Psychobiological Correlates of Aggression in Female Adolescents with Borderline Personality Disorder.

INTRODUCTION: Aggressive behavior in reaction to threats, frustration, or provocation is prevalent in borderline personality disorder (BPD). This study investigated aggressive behavior and its biological correlates in adolescents with BPD. METHODS: Twenty-one female adolescents with a DSM-IV BPD diagnosis and 25 sex- and age-matched healthy controls participated in the Taylor Aggression Paradigm (TAP), a laboratory-based experiment measuring aggressive behavior in the interpersonal context. Heart rate was measured and saliva samples were taken throughout the experiment. RESULTS: Multilevel mixed-effects linear regression analyses revealed no significant group difference in aggressive behavior induced by the TAP. Additionally, the two groups did not differ in cortisol, testosterone, and heart rate responses to the aggression induction. The BPD group showed a significant cortisol increase in the time preceding the start of the TAP in contrast to the healthy control group, in whom a significant heart rate increase from baseline to the first block of the TAP was observed. DISCUSSION: There was no evidence, either at the phenomenological or the biological level, of increased task-induced aggression in adolescents with BPD. The results may indicate that adolescents with BPD experienced fearful stress in anticipation of the experimental task in contrast to healthy controls who showed an adaptive response of the autonomic nervous system necessary to deal with the upcoming demand.

Physiological response to pain in female adolescents with nonsuicidal self-injury as a function of severity.

BACKGROUND: Preliminary evidence indicates altered hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) response to experimental pain in individuals with nonsuicidal self-injury (NSSI). This study investigated effects of NSSI severity and severity of psychopathology on the HPA axis and ANS response to pain. METHODS: N = 164 adolescents with NSSI and n = 45 healthy controls received heat pain stimulation. Salivary cortisol, α-amylase and blood pressure were repeatedly assessed before and after painful stimulation. Heart rate (HR) and heart rate variability (HRV) were assessed continuously. NSSI severity and comorbid psychopathology were derived from diagnostic assessments. Main and interaction effects of time of measurement and NSSI severity, adjusted for severity of adverse childhood experiences, borderline personality disorder and depression, on HPA axis and ANS response to pain were examined using regression analyses. RESULTS: Increasing NSSI severity predicted an increasing cortisol response (χ2(3) = 12.09, p = .007) to pain. After adjusting for comorbid psychopathology, greater NSSI severity predicted decreased α-amylase levels following pain (χ2(3) = 10.47, p = .015), and decreased HR (χ2(2) = 8.53, p = .014) and increased HRV(χ2(2) = 13.43, p = .001) response to pain. LIMITATIONS: Future research should implement several NSSI severity indicators, potentially revealing complex associations with the physiological response to pain. Assessing physiological responses to pain in NSSI in a naturalistic setting presents a promising avenue for future research in NSI. CONCLUSIONS: Findings indicate an increased pain-related HPA axis response and an ANS response characterized by reduced sympathetic and increased parasympathetic activity associated with NSSI severity. Results support claims for dimensional approaches to NSSI and its related psychopathology alongside shared, underlying neurobiological correlates.

Prefrontal oxygenation varies as a function of response inhibition performance in healthy participants but not in youth with non-suicidal self-injury.

Non-suicidal self-injury (NSSI), a highly prevalent symptom in adolescence, has been associated with impulsivity. Behavioral measures of response inhibition in combination with the recording of brain activity potentially improve the understanding of the etiology of the behavior. We therefore investigated prefrontal cortex (PFC) oxygenation during a response inhibition task using functional near-infrared spectroscopy (fNIRS) in n = 152 adolescents with NSSI and n = 47 healthy controls. We compared groups regarding behavioral performance and PFC oxygenation and tested whether the association between task performance and PFC oxygenation differed between groups. PFC oxygenation was slightly higher in adolescents with NSSI than in controls. Further, there was evidence for a group by performance interaction: In healthy controls, higher oxygenated hemoglobin was associated with better task performance, which was not the case in the NSSI group. We did not find evidence of associations between PFC oxygenation and clinical measures. Our study provides preliminary evidence of altered brain functional correlates of response inhibition in adolescents with NSSI potentially reflecting deficient top-down regulation of limbic regions through prefrontal regions. Due to methodological limitations of the current study, findings must be interpreted with caution and future studies should optimize task designs for fNIRS processing.

Adverse childhood experiences mediate the negative association between borderline personality disorder symptoms and plasma oxytocin.

Background Interpersonal dysfunction is a core symptom of borderline personality disorder (BPD) and may be closely linked to adverse childhood experiences. According to a recent model on the pathology of BPD, the neuropeptide oxytocin might play an important role in the development and maintenance of the disorder. However, so far, only few studies with small adult samples have reported reduced baseline oxytocin levels in BPD that may be linked to adverse childhood experiences. Methods We examined baseline plasma oxytocin levels in 131 female patients with BPD and 124 non-BPD female controls across a large age span (12-50 years). Additionally, 113 female patients with less than five DSM-IV BPD features were included to examine the association between plasma oxytocin levels and the number of fulfilled BPD criteria. We also explored associations between plasma oxytocin and adverse childhood experiences as well as depressive symptoms in BPD. Results Patients with BPD had reduced plasma oxytocin levels compared to non-BPD controls and this was independent of age. Plasma oxytocin was negatively associated with the number of fulfilled BPD criteria. The exploratory regression model revealed no association between plasma oxytocin and depressive symptoms but an association between plasma oxytocin and adverse childhood experiences, which in fact mediated the relationship between BPD criteria und plasma oxytocin. Conclusion In a large sample of individuals with BPD across a large age span, our results replicate and extend previous reports of reduced plasma oxytocin levels that might be related to adverse childhood experiences thus providing further evidence for a prominent role of oxytocin in BPD.

Increased immunological markers in female adolescents with non-suicidal self-injury.

BACKGROUND: Nonsuicidal self-injury (NSSI) is a prevalent health problem among adolescents and commonly associated with psychological stressors such as childhood maltreatment and comorbid psychiatric disorders (e.g., depression). There is evidence that alterations of immunological markers may occur in the context of both environmental stress and psychopathological development. METHOD: Here, we investigated differences in plasma/serum leukocytes, cortisol, c-reactive protein and interleukin-6 in a large sample of female adolescents with NSSI (n = 155) and healthy controls (HC, n = 42). Further, we assessed correlations between inflammatory markers, depression severity and the severity of childhood maltreatment. RESULTS: The absolute number of leukocytes and the leukocyte/cortisol ratio (adjusted for body mass index and smoking) were significantly higher in NSSI as compared to HC, whereas interleukin-6 and CRP levels did not differ significantly between groups. Childhood maltreatment scores were significantly correlated with the leukocyte/cortisol ratio and depression severity was significantly correlated with both, absolute leukocyte numbers and the leukocyte/cortisol ratio. CONCLUSIONS: Our results suggest that an immune activation can be detected in female adolescents with NSSI. Depression and childhood maltreatment, which are commonly reported in NSSI, may potentially underlie immune activation and partially explain group differences.

Neurocognitive functioning in adolescents with non-suicidal self-injury.

BACKGROUND: Non-suicidal self-injury (NSSI) is a highly prevalent transdiagnostic psychiatric symptom in adolescents. Research in adults has begun to investigate neurocognitive processes associated with NSSI as potential underlying phenotypes. However, research on neurocognitive function in adolescent patients with NSSI is scarce. METHODS: In this study, we examined neurocognitive functioning in the domains of processing speed, attention, learning, working memory, and executive function in a relatively large sample of n = 240 adolescent patients engaging in NSSI and n = 49 healthy controls. Further, associations between neurocognitive performance and clinical characteristics in the patient group were examined. RESULTS: While conventional regression analyses showed somewhat weaker neurocognition in the NSSI group in several domains, propensity score matching for IQ showed little evidence that patients engaging in NSSI showed worse neurocognition when general intelligence was considered. Further, a random forest machine learning algorithm was not able to classify NSSI vs. control groups based on neurocognitive features. Within the patient group, linear regression and latent class analyses yielded little evidence that neurocognitive performance was related with clinical characteristics or phenotypes. LIMITATIONS: As the study did not include a clinical control group, findings might not be specific to NSSI. CONCLUSIONS: Our findings challenge the importance of specific neurocognitive measures related to the presence or severity of NSSI in adolescents. Future studies should consider general intelligence as an important confounding factor and should focus on domains of affective cognition. Finally, longitudinal studies are needed to determine whether low neurocognitive performance serves to inform prognosis of NSSI or psychopathology in general.

Resting state prefrontal cortex oxygenation in adolescent non-suicidal self-injury - A near-infrared spectroscopy study.

INTRODUCTION: Neural alterations in limbic and prefrontal circuits in association with self-injurious behavior have been studied primarily in adult borderline personality disorder (BPD). In adolescent patients, research is still sparse. Here, we used resting functional near-infrared spectroscopy (NIRS) to examine oxygenation of the prefrontal cortex (PFC) and its association with symptom severity in adolescents engaging in non-suicidal self-injury (NSSI) and matched healthy controls (HC). METHODS: Adolescents (12-17 years) with recurrent episodes of NSSI (n = 170) and healthy controls (n = 43) performed a low-demanding resting-state vanilla baseline task. Mean oxygenation of the PFC and functional connectivity within the PFC, were measured using an 8-channel functional NIRS system (Octamon, Artinis, The Netherlands). Various clinical variables derived from diagnostic interviews and self-reports were included in statistical analyses to explore potential associations with PFC oxygenation and connectivity. RESULTS: Adolescents with NSSI showed significantly decreased PFC oxygenation compared to HC, as indexed by oxygenated hemoglobin. Lower PFC oxygenation was associated with greater adverse childhood experiences and less health-related quality of life (HRQoL). While there was no evidence for alterations in PFC connectivity in adolescents engaging in NSSI compared to HC, increased PFC connectivity in the full sample was associated with greater adverse childhood experience, greater BPD pathology, greater depression severity and psychological burden in general, as well as lower HRQoL. CONCLUSION: This study is the first to examine PFC oxygenation using NIRS technology in adolescents engaging in NSSI. Overall, results indicate small effects not specific to NSSI. Clinical implications of these findings and recommendations for further research are discussed.

Hypothalamic-pituitary-thyroid axis function in female adolescent nonsuicidal self-injury and its association with comorbid borderline personality disorder and depression.

OBJECTIVES: Behavioral disturbances in adolescence are potentially linked to aberrant functioning of the thyroid gland. Accordingly, alterations of the hypothalamic-pituitary-thyroid (HPT) axis might impact psychopathological development. Yet corresponding research in adolescents with nonsuicidal self-injury (NSSI) and comorbid mental disorders is scarce. METHODS: The present study examined HPT axis functioning in adolescents with NSSI compared to healthy controls (HC) using blood-based assays of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and the ratio of these hormones (fT3/fT4 ratio). Cortisol was additionally examined to contrast HPT axis functioning with a well-established biomarker of stress responsivity. Moreover, associations between clinical characteristics, HPT axis and HPA axis functioning were investigated. Female adolescents meeting NSSI criteria according to DSM-5 criteria (n = 117) were compared to adolescent HC (n = 41). Standardized serum-based endocrinological assays and interview- and questionnaire-based psychiatric assessments were used. Smoking status was included as covariate for all analyses. RESULTS: NSSI patients displayed altered HPT axis functioning as fT3/fT4 ratio values were blunted in comparison to HC. Negative correlations were further present between fT3, fT3/fT4 ratio and severity of BPD symptoms, depression scores and symptomatic distress. TSH correlated negatively with severity of BPD symptoms and symptomatic distress exclusively. Cortisol values differed neither significantly between experimental groups nor correlated significantly with clinical characteristics. CONCLUSIONS: Longitudinal examinations, assessing links between psychopathology and endocrinological alterations, are warranted to address potential clinical implications of thyroid markers in child and adolescent psychiatry.

Pain sensitivity and plasma beta-endorphin in adolescent non-suicidal self-injury.

BACKGROUND: Beta-endorphin (BE) has been suggested to play a central role as to why people engage in NSSI. To our knowledge, no study has systematically assessed this potential relationship in adolescents with NSSI. METHODS: 94 adolescents with NSSI (according to DSM-5 criteria) and 35 healthy controls (HC) were enrolled. All participants received heat pain stimulation, with pain threshold and tolerance measured in °C. Plasma BE levels were assessed. Sociodemographic and clinical characteristics were obtained via semi-structured interviews and self-report questionnaires. RESULTS: Adolescents with NSSI showed increased pain thresholds (t(127)=2.071, p=.040), lower pain intensity (t(114)==2.122, p=.036) and lower plasma BE levels (t127==3.182, p=.002) compared to HC. Groups did not differ on pain tolerance (t(127)=0.911, p=.364). Greater pain threshold correlated positively with borderline personality disorder (BPD) symptoms (r=0.182, p=.039), while pain intensity (r=-0.206, p=.033) and BE levels (r=-0.246, p=.007) correlated negatively with depression severity. No significant relationship was found between pain threshold and plasma BE (r=-0.013, p=.882). LIMITATIONS: Future studies should implement repeated plasma BE measures to assess BE release in association with pain in NSSI. Validity of plasma BE measures compared to central measures should be considered. Assessing the association between pain sensitivity (PS) and BE in a naturalistic setting presents a promising avenue for future research in NSSI. CONCLUSIONS: Findings support both reduced PS and basal opioid deficiency as independent biological correlates and potential risk-factors for NSSI. Further longitudinal and experimental studies are needed to investigate the role of BE levels and PS as well as their potential association.