Pain sensitivity as a state marker and predictor for adolescent non-suicidal self-injury.

BACKGROUND: The pain analgesia hypothesis suggests that reduced pain sensitivity (PS) is a specific risk factor for the engagement in non-suicidal self-injury (NSSI). Consistent with this, several studies found reduced PS in adults as well as adolescents with NSSI. Cross-sectional studies in adults with borderline personality disorder (BPD) suggest that PS may (partially) normalize after remission or reduction of BPD symptoms. The objective of the present study was to investigate the development of PS over 1 year in a sample of adolescents with NSSI and to investigate whether PS at baseline predicts longitudinal change in NSSI. METHODS: N = 66 adolescents who underwent specialized treatment for NSSI disorder participated in baseline and 1-year follow-up assessments, including heat pain stimulation for the measurement of pain threshold and tolerance. Associations between PS and NSSI as well as BPD and depressive symptoms were examined using negative binomial, logistic, and linear regression analyses. RESULTS: We found that a decrease in pain threshold over time was associated with reduced NSSI (incident rate ratio = 2.04, p = 0.047) and that higher pain tolerance at baseline predicted lower probability for NSSI (odds ratio = 0.42, p = 0.016) 1 year later. However, the latter effect did not survive Holm correction (p = 0.059). No associations between PS and BPD or depressive symptoms were observed. CONCLUSION: Our findings suggest that pain threshold might normalize with a decrease in NSSI frequency and could thus serve as a state marker for NSSI.

The quest for a biological phenotype of adolescent non-suicidal self-injury: a machine-learning approach.

Non-suicidal self-injury (NSSI) is a transdiagnostic psychiatric symptom with high prevalence and relevance in child and adolescent psychiatry. Therefore, it is of great interest to identify a biological phenotype associated with NSSI. The aim of the present study was to cross-sectionally investigate patterns of biological markers underlying NSSI and associated psychopathology in a sample of female patients and healthy controls. Comprehensive clinical data, saliva and blood samples, heart rate variability and pain sensitivity, were collected in n = 149 patients with NSSI and n = 40 healthy participants. Using machine-based learning, we tested the extent to which oxytocin, dehydroepiandrosterone (DHEA), beta-endorphin, free triiodothyronine (fT3), leukocytes, heart rate variability and pain sensitivity were able to classify participants regarding their clinical outcomes in NSSI, depression and borderline personality disorder symptomatology. We evaluated the predictive performance of several models (linear and logistic regression, elastic net regression, random forests, gradient boosted trees) using repeated cross-validation. With NSSI as an outcome variable, both logistic regression and machine learning models showed moderate predictive performance (Area under the Receiver Operating Characteristic Curve between 0.67 and 0.69). Predictors with the highest predictive power were low oxytocin (OR = 0.55; p = 0.002), low pain sensitivity (OR = 1.15; p = 0.021), and high leukocytes (OR = 1.67; p = 0.015). For the psychopathological outcome variables, i.e., depression and borderline personality disorder symptomatology, models including the biological variables performed not better than the null model. A combination of hormonal and inflammatory markers, as well as pain sensitivity, were able to discriminate between participants with and without NSSI disorder. Based on this dataset, however, complex machine learning models were not able to detect non-linear patterns of associations between the biological markers. These findings need replication and future research will reveal the extent to which the respective biomarkers are useful for longitudinal prediction of clinical outcomes or treatment response.

EEG microstate D as psychosis-specific correlate in adolescents and young adults with clinical high risk for psychosis and first-episode psychosis.

Resting-state electroencephalography (EEG) microstates are brief periods (60-120 ms) of quasi-stable scalp field potentials, indicating simultaneous activity of large-scale networks. Microstates are assumed to reflect basic neuronal information processing. A common finding in psychosis spectrum disorders is that microstates classes C and D are altered. Whereas evidence in adults with schizophrenia is substantial, little is known about effects in underage patients, particularly in those at clinical high risk for psychosis (CHR) and first-episode psychosis (FEP). The present study used 74-channel EEG to investigate microstate effects in a large sample of patients with CHR (n = 100) and FEP (n = 33), clinical controls (CC, n = 18), as well as age-matched healthy controls (HC, n = 68). Subjects span an age range from 9 to 35 years, thus, covering underage patients as well as the most vulnerable period for the emergence of psychosis and its prodrome. Four EEG microstates classes were analyzed (A-D). In class D, CHR and FEP patients showed a decrease compared to HC, and CHR patients also to CC. An increase in class C was found in CHR and FEP compared to HC but not to CC. Results were independent of age and no differences were found between the psychosis spectrum groups. The findings suggest an age-independent decrease of microstate class D to be specific to the psychosis spectrum, whereas the increase in class C seems to reflect unspecific psychopathology. Overall, present data strengthens the role of microstate D as potential biomarker for psychosis, as early as in adolescence and already in CHR status.

Brief Psychotherapeutic Intervention Compared with Treatment as Usual for Adolescents with Nonsuicidal Self-Injury: Outcomes over a 2-4-Year Follow-Up.

INTRODUCTION: The "Cutting Down Programme" (CDP), a brief psychotherapeutic intervention for treating nonsuicidal self-injury (NSSI) in adolescents, was comparable to high-quality treatment as usual (TAU) in a previous randomized controlled trial (RCT). OBJECTIVE: The aim of the study was to evaluate the long-term outcomes of the CDP over up to 4 years. METHODS: Assessments of NSSI, suicide attempts, borderline personality disorder (BPD), depression, and quality of life took place 2 to 4 years (T3) after enrollment in a RCT. The evolution of NSSI, suicide attempts, depression, and quality of life was analyzed using (generalized) linear mixed-effects models. Ordered logistic regression was used for analyzing BPD diagnoses. Data from T0, T2, and T3 are reported. RESULTS: Out of 74 patients, 70 (95%) were included in the T3 assessment. The frequency of NSSI events alongside with suicide attempts and depression further decreased between T2 and T3 and BPD between T0 and T3 in both groups. Quality of life remained stable in both groups between T2 and T3. Both groups received substantial but comparable additional treatment between T2 and T3. More treatment sessions during the follow-up period were linked to larger improvements of NSSI. CONCLUSIONS: The CDP was found to be as effective as TAU in promoting recovery from NSSI and comorbid symptoms in the long term. Results suggest that treatment effects from a brief psychotherapeutic intervention may endure and even further improve after completion of the program. However, additional treatment seems to improve chances for recovery independent from CDP versus TAU.

Resting-state functional connectivity predicting clinical improvement following treatment in female adolescents with non-suicidal self-injury.

BACKGROUND: Non-suicidal self-injury (NSSI) is highly prevalent among adolescents and predicts future psychopathology including suicide. To improve therapeutic decisions and clinical outcome of patients engaging in NSSI, it seems beneficial to determine neurobiological markers associated with treatment response. The present study investigated whether resting-state functional brain connectivity (RSFC) served to predict clinical improvements following treatment in adolescents engaging in NSSI. METHODS: N = 27 female adolescents with NSSI took part in a baseline MRI exam and clinical outcome was assessed at follow-ups one, two and three years after baseline. During the follow-up period, patients received in- and/or outpatient treatment. Mixed-effects linear regression models were calculated to examine whether RSFC was associated with clinical improvement. RESULTS: Patients' clinical outcome improved across time. Lower baseline RSFC between left paracentral gyrus and right anterior cingulate gyrus was associated with clinical improvement from baseline to one-year and from two-year to three-year follow-up. Lower and higher baseline RSFC in several inter- and intrahemispheric cortico-cortical and cortico-subcortical connections of interest were associated with clinical symptomatology and its severity, independent from time. LIMITATIONS: A relatively small sample size constrains the generalizability of our findings. Further, no control group not receiving treatment was recruited, therefore clinical changes across time cannot solely be attributed to treatment. CONCLUSIONS: While there was some evidence that RSFC was associated with clinical improvement following treatment, our findings suggest that functional connectivity is more predictive of severity of psychopathology and global functioning independent of time and treatment. We thereby add to the limited research on neurobiological markers as predictors of clinical outcome after treatment.

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.