Enhanced Processing of Painful Emotions in Patients With Borderline Personality Disorder: A Functional Magnetic Resonance Imaging Study

Previous research has demonstrated that patients with borderline personality disorder (BPD) are more sensitive to negative emotions and often show poor cognitive empathy, yet preserved or even superior emotional empathy. However, little is known about the neural correlates of empathy. Here, we examined empathy for pain in 20 patients with BPD and 19 healthy controls (HC) in a functional magnetic resonance imaging (fMRI) study, which comprised an empathy for pain paradigm showing facial emotions prior to hands exposed to painful stimuli. We found a selectively enhanced activation of the right supramarginal gyrus for painful hand pictures following painful facial expressions in BPD patients, and lower activation to nonpainful pictures following angry expressions. Patients with BPD showed less activation in the left supramarginal gyrus when viewing angry facial expressions compared to HC, independent of the pain condition. Moreover, we found differential activation of the left anterior insula, depending on the preceding facial expression exclusively in patients. The findings suggest that empathy for pain becomes selectively enhanced, depending on the emotional context information in patients with BPD. Another preliminary finding was an attenuated response to emotions in patients receiving psychotropic medication compared to unmedicated patients. These effects need to be replicated in larger samples. Together, increased activation during the observation of painful facial expressions seems to reflect emotional hypersensitivity in BPD

The OXTR Single-Nucleotide Polymorphism rs53576 Moderates the Impact of Childhood Maltreatment on Empathy for Social Pain in Female Participants: Evidence for Differential Susceptibility

Previous research has associated genetic variations of the oxytocin receptor with individual differences in human social behavior. Specifically, homozygous carriers of the G-allele of the single nucleotide polymorphism rs53576 have been reported to display more trust, empathy, and prosocial behavior and were less sensitive toward stress and maltreatment during childhood when compared to A-allele carriers. With regard to Borderline Personality Disorder (BPD), a psychiatric condition that is often associated with the experience of childhood adversity, it has been suggested that A-allele carriers are more vulnerable to developing psychopathological signs and symptoms. In the present study we investigated whether childhood trauma, as assessed by the Childhood Trauma Questionnaire (CTQ), affects empathy for somatic and psychological pain, and how this is moderated by genotype, in a sample of 302 individuals (148 of whom were diagnosed with BPD). We found a three-way interaction between genotype, group and pain condition. Posthoc comparisons revealed that patients with BPD carrying at least one A-allele, rated psychological pain as more intense compared to controls, whereas no difference between groups emerged in GG homozygotes. Moreover, a moderating effect of genotype appeared on the impact of childhood trauma on empathy for psychological pain. In addition, a positive correlation of CTQ scores and empathy appeared only in A-allele carriers (GA + AA), independent of diagnosis. Together, A-allele carriers, especially those with BPD, seemed to be responsive to the impact of adversity on empathy-for-pain, while GG homozygotes were not, which is compatible with the idea of differential susceptibility

Association between childhood maltreatment, psychopathology and DNA methylation of genes involved in stress regulation: Evidence from a study in Borderline Personality Disorder.

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 1F 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

Frontal EEG asymmetry in borderline personality disorder is associated with alexithymia

Abstract Background 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. Results 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. Conclusions 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

Short-Term Fasting and Ingestion of Caloric Drinks Affect Heartbeat-Evoked Potentials and Autonomic Nervous System Activity in Males

Central nervous systems receive and process information from the internal and external environment to maintain homeostasis. This includes interoceptive awareness of the organism’s nutritional state. Whenever food supply is required, feelings of hunger initiate the search for and the consumption of appropriate amounts of nutrients. How this is physiologically regulated in humans has been subjected to research into interoceptive awareness of body states during fasting and food consumption. However, there is no research on the distinct effects of carbohydrate or protein intake on interoception. Therefore, we aimed to investigate the impact of fasting and consumption of standardized carbohydrate and protein shakes on interoception in a repeated-measures cross-over design in a sample of 37 healthy, normal weight males. As a physiological correlate of interoception, we measured heartbeat-evoked potentials (HEPs), which are suggested to reflect the cortical representation of cardiac signals, during eight-minutes resting state EEG-recordings. After a 16-hour fasting period, the HEP amplitudes were lower over right central and parietal electrodes and increased after ingestion of the nutritional shake. Exploratory analyses indicated that the difference between fasting and satiety was more prominent at carbohydrate compared protein testing days. Correlation analyses with heart rate variability (HRV) suggested that high cardiac sympathetic activity is related to lower HEP amplitudes. Furthermore, cardiac sympathetic activity and stress indices decreased from before to after the intervention, whereas HRV increased. Together, this study shows for the first time that fasting and the intake of a nutritional shake affects cardiac measures of autonomic nervous system functioning and the neural correlates of cardiac interoception. These findings could be relevant for diets and psychosomatic disorders, including eating disorders

Altered interoception in patients with borderline personality disorder: a study using heartbeat-evoked potentials

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

Loudness Dependence of Auditory-evoked Potentials, a Marker of Central Serotonergic Activity, is Affected by Fasting and Selective Uptake of Food

Serotonin is an important neuromodulator involved in many physiological processes including mood and satiety. In the brain, serotonin is manufactured from tryptophan, as serotonin itself cannot cross the blood-brain barrier. Previous research has shown that blood-tryptophan levels increase upon ingestion of carbohydrates and decrease upon protein consumption. How this translates into serotonin availability is as yet under-researched. Therefore, we examined the effect of fasting versus consuming carbohydrates or protein on central serotonergic activity using a repeated-measures crossover design in a sample of 37 healthy men. The loudness dependence of auditory-evoked potentials (LDAEP) serves as a noninvasive method to study central serotonergic activity. Blood-glucose levels and mood changes were also monitored before and after the nutritional intervention. The intervention had a significant nutrition-specific effect on LDAEP and blood-glucose levels. A significant difference emerged between the fasting condition and satiety, with LDAEP being lower during satiety, irrespective of the type of food. Thus, this indicator of serotonergic activity increased after food consumption, which was further related to mood improvement. Moreover, the LDAEP differed between the 2 measurements only for the carbohydrate testing day, suggesting that LDAEP can be selectively modulated by the type of nutrition consumed. Our data further indicate a high intraindividual stability of LDAEP, as the electrophysiological signals were very similar in the fasting condition across the 2 testing days. Together, these findings demonstrate that the LDAEP can serve as a biological marker for central serotonergic activity, while at the same time being sensitive to nutritional changes

Association between childhood maltreatment, psychopathology and DNA methylation of genes involved in stress regulation

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

P300 and delay-discounting in obsessive–compulsive disorder

Previous research showed that dysfunctions of fronto-striatal neural networks are implicated in the pathophysiology of obsessive-compulsive disorder (OCD). Accordingly, patients with OCD showed altered performances during decision-making tasks. As P300, evoked by oddball paradigms, is suggested to be related to attentional and cognitive processes and generated in the medial temporal lobe and orbitofrontal and cingulate cortices, it is of special interest in OCD research. Therefore, this study aimed to investigate P300 in OCD and its associations with brain activity during decision-making: P300, evoked by an auditory oddball paradigm, was analysed in 19 OCD patients and 19 healthy controls regarding peak latency, amplitude and source density power in parietal cortex areas by sLORETA. Afterwards, using a fMRI paradigm, Blood-oxygen-level-dependent (BOLD) contrast imaging was conducted during a delay-discounting paradigm. We hypothesised differences between groups regarding P300 characteristics and associations with frontal activity during delay-discounting. The P300 did not differ between groups, however, the P300 latency over the P4 electrode correlated negatively with the NEO-FFI score openness to experience in patients with OCD. In healthy controls, P300 source density power correlated with activity in frontal regions when processing rewards, a finding which was absent in OCD patients. To conclude, associations of P300 with frontal brain activation during delay-discounting were found, suggesting a contribution of attentional or context updating processes. Since this association was absent in patients with OCD, the findings could be interpreted as being indeed related to dysfunctions of fronto-striatal neural networks in patients with OCD

The association between childhood maltreatment and empathic perspective taking is moderated by the 5-HTT linked polymorphic region: Another example of "differential susceptibility".

Previous research has suggested that the short (S)-allele of the 5-HT transporter gene-linked polymorphic region (5-HTTLPR) may confer "differential susceptibility" to environmental impact with regard to the expression of personality traits, depressivity and impulsivity. However, little is known about the role of 5-HTTLPR concerning the association between childhood adversity and empathy. Here, we analyzed samples of 137 healthy participants and 142 individuals diagnosed with borderline personality disorder (BPD) focusing on the 5-HTTLPR genotype (S/L-carrier) and A/G SNP (rs25531), in relation to childhood maltreatment and empathy traits. Whereas no between-group difference in 5-HTTLPR genotype distribution emerged, the S-allele selectively moderated the impact of childhood maltreatment on empathic perspective taking, whereby low scores in childhood trauma were associated with superior perspective taking. In contrast, L-homozygotes seemed to be largely unresponsive to variation in environmental conditions in relation to empathy, suggesting that the S-allele confers "differential susceptibility". Moreover, a moderation analysis and tests for differential susceptibility yielded similar results when transcriptional activity of the serotonin transporter gene was taken into account. In conclusion, our findings suggest that the S-allele of the 5-HTTLPR is responsive to early developmental contingencies for "better and worse", i.e. conferring genetic plasticity, especially with regard to processes involving emotional resonance