Frontal alpha asymmetry during emotion regulation in adults with lifetime major depression.

Emotion regulation (ER) often is impaired in current or remitted major depression (MD), although the extent of the deficits is not fully understood. Recent studies suggest that frontal alpha asymmetry (FAA) could be a promising electrophysiological measure to investigate ER. The purpose of this study was to investigate ER differences between participants with lifetime major depression (lifetime MD) and healthy controls (HC) for the first time in an experimental task by using FAA. We compared lifetime MD (n = 34) and HC (n = 25) participants aged 18-24 years in (a) an active ER condition, in which participants were instructed to reappraise negative images and (b) a condition in which they attended to the images while an EEG was recorded. We also report FAA results from an independent sample of adolescents with current MD (n = 36) and HC adolescents (n = 38). In the main sample, both groups were able to decrease self-reported negative affect in response to negative images through ER, without significant group differences. We found no differences between groups or conditions in FAA, which was replicated within the independent adolescent sample. The lifetime MD group also reported less adaptive ER in daily life and higher difficulty of ER during the task. The lack of differences between in self-reported affect and FAA between lifetime MD and HC groups in the active ER task indicates that lifetime MD participants show no impairments when instructed to apply an adaptive ER strategy. Implications for interventional aspects are discussed.

Intermittent theta burst stimulation in adolescents and young adults with depressive disorders: protocol of a randomized, sham-controlled study with a sequential Bayesian design for adaptive trials.

Intermittent theta burst stimulation (iTBS), a variant of repetitive transcranial magnetic stimulation (rTMS), is an established treatment for adults with major depressive disorder (MDD). Due to its favorable safety profile, iTBS is also a promising early intervention in the transition phase from adolescence to early adulthood, but this has not been systematically investigated to date. Thus, the EARLY-BURST trial investigates the efficacy and safety of iTBS over the left dorsolateral prefrontal cortex (lDLPFC) in treatment-seeking young patients (age 16-26 years) with depressive disorders (i.e. major depressive disorder, persistent depressive disorder, bipolar depression), allowing for relevant co-morbidities. Participants have not received antidepressant or antipsychotic medication during the last 12 months except for short-term (< 2 weeks) on-demand medication. The trial will employ a novel sequential Bayesian, randomized, double-blind, parallel-group, sham-controlled design. Up to 90 patients at two clinical sites (Munich, Augsburg) will be randomized 1:1 to the treatment groups, with sequential analyses starting after 26 patients in each group completed the treatment. The primary outcome will be the difference in depression severity at week 6 (post-treatment visit) between active iTBS and sham iTBS, assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). The trial is planned to be expanded towards a three-arm leapfrog design, contingent on securing additional funding. Thus, in addition to potentially providing evidence of iTBS's efficacy in adolescents and young adults with depressive disorders, the EARLY-BURST trial aims at setting the stage for subsequent platform trials in this dynamic research field, where novel adaptive study designs are required to meet the need for rapidly testing promising new vs established rTMS protocols.Trial registration: DRKS00033313.

A Germany-wide survey of caregiving professionals on climate change and mental health of children and adolescents - factors influencing their relevance rating of extreme weather event associated mental health impairments.

INTRODUCTION: Climate change presents a significant risk for the mental and physical health of young people. In order to identify and properly care for potential mental health impairments from extreme weather events, the relevance of these impairments must be assessed as high by the professional groups providing care for children and adolescents. This raises the question of which factors influence the individual relevance assessment of caretaking professionals? METHODS: Data was collected creating and conducting a Germany-wide online questionnaire via LimeSurvey. The questionnaire was addressed to professionals providing care for children and adolescents, in this case medical and therapeutic personnel as well as school and pedagogical personnel. Professional associations, chief physicians and school principals were contacted as multipliers and asked to forward the questionnaire to their members and staff. The data was analyzed using the R statistical software, and multiple linear regressions were performed to test the hypotheses. RESULTS: Overall, 648 questionnaires were taken into analysis. Approximately 70% of the participants considered climate change-induced impacts on the mental health of children and adolescents due to extreme weather events as relevant. Experiencing heat, storm, heavy precipitation, flood/flooding, and/or avalanches/mudflows made a modest yet significant contribution to explaining higher relevance assessments. In contrast, there was no evidence to suggest that an urban working environment increases the relevance assessment. CONCLUSION: The described influence of experiencing extreme weather events should not be regarded as the sole factor leading to higher relevance ratings. A more comprehensive understanding of the factors influencing relevance assessments is necessary to address key aspects of risk communication and increase risk awareness.

Superior facial emotion recognition in adolescents with anorexia nervosa - A replication study.

OBJECTIVE: Anorexia nervosa (AN) has been associated with alterations in the processing of socio-emotional information, including impairments in the recognition of emotions in other people's faces. However, adolescents with AN might not show the impairments found in adult patients. The present study investigated facial emotion recognition in adolescents with AN, aiming to replicate our previous results of superior emotion recognition abilities in adolescents with AN compared to adolescents without mental disorders. METHOD: Adolescent girls (12-18 years) with AN (n = 33) were compared to girls without mental disorders (n = 41). Participants completed one task requiring identification of emotions (happy, sad, afraid, angry, neutral) in faces and one control task. RESULTS: As expected, adolescents with AN showed superior emotion recognition, with higher accuracy rates specifically for afraid faces. CONCLUSION: This is the first study replicating previous results on basic emotion recognition in adolescents with AN using (almost) the same methodology. The results suggest that, in contrast to adults, adolescents with AN do not show impairments in facial emotion recognition. The impairments may arise in the longer course of the illness, however, longitudinal studies are necessary to confirm this assumption.

Seeing oneself as an unattractive loser: Similar interpretation and memory biases in adolescents with anorexia nervosa and adolescents with depression or anxiety.

OBJECTIVE: Anorexia nervosa (AN) is characterised by dysfunctional cognitive biases but these have rarely been investigated in adolescents with AN. The present study systematically assessed cognitive biases in adolescents with AN and addressed the questions of content-specificity (i.e., do biases occur only for eating disorder-related information?) and disorder-specificity (i.e., are biases unique to individuals with AN?). METHODS: Cognitive biases on three information processing levels (attention, interpretation, memory) and for two types of information content (eating disorder-related, non-eating disorder-related) were assessed within a single experimental paradigm based on the Scrambled Sentences Task. 12-18-year-old adolescents with AN (n = 40) were compared to a healthy (HC; n = 40) and a clinical (girls with depression and/or anxiety disorders; CC; n = 34) control group. RESULTS: Both clinical groups (AN and CC) showed pronounced negative interpretation and memory biases compared to the HC group, for both disorder-related and non-disorder-related information. Attention biases could not be analysed. CONCLUSION: The results support the hypothesis that adolescents with AN show negative cognitive biases but these were not limited to disorder-related information. Adolescents with depression and/or anxiety disorders showed similar biases, suggesting them to be transdiagnostic phenomena. Important implications for cognitive-behavioural theories of AN, subsequent cognitive bias modification studies in AN, as well as clinical practice are discussed.

Look me in the eyes! A preliminary study on eye-contact in adolescents with anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) is often associated with impairments in the socio-emotional domain. Avoidance of eye-contact may underlie some of these difficulties and has been found in adults with AN in several studies. This study aimed to clarify whether adolescents with AN also show reduced eye-contact when viewing social stimuli, that is, faces. METHODS: In this cross-sectional study, girls aged 12-18 years with AN (n = 38) were compared with a clinical (girls with depression and/or anxiety disorders; n = 30) and a healthy (n = 36) control group. Eye-contact was operationalised as maintenance of visual attention to the eye-area of faces showing different emotional expressions (happy, angry, afraid, sad, neutral), recorded via eye-tracking. RESULTS: Contrary to our expectations, we did not find adolescents with AN to dwell less on the eye-area than control groups; instead, we found preliminary evidence for increased attention to the eye-area in the AN group compared to the healthy control group. CONCLUSIONS: The results suggest that reduced eye-contact found in adult AN samples is not (yet) present in adolescents with AN but may develop with the prolonged duration of the disorder. However, replication and longitudinal studies are needed to confirm this assumption.

[Overview of chronobiological and sleep medical aspects of depression in adolescents]. / Überblick zu chronobiologischen und schlafmedizinischen Aspekten bei Depressionen im Jugendalter.

Changes in sleep are reported in adolescents with depression with a frequency of up to 71%. Aspects of chronobiology and sleep based on the current scientific literature are illustrated and summarized in this narrative review. The circadian clock synchronizes organisms to the light-dark structure of the environment. The individual synchronization is called "chronotype." Chronotype changes according to age, among other factors, and adolescents experience the latest chronotypes overall. The potential discrepancy between internal and external time is called "social jetlag." Social jetlag is especially pronounced during adolescence. It is associated with numerous health risks, such as depression. Changes in sleep behavior in affective disorders and its comorbidity to depression have also been well described in the literature. In this article, underlying concepts from chronobiology and sleep medicine are initially summarized. Then, health risks of disrupted sleep-wake behavior are described, and connections to depression specifically during adolescence are drawn. The article concludes with clinical recommendations for sleep disorders and depression during adolescence as well as suggestions for further research.

The relationship between bullying, learning disorders and psychiatric comorbidity.

BACKGROUND: Both learning disorders and bullying are major sources of public concern. Children with learning disorders often suffer from social rejection, potentially rendering them more susceptible to bullying involvement. Bullying involvement leads to a higher risk towards developing various problems including self-harm and suicidality. Past research on whether learning disorders are childhood bullying risk factors yielded inconsistent results. METHODS: The current study used path analyses on a representative sample of 2,925 German 3rd and 4th grades to examine whether learning disorders are a direct bullying risk factor, or whether their impact depends on psychiatric comorbidity. More so, the current study sought to examine whether associations differ between children with and without learning disorders, compare different bullying roles (i.e., only victim, only bully, or bully-victim), compare gender, and control for IQ and socioeconomic status. RESULTS: Results indicated that learning disorders are not a direct but rather an indirect childhood risk factor for bully-victim involvement, depending on psychiatric comorbidity with internalizing or externalizing disorders. Regarding the comparison between the samples of children with and without learning disorders, an overall difference and a difference in the path between spelling and externalizing disorders emerged. No difference for different bullying roles (i.e., only victim, only bully) emerged. Negligible differences emerged when IQ and socioeconomic status were controlled. An overall gender difference emerged, compatible with past research, indicating higher bullying involvement among boys compared to girls. CONCLUSION: Children with learning disorders are at a higher risk of having psychiatric comorbidity, which in turn renders them at a higher risk of bullying involvement. Implications for bullying interventions and school professionals are deduced.

Study protocol for a randomized controlled trial investigating the effect of online interpretation bias intervention on stress reactivity in the children of parents with depression: the CoCo study.

BACKGROUND: Current preventive interventions for the children of parents with depression demonstrate modest effects on depression incidence. This may be because existing interventions tend to comprise general psychotherapeutic tools, rather than targeting the specific mechanisms underlying familial transmission. Improved theoretical models of familial transmission could enhance the development of targeted interventions. Although existing models assume that cognitive and biological vulnerability factors influence one another, the precise mechanisms are unknown. This project is the first to experimentally test whether negative interpretation bias has an impact on cortisol response in children of parents with depression. This study protocol reports a randomised controlled trial of an interpretation bias intervention which aims to shift participants' interpretation bias in a more positive direction and thereby alter their stress response. METHODS: Children aged 10-14 years who have i) one parent with a current or previous depression diagnosis, with at least one episode occurring during the child's lifetime and ii) do not have a current or previous psychiatric diagnosis themselves, will be assigned to one of two conditions: an interpretation bias intervention (n = 50) or a structurally similar placebo intervention (n = 50). The interpretation bias intervention consists of a short lab-based cognitive reappraisal of interpretations training, a four-week app-based Cognitive Bias Modification of Interpretations intervention and interpretation bias specific if-then plans. Interpretation bias will be assessed before and after the intervention using the Scrambled Sentences Task. The effect of the intervention on participants' stress response will be assessed by salivary cortisol collected at five different time points: from immediately before until 45 min after administering the Trier Social Stressor Test for Children. Stress reactivity will be measured via baseline to peak cortisol and stress recovery will be measured via the 45 min cortisol marker. We hypothesise that children who participate in the interpretation bias intervention will display a positive shift in interpretation bias and this, in turn, will alter their stress response. Children who receive the placebo intervention are expected to show a smaller positive shift in interpretation bias and stress reactivity. DISCUSSION: The findings of the present study will contribute to models of familial depression transmission as well as informing preventive interventions. If training a more positive interpretation bias subsequently alters participants' stress response, then incorporating such tools may increase the efficacy of existing preventive interventions. TRIAL REGISTRATION: Deutsches Register Klinischer Studien DRKS00028842. Registered August 19, 2022.

A randomized controlled trial of a preventive intervention for the children of parents with depression: mid-term effects, mediators and moderators.

BACKGROUND: In a parallel randomized controlled trial the effectiveness of the family- and group-based cognitive-behavioural "Gug-Auf" intervention in preventing depression in children of depressed parents was evaluated. We hypothesized that the intervention would be associated with reduced incidence of depression at 15 months as well as with reduced symptom severity at 6, 9, and 15 months. We also explored the role of a number of mediators and moderators. METHODS: Families were included if a parent (n = 100, mean age = 46.06, 61% female) had experienced depression and children (n = 135, aged 8-17 years, 53% female) had no mental illness. Families (91.5% German) were randomly allocated (50:50 block-wise; stratified by child age and parental depression) to the 12-session "GuG-Auf" intervention or no intervention. Outcomes were assessed (on an intention-to-treat basis) at 0-(T1), 6-(T2), 9-(T3) and 15-months (T4) after baseline. Primary outcome (onset of depression; T4) was assessed with standardized (blinded) clinical interviews. Secondary (unblinded) outcome was risk of depression (at T2-T4) indicated by self- and parent-reported symptoms of internalizing, externalizing and depressive disorder. Potential mediators were emotion regulation, attributional style, knowledge of depression and parenting style. Potential moderators were parental depression severity and negative life events. RESULTS: None of the children who received the intervention developed depression, whereas two of those in the control group did. The intervention significantly reduced depression risk (indicated by severity of self-reported internalizing symptoms) at T3 (p = .027, d = -0.45) and T4 (p = .035, d = -0.44). Both groups showed reduced depressive symptoms (p = .029, d = -0.44). Cognitive problem-solving and negative parenting emerged as mediators. There was no evidence that the intervention was associated with parent-reported internalizing symptoms or externalizing symptoms. No adverse events were observed. CONCLUSIONS: Children of parents with depression showed an increase in self-reported (but not parent-reported) internalizing symptoms over time. This increase was not present in children who received the GuG-Auf intervention. The intervention was not associated with changes in externalizing symptoms. Conclusions regarding prevention of the onset of depression were not possible. Despite some limitations in the generalizability, these findings contribute to reducing the burden of youth depression. REGISTRATION: The trial was registered on 16/04/2014 at ClinicalTrials.gov ( NCT02115880 ) and study protocol published in BMC Psychiatry ( https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-014-0263-2 ).

Language and reading impairments are associated with increased prevalence of non-right-handedness.

Handedness has been studied for association with language-related disorders because of its link with language hemispheric dominance. No clear pattern has emerged, possibly because of small samples, publication bias, and heterogeneous criteria across studies. Non-right-handedness (NRH) frequency was assessed in N = 2503 cases with reading and/or language impairment and N = 4316 sex-matched controls identified from 10 distinct cohorts (age range 6-19 years old; European ethnicity) using a priori set criteria. A meta-analysis (Ncases  = 1994) showed elevated NRH % in individuals with language/reading impairment compared with controls (OR = 1.21, CI = 1.06-1.39, p = .01). The association between reading/language impairments and NRH could result from shared pathways underlying brain lateralization, handedness, and cognitive functions.

Economic evaluation of dyslexia intervention.

In many countries, intervention costs are not covered by public health care. A critical basis for deciding whether an intervention is covered or not is to analyse the relation between benefits and costs of the intervention, and to quantify the consequential costs. In this study, a cost-utility analysis was computed to investigate the costs of individualized dyslexia intervention while quantifying the benefit in terms of health-related quality of life in a sample of 36 individuals with dyslexia. In addition, educational outcomes and costs of untreated dyslexia for the society were estimated using information for class repetition, school success, and unemployment rates from previous studies and official statistics. A significant increase in quality of life with medium effect sizes was found across all quality-of-life measures. Increases in quality of life were domain-specific, thus occurring specifically in those domains that are affected by learning disorders. The cost-utility ratio was 9,782 Euros per quality adjusted life years (QALYs), which is in line with similar therapy forms, such as speech therapy. The loss of productivity for untreated dyslexia in the German population was estimated for class repetition and reduced income due to lower school degrees. The cost-utility analysis and the calculation of consequential costs suggest that the dyslexia intervention is cost-effective.

Biased Maintenance of Attention on Sad Faces in Clinically Depressed Youth: An Eye-Tracking Study.

The role of negative attention biases (AB), central to cognitive models of adult depression, is yet unclear in youth depression. We investigated negative AB in depressed compared to healthy youth and tested whether AB are more pronounced in depressed than at-risk youth. Negative AB was assessed for sad and angry faces with an eye-tracking paradigm [Passive Viewing Task (PVT)] and a behavioural task [Visual Search Task (VST)], comparing three groups of 9-14-year-olds: youth with major depression (MD; n = 32), youth with depressed parents (high-risk; HR; n = 49) and youth with healthy parents (low-risk; LR; n = 42). The PVT revealed MD participants to maintain attention longer on sad faces compared to HR, but not LR participants. This AB correlated positively with depressive symptoms. The VST revealed no group differences. Our results provide preliminary evidence for a negative AB in maintenance of attention on disorder-specific emotional information in depressed compared to at-risk youth.

Emotion Regulation Deficits in Adolescent Girls with Major Depression, Anorexia Nervosa and Comorbid Major Depression and Anorexia Nervosa.

In adolescence, both major depression (MD) and anorexia nervosa (AN) are associated with deficits in emotion regulation (ER). However, studies have yet to compare ER profiles within the disorders and the effect of comorbid MD+AN is unclear. This study examined the habitual use of ER in 229 girls, aged 12-18 years, with MD (n = 84), AN (n = 37), comorbid MD+AN (n = 25), and healthy girls (n = 83). Girls with MD, AN and MD+AN reported more maladaptive and less adaptive ER strategies than healthy girls. MD and MD+AN groups showed more frequent use of maladaptive ER compared to only AN, with no differences between only MD and MD+AN. This suggests that MD+AN is not necessarily associated with higher ER deficits, rather, an additional diagnosis of MD exacerbates impairments in AN. Identifying specific ER profiles can provide important targets in prevention and treatment for AN, MD and AN+MD.

Watch out! A path from anxiety to anorexia nervosa through biased attention?

OBJECTIVE: Evidence points towards heightened anxiety and attention biases (AB) towards disorder-specific (threatening) stimuli in patients with anorexia nervosa (AN). To date, it is unclear how anxiety and AB interact in eating disorders (ED). The present study tests the causal role of anxiety by inducing anxiety before a dot-probe task with either ED-specific stimuli or unspecific negative (threat-related) information. We expected that anxiety would elicit AB for ED-specific, but not for unspecific threat-related stimuli. METHODS: Adolescents with AN (AN, n = 32) or depression (DEP, n = 27) and healthy controls (HC, n = 29) underwent an anxiety induction or a low anxiety control task before a pictorial dot-probe task with either under-/overweight body-related pictures or non-disorder-related threatening pictures (angry faces). BMI, level of ED symptoms, anxiety, stress, and depression were assessed at baseline. RESULTS: The anxiety induction did not affect the observed attention pattern. AN showed an AB towards underweight body pictures compared to HC, whereas no disorder-unspecific threat-related AB emerged. Regression analyses revealed that only anxiety predicted the AB towards underweight body pictures. DISCUSSION: Further experimental research may integrate eye tracking as an additional tool, or collect information on body dissatisfaction to obtain a better understanding of how anxiety biases attention.

[The German S3 guideline for depressive disorders in childhood and adolescence: new developments]. / S3-Leitlinie Depressive Störungen im Kindes- und Jugendalter: Wo geht es hin?

The German guideline for the treatment of depressive disorders in children and adolescents was first published in July 2013. Currently, this guideline is undergoing revision, in which the recommendations of the original version of the guideline are revisited and updated. This report aims to give an overview of the current status and the next steps for this revision.As part of the revision process, the key questions posited in the original version were expanded upon. In this, new questions were added regarding complementary therapies, that is, therapies meant to be administered in addition to the usual treatment, as well as regarding the transitionary period from adolescence into adulthood. For all key questions, new systematic literature searches were conducted in order to update the relevant evidence. For this, randomized controlled studies, systematic reviews, and non-controlled intervention studies were included and rated according to their relevance as well as possible risks of bias. Thus, all studies could be assigned a level of evidence that takes into account both the quality and the importance of the study to the guideline.This report will give a brief overview of the most important insights resulting from the new evidence base identified for the revision. While insights regarding psychotherapy are largely unchanged, there are changes in the evidence for certain antidepressants. In the field of complementary therapies, new evidence has been found for physical activity. In general, it is likely that most recommendations of the original guideline regarding first- and second-line treatments will be updated. The completion of the revision and the publishing of the revised guideline are expected to take until the end of 2023.

Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia.

Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40-60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 × 10-6) enrichment of associations at the gene level, for LOC388780 (20p13; uncharacterized gene), and for VEPH1 (3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20-25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (at pT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase; p = 8 × 10-13), bipolar disorder (1.53[1.44; 1.63]; p = 1 × 10-43), schizophrenia (1.36[1.28; 1.45]; p = 4 × 10-22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30]; p = 3 × 10-12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96]; p = 5 × 10-4), educational attainment (0.86[0.82; 0.91]; p = 2 × 10-7), and intelligence (0.72[0.68; 0.76]; p = 9 × 10-29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.

Serious Adverse Drug Reactions in Children and Adolescents Treated On- and Off-Label with Antidepressants and Antipsychotics in Clinical Practice.

INTRODUCTION: Despite the growing evidence base for psychotropic drug treatment in pediatric patients, knowledge about the benefit-risk ratio in clinical practice remains limited. The 'Therapeutic Drug Monitoring (TDM)-VIGIL' study aimed to evaluate serious adverse drug reactions (ADRs) in children and adolescents treated with antidepressants and/or antipsychotics in approved ('on-label'), and off-label use in clinical practice. METHODS: Psychiatric pediatric patients aged 6-18 years treated with antidepressants and/or antipsychotics either on-label or off-label were prospectively followed between October 2014 and December 2018 within a multicenter trial. Follow-up included standardized assessments of response, serious ADRs and therapeutic drug monitoring. RESULTS: 710 youth (age=14.6±2.2 years, female=66.6%) were observed for 5.5 months on average; 76.3% received antidepressants, 47.5% antipsychotics, and 25.2% both. Altogether, 55.2% of the treatment episodes with antidepressants and 80.7% with antipsychotics were off-label. Serious ADRs occurred in 8.3% (95%CI=6.4-10.6%) of patients, mainly being psychiatric adverse reactions (77.4%), predominantly suicidal ideation and behavior. The risk of serious ADRs was not significantly different between patients using psychotropics off-label and on-label (antidepressants: 8.1% vs. 11.3%, p=0.16; antipsychotics: 8.7% vs 7.5%, p=0.67). Serious ADRs occurred in 16.6% of patients who were suicidal at enrollment versus 5.6% of patients who were not suicidal (relative risk 3.0, 95%CI=1.9-4.9). CONCLUSION: Off-label use of antidepressants and antipsychotics in youth was not a risk factor for the occurrence of serious ADRs in a closely monitored clinical setting. Results from large naturalistic trials like ours can contribute to bridging the gap between knowledge from randomized controlled trials and real-world clinical settings.

Therapeutic drug monitoring of sertraline in children and adolescents: A naturalistic study with insights into the clinical response and treatment of obsessive-compulsive disorder.

BACKGROUND: Sertraline is a selective serotonin reuptake inhibitor with specific indications in child and adolescent psychiatry. Notwithstanding its frequent use and clinical benefits, the relationship between pharmacokinetics, pharmacodynamics, efficacy, and tolerability of sertraline across indications, particularly in non-adult patients, is not fully understood. METHOD: This naturalistic therapeutic drug monitoring (TDM) study was conducted in a transdiagnostic sample of children and adolescents treated with sertraline (n = 78; mean age, 14.22 ± 2.39; range, 7-18 years) within the prospective multicenter "TDM-VIGIL" project. Associations between dose, serum concentration, and medication-specific therapeutic and side effects based on the Clinical Global Impression scale were examined. Tolerability was measured qualitatively with the 56-item Pediatric Adverse Event Rating Scale. RESULTS: A strong linear positive dose-serum concentration relationship (with dose explaining 45% of the variance in concentration) and significant effects of weight and co-medication were found. Neither dose nor serum concentration were associated with side effects. An overall mild-to-moderate tolerability profile of sertraline was observed. In contrast with the transdiagnostic analysis that did not indicate an effect of concentration, when split into depression (MDD) and obsessive-compulsive disorder (OCD) diagnoses, the probability of clinical improvement significantly increased as both dose and concentration increased for OCD, but not for MDD. CONCLUSIONS: This TDM-flexible-dose study revealed a significant diagnosis-specific effect between sertraline serum concentration and clinical efficacy for pediatric OCD. While TDM already guides clinical decision-making regarding compliance, dose calibration, and drug-drug interactions, combining TDM with other methods, such as pharmacogenetics, may facilitate a personalized medicine approach in psychiatry.

Psychopathological symptoms as precursors of depressive symptoms in adolescence: a prospective analysis of the GINIplus and LISA birth cohort studies.

INTRODUCTION: Depressive symptoms are highly prevalent in adolescence, highlighting the need for early identification of precursors. Research into psychopathological symptoms predicting depressive psychopathology in adolescents is therefore of great relevance. Moreover, given that the prevalence of depressive symptomatology in adolescence shows marked differences between girls and boys, insight into potential sex-specific differences in precursors is important. METHODS: This study examined the relationships between emotional problems, conduct problems, hyperactivity/inattention, peer problems, and difficulties in prosocial behaviour at age 10 (Strengths and Difficulties Questionnaire), and the presence of depressive symptoms at age 15 (Depression Screener for Teenagers). Using data from 2824 participants of the GINIplus and LISA birth cohorts, the association of each SDQ subscale at age 10 years with the presence of depressive symptoms at age 15 years was analyzed using sex-specific logistic regression, adjusting for potential confounders. RESULTS: Emotional problems [odds ratio (OR) 1.99, p = 0.002 for boys and OR 1.77, p < 0.001 for girls] and peer problems (OR 2.62, p < 0.001 for boys, OR 1.91, p = 0.001 for girls) at age 10 showed an increased risk for the presence of depressive symptoms at age 15. Additionally, boys with conduct problems at age 10 were at greater risk of showing depressive symptoms in adolescence (OR 2.50, p < 0.001). DISCUSSION: Based on the identified prospective relationships in our study, it might be of particular importance to tailor prevention approaches during childhood to peer and emotional problems to reduce the risk of depressive psychopathology in adolescence. Moreover, particularly in boys, it seems important to also target conduct problems in childhood as a precursor of depressive symptoms in the adolescent period.