Transcutaneous Auricular Vagus Nerve Stimulation in Adolescent Treatment Resistant Depression-A Case Report.

Adolescence is a critical time period for the onset of depression, and many patients do not respond to treatment. Transcutaneous auricular vagus nerve stimulation may be a promising alternative. Here, we present the case of an adolescent girl with treatment-resistant depression who received transcutaneous auricular vagus nerve stimulation over the course of 7.5 months.

Indicated Stress Prevention Addressing Adolescents with High Stress Levels Based on Principles of Acceptance and Commitment Therapy: A Randomized Controlled Trial.

INTRODUCTION: Stress affects many adolescents and is associated with physical and mental health symptoms that can have a negative impact on normative development. However, there are very few evidence-based, specific treatment approaches. The aim of the study was to investigate an eight-session group intervention using components of Acceptance and Commitment Therapy (ACT) enriched with elements of CBT (psychoeducation, problem solving) and art therapy, compared to a waitlist control (WLC) group, regarding its efficacy in reducing stress and associated symptoms. METHODS: We conducted a randomized controlled trial in eight cohorts. Eligible participants were 13-18 years old with elevated stress levels. Via block-randomization (n = 70), participants were allocated to receive ACT (n = 38) or WLC (n = 32) and subsequent ACT. We used a multimodal assessment (self-reports, interviews, ecological momentary assessment, physiological markers) before treatment (T1), after the training of the ACT group (T2) and after subsequent training in the WLC group (T3). Primary outcome was perceived stress at T2 assessed with the Perceived Stress Scale. The trial was preregistered at the German Clinical Trials Register (ID: DRKS00012778). RESULTS: Results showed significantly lower levels of perceived stress in the ACT group at T2, illustrating superiority of ACT compared to WLC with a medium to large effect size (d = 0.77). Furthermore, the training was effective in the reduction of symptoms of school burnout and physical symptoms associated with stress. CONCLUSION: Indicated prevention, especially when based on the principles of ACT and CBT, seems efficient in significantly decreasing stress in adolescents with increased stress.

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.

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.

A sex-specific pathway linking early life maltreatment, vagal activity, and depressive symptoms.

Background: Experiences of early life maltreatment (ELM) are alarmingly common and represent a risk factor for the development of psychopathology, particularly depression. Research has focused on alterations in autonomic nervous system (ANS) functioning as a mediator of negative mental health outcomes associated with ELM. Early alterations in autonomic vagal activity (vmHRV) may moderate the relationship between ELM and depression, particularly when considering forms of emotional maltreatment. Recent evidence suggests that the relationships of both ELM and vmHRV with depression may be non-linear, particularly considering females.Objective: Building on and extending theoretical considerations and previous work, the present work aims to further the current understanding of the complex relationships between ELM exposure, vmHRV, and depression.Methods: This study uses an adaptive modelling approach, combining exploratory network-based analyses with linear and quadratic moderation analyses, drawing on a large sample of males and females across adolescence (total N = 213; outpatient at-risk sample and healthy controls) and adulthood (total N = 85; community-based convenience sample).Results: Exploratory network-based analyses reveal that exposure to emotional abuse is particularly central within a network of ELM subtypes, depressive symptoms, and concurrent vmHRV in both adolescents and adults. In adults, emotional neglect shows strong associations with both emotional abuse and vmHRV and is highly central as a network node, which is not observed in adolescents. Moderator analyses reveal significant interactions between emotional maltreatment and vmHRV predicting depressive symptoms in adult females. Significant quadratic relationships of emotional maltreatment and vmHRV with depression are observed in both adolescent and adult females.Conclusions: The present findings contribute to the understanding of the psychological and physiological mechanisms by which ELM acts as a risk factor for the development of depression. Ultimately, this will contribute to the development of targeted and effective intervention strategies to mitigate the detrimental effects of early adversity.

Early exposure to chronic and severe adversity, which includes experiences of maltreatment, defined by the World Health Organization as physical, sexual, emotional abuse and/or neglect of children under the age of 18, is highly prevalent in the general population (estimated at 40­50 percent), and is a well-documented risk factor for depression.The present work combines network-based analyses with tests of different functions (i.e. linear, nonlinear quadratic) in moderator analyses to further explore the complex relationships among ELM exposure, vmHRV, and depression.The present findings contribute to the understanding of the psychological and physiological mechanisms by which early exposure to chronic and severe maltreatment acts as a risk factor for the development of depression.Ultimately, this will contribute to the development of targeted and effective intervention strategies to mitigate the detrimental effects of early adversity.

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).

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.

Resting heart rate variability is associated with neural adaptation when repeatedly exposed to emotional stimuli.

Higher heart rate variability (HRV) at rest is associated with better emotion regulation ability. While the neurovisceral integration model explains this by postulating that HRV can index how the brain adaptively modulates responses to emotional stimuli, neuroimaging studies directly supporting this idea are scarce. We examined the neural correlates of regulating negative and positive emotion in relation to resting HRV based on the neuroimaging and heart rate data of one hundred young adults. The results showed that those with higher HRV better recruit the medial prefrontal cortex while intensifying positive compared to negative emotion. We also examined how individual differences in resting HRV are associated with adjusting brain activity to repeated emotional stimuli. During repeated viewing of emotional images, subjects with higher resting HRV better reduced activity in the medial prefrontal cortex, posterior cingulate gyrus, and angular gyrus, most of which overlapped with the default mode network. This HRV-DMN association was observed during passively viewing emotional images rather than during actively regulating emotion. While the regulating trials can better detect task-induced changes, the viewing trials might approximate resting state, better revealing individual differences. These findings suggest two possibilities: people with higher resting HRV might have a tendency to spontaneously engage with emotion regulation or possess a trait helping emotional arousal fade away.

Age dependent effects of early intervention in borderline personality disorder in adolescents.

BACKGROUND: Psychological treatments for young people with sub-threshold or full-syndrome borderline personality disorder (BPD) are found to be effective. However, little is known about the age at which adolescents benefit from early intervention. This study investigated whether age affects the effectiveness of early intervention for BPD. METHODS: N = 626 participants (M age = 15 years, 82.7% female) were consecutively recruited from a specialized outpatient service for early intervention in BPD in adolescents aged 12- to 17-years old. DSM-IV BPD criteria were assessed at baseline, one-year (n = 339) and two-year (n = 279) follow-up. RESULTS: Older adolescents presented with more BPD criteria (χ2(1) = 58.23, p < 0.001) and showed a steeper decline of BPD criteria over the 2-year follow-up period compared with younger adolescents (χ2(2) = 13.53, p = 0.001). In an attempt to disentangle effects of early intervention from the natural course of BPD, a parametrized regression model was used. An exponential decrease (b = 0.10, p < 0.001) in BPD criteria was found when starting therapy over the 2-year follow-up. This deviation from the natural course was impacted by age at therapy commencement (b = 0.06, p < 0.001), although significant across all ages: older adolescents showed a clear decrease in BPD criteria, and young adolescents a smaller decrease. CONCLUSIONS: Early intervention appears effective across adolescence, but manifests differently: preventing the normative increase of BPD pathology expected in younger adolescents, and significantly decreasing BPD pathology in older adolescents. The question as to whether developmentally adapted therapeutic interventions could lead to an even increased benefit for younger adolescents, should be explored in future studies.

Risk-taking and self-harm behaviors as markers of adolescent borderline personality disorder.

Adolescence is a critical period for early identification and intervention of borderline personality disorder (BPD). Risk-taking and self-harm behaviors (RSB) have been identified as promising early markers of BPD and correlates of depression in school-based samples. The present study aimed, first, to examine the association between RSB and BPD in a clinical sample of adolescents and, second, to examine whether RSB are also linked to depression. N = 405 participants (82.7% female) were recruited from an outpatient clinic for adolescents with RSB. RSB assessed included truancy, excessive media use, alcohol, tobacco, and illicit drug use, sexual risk-taking, and self-harm behavior. Regression analyses and generalized linear models were performed to examine the associations between individual RSB or patterns of RSB (identified using latent class analysis, LCA) and a diagnosis and severity of BPD or depression. All RSB (except excessive media use) were positively associated with BPD diagnosis and severity. In contrast, only non-suicidal self-injury (NSSI) and suicide attempts were positively associated with depression diagnosis and severity, while illicit drug use was negatively associated with depression severity. The LCA yielded two classes differing in the occurrence of RSB. The high RSB class was more likely to have a BPD diagnosis and greater BPD severity than the low RSB class. Classes did not differ regarding depression diagnosis or severity. As NSSI and suicide attempts were associated with both BPD and depression, the presence of additional RSB, besides self-harm behavior, may represent a specific risk marker for BPD in adolescents.

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.

Child temperament as a longitudinal predictor of mother-adolescent interaction quality: are effects independent of child and maternal mental health?

Adaptive parent-child interaction plays a major role in healthy child development. Caregiver mental health problems can negatively impact parent-child interaction. In turn, interactional quality is often studied as a predictor of child outcome. However, child characteristics supposedly shape parent-child interactions as well. Given associations between child and caregiver mental health and child temperament, this study aimed at differentiating their effects on dyadic interaction quality in adolescence. Child temperament and character at age 5 were investigated as longitudinal predictors of observed mother-adolescent interactional quality at age 14 in a community sample (N = 76). It was examined whether these effects were independent of maternal and child mental health and earlier dysfunctional interaction. Lower novelty seeking, higher reward dependence, and higher cooperativeness separately predicted higher dyadic interactional quality at age 14. Controlling regressions for dysfunctional interaction at age 5, which was a significant negative predictor of later interactional quality, cancelled out the effects of novelty seeking and cooperativeness. Past or concurrent maternal or child psychopathology did not explain variance in mother-adolescent interaction. Applying backward selection, a model including reward dependence and dysfunctional interaction at age 5 and concurrent maternal stress showed the best fit for explaining dyadic interaction quality. Results suggest that enduring rather than transient child features predict interactional quality in a community sample. Effects of temperament are not better explained by those of psychopathology, but a combination of child, maternal, and dyadic features predicted dyadic behaviour best. Selective prevention should target parenting in the context of challenging child characteristics specifically.

Diurnal variation of cardiac autonomic activity in adolescent non-suicidal self-injury.

Heart rate (HR) and vagally mediated heart rate variability (HRV) are two distinct biomarkers of cardiac autonomic activity. Decreased cardiac vagal activity (or decreased HRV) in particular has been linked with impairments in the functional flexibility of the central autonomic network (CAN), resulting in impaired stress and emotion regulatory capacities. Decreased HRV is widely used as trait marker of psychopathology. Repetitive engagement in non-suicidal self-injury (NSSI) in adolescence correlates with both deficits in stress and emotion regulation, as well as decreased HRV. Existing research has, however, focused on short-term recordings of HR and HRV under resting and phasic conditions. In this study, we examined whether diurnal variation of cardiac autonomic activity, indexed by cosinor parameters of HR and HRV derived from 48 h of ambulatory ECG recording under natural conditions over a weekend, are altered in female adolescents with NSSI disorder compared to controls (HC; N = 30 per study group). Several important confounds, including physical activity, were controlled for. Female adolescents with NSSI show higher rhythm-adjusted 24 h mean levels and greater respective amplitude of HR, as well as lower rhythm-adjusted 24 h mean levels and smaller respective amplitude of HRV. Peak levels in both HR and HRV in the NSSI group were reached approximately 1 h later compared to HC. Severity of exposure to early life maltreatment might be linked with altered amplitudes of 24 h HR and HRV. Diurnal rhythms of cardiac autonomic activity might hold promise as objective indicators of disordered stress and emotion regulation in developmental psychopathology, and as such should be investigated in future studies with rigorous assessment and control of potential confounds.

Differential outcomes of outpatient only versus combined inpatient/outpatient treatment in early intervention for adolescent borderline personality disorder.

Clinical guidelines for adults with borderline personality disorder (BPD) recommend outpatient psychotherapy as first-line treatment. Little is known whether this recommendation is also applicable to adolescents. The current study examined the relationship between treatment setting and the outcome of early intervention for adolescents with BPD pathology. One-hundred and seventy-eight adolescents from a specialized outpatient clinic were assessed at baseline, and at 1- and 2-year follow-up. Sixty-three participants who received inpatient treatment during the first year were assigned to the "combined inpatient/outpatient group", 115 participants to the "outpatient only group". Generalized linear and mixed models with inverted probability weights to adjust for baseline differences were applied to examine the impact of group on clinical changes over time. Both groups demonstrated a significant decrease in BPD features, depressive symptoms, psychopathological distress, non-suicidal self-injury (NSSI), suicidal thoughts, suicide attempts, and overall illness severity, and a significant increase in quality of life and psychosocial functioning from baseline to follow-up 2. The decrease in NSSI and overall illness severity, and the increase in psychosocial functioning from baseline to follow-up 1 were greater in the outpatient only group, with comparable improvements between groups from follow-up 1 to follow-up 2. Both outpatient treatment and combined outpatient/inpatient treatment resulted in clinical improvements over time, with some indication for faster changes in the outpatient only setting. The findings provide preliminary evidence that the recommendation of outpatient psychotherapy as the first-line treatment for BPD also holds true for adolescents.

Tension and disordered eating behaviors in the daily lives of adolescents and young adults from the general population: Associations and moderating role of trait emotion regulation.

Experiences of tension and difficulties in emotion regulation have been linked to eating pathology in clinical samples and are targeted in respective treatment approaches. The present study aimed to investigate the impact of tension on engagement in disordered eating behaviors (DEBs) and potential moderating effects of trait emotion regulation in young people from the general population. A subsample of 971 adolescents and young adults from an epidemiological cohort study reported on levels of tension and four different DEBs (skipping eating, restrained eating, eating large amounts of food, loss-of-control-eating) via ecological momentary assessment (EMA), as well as on trait emotion regulation via questionnaire. In multilevel models, momentary tension did not predict levels of subsequent DEBs. However, higher average levels of tension across the EMA period predicted higher levels of all DEBs. No interactions with emotion regulation emerged. Individuals experiencing overall higher levels of tension appear to be more prone to engaging in DEBs.

Higher striatal glutamate in male youth with internet gaming disorder.

Internet gaming disorder (IGD) was included in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a research diagnosis, but little is known about its pathophysiology. Alterations in frontostriatal circuits appear to play a critical role in the development of addiction. Glutamate is considered an essential excitatory neurotransmitter in addictive disorders. This study's aim was to investigate striatal glutamate in youth with IGD compared to healthy controls (HC). Using a cross-sectional design, 25 adolescent male subjects fulfilling DSM-5 criteria for IGD and 26 HC, matched in age, education, handedness and smoking, were included in the analysis. A structural MPRAGE T1 sequence followed by a single-voxel magnetic resonance spectroscopy MEGA-PRESS sequence (TR = 1500 ms, TE = 68 ms, 208 averages) with a voxel size of 20 mm3 were recorded on 3 T Siemens Magnetom Prisma scanner. The voxel was placed in the left striatum. Group comparison of the relative glutamate and glutamine (Glx) was calculated using regression analysis. IGD subjects met an average of 6.5 of 9 DSM-5 IGD criteria and reported an average of 29 h of weekly gaming. Regression analysis showed a significant group effect for Glx, with higher Glx levels in IGD as compared to HC (coef. = .086, t (50) = 2.17, p = .035). Our study is the first to show higher levels of Glx in the striatum in youth with IGD. The elevation of Glx in the striatum may indicate hyperactivation of the reward system in IGD. Thus, results confirm that neurochemical alterations can be identified in early stages of behavioral addictions.

A paucity of evidence in youth: The curious case of transcranial direct current stimulation for depression.

A significant proportion of youth with depression do not respond to available treatment. Transcranial direct current stimulation (tDCS) is a promising third-line treatment in depressed adults, but evidence in youth seems scarce. Following the PRISMA guidelines, we conducted a systematic literature review on tDCS treatment for depression in children and adolescents. No published studies were found on the use of tDCS in youth with depression. Given the null-findings, no conclusion can be drawn about the effectiveness of tDCS treatment for adolescent depression. The reasons for this paucity of evidence in light of existing regulatory frameworks and technical challenges are discussed.

Pharmacological anti-inflammatory treatment in children and adolescents with depressive symptoms: A systematic-review and meta-analysis.

Growing evidence suggests an association between inflammatory processes and depressive disorders (DD). DD typically emerge during adolescence. Treatment effects of agents with anti-inflammatory properties in youth DD have not been systematically reviewed. Here, the existing evidence on the use of anti-inflammatory drugs (including polyunsaturated fatty acids, nonsteroidal anti-inflammatory drugs, cytokine inhibitors, statins, pioglitazone, corticosteroids, and minocycline or modafinil) in children and adolescents with DD was synthesized using meta-analysis. The PROSPERO preregistered search yielded 22 records meeting search criteria. Of these, data from 19 primary studies (n = 1366 subjects) were subjected to meta-analysis. A significant but small effect in favor of anti-inflammatory agents in reducing depressive symptoms in youth with DD was found (SMD = -0.29, 95 % CI = -0.514; -0.063, p = 0.01). Post-hoc analyzes of drug subclasses found a significant effect of omega-3 fatty acids in reducing depressive symptoms. Results underline the importance to consider inflammatory pathways in the supplemental treatment of youth with DD. Further research is warranted, to clarify if anti-inflammatory agents are only effective in a subpopulation of patients (inflammatory biotype of depression in youth) and/or to alleviate specific symptom domains of depression (e.g., cognitive symptoms).

Interventions Based on Acceptance and Commitment Therapy for Stress Reduction in Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Recently, acceptance- and commitment therapy (ACT) gained increasing interest. Studies show good efficacy in the treatment of patients presenting with several psychologic and somatic complaints. The present systematic review and meta-analysis addresses effectiveness of ACT-based interventions to reduce stress in children, adolescents, and young adults compared to control conditions. METHODS: The meta-analysis was pre-registered at PROSPERO (CRD42019117440). Randomized controlled trials (RCTs) and quasi-randomized controlled trials (qRCT) in German or English language comparing the effects of ACT-based interventions to control conditions (e.g., treatment as usual, waitlist control) on stress-related outcome measures in youth were considered for inclusion. The target population was subjects 0-18 years of age. The databases PubMed, PsychInfo, Cochrane Database, CINAHL, and Web of Science were searched systematically up to July 2023. A random effect meta-analysis and a risk of bias assessment according to the procedure outlined in the Cochrane Handbook of Systematic Reviews were conducted. RESULTS: The search resulted in 187 studies, of which eight studies with 976 participants were finally subjected to meta-analysis. Studies implemented ACT both in school-based group settings and in single settings and both as a universal and indicated prevention. Analyses yielded a significant main effect (Hedges' g = -0.20; 95% confidence interval [-0.36; -0.05]), indicating that interventions based on ACT resulted in greater reduction of stress compared to control conditions. CONCLUSION: ACT appears effective at reducing stress in youth. Further research is needed due to methodological shortcomings of existing studies. Small sample sizes, heterogenous studies, methodological shortcomings, and evidence of publication bias limit the conclusions that can be drawn from this meta-analysis.