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Objective: Impairments in personality functioning (PF) according to the Alternative Model of Personality Disorders (AMPD) may affect anorexia nervosa (AN) and its treatment. However, PF impairments in adolescents with AN have not been studied. This case-control study analysed PF impairments in adolescent inpatients suffering from AN compared to a clinical control group (CC) and investigated the relationship of PF with AN severity., Method: Adolescent patients with AN (n = 43) and CC (n = 127) were matched by age, sex, and global functioning. Validated interviews were applied to assess impairments in PF (Semi-Structured Interview for Personality Functioning, STiP-5.1) and severity of AN (Eating Disorder Examination, EDE), as well as weight measures. Group comparisons of PF impairment and the relationship between PF impairment and AN severity were analysed using multiple linear regression., Results: AN patients showed greater impairment in the facet 'self-esteem' (p = 0.033, Cohen's f 2  = 0.036) than CC. In AN patients, impairments in the domain 'self-functioning' (p = 0.003, Cohen's f 2  = 0.254) and its underlying element 'identity' (p = 0.016, Cohen's f 2  = 0.172) were associated with AN severity (EDE). Additionally, higher impairments in two facets of 'empathy' (p = 0.019, Cohen's f 2  = 0.223) and 'intimacy' (p = 0.026, Cohen's f 2  = 0.199) were associated with higher AN severity (lower BMI percentiles)., Conclusions: These results support theoretical frameworks of AN and highlight the importance of PF impairments in understanding and treating AN. Future research should investigate how impairments in PF affect AN development and treatment response through longitudinal studies., (© 2024 The Author(s). European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)

Background: The intricate role of pain in non-suicidal self-injury (NSSI) makes the investigation of alterations in brain function during pain processing a critical yet underexplored topic. The aim of this study was to investigate fNIRS correlates of experimental pain and how these differed between adolescent patients engaging in NSSI and healthy controls., Methods: 154 adolescent patients with NSSI and 48 healthy controls underwent a heat pain stimulation with linearly increasing temperature from 32 °C to max. 50 °C, during which fNIRS activity was recorded. Associations between fNIRS activity and pain perception (i.e. pain threshold, pain tolerance and pain intensity) were examined using linear mixed models and linear regression analyses., Results: Across groups, we found a decrease in prefrontal oxygenation during increasing pain stimulation: Oxygenated hemoglobin was higher during baseline than during pain threshold (b = -0.36, p < .001) and higher during pain threshold than during pain tolerance (b = -0.10, p < .001). We did not find differential patterns of prefrontal oxygenation across the pain assessment between patients and healthy controls. Also, no association between pain intensity and fNIRS activity was found., Limitations: fNIRS was only recorded in prefrontal regions and our design did not include a non-painful stimulation as a control condition., Conclusion: While our study adds to the understanding of prefrontal hemodynamic changes associated with pain processing, it did not contribute further evidence to the few existing findings regarding altered neural processing of pain in adolescents engaging in NSSI., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Among youths, pathological irritability is highly prevalent and severely disabling. As a frequent symptom, it often leads to referrals to child and adolescent mental health services. Self-regulatory control (SRC) processes are a set of socio-psycho-physiological processes that allow individuals to adapt to their ever-changing environments. This conceptual framework may enhance the current understanding of the cognitive, emotional, behavioural and social dysregulations underlying irritability. The present systematic review (PROSPERO registration: #CRD42022370390) aims to synthesize existing studies that examine irritability through the lens of SRC processes among youths (< 18 years of age). We conducted a comprehensive literature search among six bibliographic databases: Embase.com, Medline ALL Ovid, APA PsycInfo Ovid, Web of Science Core Collection, the Cochrane Database of Systematic Reviews Wiley and ProQuest Dissertations & Theses A&I. Additional searches were performed using citation tracing strategies. The retrieved reports totalled 2612, of which we included 82 (i.e., articles) from 74 studies. More than 85% of reports were published during the last 6 years, highlighting the topicality of this work. The studies sampled n = 26,764 participants (n = 12,384 girls and n = 12,905 boys, n = 1475 no information) with an average age of 8.08 years (SD = 5.26). The included reports suggest that irritability has an association with lower effortful control, lower cognitive control and delay intolerance. Further, evidence indicates both cross-sectional and longitudinal associations between irritability and a lack of regulation skills for positive and negative emotions, particularly anger. Physiological regulation seems to moderate the association between irritability and psychopathology. Finally, the mutual influence between a child's irritability and parenting practice has been established in several studies. This review uses the lens of SRC to illustrate the current understanding of irritability in psychopathology, discusses important gaps in the literature, and highlights new avenues for further research., (© 2024. The Author(s).)

Homeostasis models posit that nonsuicidal self-injury (NSSI) serves, in part, to upregulate the endogenous opioid system in order to compensate for an opioid deficiency. A few studies have demonstrated lower basal levels of beta-endorphin (BE), an endogenous opioid, in individuals with NSSI. However, longitudinal studies are missing. Hence, the present study aimed to investigate the longitudinal associations between NSSI, comorbid psychopathology (i.e., borderline personality disorder and depressive symptoms), pain sensitivity and basal BE levels in adolescents with NSSI. N = 53 adolescents with NSSI disorder undergoing specialized treatment participated in baseline and one-year follow-up assessments. BE was measured in plasma; pain sensitivity was assessed with a heat pain stimulation paradigm. Associations between BE and change in NSSI, borderline personality disorder and depressive symptoms as well as pain sensitivity were examined using negative binomial and linear regression analyses. We found that an increase in basal BE was significantly associated with a decrease in depressive symptoms. No associations between BE and NSSI, borderline personality disorder symptoms or pain sensitivity were observed. Our findings may confirm a role of plasma BE in the etiology of depressive symptoms but challenge current models of endogenous opioid homeostasis in NSSI., Competing Interests: Declaration of competing interest The authors have nothing to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Declarations Conflict of interest No conflicts of interest present. Ethical approval Ethics approval obtained, see section Participants and procedures. Informed consent Informed consent obtained, see section Participants and Procedures. Consent for publication Not applicable., (© 2024. The Author(s).)

Borderline personality disorder (BPD) is an established diagnosis in adolescence with high comorbidity and psychosocial impairment. With the introduction of the alternative model for personality disorders in DSM-5 (AMPD), personality functioning is operationalized using the Level of Personality Functioning Scale (LPFS), which has been shown to be associated with severity of personality pathology. The present study aimed at examining differential psychopathological and psychosocial correlates of LPFS and BPD. A total of 526 adolescent in- and outpatients were interviewed with the STiP-5.1 (LPFS) and the SCID-II. Mixed linear regression was used to investigate the associations between the two interviews with measures of psychopathology and psychosocial impairment. 11.4% met the diagnostic threshold of both interviews, 16.1% only of the LPFS, and 64.1% were below the diagnostic threshold in both interviews (no PD). The BPD only group was larger than expected-8.4% of patients who met criteria for BPD did not fulfill criteria for significant impairment in the LPFS. The highest burden was found in individuals concurrently showing significant impairment in LPFS and fulfilling BPD diagnosis (LPFS + BPD). Differences between the LPFS only group and the BPD only group were found in risk behavior and traumatic experiences, with higher prevalence in the BPD group. Findings confirm the high psychopathological burden and psychosocial impairment associated with both BPD and LPFS. Those exceeding the diagnostic threshold of LPFS in combination with a BPD diagnosis are characterized by greatest disability. Not all adolescents fulfilling formal BPD diagnosis showed a clinically significant impairment in LPFS, which may refer to a distinct diagnostic group., (© 2024. The Author(s).)

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.

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 (β = .41, p < .001), empathy (β = .26, p = .002), and intimacy (β = .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).

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., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

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., (© 2022. The Author(s).)

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 (χ 2 (3) = 12.09, p = .007) to pain. After adjusting for comorbid psychopathology, greater NSSI severity predicted decreased α-amylase levels following pain (χ 2 (3) = 10.47, p = .015), and decreased HR (χ 2 (2) = 8.53, p = .014) and increased HRV(χ 2 (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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest None of the authors have any financial disclosures to make nor any conflicts of interest to report., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

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).

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., Competing Interests: Conflict of interest The authors have no conflict of interest to declare. Disclosures The study was funded by the Dres. Majic/Majic-Schelz-Foundation and the Dietmar Hopp Foundation [23011121]. The foundations were not involved in the collection, analysis or interpretation of data, in the writing of the manuscript or the decision to submit the article for publication., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (© 2021. The Author(s).)

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., (© The Author(s) 2022. Published by Oxford University Press.)

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., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Infants born very preterm are at higher risk of long-term neurodevelopmental problems than children born at term. Although there are increasing numbers of reports on outcomes from international cohorts of premature infants, a Swiss national report on infants after 2 years of age is lacking., Aims of the Study: To describe neurodevelopmental outcomes at early school age of preterm children born in Switzerland with a special focus on the cognitive abilities., Methods: This prospective national cohort study included children born alive before 30 weeks of gestation in 2006. At 5 years of age, children underwent a neurological examination and intelligence testing with the Kaufman Assessment Battery for Children first edition (K-ABC). We assessed the mental processing composite score (MPC) and its subscales to explore specific cognitive deficits. The primary outcome was cognitive impairment (MPC score &lt;-1 standard deviation from the normative mean), motor impairment (cerebral palsy), or sensory impairment (any visual or hearing deficiency). The need for early intervention or therapies and the association of perinatal factors with cognitive impairment were secondary and tertiary outcomes. Logistic regression models were used to analyse associations between neonatal factors and cognitive outcome., Results: Of 289 survivors, 235 were assessed. Of the 199 children with results obtained from the K-ABC, 42 (21%) showed cognitive impairment and 80 (40%) showed impairment in short-term memory. Cerebral palsy was diagnosed in 14 (6%), and visual and auditory impairment in 36 (15%) and 12 (5%) children, respectively; 63 (27%) needed early intervention or therapies. Cognitive impairment was associated with low socioeconomic status, but not with gestational age, small birthweight for gestational age, bronchodysplasia, or significant brain injury. A total of 146 children (63%) survived without any impairment., Conclusion: This is the first study to report neurodevelopmental outcomes at early school age in a Swiss cohort. The majority had favourable outcomes, but 21% of children demonstrated cognitive impairment, which was most pronounced in short-term memory. Our findings were similar to those of international cohorts and indicate that preterm children born before 300/7 gestational weeks, especially those living in unfavourable social environments, are at an increased risk of cognitive impairment and need close monitoring beyond early school age. Trial registration no: KEK-ZH-Nr.2014-0552 &nbsp.

Preterm-born individuals are at risk for poorer executive functions. Longitudinal studies investigating whether preterm-born individuals present persistent cognitive deficits, or a transient delay of development are scarce. We assessed developmental trajectories of executive functions (inhibition, working memory, cognitive flexibility) in 29 very preterm-born individuals (<32 weeks' gestation) and 25 term-born controls longitudinally over two time points, namely in childhood (7-12 years of age, TP1) and adolescence (13-16 years of age, TP2). Individual changes in executive functions were examined using relative difference scores (TP2 - TP1) / TP1). There was a significantly stronger improvement of inhibition (U = 477, p = .024) and cognitive flexibility (U = 312, p = .029) between childhood and adolescence in very preterm-born individuals than in term-born controls. Preterm-born individuals improved their performance in the domain of cognitive flexibility significantly more often (76%) between childhood and adolescence than controls (31%, χ 2  = 8.6, p = .003). Controls worsened significantly more often (36%) in the domain of inhibition than the preterm group (14%, χ 2  = 4.8, p = .028). Results indicate that healthy preterm-born individuals show prolonged development of executive functions throughout childhood up into adolescence., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Individuals born very preterm (VPT; <32 weeks' gestational age) are at increased risk of impaired mathematics and word reading performance, as well as widespread white matter microstructural alterations compared with individuals born full term (FT; ≥37 weeks' gestational age). To date, the link between academic performance and white matter microstructure is not well understood. This study aimed to investigate the associations between mathematics and reading performance with white matter microstructure in 114 VPT and 36 FT 13-year-old children. Additionally, we aimed to investigate whether the association of mathematics and reading performance with white matter microstructure in VPT children varied as a function of impairment. To do this, we used diffusion tensor imaging and advanced diffusion modelling techniques (Neurite Orientation Dispersion and Density Imaging and the Spherical Mean Technique), combined with a whole-brain analysis approach (Tract-Based Spatial Statistics). Mathematics performance across VPT and FT groups was positively associated with white matter microstructural measurements of fractional anisotropy and neurite density, and negatively associated with radial and mean diffusivities in widespread, bilateral regions. Furthermore, VPT children with a mathematics impairment (>1 standard deviation below FT mean) had significantly reduced neurite density compared with VPT children without an impairment. Reading performance was not significantly associated with any of the white matter microstructure parameters. Additionally, the associations between white matter microstructure and mathematics and reading performance did not differ significantly between VPT and FT groups. Our findings suggest that alterations in white matter microstructure, and more specifically lower neurite density, are associated with poorer mathematics performance in 13-year-old VPT and FT children. More research is required to understand the association between reading performance and white matter microstructure in 13-year-old children., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Very preterm birth influences brain development and may result in alterations of cortical morphometry. These structural alterations may interact with cognitive development. The aim of the present study was to investigate the structure-function relationship in school-aged very preterm and term-born control children. A comprehensive neuropsychological test battery was administered to 41 very preterm (<32 weeks of gestation) and 30 term-born control children aged seven to twelve years. The automated method FreeSurfer was used to obtain cortical thickness and cortical surface area measures from T1-weighted MRI images. Regional cortical thickness differed between groups but differences disappeared when controlling for age. Global cortical thickness differed between groups in the right hemisphere (very preterm children>controls). No group differences occurred for cortical surface area. The relationship between cortical morphometry and cognition differed between very preterm and control children. In very preterm children, some cognitive domains correlated positively and others negatively with regional cortical thickness and cortical surface area. Our findings contribute to the understanding of the structure-function relationship in very preterm children and their term-born peers. They add to the notion that this relationship varies depending on the brain region and the cognitive function in question and suggest developmental differences between very preterm and term-born children., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: There is mixed evidence regarding neural change following cognitive training. Brain activation increase, decrease, or a combination of both may occur. We investigated training-induced neural change using two different memory training approaches., Methods: Very preterm born children (aged 7-12 years) were randomly allocated to a memory strategy training, an intensive working memory practice or a waiting control group. Before and immediately after the trainings and the waiting period, brain activation during a visual working memory task was measured using fMRI and cognitive performance was assessed., Results: Following both memory trainings, there was a significant decrease of fronto-parietal brain activation and a significant increase of memory performance. In the control group, no neural or performance change occurred after the waiting period., Conclusion: These pilot data point towards a training-related decrease of brain activation, independent of the training approach. Our data highlight the high training-induced plasticity of the child's brain during development.

Background: Cortical gray matter thinning occurs during childhood due to pruning of inefficient synaptic connections and an increase in myelination. Preterms show alterations in brain structure, with prolonged maturation of the frontal lobes, smaller cortical volumes and reduced white matter volume. These findings give rise to the question if there is a differential influence of age on cortical thinning in preterms compared to controls., Aims: To investigate the relationship between age and cortical thinning in school-aged preterms compared to controls., Study Design and Outcome Measures: The automated surface reconstruction software FreeSurfer was applied to obtain measurements of cortical thickness based on T1-weighted MRI images., Subjects: Forty-one preterms (<32weeks gestational age and/or <1500g birth weight) and 30 controls were included in the study (7-12years)., Results: In preterms, age correlated negatively with cortical thickness in right frontal, parietal and inferior temporal regions. Furthermore, young preterms showed a thicker cortex compared to old preterms in bilateral frontal, parietal and temporal regions. In controls, age was not associated with cortical thickness., Conclusion: In preterms, cortical thinning still seems to occur between the age of 7 and 12years, mainly in frontal and parietal areas whereas in controls, a substantial part of cortical thinning appears to be completed before they reach the age of 7years. These data indicate slower cortical thinning in preterms than in controls., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

This study investigates neural language organization in very preterm born children compared to control children and examines the relationship between language organization, age, and language performance. Fifty-six preterms and 38 controls (7-12 y) completed a functional magnetic resonance imaging language task. Lateralization and signal change were computed for language-relevant brain regions. Younger preterms showed a bilateral language network whereas older preterms revealed left-sided language organization. No age-related differences in language organization were observed in controls. Results indicate that preterms maintain atypical bilateral language organization longer than term born controls. This might reflect a delay of neural language organization due to very premature birth.

This study describes the influence of age, sex, and working memory (WM) performance on the visuospatial WM network. Thirty-nine healthy children (7-12 years) completed a dot location functional magnetic resonance imaging (fMRI) task. Percent signal change measured the intensity and laterality indices measured the asymmetry of activation in frontal and parietal brain regions. Old children showed greater intensity of activation in parietal regions than young children but no differences in lateralization were observed. Intensity of activation was similar across sex and WM performance groups. Girls and high WM performers showed more right-sided lateralization of parietal regions than boys and low WM performers.