suicidality in patients with somatoform disorders. METHODS: A sample of 155 consecutive patients diagnosed with somatoform disorders at the Psychosomatic Ambulance of Bonn University Hospital filled in several questionnaires including the Symptom Checklist 90-Revised Version (SCL-90-R), the Toronto Alexithymia Scale (TAS-20), and the State Trait Anger Expression Inventory (STAXI). Our aim was to compare patients with suicide attempts to patients without suicide attempts via a MANCOVA (IV: Group; DV: SCL-90-R, TAS-20, STAXI; covariates: sex, age, depression, borderline personality disorder). RESULTS: Lifetime suicide attempts were documented in 20 patients (12.9%), current active suicidal ideation in 33.6%, and thoughts of death or dying in 55.9%. Patients with lifetime suicide attempts showed significantly more psychological distress, a significantly higher alexithymia sum score, a significantly higher score on trait anger, state anger, and a stronger tendency to express anger. CONCLUSION: Somatoform disorder patients with lifetime suicide attempts might have greater difficulties in identifying and describing emotions, and a tendency to intensely experience and express anger. Future longitudinal studies should further investigate possible links between difficulties in coping with anger and suicidality to improve prophylaxis and treatment of suicidal behaviour in somatoform disorder patients.

Psychosocial assessment of living kidney donors: What implications have temperament and character for decision-making?

OBJECTIVE: We compared the personality of kidney donor candidates to non-donor controls and analyzed the personality profile of candidates psychosocially at risk. METHODS: 49 consecutive living kidney donor candidates underwent an extensive psychosocial evaluation. Psychosocial risk factors concerning knowledge of donation risks (1), donor-recipient-relationship (2), and/or mental health (3) were rated on a 3-point rating scale (0=high risk, 2=no risk). Furthermore, candidates as well as 49 age-and gender-matched non-donor controls filled in questionnaires concerning psychological distress (Symptom Checklist 90-R) and personality (Temperament and Character Inventory). RESULTS: There were no significant differences between candidates and controls concerning psychological distress or personality. Psychosocial assessment identified 13 candidates (26.5%) with increased psychosocial risk. This group displayed compared to candidates without psychosocial risk no difference concerning age, gender, formal education, donor-recipient relationship and psychological distress. However, this group scored significantly higher on reward dependence compared to suitable donors and controls (p<0.05). Reward dependence was associated with a lack of adequate knowledge on donation (r=-0.35, p<0.05). CONCLUSION: Reward dependence has important implications for decision-making, because it is associated with an increased tendency to deny potential risks of donation. Careful identification and assessment of reward dependent donor candidates is needed to ensure a free-willed decision.

The association between depressive symptoms and emotion recognition is moderated by emotion regulation.

In this study, we examined the associations between depression and aspects of emotional functioning, namely emotion recognition, affectivity and interpersonal problems. Particularly, the moderating role of emotion regulation in these interrelations was tested in a sample of 85 women, who exhibited a wide range of depressive symptoms (Composite International Diagnostic Interview (CIDI), Beck Depression Inventory (BDI)). Emotion recognition was assessed with a paradigm displaying a widely used set of photographs of the six basic emotions in graded intensities. Further, participants were examined regarding emotion regulation (Emotion Regulation Questionnaire (ERQ)), interpersonal problems (Inventory of Interpersonal Problems-Circumplex (IIP-C)) and affectivity (Affect Intensity Measure (AIM), Positive and Negative Affect Schedule (PANAS)). Besides correlation analyses, Johnson-Neyman technique for probing interactions in linear regression models was applied to test for possible moderating effects. Depressive symptoms were positively correlated with error rates in anger recognition, but not with the other basic emotions. This association was moderated by suppression in that regard that more severely depressed women who more frequently used suppression showed superior recognition of angry faces than those with lower suppression values. Further, suppression was associated with an affective imbalance and interpersonal problems in women with current depressive disorder. In sum, our results emphasize the importance of differentiating subtypes of depression depending on emotion regulation capabilities for research on or treatment of emotional functioning in depression.