The implications of the COVID-19 pandemic on eating disorder features and comorbid psychopathology among adolescents with anorexia nervosa and matched controls: a comparative cohort design study.

PURPOSE: To examine implications of the COVID-19 pandemic on eating disorder (ED) features and psychopathology in female adolescents with anorexia nervosa (AN). METHOD: In total 79 females with first-onset AN (aged 12-22 years) were included and were followed up across a period of 1 year. We assessed AN participants recruited pre-pandemic (n = 49) to those recruited peri-pandemic (n = 30). Pre- (n = 37) and peri-pandemic (n = 38) age-, and education-matched typically developing (TD) girls (n = 75) were used as a reference cohort. ED features and psychopathology were assessed at baseline. After 1 year of follow-up the association between pandemic timing and clinical course was assessed. Analyses of covariance were used to examine differences in ED features and psychopathology. RESULTS: Peri-pandemic AN participants experienced less ED symptoms at baseline compared to pre-pandemic AN participants. In particular, they were less dissatisfied with their body shape, and experienced less interpersonal insecurity. In addition, the peri-pandemic AN group met fewer DSM-IV criteria for comorbid disorders, especially anxiety disorders. In contrast, peri-pandemic AN participants had a smaller BMI increase over time. In TD girls, there were no differences at baseline in ED features and psychopathology between the pre- and peri-pandemic group. CONCLUSION: Overall, peri-pandemic AN participants were less severely ill, compared to pre-pandemic AN participants, which may be explained by less social pressure and peer contact, and a more protective parenting style during the pandemic. Conversely, peri-pandemic AN participants had a less favorable clinical course, which may be explained by reduced access to health care facilities during the pandemic. LEVEL OF EVIDENCE: Level III: Evidence obtained from well-designed cohort or case-control analytic studies.

Child Autistic Traits, Food Selectivity, and Diet Quality: A Population-Based Study.

BACKGROUND: Children with Autism Spectrum Disorders (ASDs) tend to be selective in their food intake, which may compromise their diet quality. While ASD diagnoses capture severe levels of impairment, autistic traits vary on a continuum throughout the population. Yet, little is known about how autistic traits relate to diet quality at the population level. OBJECTIVES: This study examines the association between autistic traits in early childhood and diet quality in mid-childhood and explores the mediating role of food selectivity. METHODS: Participants were children (n = 4092) from the population-based Generation R Study. Parents reported their child's autistic traits at 1.5, 3, and 6 years; food selectivity at 4 years; and food intake at 8 years, from which a diet quality score was derived. Associations of autistic traits and the autistic trait trajectory (identified using Latent Class Growth Modelling) with diet quality were examined using multiple linear regression models. The indirect effect of food selectivity in the association between autistic traits at 1.5 years and diet quality was examined using mediation analysis. RESULTS: Autistic traits were associated with diet quality (e.g., 1.5 years: ß = -0.09; 95% CI: -0.13 to -0.06). Two classes captured the autistic trait trajectories from 1.5 to 6 years: children with "low and stable" (95%) and "high and increasing" (5%) mean scores. Children in the high and increasing group had poorer diet quality than those in the low and stable group (ß = -0.28; 95% CI: -0.44 to -0.11). Food selectivity mediated the association between autistic traits at 1.5 years and diet quality at 8 years (ßindirect = -0.03; 95% CI: -0.03 to -0.02). CONCLUSIONS: Autistic traits in early childhood are associated with poorer diet quality in mid-childhood, and food selectivity appears to mediate this association. Interventions intended to optimize nutrition in children with elevated autistic traits may integrate behavioral strategies to support parents' responding to their child's food selectivity.

The predictive capacity of psychiatric and psychological polygenic risk scores for distinguishing cases in a child and adolescent psychiatric sample from controls.

BACKGROUND: Psychiatric traits are heritable, highly comorbid and genetically correlated, suggesting that genetic effects that are shared across disorders are at play. The aim of the present study is to quantify the predictive capacity of common genetic variation of a variety of traits, as captured by their PRS, to predict case-control status in a child and adolescent psychiatric sample including controls to reveal which traits contribute to the shared genetic risk across disorders. METHOD: Polygenic risk scores (PRS) of 14 traits were used as predictor phenotypes to predict case-control status in a clinical sample. Clinical cases (N = 1,402), age 1-21, diagnostic categories: Autism spectrum disorders (N = 492), Attention-deficit/ hyperactivity disorders (N = 471), Anxiety (N = 293), disruptive behaviors (N = 101), eating disorders (N = 97), OCD (N = 43), Tic disorder (N = 50), Disorder of infancy, childhood or adolescence NOS (N = 65), depression (N = 64), motor, learning and communication disorders (N = 59), Anorexia Nervosa (N = 48), somatoform disorders (N = 47), Trauma/stress (N = 39) and controls (N = 1,448, age 17-84) of European ancestry. First, these 14 PRS were tested in univariate regression analyses. The traits that significantly predicted case-control status were included in a multivariable regression model to investigate the gain in explained variance when leveraging the genetic effects of multiple traits simultaneously. RESULTS: In the univariate analyses, we observed significant associations between clinical status and the PRS of educational attainment (EA), smoking initiation (SI), intelligence, neuroticism, alcohol dependence, ADHD, major depression and anti-social behavior. EA (p-value: 3.53E-20, explained variance: 3.99%, OR: 0.66), and SI (p-value: 4.77E-10, explained variance: 1.91%, OR: 1.33) were the most predictive traits. In the multivariable analysis with these eight significant traits, EA and SI, remained significant predictors. The explained variance of the PRS in the model with these eight traits combined was 5.9%. CONCLUSION: Our study provides more insights into the genetic signal that is shared between childhood and adolescent psychiatric disorders. As such, our findings might guide future studies on psychiatric comorbidity and offer insights into shared etiology between psychiatric disorders. The increase in explained variance when leveraging the genetic signal of different predictor traits supports a multivariable approach to optimize precision accuracy for general psychopathology.

Risperidone plasma concentrations are associated with side effects and effectiveness in children and adolescents with autism spectrum disorder.

AIM: Risperidone is the most commonly prescribed antipsychotic drug to children and adolescents worldwide, but it is associated with serious side effects, including weight gain. This study assessed the relationship of risperidone and 9-hydroxyrisperidone trough concentrations, maximum concentrations and 24-hour area under the curves (AUCs) with body mass index (BMI) z-scores in children and adolescents with autism spectrum disorder (ASD) and behavioural problems. Secondary outcomes were metabolic, endocrine, extrapyramidal and cardiac side effects and effectiveness. METHODS: Forty-two children and adolescents (32 males) aged 6-18 years were included in a 24-week prospective observational trial. Drug plasma concentrations, side effects and effectiveness were measured at several time points during follow-up. Relevant pharmacokinetic covariates, including medication adherence and CYP2D6, CYP3A4, CYP3A5 and P-glycoprotein (ABCB1) genotypes, were measured. Nonlinear mixed-effects modelling (NONMEM®) was used for a population pharmacokinetic analysis with 205 risperidone and 205 9-hydroxyrisperidone concentrations. Subsequently, model-based trough concentrations, maximum concentrations and 24-hour AUCs were analysed to predict outcomes using generalized and linear mixed-effects models. RESULTS: A risperidone two-compartment model combined with a 9-hydroxyrisperidone one-compartment model best described the measured concentrations. Of all the pharmacokinetic parameters, higher risperidone sum trough concentrations best predicted higher BMI z-scores during follow-up (P < .001). Higher sum trough concentrations also predicted more sedation (P < .05), higher prolactin levels (P < .001) and more effectiveness measured with Aberrant Behavior Checklist irritability score (P < .01). CONCLUSION: Our results indicate a therapeutic window exists, which suggests that therapeutic drug monitoring of risperidone might increase safety and effectiveness in children and adolescents with ASD and behavioural problems.

The longitudinal relationship between set-shifting at 4 years of age and eating disorder related features at 9 years of age in the general pediatric population.

BACKGROUND: Individuals with anorexia nervosa (AN) tend to have rigid thoughts and behaviors regarding their body weight, body image, and eating habits. While a diagnosis of AN implies severe levels of impairment, AN traits can vary on a continuum within the population. However, little is known about how early markers of AN relate to rigid thought patterns and to what extent cognitive rigidity is already present in early childhood. We examined the association of set-shifting abilities as a measure of cognitive flexibility in preadolescents with AN-related features. METHODS: Participants included 3,987 children participating in the Generation R Study, a Dutch population-based birth cohort. Set-shifting abilities (mother report) were assessed at 4 years of age, body mass index (BMI) was determined at 4 and 9 years and restrictive eating patterns (mother report) and body image (child report) were assessed at 9 years. RESULTS: Lower set-shifting abilities at 4 years were associated with a lower BMI (ß = -.44, p = 2.2 × 10-4 ) in girls, and more restrictive eating (ß = 0.15, p = 2.7 × 10-6 ) in both boys and girls at 9 years of age. Moreover, set-shifting at age 4 was not associated with body image at age 9. CONCLUSION: These findings contribute to the idea that the association between set-shifting problems and AN-related features are present early in childhood, prior to the typical range of the onset of eating disorders (EDs). Longitudinal studies that capture the peak age for the development of EDs will be important to assess whether early cognitive inflexibility is an early marker of AN.

Risk factors and pattern of weight gain in youths using antipsychotic drugs.

Antipsychotic-induced weight gain is a major health concern in children and adolescents. The aim of this study was to identify risk factors for weight gain during short-, middle- and long-term treatment with antipsychotic drugs in this young population. We analysed a combined prospective and a retrospective observational cohort of Dutch children and adolescents, starting with risperidone, aripiprazole or pipamperone treatment. Linear mixed models were used to test whether sex, age, baseline body-mass-index (BMI) z score, type of antipsychotic, dose equivalent/kg, duration of use, previous antipsychotic use, ethnicity, physical exercise, IQ, concomitant medication, and psychiatric classification predicted the BMI z score for a follow-up of < 15 weeks, 15-52 weeks or > 52 weeks. A total of 144 patients were included with a median [interquartile range ([IQR)] age of 9 (4) years and median follow-up of 30 (73) weeks. During the complete follow-up, the median (IQR) weight gain was 0.37 (0.95) BMI z score points. Antipsychotic-induced weight gain was found to be most pronounced during the first 15 weeks of use (BMI z score increase per week ß = 0.02, 95% CI 0.01-0.03, p = 0.002). A higher baseline BMI z score and the absence of stimulant use were associated with a higher BMI z score during the entire follow-up and after 15 weeks, respectively. Previous treatment with an antipsychotic drug was associated with less weight gain during the first 15 weeks of treatment. Our findings underscore the importance of close patient monitoring during the first weeks of antipsychotic treatment with a focus on patients with a high baseline BMI z score.

Psychiatric Polygenic Risk Scores as Predictor for Attention Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in a Clinical Child and Adolescent Sample.

Neurodevelopmental disorders such as attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable and influenced by many single nucleotide polymorphisms (SNPs). SNPs can be used to calculate individual polygenic risk scores (PRS) for a disorder. We aim to explore the association between the PRS for ADHD, ASD and for Schizophrenia (SCZ), and ADHD and ASD diagnoses in a clinical child and adolescent population. Based on the most recent genome wide association studies of ADHD, ASD and SCZ, PRS of each disorder were calculated for individuals of a clinical child and adolescent target sample (N = 688) and for adult controls (N = 943). We tested with logistic regression analyses for an association with (1) a single diagnosis of ADHD (N = 280), (2) a single diagnosis of ASD (N = 295), and (3) combining the two diagnoses, thus subjects with either ASD, ADHD or both (N = 688). Our results showed a significant association of the ADHD PRS with ADHD status (OR 1.6, P = 1.39 × 10-07) and with the combined ADHD/ASD status (OR 1.36, P = 1.211 × 10-05), but not with ASD status (OR 1.14, P = 1). No associations for the ASD and SCZ PRS were observed. In sum, the PRS of ADHD is significantly associated with the combined ADHD/ASD status. Yet, this association is primarily driven by ADHD status, suggesting disorder specific genetic effects of the ADHD PRS.

Feasibility of Dried Blood Spots in Children with Behavioral Problems.

BACKGROUND: Minimally invasive sampling methods are important to facilitate therapeutic drug monitoring and pharmacokinetic research in children with behavioral problems. This study assessed the feasibility and pain of dried blood spot (DBS) sampling in this population. METHODS: Repeated DBS sampling was performed in children with autism spectrum disorder (ASD) and severe behavioral problems using antipsychotic drugs, aged between 6 and 18 years. The child, guardian, and DBS performer assessed pain using the numeric rating scale (NRS-11) or 5-face Faces Pain Scale. The influence of age, sex, and the fingerprick performer on the child's pain intensity was analyzed using linear mixed models. RESULTS: Overall, 247 fingerpricks were performed in 70 children. Seven children refused all DBS sampling. The median (interquartile range) NRS-11 pain scores were 2 (3) rated by children, 3 (2.5) by guardians, and 2 (2) by fingerprick performers. The child's age and sex, and fingerprick performer had no significant influence on pain intensity. CONCLUSIONS: DBS sampling could be performed in most children with ASD and severe behavioral problems. However, 1 in 5 children refused one or more DBS fingerpricks owing to distress. Most expressed minimal pain (NRS < 4). Repeated sampling with DBS is feasible in children with ASD and severe behavioral problems.

Transition as a topic in psychiatry training throughout Europe: trainees' perspectives.

The majority of adolescents with mental health problems do not experience continuity of care when they reach the transition boundary of their child and adolescent mental health service. One of the obstacles for a smooth transition to adult mental health services concerns the lack of training for health-care professionals involved in the transition process. This study aims to seek psychiatric trainees' opinions regarding training on transition and the knowledge and skills required for managing transition. A survey was distributed to trainees residing in European countries. Trainees from 36 countries completed the questionnaire, of which 63% reported that they came into contact with youth and young adults (16-26 years) during their clinical practice. Twenty-seven percent of trainees stated they have good to very good knowledge about the transition process. Theoretical training about transition was reported in only 17% of the countries, and practical training in 28% of the countries. Ninety-four percent of trainees indicated that further training about transition is necessary. The content of subsequent transition-related training can be guided by the findings of the MILESTONE project.

Training of adult psychiatrists and child and adolescent psychiatrists in europe: a systematic review of training characteristics and transition from child/adolescent to adult mental health services.

BACKGROUND: Profound clinical, conceptual and ideological differences between child and adult mental health service models contribute to transition-related discontinuity of care. Many of these may be related to psychiatry training. METHODS: A systematic review on General Adult Psychiatry (GAP) and Child and Adult Psychiatry (CAP) training in Europe, with a particular focus on transition as a theme in GAP and CAP training. RESULTS: Thirty-four full-papers, six abstracts and seven additional full text documents were identified. Important variations between countries were found across several domains including assessment of trainees, clinical and educational supervision, psychotherapy training and continuing medical education. Three models of training were identified: i) a generalist common training programme; ii) totally separate training programmes; iii) mixed types. Only two national training programs (UK and Ireland) were identified to have addressed transition as a topic, both involving CAP exclusively. CONCLUSION: Three models of training in GAP and CAP across Europe are identified, suggesting that the harmonization is not yet realised and a possible barrier to improving transitional care. Training in transition has only recently been considered. It is timely, topical and important to develop evidence-based training approaches on transitional care across Europe into both CAP and GAP training.

Dried Blood Spot Analysis for Therapeutic Drug Monitoring of Antipsychotics: Drawbacks of Its Clinical Application.

BACKGROUND: Dried blood spot (DBS) sampling offers a minimally invasive sampling method for therapeutic drug monitoring of antipsychotics. To facilitate implementation in clinical practice, the aim of this study was to perform a clinical validation study of a DBS method for quantification of risperidone, aripiprazole, pipamperone, and their major metabolites 9-OH risperidone and dehydro-aripiprazole in a real-life, clinical setting. METHODS: Paired DBS and venous plasma samples were analyzed (n = 35 for risperidone, n = 21 for aripiprazole, n = 21 for pipamperone). Estimated plasma concentrations were calculated from DBS concentrations based on hematocrit and/or Deming regression formulas. Deming regression and Bland-Altman analyses were used to determine the agreement between the calculated and measured plasma concentrations. For Bland-Altman analysis, the following acceptance limit was used: for a minimum of 67% of the samples, the difference of the 2 measurements should be within 20% of their mean. RESULTS: The median venous plasma levels were 0.9 mcg/L for risperidone, 14.8 mcg/L for 9-OH risperidone, 135.4 mcg/L for aripiprazole, 54.9 mcg/L for dehydro-aripiprazole, and 56.4 mcg/L for pipamperone. All antipsychotics required different correction formulas of DBS concentrations for best agreement. Subsequently, no constant or proportional bias was observed using Deming regression analysis. With Bland-Altman analyses, for risperidone, 45% of the samples were within the 20% limits; for 9-OH risperidone, 36%; for aripiprazole, 45%; for dehydro-aripiprazole, 35%; and for pipamperone, 43%. CONCLUSIONS: The DBS method to quantify risperidone, aripiprazole, pipamperone, and their major metabolites did not meet the acceptance criteria in the Bland-Altman analyses. Therefore, this DBS method was not clinically valid. This study shows the importance of a clinical validation study with use of Bland-Altman plots before clinical implementation.

Validation of the SOS-PD scale for assessment of pediatric delirium: a multicenter study.

BACKGROUNDS: Reports of increasing incidence rates of delirium in critically ill children are reason for concern. We evaluated the measurement properties of the pediatric delirium component (PD-scale) of the Sophia Observation Withdrawal Symptoms scale Pediatric Delirium scale (SOS-PD scale). METHODS: In a multicenter prospective observational study in four Dutch pediatric ICUs (PICUs), patients aged ≥ 3 months and admitted for ≥ 48 h were assessed with the PD-scale thrice daily. Criterion validity was assessed: if the PD-scale score was ≥ 4, a child psychiatrist clinically assessed the presence or absence of PD according to the Diagnostic and statistical manual of mental disorders (DSM)-IV. In addition, the child psychiatrist assessed a randomly selected group to establish the false-negative rate. The construct validity was assessed by calculating the Pearson coefficient (rp) for correlation between the PD-scale and Cornell Assessment Pediatric Delirium (CAP-D) scores. Interrater reliability was determined by comparing paired nurse-researcher PD-scale assessments and calculating the intraclass correlation coefficient (ICC). RESULTS: Four hundred eighty-five patients with a median age of 27.0 months (IQR 8-102) were included, of whom 48 patients were diagnosed with delirium by the child psychiatrist. The PD-scale had overall sensitivity of 92.3% and specificity of 96.5% compared to the psychiatrist diagnosis for a cutoff score ≥4 points. The rp between the PD-scale and the CAP-D was 0.89 (CI 95%, 0.82-0.93; p < 0.001). The ICC of 75 paired nurse-researcher observations was 0.99 (95% CI, 0.98-0.99). CONCLUSIONS: The PD-scale has good reliability and validity for early screening of PD in critically ill children. It can be validly and reliably used by nurses to this aim.

Tuberous sclerosis complex: Concerns and needs of patients and parents from the transitional period to adulthood.

INTRODUCTION: Transitioning into adulthood and from pediatric services to adult healthcare are both challenging processes for young adults with rare chronic disorders such as tuberous sclerosis complex (TSC) and their parents. Adult healthcare systems are often less family-oriented and lack multidisciplinary care and experience with TSC, which can result in increased health risks and morbidity. Patient-driven data on care needs are necessary to optimize support for this vulnerable patient group. AIM: The aim of this study was to explore the concerns and care needs of young adult patients with TSC in medical, psychological, and socioeconomical domains. METHOD: A qualitative study was performed using semistructured interviews with 16 patients (median age: 21years; range: 17 to 30) and 12 parents. Concerns and care needs were organized using the International Classification of Functioning, Disability, and Health (ICF). RESULTS: Main concerns involved mental and physical health, participation, self-management skills, family planning, and side effects of medications. Patients expressed the need for multidisciplinary care that is well-informed, easily accessible, and focused on the patient as a whole, including his/her family. Parents reported high stress levels. CONCLUSION: The current study provides patient-driven information, allowing recommendations to facilitate the (transition of) care for young adults with TSC. In addition to seizures, tumor growth, and TSC-associated neuropsychiatric disorders (TAND), more attention is needed for concerns and care needs specific to the transitional period, participation, and environmental factors. Adult healthcare providers should offer expert multidisciplinary care for adult patients with TSC, including attention for parental stress.

Correction to: The interface between child/adolescent and adult mental health services: results from a European 28­country survey.

The original version of this article contained an error in Table 1. The correct table is presented below.

The interface between child/adolescent and adult mental health services: results from a European 28-country survey.

Transition-related discontinuity of care is a major socioeconomic and societal challenge for the EU. The current service configuration, with distinct Child and Adolescent Mental Health (CAMHS) and Adult Mental Health Services (AMHS), is considered a weak link where the care pathway needs to be most robust. Our aim was to delineate transitional policies and care across Europe and to highlight current gaps in care provision at the service interface. An online mapping survey was conducted across all 28 European Countries using a bespoke instrument: The Standardized Assessment Tool for Mental Health Transition (SATMEHT). The survey was directed at expert(s) in each of the 28 EU countries. The response rate was 100%. Country experts commonly (12/28) reported that between 25 and 49% of CAMHS service users will need transitioning to AMHS. Estimates of the percentage of AMHS users aged under 30 years who had has previous contact with CAMHS were most commonly in the region 20-30% (33% on average).Written policies for managing the interface were available in only four countries and half (14/28) indicated that no transition support services were available. This is the first survey of CAMHS transitional policies and care carried out at a European level. Policymaking on transitional care clearly needs special attention and further elaboration. The Milestone Study on transition should provide much needed data on transition processes and outcomes that could form the basis for improving policy and practice in transitional care.

Dried Blood Spots Combined With Ultra-High-Performance Liquid Chromatography-Mass Spectrometry for the Quantification of the Antipsychotics Risperidone, Aripiprazole, Pipamperone, and Their Major Metabolites.

BACKGROUND: Risperidone, aripiprazole, and pipamperone are antipsychotic drugs frequently prescribed for the treatment of comorbid behavioral problems in children with autism spectrum disorders. Therapeutic drug monitoring (TDM) could be useful to decrease side effects and to improve patient outcome. Dried blood spot (DBS) sample collection seems to be an attractive technique to develop TDM of these drugs in a pediatric population. The aim of this work was to develop and validate a DBS assay suitable for TDM and home sampling. METHODS: Risperidone, 9-OH risperidone, aripiprazole, dehydroaripiprazole, and pipamperone were extracted from DBS and analyzed by ultra-high-performance liquid chromatography-tandem mass spectrometry using a C18 reversed-phase column with a mobile phase consisting of ammonium acetate/formic acid in water or methanol. The suitability of DBS for TDM was assessed by studying the influence of specific parameters: extraction solution, EDTA carryover, hematocrit, punching location, spot volume, and hemolysis. The assay was validated with respect to conventional guidelines for bioanalytical methods. RESULTS: The method was linear, specific without any critical matrix effect, and with a mean recovery around 90%. Accuracy and imprecision were within the acceptance criteria in samples with hematocrit values from 30% to 45%. EDTA or hemolysis did not skew the results, and no punching carryover was observed. No significant influence of the spot volume or the punch location was observed. The antipsychotics were all stable in DBS stored 10 days at room temperature and 1 month at 4 or -80°C. The method was successfully applied to quantify the 3 antipsychotics and their metabolites in patient samples. CONCLUSIONS: A UHPLC-MS/MS method has been successfully validated for the simultaneous quantification of risperidone, 9-OH risperidone, aripiprazole, dehydroaripiprazole, and pipamperone in DBS. The assay provided good analytical performances for TDM and clinical research applications.

The Age of Onset of Anxiety Disorders.

OBJECTIVE: The objective was to estimate the age of onset (AOO) for all anxiety disorders and for specific subtypes. Gender differences in the AOO of anxiety disorders were examined, as were the influence of study characteristics on reported AOOs. METHODS: Seven electronic databases were searched up to October 2014, with keywords representing anxiety disorder subtypes, AOO, and study design. The inclusion criteria were studies using a general population sample that provided data on the AOO for all anxiety disorders, or specific anxiety disorders, according to DSM-III-R, DSM-IV, or ICD-10 criteria. RESULTS: There were 1028 titles examined, which yielded 24 studies meeting the inclusion criteria. Eight studies reported the AOO and gender. Meta-analysis found a mean AOO of all anxiety disorders of 21.3 years (95% CI 17.46 to 25.07). Separation anxiety disorder, specific phobia, and social phobia had their mean onset before the age of 15 years, whereas the AOO of agoraphobia, obsessive-compulsive disorder, posttraumatic stress disorder, panic disorder, and generalized anxiety disorder began, on average, between 21.1 and 34.9 years. Meta-analysis revealed no difference in the AOO between genders. A prospective study design and higher developmental level of the study country were associated with an earlier AOO. CONCLUSIONS: Results from this meta-analysis indicate that anxiety disorder subtypes differ in the mean AOO, with onsets ranging from early adolescence to young adulthood. These findings suggest that prevention strategies of anxiety disorders should be directed towards factors associated with the development of anxiety disorder subtypes in the age groups with the greatest vulnerability for developing those disorders.

Parent-Adolescent Cross-Informant Agreement in Clinically Referred Samples: Findings From Seven Societies.

To conduct international comparisons of parent-adolescent cross-informant agreement in clinical samples, we analyzed ratings on the Child Behavior Checklist (CBCL) and Youth Self-Report (YSR) for 6,762 clinically referred adolescents ages 11-18 from 7 societies (M = 14.5 years, SD = 2.0 years; 51% boys). Using CBCL and YSR data, we asked the following questions: (a) Do parents report more problems for their adolescent children than the adolescents report about themselves? (b) How do cross-informant correlations (rs) for scale scores differ by problem type and by society? (c) How well do parents and adolescents, on average, agree regarding which problems they rate as low, medium, or high? (d) How does within-dyad item agreement vary within and between societies? (e) How do societies vary in dichotomous cross-informant agreement with respect to the deviance status of the adolescents? CBCL and YSR scores were quite similar, with small and inconsistent informant effects across societies. Cross-informant rs averaged .47 across scales and societies. On average, parents and adolescents agreed well regarding which problem items received low, medium, or high ratings (M r = .87). Mean within-dyad item agreement was moderate across all societies, but dyadic agreement varied widely within every society. In most societies, adolescent noncorroboration of parent-reported deviance was more common than parental noncorroboration of adolescent-reported deviance. Overall, somewhat better parent-adolescent agreement and more consistency in agreement patterns across diverse societies were found in these seven clinical samples than in population samples studied using the same methods.

Bright light therapy in pregnant women with major depressive disorder: study protocol for a randomized, double-blind, controlled clinical trial.

BACKGROUND: Depression during pregnancy is a common and high impact disease. Generally, 5-10 % of pregnant women suffer from depression. Children who have been exposed to maternal depression during pregnancy have a higher risk of adverse birth outcomes and more often show cognitive, emotional and behavioural problems. Therefore, early detection and treatment of antepartum depression is necessary. Both psychotherapy and antidepressant medication, first choice treatments in a non-pregnant population, have limitations in treating depression during pregnancy. Therefore, it is urgent and relevant to investigate alternative treatments for antepartum depression. Bright light therapy (BLT) is a promising treatment for pregnant women with depressive disorder, for it combines direct availability, sufficient efficacy, low costs and high safety, taking the safety for the unborn child into account as well. METHODS: In this study, 150 pregnant women (12-18 weeks pregnant) with a DSM-V diagnosis of depressive disorder will be randomly allocated in a 1:1 ratio to one of the two treatment arms: treatment with BLT (9.000 lux) or treatment with dim red light therapy (100 lux). Both groups will be treated for 6 weeks at home on a daily basis for 30 min, within 30 min of habitual wake-up time. Follow-up will take place after 6 weeks of therapy, 3 and 10 weeks after end of therapy, at birth and 2, 6 and 18 months postpartum. Primary outcome will be the average change in depressive symptoms between the two groups, as measured by the Structured Interview Guide for the Hamilton Depression Scale - Seasonal Affective Disorder version and the Edinburg Postnatal Depression Scale. Changes in rating scale scores of these questionnaires over time will be analysed using generalized linear mixed models. Secondary outcomes will be the changes in maternal cortisol and melatonin levels, in maternal sleep quality and gestational age, birth weight, infant behaviour, infant cortisol exposure and infant cortisol stress response. DISCUSSION: If BLT reduces depressive symptoms in pregnant women, it will provide a safe, cheap, non-pharmacological and efficacious alternative treatment for psychotherapy and antidepressant medication in treating antepartum depression, without any expected adverse reactions for the unborn child. TRIAL REGISTRATION: Netherlands Trial Register NTR5476 . Registered 5 November 2015.

Identification and quantification of the antipsychotics risperidone, aripiprazole, pipamperone and their major metabolites in plasma using ultra-high performance liquid chromatography-mass spectrometry.

The antipsychotics risperidone, aripiprazole and pipamperone are frequently prescribed for the treatment in children with autism. The aim of this study was to validate an ultra-high performance liquid chromatography-mass spectrometry method for the quantification of these antipsychotics in plasma. An ultra-high performance liquid chromatography-mass spectrometry assay was developed for the determination of the drugs and metabolites. Gradient elution was performed on a reversed-phase column with a mobile phase consisting of ammonium acetate, formic acid in methanol or in Milli-Q ultrapure water at a flow rate of 0.5 mL/min. The method was validated according to the US Food and Drug Administration guidelines. The analytes were found to be stable enough after reconstitution and injection of only 5 µL improved the accuracy and precision in combination with the internal standard. Calibration curves of all five analytes were linear. All analytes were stable for at least 72 h in the autosampler and the high quality control of 9-OH-risperidone was stable for 48 h. The method allows quantification of all analytes. The advantage of this method is the combination of a minimal injection volume, a short run-time, an easy sample preparation method and the ability to quantify all analytes in one run. Copyright © 2015 John Wiley & Sons, Ltd.