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 (RSFC) in n = 33 female adolescents aged 12-17 years engaging in NSSI, and n = 29 age-matched healthy controls using graph theory. Mixed linear models were evaluated with the Bayes Factor (BF) 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

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

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

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

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 1/4 112 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

Normierung der Testbatterie COGBAT bei Jugendlichen im Alter von 12 bis 15 Jahren

Das Jugendalter stellt eine wichtige Phase in der Entwicklung der Verarbeitungsgeschwindigkeit, der Aufmerksamkeit, des Gedächtnisses und der exekutiven Funktionen dar. Im Rahmen einer Normierungsstudie der kognitiven Basistestung (COGBAT) für das Jugendalter wurden Testwerte bei n = 269 Jugendlichen im Alter von 12 bis 15 Jahren erhoben und mit den Normen der Altersgruppe der 16- bis 30-Jährigen verglichen. Zusätzlich wurde überprüft, inwiefern sich diese Testergebnisse in der subjektiven Einschätzung zur Leistungsfähigkeit (FLei) und Psychopathologie (SDQ) abbilden lassen. Im Jugendalter zeigte sich ein starker Zuwachs in der kognitiven Flexibilität, der Verarbeitungs- und Reaktionsgeschwindigkeit sowie der Inhibitions- und Planungsfähigkeit. Ein bedeutsamer Geschlechtsunterschied fand sich in der Inhibition, mit stärkeren Leistungen bei Mädchen als bei Jungen. Zwischen den Testergebnissen und den subjektiven Einschätzungen zeigten sich keine Zusammenhänge

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

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

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