Error-related brain activity as a transdiagnostic endophenotype for obsessive-compulsive disorder, anxiety and substance use disorder

Background Increased neural error-signals have been observed in obsessive-compulsive disorder (OCD), anxiety disorders, and inconsistently in depression. Reduced neural error-signals have been observed in substance use disorders (SUD). Thus, alterations in error-monitoring are proposed as a transdiagnostic endophenotype. To strengthen this notion, data from unaffected individuals with a family history for the respective disorders are needed. Methods The error-related negativity (ERN) as a neural indicator of error-monitoring was measured during a flanker task from 117 OCD patients, 50 unaffected first-degree relatives of OCD patients, and 130 healthy comparison participants. Family history information indicated, that 76 healthy controls were free of a family history for psychopathology, whereas the remaining had first-degree relatives with depression (n = 28), anxiety (n = 27), and/or SUD (n = 27). Results Increased ERN amplitudes were found in OCD patients and unaffected first-degree relatives of OCD patients. In addition, unaffected first-degree relatives of individuals with anxiety disorders were also characterized by increased ERN amplitudes, whereas relatives of individuals with SUD showed reduced amplitudes. Conclusions Alterations in neural error-signals in unaffected first-degree relatives with a family history of OCD, anxiety, or SUD support the utility of the ERN as a transdiagnostic endophenotype. Reduced neural error-signals may indicate vulnerability for under-controlled behavior and risk for substance use, whereas a harm- or error-avoidant response style and vulnerability for OCD and anxiety appears to be associated with increased ERN. This adds to findings suggesting a common neurobiological substrate across psychiatric disorders involving the anterior cingulate cortex and deficits in cognitive control

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

Spatial working memory performance in people with obsessive–compulsive disorder, their unaffected first-degree relatives and healthy controls

Studies have shown that people with obsessive–compulsive disorder (OCD) have impairments in spatial working memory (SWM) performance. However, it remains unclear whether this deficit represents a cognitive endophenotype preceding symptoms or a correlate of OCD. We investigated SWM in 69 people with OCD, 77 unaffected first-degree relatives of people with OCD and 106 healthy control participants. Taking age effects into account, SWM performance was best in healthy controls, intermediate in relatives and worst in OCD participants. However, since performance did not differ significantly between healthy controls and relatives, our study does not fully support SWM performance as a core cognitive endophenotype of OCD

Neural correlates of working memory deficits and associations to response inhibition in obsessive compulsive disorder

Previous research in patients with obsessive-compulsive disorder (OCD) has indicated performance decrements in working memory (WM) and response inhibition. However, underlying neural mechanisms of WM deficits are not well understood to date, and empirical evidence for a proposed conceptual link to inhibition deficits is missing.We investigated WM performance in a numeric n-back task with four WM load conditions during functional Magnetic Resonance Imaging (fMRI) in 51 patients with OCD and 49 healthy control participants who were matched for age, sex, and education. Additionally, a stop signal task was performed outside the MRI scanner in a subsample.On the behavioral level, a significant WM load by group interaction was found for both accuracy (p<0.02) and reaction time measures (p<0.03), indicating increased reaction times as well as reduced accuracy specifically at high WM load (3-back) in patients with OCD. Whole-brain analyses of fMRI-data identified neural correlates of a load-dependent WM decrement in OCD in the supplementary motor area (SMA) and the inferior parietal lobule (IPL). Within the OCD sample, SMA-activity as well as n-back performance were correlated with stop signal task performance.Results from behavioral and fMRI-analyses indicate a reduced WM load-dependent modulation of neural activity in OCD and suggest a common neural mechanism for inhibitory dysfunction and WM decrements in OCD. Keywords: Obsessive-compulsive disorder, Working memory, fMRI, Neuroimaging, Stop signal task, Inhibitio

Cognitive distortions associated with imagination of the thin ideal: validation of the thought-shape fusion body questionnaire (TSF-B)

Thought-shape fusion (TSF) describes the experience of body-related cognitive distortions associated with eating disorder (ED) pathology. In the laboratory TSF has been activated by thoughts about fattening/forbidden foods and thin ideals. This study aims at validating a questionnaire to assess the trait susceptibility to TSF (i.e., body-related cognitive distortions) associated with the imagination of thin ideals, and developing an adapted version of the original TSF trait questionnaire, the Thought-Shape Fusion Body Questionnaire (TSF-B). Healthy control women (HC, n = 317) and women diagnosed with subthreshold and clinical EDs (n = 243) completed an online-questionnaire. The factor structure of the TSF-B questionnaire was examined using exploratory (EFA) and subsequent confirmatory factor analysis (CFA). EFA pointed to a two-factor solution, confirmed by CFA. Subscale 1 was named Imagination of thin ideals, containing five items referring to the imagination of female thin ideals. Subscale 2 was named Striving for own thin ideal, with seven items about pursuing/abandoning attempts to reach one’s own thin ideal. The total scale and both subscales showed good convergent validity, excellent reliability, and good ability to discriminate between individuals with subthreshold/clinical EDs and HCs. Results indicate that cognitive distortions are also related to the imagination of thin ideals, and are associated with ED pathology. With two subscales, the TSF-B trait questionnaire appropriately measures this construct. Future studies should clarify whether TSF-B is predictive for the development and course of EDs. Assessing cognitive distortions with the TSF-B questionnaire could improve understanding of EDs and stimulate the development of cognitively oriented interventions. Clinical Trial Registration Number: DRKS-ID: DRKS00005709

Impaired Antisaccades in Obsessive-Compulsive Disorder: Evidence From Meta-Analysis and a Large Empirical Study

Increasing evidence indicates that patients with obsessive-compulsive disorder (OCD) exhibit alterations in fronto-striatal circuitry. Performance deficits in the antisaccade task would support this model, but results from previous small-scale studies have been inconclusive as either increased error rates, prolonged antisaccade latencies, both or neither have been reported in OCD patients. In order to address this issue, we investigated antisaccade performance in a large sample of OCD patients (n = 169) and matched control subjects (n = 183). As impaired antisaccade performance constitutes a potential endophenotype of OCD, unaffected first-degree relatives of OCD patients (n = 100) were assessed, as well. Furthermore, we conducted a quantitative meta-analysis to integrate our data with previous findings. In the empirical study, OCD patients exhibited significantly increased antisaccade latencies, intra-subject variability (ISV) of antisaccade latencies, and antisaccade error rates. The latter effect was driven by errors with express latency (80–130 ms), as patients did not differ significantly from controls with regards to regular errors (>130 ms). Notably, unaffected relatives of OCD patients showed elevated antisaccade express error rates and increased ISV of antisaccade latencies, as well. Antisaccade performance was not associated with state anxiety within groups. Among relatives, however, we observed a significant correlation between antisaccade error rate and harm avoidance. Medication status of OCD patients, symptom severity, depressive comorbidity, comorbid anxiety disorders and OCD symptom dimensions did not significantly affect antisaccade performance. Meta-analysis of 10 previous and the present empirical study yielded a medium-sized effect (SMD = 0.48, p < 0.001) for higher error rates in OCD patients, while the effect for latencies did not reach significance owing to strong heterogeneity (SMD = 0.51, p = 0.069). Our results support the assumption of impaired antisaccade performance in OCD, although effects sizes were only moderately large. Furthermore, we provide the first evidence that increased antisaccade express error rates and ISV of antisaccade latencies may constitute endophenotypes of OCD. Findings regarding these more detailed antisaccade parameters point to potentially underlying mechanisms, such as early pre-stimulus inhibition of the superior colliculus.Peer Reviewe

Cognitive Distortions Associated with Imagination of the Thin Ideal : Validation of the Thought-Shape Fusion Body Questionnaire (TSF-B)

Thought-shape fusion (TSF) describes the experience of body-related cognitive distortions associated with eating disorder (ED) pathology. In the laboratory TSF has been activated by thoughts about fattening/forbidden foods and thin ideals. This study aims at validating a questionnaire to assess the trait susceptibility to TSF (i.e., body-related cognitive distortions) associated with the imagination of thin ideals, and developing an adapted version of the original TSF trait questionnaire, the Thought-Shape Fusion Body Questionnaire (TSF-B). Healthy control women (HC, n = 317) and women diagnosed with subthreshold and clinical EDs (n = 243) completed an online-questionnaire. The factor structure of the TSF-B questionnaire was examined using exploratory (EFA) and subsequent confirmatory factor analysis (CFA). EFA pointed to a two-factor solution, confirmed by CFA. Subscale 1 was named Imagination of thin ideals, containing five items referring to the imagination of female thin ideals. Subscale 2 was named Striving for own thin ideal, with seven items about pursuing/abandoning attempts to reach one’s own thin ideal. The total scale and both subscales showed good convergent validity, excellent reliability, and good ability to discriminate between individuals with subthreshold/clinical EDs and HCs. Results indicate that cognitive distortions are also related to the imagination of thin ideals, and are associated with ED pathology. With two subscales, the TSF-B trait questionnaire appropriately measures this construct. Future studies should clarify whether TSF-B is predictive for the development and course of EDs. Assessing cognitive distortions with the TSF-B questionnaire could improve understanding of EDs and stimulate the development of cognitively oriented interventions. Clinical Trial Registration Number: DRKS-ID: DRKS00005709.publishe