Background: Patients with borderline personality disorder (BPD) experience difficulties in emotional awareness (alexithymia), and often develop dissociative symptoms, which may reflect broader deficits in interoceptive awareness. Whether this is associated with alterations in cortical processing of interoception is currently unknown. Methods: We utilized an electrophysiological marker of interoception, i.e. heartbeat-evoked potentials (HEP), and examined its relationship with electrocardiographic correlates of autonomic nervous system (ANS) functioning (heart rate variability), and with self-report measures of alexithymia, dissociation and borderline symptom severity in patients with BPD. Results: Individuals with BPD had higher HEP amplitudes over frontal electrodes compared to healthy controls. Sympathetic ANS activity was greater in BPD patients than in controls. Across groups, HEP amplitudes were associated with parasympathetic activity over central electrodes and correlated with alexithymia over frontal electrodes. Conclusions: These findings support the idea that difficulties in emotional awareness in BPD are reflected in altered frontal electrophysiological markers of interception. Therefore, emotional awareness can be understood as failures of modulation between interoceptive and exteroceptive attention. Future research may aim to investigate whether altered interoception and its electrophysiological correlates are malleable by therapeutic intervention.

DNA methylation analysis is increasingly used in stress research. Available methods are expensive, laborious and often limited by either the analysis of short CpG stretches or low assay sensitivity. Here, we present a cost-efficient next generation sequencing-based strategy for the simultaneous investigation of multiple candidate genes in large cohorts. To illustrate the method, we present analysis of four candidate genes commonly assessed in psychoneuroendocrine research: Glucocorticoid receptor (NR3C1), Serotonin transporter (SLC6A4), FKBP Prolyl isomerase 5 (FKBP5), and the Oxytocin receptor (OXTR). DNA methylation standards (100 %; 75 %; 50 %; 25 % and 0 %) and DNA of a female and male donor were bisulfite treated in three independent trials and were used to generate sequencing libraries for 42 CpGs from the NR3C1 1 F promoter region, 84 CpGs of the SLC6A4 5' regulatory region, 5 CpGs located in FKBP5 intron 7, and additional 12 CpGs located in a potential enhancer element in intron 3 of the OXTR. In addition, DNA of 45 patients with borderline personality disorder (BPD) and 45 healthy controls was assayed. Multiplex libraries of all samples were sequenced on a MiSeq system and analyzed for mean methylation values of all CpG sites using amplikyzer2 software. Results indicated excellent accuracy of the assays when investigating replicates generated from the same bisulfite converted DNA, and very high linearity (R² > 0.9) of the assays shown by the analysis of differentially methylated DNA standards. Comparing DNA methylation between BPD and healthy controls revealed no biologically relevant differences. The technical approach as described here facilitates targeted DNA methylation analysis and represents a highly sensitive, cost-efficient and high throughput tool to close the gap between coverage and precision in epigenetic research of stress-associated phenotypes.

Previous research suggests that childhood maltreatment is associated with epigenetic modification of genes involved in hypothalamic-pituitary-adrenal (HPA) functioning, which could cause dysregulation of the stress response system. If pervasive, this may be associated with the development of stress-related disorder in adults, including affective disorders, anxiety disorders, post-traumatic stress disorder (PTSD) or borderline-personality disorder (BPD). The majority of studies have focused on DNA methylation of the glucocorticoid receptor gene (NR3C1) and the FKBP5 encoding gene, which regulates the sensitivity of the glucocorticoid receptor (GR). How methylation of NR3C1 and FKBP5 interferes with childhood adversity and psychopathology as well as empathy is an under-researched issue. Here, we sought to investigate the association of childhood maltreatment in a sample of 89 individuals (44 healthy participants and 45 patients diagnosed with BPD) with the methylation of the 1_F promoter region of NR3C1 and the intron 7 of FKBP5 as well as with different measures of psychopathology and empathy. Methylation of FKBP5 (bin 2) correlated with anxiety (SCL-90-R) and the global psychopathological symptom load index (GSI), as well as with lower empathic perspective-taking abilities. Psychopathology and empathy impairments correlated with the level of childhood maltreatment. No difference in FKBP5 methylation was observed between the clinical and the non-clinical group. Methylation of NR3C1 was lower in BPD patients compared to controls, yet with small differences. The results are discussed regarding their biological relevance, including possible evolutionary explanations. In short, the regulation of the GR sensitivity by methylation of FKBP5 correlated with psychopathology and empathy scores, while no correlation emerged with the severity of childhood adversity.

Introduction Dissociative seizures often occur in the context of dysregulated affective arousal and entail dissociative symptoms such as a disintegration of bodily awareness. However, the interplay between affective arousal and changes in interoceptive processing at the onset of dissociative seizures is not well understood. Methods Using retrospective routine data obtained from video-electroencephalography telemetry in a university hospital epilepsy monitoring unit, we investigate ictal changes in cardiac indices of autonomic arousal and heartbeat evoked potentials (HEPs) in 24 patients with dissociative seizures. Results Results show autonomic arousal during seizures with increased heart rate and a shift towards sympathetic activity. Compared with baseline, ictal HEP amplitudes over central and right prefrontal electrodes (F8, Fz) were significantly less pronounced during seizures, suggesting diminished cortical representation of interoceptive information. Significant correlations between heart rate variability measures and HEPs were observed at baseline, with more sympathetic and less parasympathetic activity related to less pronounced HEPs. Interestingly, these relationships weakened during seizures, suggesting a disintegration of autonomic arousal and interoceptive processing during dissociative seizures. In a subgroup of 16 patients, MRI-based cortical thickness analysis found a correlation with HEP amplitudes in the left somatosensory association cortex. Conclusions These findings possibly represent an electrophysiological hint of how autonomic arousal could negatively impact bodily awareness in dissociative seizures, and how these processes might be related to underlying brain structure.

Objective Despite the numerous findings on the altered emotion recognition and dysfunctional social interaction behavior of depressive patients, a lot of the relationships are not clearly clarified.Methods In this pilot study, 20 depressive patients (mean±SD, 38.4±14.2) and 20 healthy subjects (mean±SD, 38.9±15.3) (each in dyads) were videographed. We then analyzed their social interaction behavior and emotion processing in terms of emotion recognition, their own emotional experience, and the expression of emotions under the conditions of a semi-structured experimental paradigm.Results Patients showed more significant impairment regarding the dimensions of social interaction behavior (i.e., attention, interest, and activity) and their interaction behavior was characterized by neutral affectivity, silence, and avoidance of direct eye contact. This interactive behavioral style was statistically related to depressive psychopathology. There were no differences concerning emotion recognition.Conclusion Impairments of non-verbal and verbal social interaction behavior of depressive patients seem to be less associated with disturbances of basic skills of emotion recognition.

Frontal EEG asymmetry is a widely studied correlate of emotion processing and psychopathology. Recent research suggests that frontal EEG asymmetry during resting state is related to approach/withdrawal motivation and is also found in affective disorders such as major depressive disorder. Patients with borderline personality disorder (BPD) show aberrant behavior in relation to both approach and withdrawal motivation, which may arguably be associated with their difficulties in emotion processing. The occurrence and significance of frontal EEG asymmetry in BPD, however, has received little attention. Thirty-seven BPD patients and 39 controls underwent resting EEG and completed several psychometric questionnaires. While there were no between-group differences in frontal EEG asymmetry, in BPD frontal EEG asymmetry scores correlated significantly with alexithymia. That is, higher alexithymia scores were associated with relatively lower right-frontal activity. A subsequent analysis corroborated the significant interaction between frontal EEG asymmetry and alexithymia, which was moderated by group. Our findings reveal that lower right frontal EEG asymmetry is associated with alexithymia in patients with BPD. This finding is in accordance with neurophysiological models of alexithymia that implicate a right hemisphere impairment in emotion processing, and could suggest frontal EEG asymmetry as a potential biomarker of relevant psychopathology in these patients.