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.

Positive psychotic symptoms as a marker of clinical severity in a transdiagnostic sample of help-seeking adolescents.

The present study aimed to examine the association between the presence, number, and type of positive psychotic symptoms (PPS) and clinical severity in adolescent patients. Five hundred-six patients aged 11-17 years were assigned to either the noPPS (n = 341), the delusional beliefs only (del; n = 32), the hallucinations only (hall; n = 80), or the delusional beliefs and hallucinations (del&hall; n = 53) group. Generalized Structural Equation Modeling was applied to identify the best-fitting model representing clinical severity indicated by psychiatric diagnoses, depressivity, personality pathology, non-suicidal self-injury, suicide attempts, perceived stress, and psychosocial impairments, assessed by interviews and questionnaires. The groups were compared concerning the final model's factors. The final model consisted of three factors representing psychopathology and functional impairments, self-harming behavior, and perceived stress (BIC difference to reference model: 103.99). Participants with any PPS scored higher on all factors than the noPPS group (differences in SD: 0.49-1.48). Additionally, the del&hall group scored 1.31 SD higher on psychopathology and functional impairments than the hall group, and 1.16 SD higher on self-harming behavior compared to the del group. Finally, the hall group scored 0.84 SD higher on self-harming behavior than the del group, with no group differences in the other factors. In adolescent patients, the presence of PPS may represent a marker for a more severe form of mental disorder, with hallucinations being indicative of self-harming behavior. Early transdiagnostic assessment of PPS seems indicated as it may inform treatment in the context of clinical staging.

Child maltreatment and hypothalamic-pituitary-adrenal axis functioning: A systematic review and meta-analysis.

Alterations in hypothalamic-pituitary-adrenal (HPA) axis and its effector hormone cortisol have been proposed as one possible mechanism linking child maltreatment experiences to health disparities. In this series of meta-analyses, we aimed to quantify the existing evidence on the effect of child maltreatment on various measures of HPA axis activity. The systematic literature search yielded 1,858 records, of which 87 studies (k = 132) were included. Using random-effects models, we found evidence for blunted cortisol stress reactivity in individuals exposed to child maltreatment. In contrast, no overall differences were found in any of the other HPA axis activity measures (including measures of daily activity, cortisol assessed in the context of pharmacological challenges and cumulative measures of cortisol secretion). The impact of several moderators (e.g., sex, psychopathology, study quality), the role of methodological shortcomings of existing studies, as well as potential directions for future research are discussed.

Diagnostic instruments for the assessment of disruptive mood dysregulation disorder: a systematic review of the literature.

Disruptive mood dysregulation disorder (DMDD) involves non-episodic irritability and frequent severe temper outbursts in children. Since the inclusion of the diagnosis in the DSM-5, there is no established gold-standard in the assessment of DMDD. In this systematic review of the literature, we provide a synopsis of existing diagnostic instruments for DMDD. Bibliographic databases were searched for any studies assessing DMDD. The systematic search of the literature yielded K = 1167 hits, of which n = 110 studies were included. The most frequently used measure was the Kiddie Schedule for Affective Disorders and Schizophrenia DMDD module (25%). Other studies derived diagnostic criteria from interviews not specifically designed to measure DMDD (47%), chart review (7%), clinical diagnosis without any specific instrument (6%) or did not provide information about the assessment (9%). Three structured interviews designed to diagnose DMDD were used in six studies (6%). Interrater reliability was reported in 36% of studies (ranging from κ = 0.6-1) while other psychometric properties were rarely reported. This systematic review points to a variety of existing diagnostic measures for DMDD with good reliability. Consistent reporting of psychometric properties of recently developed DMDD interviews, as well as their further refinement, may help to ascertain the validity of the diagnosis.

The added value of a micro-level ecological approach when mapping self-regulatory control processes and externalizing symptoms during adolescence: a systematic review.

Deficits in self-regulatory control (SRC) represent a core characteristic of externalizing (EXT) symptoms (e.g., rule-breaking behavior or aggressive behaviors) in adolescents. This review aims to specify the added value of ecologically valid assessments at a micro-level when examining the associations between SRC and EXT symptoms in adolescents. This systematic review was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020. The search strategy addressed the added value of (1) naturalistic assessment for the understanding of the relationship between (2) SRC and (3) EXT symptoms in (4) adolescents. We conducted comprehensive searches in bibliographic databases. An additional search was conducted in Google Scholar and supplementary studies were identified through backward and forward citation tracking. Twenty-four studies (n = 4071 adolescents) met the inclusion criteria. The methods used to assess naturalistic aspects included the experience sampling method (ecological momentary- or ambulatory assessment) and the time-course approach (i.e., real-time assessment of SRC processes referring to situations approximating real-life experience where SRC are to be engaged such as in frustrating situations). Micro-level ecological assessments, when mapping the intra-individual relationships between SRC processes and EXT symptoms over time in adolescents within their natural context (i.e., real world) of expression in real time, added a finer-grained observation alongside with a higher ecological validity. Micro-level approaches may enhance the understanding of the complex interplay between SRC and EXT symptoms in adolescence, especially in interventional studies, allowing for the acquisition of endpoints with a higher relevance for everyday functioning.

Thirteen-Year Outcomes in Very Preterm Children Associated with Diffuse Excessive High Signal Intensity on Neonatal Magnetic Resonance Imaging.

OBJECTIVE: To investigate the association between white matter diffuse excessive high signal intensity (DEHSI) on neonatal magnetic resonance imaging in very preterm infants and neurobehavioral outcomes at the age of 13 years. STUDY DESIGN: Magnetic resonance images of very preterm children (<30 weeks gestational age or <1250 g birth weight) were evaluated at term-equivalent age with DEHSI classified into 5 grades. Additionally, visibility of the posterior periventricular crossroads was assessed. General intelligence, memory, attention, executive function, motor abilities, and behavior were examined in 125 children at age 13 years and related to DEHSI grades using linear regression. RESULTS: DEHSI was detected in 93% of infants; 21% grade 1, 22% grade 2, 32% grade 3, and 18% grade 4. Neurobehavioral outcomes were similar for all DEHSI groups. There was weak evidence that higher DEHSI grades related to higher verbal IQ and attention and that lower DEHSI grades related to better planning ability. Adjustment for gestational age, birth weight standard score, and sex further weakened these effects. Only 12 children had invisible posterior crossroads and showed slightly poorer outcomes at 13 years of age. CONCLUSIONS: There was little evidence that neonatal DEHSI serves as a sensitive biomarker for later impairment. Further investigation on the importance of invisible posterior periventricular crossroads in larger samples is needed.

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.

Clinical profiles of adolescent personality pathology: a latent structure examination of the Semi-Structured Interview for Personality Functioning DSM-5 (STiP-5.1) in a help-seeking sample.

BACKGROUND: Despite the introduction of dimensional conceptualisations of personality functioning in the latest classification systems, such as Criterion A of the Alternative Model of Personality Disorders in the DSM-5, heterogeneous clinical presentation of personality pathology remains a challenge. Relatedly, the latent structure of personality pathology as assessed by the Semi-Structured Interview for Personality Functioning DSM-5 (STiP-5.1) has not yet been comprehensively examined in adolescents. Therefore, this study aimed to examine the latent structure of the STiP-5.1, and, based on those findings, to describe any unique clinical profiles that might emerge. METHODS: The final sample comprised 502 participants aged 11-18 years consecutively recruited from a specialised personality disorder outpatient service, as well as general day clinic and inpatient wards at the University Hospital University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University Hospital Bern, Switzerland. Participants were assessed using the STiP-5.1, as well as a battery of other psychological measures by clinical psychologists or trained doctoral students. Variations of Factor Analysis, Latent Class Analysis and Factor Mixture Models (FMM) were applied to the STiP-5.1 to determine the most appropriate structure. RESULTS: The best fitting model was an FMM comprising four-classes and two factors (corresponding to self- and interpersonal-functioning). The classes differed in both overall severity of personality functioning impairment, and in their scores and clinical relevance on each element of the STiP-5.1. When compared to the overall sample, classes differed in their unique clinical presentation: class 1 had low impairment, class 2 had impairments primarily in self-functioning with high depressivity, class 3 had mixed levels of impairment with emerging problems in identity and empathy, and class 4 had severe overall personality functioning impairment. CONCLUSIONS: A complex model incorporating both dimensional and categorical components most adequately describes the latent structure of the STiP-5.1 in our adolescent sample. We conclude that Criterion A provides clinically useful information beyond severity (as a dimensional continuum) alone, and that the hybrid model found for personality functioning in our sample warrants further attention. Findings can help to parse out clinical heterogeneity in personality pathology in adolescents, and help to inform early identification and intervention efforts.

The relationship between bullying victimization and impairment in personality functioning in a clinical adolescent sample.

Problematic interpersonal relationships may represent both, a risk factor for the development or trigger of personality disorder (PD) symptoms and its consequences. Since peer relationships become more and more important in adolescence, the current study explores the cross-sectional association between recent bullying experiences and levels of impairment in personality functioning according to the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) alternative model of personality disorders (AMPD; Criterion A) in help-seeking adolescents (N = 493). Logistic and multiple regression analyses revealed that patients who were frequently bullied in the past 3 months (i.e., at least once a week) were more likely to reach the diagnostic threshold for PD according to the AMPD (OR = 1.71, p = .025) and showed higher levels of impairment in identity (ß = .41, p < .001), empathy (ß = .26, p = .002), and intimacy (ß = .30, p = .001), but not self-direction, compared to patients who did not report any bullying experiences. Occasional bullying in the past 3 months (i.e., every few weeks) was neither associated with a greater likelihood to reach the diagnostic threshold for PD nor with greater impairments in identity, self-direction, empathy, or intimacy compared to no bullying. While the current study provides support for a correlation between bullying experiences and personality dysfunction (particularly in the elements identity and intimacy), longitudinal research is needed to clarify whether experiences of bullying cause or trigger personality dysfunction or/and vice versa. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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.

Associations between different measures of personality pathology and resting-state autonomic function among adolescents.

Borderline personality disorder (BPD) has been associated with a reduced functional flexibility of the autonomic nervous system (ANS), indexed by decreased vagally mediated heart rate variability (vmHRV). Employing a comprehensive Section II-based assessment approach and a partial Section III-based assessment approach (including Criterion A of the alternative model of personality disorders [AMPD]), the present study investigates how different conceptualizations of personality disorders (PDs) according to the Diagnostic and Statistical Manual for Mental Disorders, 5th edition relate to ANS function. Using the BPD section of the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II, a Section II-based assessment approach) and the Semistructured Interview for Personality Functioning DSM-5 (STiP-5.1, a Section III-based assessment approach), we conducted linear regression analyses to examine how categorical (BPD diagnosis) and dimensional (severity and domain) measures of PD are associated with ANS activity among adolescent psychiatric patients (N = 147, Mage = 15.25 years). Replicating earlier findings, analyses revealed a statistically significant positive association between the SCID-II measures of BPD and heart rate (HR), b = 0.43, t(59) = 3.57, p = .001, f = .57, as well as a statistically significant negative association between the SCID-II measures of BPD and vmHRV, b = -0.34, t(59) = -2.74, p = .008, f = .47. Neither the STiP-5.1 total score nor the subscales of the Level of Personality Functioning Scale (LPFS) were associated with HR or vmHRV. The present findings indicate that the SCID-II may capture features of PD that are more informative of variance in physiological function than the STiP-5.1. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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.

Is a brief screen for personality disorder clinically useful for the detection of impairment in personality functioning in adolescents?

The Standardized Assessment of Personality-Abbreviated Scale (SAPAS) has been used extensively to screen for personality disorders (PD), including adolescents. Yet, it is unclear how well the SAPAS performs in screening for impairment in personality functioning (IPF), Criterion A of the alternative Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition model for PD (AMPD) in adolescent samples. We examined the performance of the SAPAS in detecting IPF at a diagnostic threshold for PD in the AMPD. A consecutive clinical sample of adolescents in Bern, Switzerland (N = 293), were first administered the SAPAS, then the Semistructured Interview for Personality Functioning Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (STiP-5.1). A receiver operating characteristic (ROC) analysis was used to determine the diagnostic accuracy of the SAPAS in relation to the STiP-5.1. ROC regression analyses were conducted to determine if other variables moderated the discriminant performance of the SAPAS. Internal consistency of the SAPAS was low (α = .54) and overall discriminatory accuracy was moderate (area under the curve = .73). The optimum cut-off point was 5, with the best balance of sensitivity and specificity (63.22 and 69.90, respectively), correctly classifying 67.92% of participants. Agreement between the SAPAS and the STiP-5.1 using this cut-off was low (κ = .30). Age yielded statistically significant effects on the discriminant performance of the SAPAS-performance improving among older adolescents. Findings suggest that the SAPAS may not be the optimal method of screening for Criterion A IPF among adolescents in clinical settings but might also be more suited to Criterion B. Our findings call for a developmentally adapted screener for early detection of PD represented by IPF in adolescents. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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.

Altered resting-state networks in adolescent non-suicidal self-injury-a graph theory analysis.

Non-suicidal self-injury (NSSI) is a highly prevalent transdiagnostic symptom and risk marker for mental health problems among adolescents. Research on the neurobiological mechanisms underlying NSSI is needed to clarify the neural correlates associated with the behavior. We examined resting-state functional connectivity in n = 33 female adolescents aged 12-17 years engaging in NSSI, and in n = 29 age-matched healthy controls using graph theory. Mixed linear models were evaluated with the Bayes Factor to determine group differences on global and regional network measures and associations between network measures and clinical characteristics in patients. Adolescents engaging in NSSI demonstrated longer average characteristic path lengths and a smaller number of weighted hubs globally. Regional measures indicated lower efficiency and worse integration in (orbito)frontal regions and higher weighted coreness in the pericalcarine gyrus. In patients, higher orbitofrontal weighted local efficiency was associated with NSSI during the past month while lower pericalcarine nodal efficiency was associated with suicidal thoughts in the past year. Higher right but lower left pericalcarine weighted hubness was associated with more suicide attempts during the past year. Using a graph-based technique to identify functional connectivity networks, this study adds to the growing understanding of the neurobiology of NSSI.

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.

Pituitary volume in adolescents with non-suicidal self-injury: Preliminary evidence for alterations in pituitary maturation.

BACKGROUND: Non-suicidal self-injury (NSSI), typically observed in the context of various mental disorders, represents a highly prevalent and serious problem among adolescents. Based on studies linking NSSI with stress, alterations in hypothalamic-pituitary-adrenal (HPA) axis functioning have been suggested to contribute to the development and maintenance of this behavior. While research has mainly focused on cortisol - the main hormonal output of this system - to our knowledge, no study has examined pituitary gland volume (PGV) - an alternative approach of assessing HPA axis functionality that is less state-dependent - in adolescents engaging in NSSI. METHODS: Magnetic Resonance Imaging (MRI) was performed among n = 35 adolescents (aged 12-17 years) fulfilling the diagnostic criteria for NSSI disorder according to DSM-5 and n = 31 age-matched healthy controls; PGV was obtained by manual tracing. To test for group differences - our primary aim - a hierarchical linear regression model was computed, controlling for several potential confounding variables. Since adolescence reflects a time period for significant brain development - including changes in PGV - we also tested for an age-dependent group effect. In a second step, we aimed to investigate whether differences in PGV are accounted for by the experience of childhood adversity or psychopathology. Finally, following an exploratory approach, the dimensional association between PGV and various clinical characteristics (e.g., frequency of NSSI) were explored. RESULTS: No evidence was found for overall volumetric differences between healthy control participants and adolescents engaging in NSSI (p > 0.05) - recognizing that small effect size differences could not be detected in the present study - but group membership significantly interacted with age in predicting PGV (p = 0.02). Particularly, while PGV increased linearly with age in healthy controls (B = 61.39, SE = 14.94, p < 0.01), no corresponding association was found in NSSI patients (B = 16.83, SE = 12.20, p = 0.17). PGV was not related to adverse experiences during childhood and none of the clinical characteristics (e.g., frequency of NSSI) significantly correlated with PGV (p > 0.05). CONCLUSION: These results provide preliminary evidence for alterations in pituitary maturation in adolescents engaging in NSSI, although replication in longitudinal studies with larger samples is warranted.

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.

Early life maltreatment and resting-state heart rate variability: A systematic review and meta-analysis.

Recent focus on the consequences of early life adversity (ELA) in neurobiological research led to a variety of findings suggesting alterations in several physiological systems, such as the cardiovascular system. In this systematic review and meta-analysis, we focused on the relationship between early life maltreatment (ELM), one form of ELA, and resting vagal activity indexed by resting-state heart rate variability (HRV). A systematic search of the literature yielded 1'264 hits, of which 32 studies reporting data for group comparisons or correlations were included. By quantitative synthesis of existing studies using random-effect models, we found no evidence for a relationship between ELM exposure and resting vagal activity in principal. Conducting meta-regression analyses, however, we found the relationship between ELM and resting vagal activity to significantly vary as a function of both age and the presence of psychopathology. In light of the current multitude of vastly unclear pathways linking ELM to the onset of disease, we emphasize the need for further research and outline several aspects to consider in future studies.

Neuropsychological development in adolescents: Longitudinal associations with white matter microstructure.

Important neuropsychological changes during adolescence coincide with the maturation of white matter microstructure. Few studies have investigated the association between neuropsychological development and white matter maturation longitudinally. We aimed to characterize developmental trajectories of inhibition, planning, emotion recognition and risk-taking and examine whether white matter microstructural characteristics were associated with neuropsychological development above and beyond age. In an accelerated longitudinal cohort design, n = 112 healthy adolescents between ages 9 and 16 underwent cognitive assessment and diffusion MRI over three years. Fractional anisotropy (FA) and mean diffusivity (MD) were extracted for major white matter pathways using an automatic probabilistic reconstruction technique and mixed models were used for statistical analyses. Inhibition, planning and emotion recognition performance improved linearly across adolescence. Risk-taking developed in a quadratic fashion, with stable performance between 9 and 12 and an increase between ages 12 and 16. Including cingulum and superior longitudinal fasciculus FA slightly improved model fit for emotion recognition across age. We found no evidence that FA or MD were related to inhibition, planning or risk-taking across age. Our results challenge the additional value of white matter microstructure to explain neuropsychological development in healthy adolescents, but more longitudinal research with large datasets is needed to identify the potential role of white matter microstructure in cognitive development.