Mental health of non-binary youth: a systematic review and meta-analysis.

BACKGROUND: Non-binary identities are increasingly recognized within the spectrum of gender diversity, yet there is a dearth of research exploring the mental health challenges specific to this population. Therefore, this systematic review and meta-analysis aimed to comprehensively assess the mental health outcomes of non-binary youth in comparison to their transgender and cisgender peers. METHODS: A systematic search was conducted to identify relevant studies across three electronic databases (PubMed, Scopus, Web of Science) covering the period from inception to October 2023. The meta-analysis was performed employing a random-effects model. Inclusion criteria encompassed studies comparing non-binary youth with transgender or cisgender youth, providing data on mental health outcomes such as general mental health, depressive and anxiety symptoms, self-harm and suicidality. RESULTS: Twenty-one studies, meeting the inclusion criteria and originating from six different countries, were included in the analysis. The sample encompassed 16,114 non-binary, 11,925 transgender, and 283,278 cisgender youth, with ages ranging from 11 to 25 years. Our meta-analysis revealed that non-binary youth exhibit significantly poorer general mental health compared to both transgender (d = 0.24, 95% CI, 0.05-0.43, p =.013) and cisgender youth (d = 0.48, 95% CI, 0.35-0.61, p <.001), indicating a more impaired general mental health in non-binary youth. Regarding depressive symptoms, when comparing non-binary and cisgender individuals, a moderate and significant effect was observed (d = 0.52, 95% CI, 0.41-0.63, p <.001). For anxiety symptoms, a small but significant effect was observed in the comparison with cisgender individuals (d = 0.44, 95% CI, 0.19-0.68, p =.001). Furthermore, non-binary individuals exhibited lower rates of past-year suicidal ideation than transgender peers (OR = 0.79, 95% CI, 0.65-0.97, p =.023) and higher rates of lifetime suicidal ideation than cisgender youth (OR = 2.14, 95% CI, 1.46-3.13, p <.001). CONCLUSION: Non-binary youth face distinct mental health challenges, with poorer general mental health, elevated depressive and anxiety symptoms compared to cisgender, and similar rates of self-harm and suicidal behavior compared to transgender individuals. These findings underscore the urgent need for targeted interventions, including gender-affirming mental health support, to address the specific needs of non-binary youth.

Exploring the relationship between media use and depressive symptoms among gender diverse youth: findings of the Mental Health Days Study.

BACKGROUND: Over the past decades, media use has become a key aspect of young people's daily lives, significantly shaping their social interactions, learning processes, and recreational pursuits. At the same time, healthcare professionals and researchers are increasingly concerned about the impact of media use on young people's mental health. This concern is particularly relevant for gender diverse youth who may have distinct experiences with media that could impact their mental health uniquely compared to their peers, such as increased exposure to cyberbullying and negative content regarding their gender identity. This study aims to explore the associations between media use and depressive symptoms among youth and examine if gender moderates this association. METHODS: This study utilized a cross-sectional design involving a school-based sample of 8158 participants (Mage = 14.05 years, SD = 2.45, Ndiverse = 144) from Austria. Participants completed a survey assessing their media use and depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9). Media use was measured by asking participants to report their daily usage in hours and minutes across various categories, including smartphone use, streaming services, social networks, and other media types. Multiple regression analyses were conducted to examine relationships between different forms of media use and depressive symptoms. Moderation analyses were performed using the PROCESS macro for SPSS to explore the role of gender. RESULTS: For gender diverse youth, multiple regression analysis identified streaming services (ß = 0.265, p = .005) and social networks (ß = 0.189, p = .037) as significant predictors of depressive symptoms in gender diverse youth. Moderation analyses conducted with the entire sample showed that gender moderates the relationship between depressive symptoms and smartphone use (B = - 0.008, p = .014), with the effect being the most negative for gender diverse individuals. CONCLUSION: The findings underscore the complex relationship between media use and depressive symptoms among gender diverse youth, emphasizing the moderating role of gender. These results underline the need for gender-sensitive approaches in media literacy and mental health interventions. Stakeholders should be aware of risks and benefits of different media types to foster healthy media engagement.

Exploring neurocognitive features in adolescents and young adults with anorexia nervosa: Evidence from a longitudinal study.

OBJECTIVE: We aimed to evaluate longitudinal changes in set-shifting and central coherence in a predominantly adolescent cohort with anorexia nervosa (AN) and to explore whether these factors predict long-term eating disorder outcomes. METHOD: Ninety-two female patients with AN (mean age: 16.2, range: 13-21 years) completed neurocognitive tests (Rey Complex Figure Test, Adapted Version of the Wisconsin Card Sorting Test) before and after 12 months of psychotherapeutic treatment (n = 45 Maudsley AN Treatment, MANTRa; n = 47 standard psychotherapy; groups not randomised). Eating disorder severity was assessed at baseline, after 6, 12 and 18 months. RESULTS: Central coherence (indicated by an increase in the Rey Figure Style Index) and set-shifting (indicated by a reduction in the percentage of perseverative errors) significantly improved over the course of treatment, with similar outcomes across groups. Lower central coherence was associated with higher eating disorder severity. Individuals with lower baseline set-shifting ability tended to have worse eating disorder outcomes in the long-term. However, this trend did not reach statistical significance in a multilevel linear mixed model. CONCLUSIONS: Neurocognitive difficulties in adolescents and young adults with AN can improve after treatment. Interventions specifically addressing flexibility in thinking and behaviour may contribute to treatment success.

Acceptability and feasibility of SUCCEAT, an intervention for parents of adolescents with anorexia nervosa.

OBJECTIVE: "Supporting Carers of Children and Adolescents with Eating Disorders in Austria" (SUCCEAT), a skills training for parents, delivered via workshops (WS) or online modules (ONL), has been proven to be effective in terms of parental distress, caregiver skills, and adolescents' outcome. This study examined the adherence to and the acceptability and feasibility of SUCCEAT. METHOD: One-hundred parents (86% mothers) of adolescents with anorexia nervosa participated in the 8-week training. Parents were assigned to the WS (n = 50) or ONL (n = 50) format using a quasi-randomised design. Adherence, acceptability, and feasibility were assessed using self-report questionnaires. RESULTS: Adherence to the sessions was high (66%-98%) for both groups. The usage of the material was comparable between the groups. However, in the WS group, participants actively approached the coaches (71.8% vs. 48.9% often/very often) or other parents (63% vs. 4.4% often/very often) more often. Perceived helpfulness was high in both groups, overall satisfaction and practicability were higher in the WS group. CONCLUSIONS: Good adherence, acceptability, and feasibility were confirmed for both formats of SUCCEAT, with minimal advantages of the WS regarding satisfaction and contact with other parents and coaches. Thus, both formats can be recommended for implementation in clinical routine.

Do risk factors differentiate DSM-5 and drive for thinness severity groups for anorexia nervosa?

BACKGROUND: The current study examined whether risk factors for anorexia nervosa (AN) were related to different levels of severity based on (a) the DSM-5/body mass index (BMI) and (b) drive for thinness (DT) severity ratings. METHODS: The sample comprised 153 pairs of individuals with a lifetime diagnosis AN per DSM-IV criteria and their non-ED sisters (N = 306, mean age = 26.53; mean current BMI = 20.42 kg/m2). The Oxford risk factor interview was used to establish AN-related risk factors. Individuals were categorised into the DSM-5 severity groups based on their lowest BMI, while the DT subscale from the eating disorder inventory-2 was used to classify individuals with AN into low and high DT groups. RESULTS: Multinominal regression models showed similar risk factors (e.g., perfectionism, having a history of being teased about weight and shape) contributed to the development of AN using the DSM-5 and DT severity ratings. Follow-up analyses across the severity groups for both indices revealed that only childhood perfectionism was found to be more common in the extreme severe DSM-5 BMI severity group compared to the severe DSM-5 group. CONCLUSION: Overall, this study found little evidence for AN risk factors being related to the DSM-5 and DT severity ratings. However, given the novelty of this study, replication of the current results is warranted.

Several risk factors, such as childhood obesity, have been found to contribute to the development of Anorexia Nervosa (AN). Yet, we are unsure if there is a set of risk factors that influence different levels of AN severity. While the DSM-5 suggests using BMI to measure severity, recent support favour the usage of drive for thinness (DT) as an alternative severity measure. Therefore, this study aimed to explore risk factors specifically associated with the development of different AN severity levels using both the DSM-5 BMI and DT severity classification systems. We recruited 153 pairs of individuals with a lifetime diagnosis AN per DSM-IV criteria and their non-ED sisters. The Oxford risk factor interview was used to establish AN-related risk factors. We found childhood perfectionism, weight/shape teasing, childhood obesity, and breast-related embarrassment to be significant risk factors for AN. Additionally, childhood perfectionism was more common in the extreme severe DSM-5 group compared to the severe DSM-5 group. This suggests that adding perfectionism-related aspects to prevention and early intervention programs for AN may be beneficial. Considering the novelty of this study, replication of the current results is needed.

Therapeutic Drug Monitoring in Children and Adolescents: Findings on Fluoxetine from the TDM-VIGIL Trial.

Fluoxetine is the recommended first-line antidepressant in many therapeutic guidelines for children and adolescents. However, little is known about the relationships between drug dose and serum level as well as the therapeutic serum reference range in this age group. Within a large naturalistic observational prospective multicenter clinical trial ("TDM-VIGIL"), a transdiagnostic sample of children and adolescents (n = 138; mean age, 15; range, 7-18 years; 24.6% males) was treated with fluoxetine (10-40 mg/day). Analyses of both the last timepoint and all timepoints (n = 292 observations), utilizing (multiple) linear regressions, linear mixed-effect models, and cumulative link (mixed) models, were used to test the associations between dose, serum concentration, outcome, and potential predictors. The receiver operating curve and first to third interquartile methods, respectively, were used to examine concentration cutoff and reference values for responders. A strong positive relationship was found between dose and serum concentration of fluoxetine and its metabolite. Higher body weight was associated with lower serum concentrations, and female sex was associated with lower therapeutic response. The preliminary reference ranges for the active moiety (fluoxetine+norfluoxetine) were 208-328 ng/mL (transdiagnostically) and 201.5-306 ng/mL (depression). Most patients showed marked (45.6%) or minimal (43.5%) improvements and reported no adverse effects (64.9%). This study demonstrated a clear linear dose-serum level relationship for fluoxetine in youth, with the identified reference range being within that established for adults.

Fathers in the spotlight: parental burden and the effectiveness of a parental skills training for anorexia nervosa in mother-father dyads.

PURPOSE: Research on the engagement of fathers in the treatment of childhood psychiatric disorders is scarce. This study aims to investigate differences between mothers and fathers of adolescents with anorexia nervosa regarding parental burden and effectiveness of a parental skills training. METHODS: Ninety-one mother-father dyads caring for a child with anorexia nervosa participated in an 8-week parental skills training and completed a set of questionnaires assessing parental psychopathology, eating disorder related burden, caregiver skills and expressed emotion at baseline and post-intervention. RESULTS: Fathers showed lower levels of general psychological distress, depression, anxiety and eating disorder related burden as well as lower emotional overinvolvement compared to mothers. The skills training was effective in reducing parental psychopathology, eating disorder-related burden and emotional overinvolvement as well as in increasing caregiver skills with no differences between mothers and fathers. However, session adherence and the willingness to practice skills between the sessions were slightly lower in fathers. CONCLUSIONS: These findings show that fathers are a great resource for the child's eating disorder treatment as they may counterbalance maternal emotional overinvolvement and over-protection. Furthermore, this is the first study demonstrating that fathers can profit from a parental skills training for anorexia nervosa in a similar way as mothers. LEVEL III: Evidence obtained from well-designed cohort or case-control analytic studies.

Therapeutic drug monitoring in adolescents with anorexia nervosa for safe treatment with adjunct olanzapine.

OBJECTIVE: Medication is commonly used in anorexia nervosa (AN) despite largely missing high grade evidence. Olanzapine (OLZ) is the best-evidenced substance used off-label in this group, with conflicting outcome regarding BMI, clinical and safety parameters. Therefore, it is important to strictly assure quality of treatment with OLZ in AN by using 'Therapeutic Drug Monitoring' according to AGNP-guidelines, including serum levels and adverse drug reactions (ADRs) to support safety for adolescents with AN and attempt to generate an initial age- and disorder-specific therapeutic reference range. METHOD: Sixty-five adolescents with AN (aged 10-18) treated with OLZ (98% female; 97.5% AN-restricting-type) were prospectively observed, ADRs reported, and correlations between dosage and serum levels measured at trough level were calculated, a preliminary therapeutic range defined. RESULTS: Mean dosage of OLZ was 8.15 (SD: 2.91) mg and 0.19 (SD: 0.07) mg/kg respectively, average concentration was 26.57 (SD: 13.46) ng/mL. Correlation between daily dosage/dosage per kg and serum level was 0.72 (**p < 0.001)/0.65 (**p < 0.001), respectively. ADRs with impairment were rare (6.3%). 75% improved clinically (CGI). BMI increased significantly by 1.5 kg/m2 (t = 10.6, p < 0.001). A preliminary therapeutic reference range is 11.9 and 39.9 ng/mL. CONCLUSIONS: OLZ in the hands of specialists is a well-tolerated and safe treatment adjunct for adolescents with AN.

Mental Health of Transgender Youth: A Comparison of Assigned Female at Birth and Assigned Male at Birth Individuals.

Gender dysphoric adolescents report a gender identity which is incongruent with their assigned sex at birth, whereby the experienced incongruence is accompanied by clinically relevant distress. The aim of the study was to assess and compare the mental health of transgender youth by assigned sex at birth. A total of n = 49 adolescents (n = 29 assigned females at birth, n = 20 assigned male at birth) aged 12 to 18 years with the diagnosis of gender dysphoria according to DSM-5 were included in the study. The adolescents underwent a psychological assessment in a child and adolescent psychiatry outpatient department prior to starting gender-affirming medical treatment, completing relevant mental health questionnaires. Although no differences were found in psychiatric disorders, more externalizing problems above the clinical threshold were reported by parents in assigned female at birth (AFAB) adolescents. On the other hand, internalizing problems, both in general and within the clinical range, were found to be more prevalent in assigned male at birth (AMAB) adolescents, as indicated by self-report. Our results suggest that a comprehensive assessment of mental health in gender dysphoric adolescents is crucial for understanding the diverse range of challenges they may face and tailoring appropriate interventions to address their specific needs.

The Maudsley model of anorexia nervosa treatment for adolescents and emerging adults: A multi-centre cohort study.

OBJECTIVE: The aim of this study was examining the efficacy of the Maudsley Model of Anorexia Nervosa Treatment for Adolescents and Young Adults (MANTRa) compared to individual psychotherapy that can be considered as standard in Austria (TAU-O). METHOD: In this cohort study, 92 patients between 13 and 21 years suffering from full-syndrome, atypical or weight-restored anorexia nervosa (AN) received either 24-34 individual MANTRa sessions (n = 45) or TAU-O (n = 47). Outcome variables were age- and sex-related BMI, eating disorder and comorbid psychopathology at 6-, 12- and 18-month post baseline as well as acceptability of treatment and therapeutic alliance. RESULTS: Both treatments resulted in significant improvements in age- and sex related BMI and reductions in eating disorder and comorbid psychopathology over time with significant differences between groups in favour of MANTRa. The percentage of participants with fully remitted AN was significantly higher in the MANTRa group compared to TAU-O at 18-month follow-up (MANTRa: 46% vs. TAU-O: 16%, p = 0.006). Satisfaction with both treatments was high. CONCLUSIONS: MANTRa is an effective treatment programme for adolescents and young adults with AN. Randomised controlled trials comparing MANTRa with existing treatments are necessary. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (Identifier: NCT03535714).

World Federation of Societies of Biological Psychiatry (WFSBP) guidelines update 2023 on the pharmacological treatment of eating disorders.

OBJECTIVES: This 2023 update of the WFSBP guidelines for the pharmacological treatment of eating disorders (EDs) reflects the latest diagnostic and psychopharmacological progress and the improved WFSBP recommendations for the assessment of the level of evidence (LoE) and the grade of recommendation (GoR). METHODS: The WFSBP Task Force EDs reviewed the relevant literature and provided a timely grading of the LoE and the GoR. RESULTS: In anorexia nervosa (AN), only a limited recommendation (LoE: A; GoR: 2) for olanzapine can be given, because the available evidence is restricted to weight gain, and its effect on psychopathology is less clear. In bulimia nervosa (BN), the current literature prompts a recommendation for fluoxetine (LoE: A; GoR: 1) or topiramate (LoE: A; GoR: 1). In binge-eating disorder (BED), lisdexamfetamine (LDX; LoE: A; GoR: 1) or topiramate (LoE: A; GoR: 1) can be recommended. There is only sparse evidence for the drug treatment of avoidant restrictive food intake disorder (ARFID), pica, and rumination disorder (RD). CONCLUSION: In BN, fluoxetine, and topiramate, and in BED, LDX and topiramate can be recommended. Despite the published evidence, olanzapine and topiramate have not received marketing authorisation for use in EDs from any medicine regulatory agency.

[The Therapeutic Potential of Prebiotics and Probiotics in Child and Adolescent Psychiatric Disorders]. / Zum therapeutischen Potenzial der Gabe von Präbiotika und Probiotika bei kinder- und jugendpsychiatrischen Erkrankungen.

The Therapeutic Potential of Prebiotics and Probiotics in Child and Adolescent Psychiatric Disorders Abstract: This short review summarizes the literature available on therapeutic interventions with prebiotics and probiotics and their potential use in psychiatric disorders in childhood, adolescence, and adulthood. Most studies of children and adolescents are done on ADHD and autism spectrum disorders, whereas single reports exist largely on positive effects on cognitive symptoms and quality of life. Initial studies regarding anorexia nervosa point to a potential effect of weight gain and reduction of gastrointestinal symptoms. To date, the effects of prebiotics and probiotics in depression, bipolar disorder, anxiety disorders, and schizophrenia have been mainly investigated in adults. The best reported evidence exists for depression, whereas the effects on depressive symptomatology are small. Positive effects are seen on gastrointestinal symptoms in these disorders. Given these positive effects, the mixed literature reports may result from very heterogeneous study designs. Nevertheless, the high potential of prebiotics and probiotics may be seen for minors with mental health problems. Further studies that include child and adolescent psychiatric populations and reflect the complexity of the gut-brain axis are urgently needed.

Mental Health and Health-Related Quality of Life in Austrian Adolescents with Chronic Physical Health Conditions: Results from the MHAT Study.

Chronic physical health conditions (CPHC) are on the rise in younger age groups and might have a negative impact on children and adolescents. In a representative sample of Austrian adolescents aged 10-18 years, internalizing, externalizing, and behavioral problems were assessed cross-sectionally using the Youth Self-Report and health-related quality of life (HrQoL) using the KIDSCREEN questionnaire. Sociodemographic variables, life events, and chronic illness specific parameters were considered as associated variables with mental health problems in individuals with CPHC. Of 3469 adolescents, 9.4% of girls and 7.1% of boys suffered from a chronic pediatric illness. Of these individuals, 31.7% and 11.9% had clinically relevant levels of internalizing and externalizing mental health problems, respectively, compared to 16.3% and 7.1% adolescents without a CPHC. Anxiety, depression, and social problems were twice as high in this population. Medication intake due to CPHC and any traumatic life-event were related to mental health problems. All HrQoL domains were deteriorated in adolescents with a double burden of mental and CPHC, whereas adolescents with a CPHC without mental health problems did not differ significantly from adolescents without a chronic illness. Targeted prevention programs for adolescents with a CPHC are urgently needed to prevent mental health problems in the long term.

Psychological distress and caregiving experience during the first two years of the COVID-19 pandemic among parents of an offspring with anorexia nervosa.

OBJECTIVE: To compare different aspects of caregiving distress and experience in parents of patients with anorexia nervosa (AN) before and during the COVID-19 pandemic. METHODS: Three cohorts of parents of AN patients (cohort 1-pre-pandemic: N = 78, cohort 2-first pandemic year: N = 51, cohort 3-second pandemic year: N = 119) were recruited from child and adolescent psychiatry wards and cross-sectionally assessed as part of the clinical routine. Quantitative measures of psychological distress, psychopathology, eating disorder (ED)-related burden, expressed emotion and caregiver skills were obtained at the beginning of the child's inpatient or outpatient treatment. RESULTS: Cohort 2 showed lower levels of anxiety and a tendency of lower emotional overinvolvement and higher caregiving skills compared to the pre-pandemic cohort. In contrast, the levels of general psychological distress, depression, ED-related burden and criticism observed in cohort 3 significantly exceeded pre-pandemic levels. The prevalence of clinically relevant depression was higher in cohort 3 (41.5%) compared to cohorts 1 (24.4%) and 2 (21.6%). DISCUSSION: The pandemic effects on parents seem to be time-specific. Lower distress in the early phase of the pandemic may be associated with improvements in parent-child-relationships reported in previous studies. However, the pandemic may has negative consequences in the long-term emphasising the need of ongoing parental support.

Psychosocial impact of the COVID-19 pandemic for adolescents with type-1-diabetes: a qualitative interview study involving adolescents and parents.

This study aims to investigate the psychosocial impact of the COVID-19 pandemic on adolescents with type-1-diabetes (T1D). We conducted 18 semi-structured interviews including adolescents with T1D (n = 10, 50% female, 15-18 years) and their parents (n = 8, 88% mothers). The main topics addressed were experiences during confinement regarding everyday life, lifestyle behaviors, diabetes management and treatment. We applied thematic analysis to identify common patterns of meanings. Being aware of belonging to a potential COVID-19 risk group caused worries especially in parents which resulted in strict adherence to preventive measures. Information from trustworthy sources regarding the actual risk mitigated the concerns. Digital diabetes treatment was well accepted and experienced as highly usable. The pandemic situation either facilitated or hindered the transition from parental control to diabetes self-management. While some patients managed to improve healthy lifestyle behaviors as their everyday lives seemed more predictable, others had difficulties in adapting to changed daily routines resulting in increased sedentary behavior and snacking. The perceived level of stress was directly associated with blood glucose levels. In conclusion, the implementation of psychological interventions (both for adolescents with T1D and their parents) addressing mental health literacy and media literacy seems to be important to promote positive coping skills for dealing with the pandemic situation.

An investigation of the factor structure of a German version of the Eating Disorder Symptom Impact Scale (EDSIS) among parents of adolescents and young adults with anorexia nervosa.

The aim of this study was to explore the factor structure, scale characteristics and convergent validity of a German version of the Eating Disorder Symptom Impact Scale (EDSIS). A total of 335 parents of adolescents and young adults with anorexia nervosa in inpatient or outpatient treatment completed the 24-item German translation of the EDSIS and other measures of caregiving burden and psychological distress. We tested a 4 vs. 6-factor model of the EDSIS using confirmatory factor analyses. The 6-factor model treating items as ordinal variables showed the best fit to the data (CFI = 0.949, RMSEA = 0.064). Strong invariance of this model was shown between the sample of mothers and fathers. Internal consistencies of the EDSIS scales were in the acceptable-to-good range. Bottom effects were observed for the 'Binge-Purge-Impacts' subscale only. Mothers had significantly higher EDSIS scores compared to fathers. The EDSIS total score and most of the subscores showed substantial positive correlations with caregivers' psychological distress, level of depression, anxiety and expressed emotion as well as negative associations with the level of perceived caregiving skills. The German version of the EDSIS is a useful tool to assess caregiving burden in mothers and fathers of patients with anorexia nervosa.

[Current situation of child and adolescent psychiatric care in Austria in the outpatient setting]. / Die aktuelle Situation der kinder- und jugendpsychiatrischen Versorgung in Österreich im niedergelassenen Bereich.

The status of care in child and adoelscent psychiatry in Austria is still incomplete but increasing since the foundation of this medical specialty. Corona pandemia increases the pressure on the caring structures.In this paper the current state of publically paid outpatient care is reviewed and summarized. Differences between current state and the desired/planned state of care will document existing deficits and needed developments.The 9 federal states of Austria have made variable progress in developing the general child psychiatric care. We conclude with recommendations for further implementations.

The effects of polyunsaturated fatty acid (PUFA) administration on the microbiome-gut-brain axis in adolescents with anorexia nervosa (the MiGBAN study): study protocol for a longitudinal, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Anorexia nervosa (AN) is a severe psychiatric disease that often takes a chronic course due to insufficient treatment options. Emerging evidence on the gut-brain axis offers the opportunity to find innovative treatments for patients with psychiatric disorders. The gut microbiome of patients with AN shows profound alterations that do not completely disappear after weight rehabilitation. In previous studies, the administration of polyunsaturated fatty acids (PUFA) resulted in effects that might be beneficial in the treatment of AN, affecting the microbiome, body weight and executive functions. Therefore, the MiGBAN study aims to examine the effects of a nutritional supplementation with PUFA on the gut microbiome and body mass index (BMI) in patients with AN. METHODS: This is a longitudinal, double-blind, randomized, placebo-controlled trial. Within 2 years, 60 adolescent patients aged 12 to 19 years with AN will receive either PUFA or placebo for 6 months additional to treatment as usual. After 1 year, the long-term effect of PUFA on the gut microbiome and consecutively on BMI will be determined. Secondary outcomes include improvement of gastrointestinal symptoms, eating disorder psychopathology, and comorbidities. Additionally, the interaction of the gut microbiome with the brain (microbiome-gut-brain axis) will be studied by conducting MRI measurements to assess functional and morphological changes and neuropsychological assessments to describe cognitive functioning. Anti-inflammatory effects of PUFA in AN will be examined via serum inflammation and gut permeability markers. Our hypothesis is that PUFA administration will have positive effects on the gut microbiota and thus the treatment of AN by leading to a faster weight gain and a reduction of gastrointestinal problems and eating disorder psychopathology. DISCUSSION: Due to previously heterogeneous results, a systematic and longitudinal investigation of the microbiome-gut-brain axis in AN is essential. The current trial aims to further analyse this promising research field to identify new, effective therapeutic tools that could help improve the treatment and quality of life of patients. If this trial is successful and PUFA supplementation contributes to beneficial microbiome changes and a better treatment outcome, their administration would be a readily applicable additional component of multimodal AN treatment. TRIAL REGISTRATION: German Clinical Trials Register DRKS00017130 . Registered on 12 November 2019.

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.