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Eating disorders (EDs) are known to be associated with high mortality and often chronic and severe course, but a recent comprehensive systematic review of their outcomes is currently missing. In the present systematic review and meta-analysis, we examined cohort studies and clinical trials published between 1980 and 2021 that reported, for DSM/ICD-defined EDs, overall ED outcomes (i.e., recovery, improvement and relapse, all-cause and ED-related hospitalization, and chronicity); the same outcomes related to purging, binge eating and body weight status; as well as mortality. We included 415 studies (N=88,372, mean age: 25.7±6.9 years, females: 72.4%, mean follow-up: 38.3±76.5 months), conducted in persons with anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), other specified feeding and eating disorders (OSFED), and/or mixed EDs, from all continents except Africa. In all EDs pooled together, overall recovery occurred in 46% of patients (95% CI: 44-49, n=283, mean follow-up: 44.9±62.8 months, no significant ED-group difference). The recovery rate was 42% at <2 years, 43% at 2 to <4 years, 54% at 4 to <6 years, 59% at 6 to <8 years, 64% at 8 to <10 years, and 67% at ≥10 years. Overall chronicity occurred in 25% of patients (95% CI: 23-29, n=170, mean follow-up: 59.3±71.2 months, no significant ED-group difference). The chronicity rate was 33% at <2 years, 40% at 2 to <4 years, 23% at 4 to <6 years, 25% at 6 to <8 years, 12% at 8 to <10 years, and 18% at ≥10 years. Mortality occurred in 0.4% of patients (95% CI: 0.2-0.7, n=214, mean follow-up: 72.2±117.7 months, no significant ED-group difference). Considering observational studies, the mortality rate was 5.2 deaths/1,000 person-years (95% CI: 4.4-6.1, n=167, mean follow-up: 88.7±120.5 months; significant difference among EDs: p<0.01, range: from 8.2 for mixed ED to 3.4 for BN). Hospitalization occurred in 26% of patients (95% CI: 18-36, n=18, mean follow-up: 43.2±41.6 months; significant difference among EDs: p<0.001, range: from 32% for AN to 4% for BN). Regarding diagnostic migration, 8% of patients with AN migrated to BN and 16% to OSFED; 2% of patients with BN migrated to AN, 5% to BED, and 19% to OSFED; 9% of patients with BED migrated to BN and 19% to OSFED; 7% of patients with OSFED migrated to AN and 10% to BN. Children/adolescents had more favorable outcomes across and within EDs than adults. Self-injurious behaviors were associated with lower recovery rates in pooled EDs. A higher socio-demographic index moderated lower recovery and higher chronicity in AN across countries. Specific treatments associated with higher recovery rates were family-based therapy, cognitive-behavioral therapy (CBT), psychodynamic therapy, and nutritional interventions for AN; self-help, CBT, dialectical behavioral therapy (DBT), psychodynamic therapy, nutritional and pharmacological treatments for BN; CBT, nutritional and pharmacological interventions, and DBT for BED; and CBT and psychodynamic therapy for OSFED. In AN, pharmacological treatment was associated with lower recovery, and waiting list with higher mortality. These results should inform future research, clinical practice and health service organization for persons with EDs., (© 2024 World Psychiatric Association.)

There are pronounced developmental changes in perceived social support during adolescence. The present study used the newly developed Adolescent Social Support Questionnaire (ASSQ) to examine both the consultation frequency of, and the satisfaction with perceived social support across adolescence in a longitudinal study focusing on nine different familial and non-familial supporters. The sample of N = 857 adolescents was derived from the Zurich Adolescent Psychology and Psychopathology Study (ZAPPS) and included three measurement time points. Overall, there was a decrease in the perceived frequency and satisfaction from adolescents with social support from both parents and grandparents from preadolescence to late adolescence. Best friends and romantic partners were consulted more frequently, and their support was perceived as more satisfying with increasing age. Teachers were contacted more frequently with increasing age, while satisfaction with their support remained stable. In contrast, though contacted less frequently, brothers and other relatives showed no changes in perceived satisfaction with support during adolescence. Parents and best friends were perceived as the most satisfying supporters during adolescence followed by romantic partners in later adolescence. Grandparents were perceived as an important support source but only in preadolescence. There were developmental differences during the various stages of adolescence with regard to the importance placed on each social support source. Both parents remained a very a satisfying support source, although they were consulted less often. Romantic partners and best friends gained importance as supporters in older adolescents, whereas grandparents represented a more important support source for preadolescents. Although teachers were not frequently consulted, they remained a stable and satisfying source of support., (Copyright © 2020 Spitz, Winkler Metzke and Steinhausen.)

Background: Selective mutism (SM) is nowadays considered a relatively rare anxiety disorder characterized by children failing to speak in certain situations. Research on risk factors for SM are limited in comparison to other psychiatric disorders. The aim of this study was to examine several potential risk factors for SM in a large nationwide cohort, namely parental psychopathology, parental age, maternal SES, urbanicity, maternal marital status and parental immigration status., Methods: This nested case-control study comprised 860 cases with SM, identified from the Finnish Hospital Discharge Register and 3250 controls matched for sex and age from the Finnish Central Population Register. Conditional logistic regression was used to examine the association between the risk factors and SM., Results: If both parents had any psychiatric disorder, this almost tripled their odds of having a child with SM (OR 2.8, 95% CI 2.0-4.0). There were increased rates of all types of psychiatric disorders in the parents of the children with SM, with a wider range of diagnoses among the mothers than fathers. Fathers over 35 years (OR 1.4, 95% CI 1.1-1.8) were significantly more likely to have children with SM. Offspring of a single mother had a 2-fold (OR = 2.0, 95% CI 1.4-3.0) increased odds of SM than mothers who were married or in a relationship., Conclusions: Several parental psychiatric disorders were associated with offspring SM. This points towards a shared aetiology of psychiatric disorders. Findings on paternal age and single motherhood help to improve our understanding of risk factors for SM.

Objectives: This study aims to ascertain whether the differences of prevalence and severity of attention deficit hyperactivity disorder (ADHD) are true or whether children are perceived and rated differently by parent and teacher informant assessments (INFAs) according to gender, age, and co-occurring disorders, even at equal levels of latent ADHD traits., Methods: Use of latent trait models (for binary responses) to evaluate measurement invariance in children with ADHD and their siblings from the International Multicenter ADHD Gene data., Results: Substantial measurement noninvariance between parent and teacher INFAs was detected for seven out of nine inattention (IA) and six out of nine hyperactivity/impulsivity (HI) items; the correlations between parent and teacher INFAs for six IA and four HI items were not significantly different from zero, which suggests that parent and teacher INFAs are essentially rating different kinds of behaviours expressed in different settings, instead of measurement bias. However, age and gender did not affect substantially the endorsement probability of either IA or HI symptom criteria, regardless of INFA. For co-occurring disorders, teacher INFA ratings were largely unaffected by co-morbidity; conversely, parental endorsement of HI symptoms is substantially influenced by co-occurring oppositional defiant disorder., Conclusions: Our findings suggest general robustness of Diagnostic and Statistical Manual of Mental Disorders ADHD diagnostic items in relation to age and gender. Further research on classroom presentations is needed., (© 2019 John Wiley & Sons, Ltd.)

Objective: This nation-wide register-based study investigated how often substance use disorders (SUD) and co-morbid disorders occurred in affected families compared to control families., Method: A total of N = 2504 child and adolescent psychiatric participants who were born between 1969 and 1986 and were registered in the Danish Psychiatric Central Research Register (DPCRR) had a mental disorder before the age of 18 and developed SUD at some point during their life-time. In addition, N = 7472 controls without any psychiatric diagnosis before age 18 and matched for age, sex, and residential region were included. Psychiatric diagnoses of the first-degree relatives were also obtained. A family load component was assessed., Results: SUD occurred significantly more often in case families than in control families. SUD risk factors included SUD, depression, anxiety disorders, personality disorders, or conduct disorders in the family. Furthermore, male sex, more recent year of birth, and living in the capital city of Copenhagen were also significantly associated with having SUD. The family load explained 30% of the SUD manifestation in the case-probands. The findings in the total SUD group were mostly replicated in the two major subgroups of pure alcohol or multiple substance use disorders., Discussion: These findings based on a very large and representative dataset provide additional evidence for the strong family aggregation and further risk factors in SUD. The pattern of risk factors is largely the same for the total group of SUD and the major subgroups of pure alcohol and multiple substance use disorders.

Background: Discrepancies between multiple informants often create considerable uncertainties in delivering services to youth. The present study assessed the ability of the parent and youth scales of the Strength and Difficulties Questionnaire (SDQ) to predict mental health problems/disorders across several mental health domains as validated against two contrasting indices of validity for psychopathology derived from the Development and Well Being Assessment (DAWBA): (1) an empirically derived computer algorithm and (2) expert based ICD-10 diagnoses., Methods: Ordinal and logistic regressions were used to predict any problems/disorders, emotional problems/disorders and behavioural problems/disorders in a community sample (n = 252) and in a clinic sample (n = 95)., Results: The findings were strikingly similar in both samples. Parent and youth SDQ scales were related to any problem/disorder. Youth SDQ symptom and impact had the strongest association with emotional problems/disorder and parent SDQ symptom score were most strongly related to behavioural problems/disorders. Both the SDQ total and the impact scores significantly predicted emotional problems/disorders in males whereas this was the case only for the total SDQ score in females., Conclusion: The present study confirms and expands previous findings on parent and youth informant validity. Clinicians should include both parent and youth for identifying any mental health problems/disorders, youth information for detecting emotional problems/disorders, and parent information to detect behavioural problems/disorders. Not only symptom scores but also impact measures may be useful to detect emotional problems/disorders, particularly in male youth.

Background: Understanding motivation to change is a key issue in both the assessment and the treatment of eating disorders. Therefore, sound instruments assessing this construct are of great help to clinicians. Accordingly, the present study analysed the psychometric properties of the Anorexia Nervosa Stages of Change Questionnaire (ANSOCQ), including its relation to coping style and self-esteem., Methods: N  = 92 adolescents referred to an eating disorders outpatient clinic meeting criteria for anorexia nervosa gave written informed consent to participate in this study and completed the ANSOCQ, the Eating Disorder Inventory, the Eating Attitudes Test, the Body Image Questionnaire, two questionnaires measuring Self-Related Cognitions and the Coping Across Situations Questionnaire. After a treatment period of nine months, clinical anorexia nervosa diagnosis and the body mass index were re-assessed. In addition to exploratory factor analysis, correlational analysis was used to test for the convergent validity of the ANSOCQ and logistic regression analysis was used to test its predictive validity., Results: The ANSOCQ had good psychometric properties. Factor analysis yielded two meaningful factors labelled as 'weight gain and control' and 'attitudes and feelings'. Internal consistencies of the two factors amounted to Cronbach's alpha = .87 and .76, respectively. Significant correlations with other scales measuring eating disorder psychopathology were indicative of meaningful construct validity. Higher motivation to change was related to higher self-esteem and a more active coping style. Higher (positive) ANSOCQ total scores predicted remission of anorexia nervosa after nine months of treatment. A higher score on 'attitudes and feelings' was a protective factor against drop-out from intervention., Conclusions: The ANSOCQ is a clinically useful instrument for measuring motivation to change in adolescents with AN. Two factorial dimensions explain most of the variation. Self-esteem and coping style are relevant additional constructs for the understanding of the motivation to change in anorexia nervosa., Trial Registration: NCT02828956. Retrospectively registered July 2016.

Background: There is a major gap between the US and most European countries regarding the implementation of early intensive behavioural intervention (EIBI) for children with autism. The present paper reports on the current status of EIBI in Switzerland and on the effectiveness of EIBI under clinical conditions in a Swiss pilot project., Methods: The paper combines a narrative report of the care system for children with autism in Switzerland and an initial evaluation of EIBI as implemented in the Department of Child and Adolescent Psychiatry, University of Zurich., Results: The current situation of the implementation of EIBI for children with autism in Switzerland is characterized by marked deficits in its acceptance. Major reasons include insufficient governmental approval and lacking legal and financial support. In addition, ignorance among health care providers and educational professionals has contributed to this situation precluding that children with autism receive the most beneficial assistance. The authors have initiated and been working in an intervention centre offering EIBI for a decade and report on their experience with the implementation of EIBI. Based on their clinical practice, they document that EIBI also works efficiently under ordinary mental health service conditions., Conclusions: EIBI needs to be implemented more intensively in Switzerland. Although the effects of EIBI as implemented in Zurich are promising, the results are not as pronounced as under controlled research conditions.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a major public health issue. Pharmacological treatments play an important role in the multimodal treatment of ADHD. Currently, there is a lack of up-to-date and comprehensive evidence on how available ADHD drugs compare and rank in terms of efficacy and tolerability, in children or adolescents as well as in adults. We will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomised controlled trials (RCTs), to rank pharmacological treatments for ADHD according to their efficacy and tolerability profiles., Methods and Analysis: We will search a broad range of electronic databases, including PubMed, MEDLINE, EMBASE, PsycINFO, ERIC and Web of Science, with no date or language restrictions. We will also search for unpublished studies using international clinical trial registries and contacting relevant drug companies. We will identify and include available parallel-group, cross-over and cluster randomised trials that compare methylphenidate, dexmethylphenidate, amphetamine derivatives (including lisdexamfetamine), atomoxetine, clonidine, guanfacine, bupropion or modafinil (as oral therapy) either with each other or to placebo, in children, adolescents or adults with ADHD. Primary outcomes will be efficacy (indicated by reduction in severity of ADHD core symptoms measured on a standardised scale) and tolerability (the proportion of patients who left a study early due to side effects). Secondary outcomes will be global functioning, acceptability (proportion of patients who left the study early by any cause) and changes in blood pressure and body weight. NMA will be conducted in STATA within a frequentist framework. The quality of RCTs will be evaluated using the Cochrane risk of bias tool, and the quality of the evidence will be assessed using the GRADE approach. Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings., Ethics and Dissemination: No ethical issues are foreseen. Results from this study will be published in a peer-reviewed journal and possibly presented at relevant national and international conferences., Trial Registration Number: CRD42014008976., Competing Interests: SC has received reimbursement for travel and accommodation expenses from the Association for Child and Adolescent Central Health (ACAMH), a non-profit organisation, in relation to lectures that he delivered for ACAMH. CM-J has been a speaker for HB Pharma/Medice. SC collaborated within projects from the European Union (7FP) and has received travel support from Shire Pharmaceutical Company; she collaborated as subinvestigator in sponsored clinical trial by Shire Pharmaceutical Company. TB served in an advisory or consultancy role for Actelion, Hexal Pharma, Lilly, Medice, Novartis, Oxford outcomes, Otsuka, PCM scientific, Shire and Viforpharma. He received conference support or speaker's fee by Medice, Novartis and Shire. He is/has been involved in clinical trials conducted by Shire and Viforpharma. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. AZ has received honoraria for participating to Advisory board or Data Safety Monitory Boards from Eli Lilly, Otsuka, Lundbeck, Takeda and EduPharma. He has also received royalties from Oxford University Press and Giunti OS, and research grants from Lundbeck, Roche, Shire and Vifor. H-CS has worked as an advisor and speaker for the following pharmaceutical companies: Janssen-Cilag, Eli Lilly, Novartis, Medice, Shire and UCB and has also received unrestricted grants for postgraduate training courses or conferences and research by Janssen-Cilag, Eli Lilly, Novartis, Medice and Swedish Orphan International. He receives book royalties from Cambridge University Press, Elsevier, Hogrefe, Huber, Klett and Kohlhammer publishers. AC has served as an expert witness for a patent litigation case about quetiapine extended-release and is supported by the NIHR Oxford Cognitive Health Clinical Research Facility. DC reports grants and personal fees from Shire, personal fees from Eli Lilly, grants from Vifor, personal fees from Novartis, personal fees from Oxford University Press., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Adverse childhood experiences (ACEs) and psychiatric disorders are common in juvenile detainees. Emotional dysregulation resulting from cumulated ACEs may be characterized by symptoms of irritability. The present study examined whether the accumulation of ACEs, irritability, or both predicted mental disorders in incarcerated adolescents with and without controlling for one another and for socio-demographic factors., Methods: One hundred thirty male detained juvenile offenders (aged 13.8-19.5 years) were assessed by structured clinical interviews and a self-reporting scale for irritability. Univariate and multivariate regression models were used to examine the shared and distinct associations of ACEs and irritability with psychiatric diagnoses., Results: A total of 75 % of the participants reported more than one ACE. The ACE total score was positively related to self-reported irritability. The ACE total score predicted depressive disorders, suicidality, post-traumatic stress disorder (PTSD), and anxiety disorders. Irritability was positively related to depressive disorders, suicidality, disruptive behavior disorder (DBD), substance use disorder (SUD), and attention deficit hyperactivity disorder (ADHD). These associations remained significant in multivariate models., Conclusions: This study provides evidence for the predictive impact of self-reported ACEs and irritability with regard to adolescent psychiatric disorders in young male inmates. Both variables differed in their predictive power for PTSD, internalizing, and externalizing disorders indicating the need for specific therapeutic interventions. Taking a close look at their trauma history seems to be of special importance for juveniles suffering from PTSD and anxiety disorders. For delinquent adolescents with DBD, ADHD and SUD, the training of emotion regulation techniques appears most promising. Approaches focusing on both, ACEs and emotion-focused contents may be implemented in the treatment of depressive disorders and suicidality.

Background: The association of attention-deficit/hyperactivity disorder (ADHD) and tic disorder (TD) is frequent and clinically important. Very few and inconclusive attempts have been made to clarify if and how the combination of ADHD+TD runs in families., Aim: To determine the first time in a large-scale ADHD sample whether ADHD+TD increases the risk of ADHD+TD in siblings and, also the first time, if this is independent of their psychopathological vulnerability in general., Methods: The study is based on the International Multicenter ADHD Genetics (IMAGE) study. The present sub-sample of 2815 individuals included ADHD-index patients with co-existing TD (ADHD+TD, n = 262) and without TD (ADHD-TD, n = 947) as well as their 1606 full siblings (n = 358 of the ADHD+TD index patients and n = 1248 of the ADHD-TD index patients). We assessed psychopathological symptoms in index patients and siblings by using the Strength and Difficulties Questionnaire (SDQ) and the parent and teacher Conners' long version Rating Scales (CRS). For disorder classification the Parental Account of Childhood Symptoms (PACS-Interview) was applied in n = 271 children. Odds ratio with the GENMOD procedure (PROCGENMOD) was used to test if the risk for ADHD, TD, and ADHD+TD in siblings was associated with the related index patients' diagnoses. In order to get an estimate for specificity we compared the four groups for general psychopathological symptoms., Results: Co-existing ADHD+TD in index patients increased the risk of both comorbid ADHD+TD and TD in the siblings of these index patients. These effects did not extend to general psychopathology., Interpretation: Co-existence of ADHD+TD may segregate in families. The same holds true for TD (without ADHD). Hence, the segregation of TD (included in both groups) seems to be the determining factor, independent of further behavioral problems. This close relationship between ADHD and TD supports the clinical approach to carefully assess ADHD in any case of TD.

Objective: This nation-wide register-based study investigated how often phobic disorders (PHO) and co-morbid disorders occur in affected families compared to control families. Furthermore, the study addressed the impact of sex, year of birth, and degree of urbanization in terms of risk factors., Method: A total of N = 746 child and adolescent psychiatric participants born between 1969 and 1986 and registered in the Danish Psychiatric Central Research Register (DPCRR) with a diagnosis of a mental disorder before the age of 18, and developed PHO at some point during their life-time until a maximum age of 40 years were included. In addition, N = 2229 controls without any diagnosis of mental disorders before age 18 and that were matched for age, sex, and residential region were included. Diagnoses of mental disorders were also obtained from the first- degree relatives as a part of the Danish Three Generation Study (3GS). A family load component was obtained by using various mixed regression models., Results: PHO occurred significantly more often in case than in control families, in particular, in mothers and siblings. Substance use disorders (SUD), Depressive disorders (DEP), anxiety disorders (ANX) and personality disorders (PERS) in the family were significantly associated with specific phobia in the case-probands. After controlling for various mental disorders comorbid to PHO it was found that some of the family transmission could be caused by various other mental disorders in family members rather than the PHO itself. Female sex and more recent year of birth were further risk factors while region of residence was not related to the manifestation of PHO. Case-relatives did not develop PHO earlier than control relatives. After adjusting for various additional explanatory variables, the family load explained only 0.0013% of the variance in the manifestation of PHO in the case-probands., Discussion: These findings, based on a very large and representative dataset, provide evidence for the family aggregation and further risk factors in PHO. In contrast to anxiety disorders and other major mental disorders the family load of PHO in this nation-wide study was rather low.

Background: The aim of this comparative study was to investigate the type and frequency of diagnoses preceding adult bipolar disorder (BD) and schizophrenia (SZ)., Methods: A follow-back study of all preceding diagnoses in all patients aged 21-34 years with a primary, first time diagnosis of BD (N = 784) or SZ (N = 1667) in 2008 to 2010. Data were taken from the Danish Psychiatric Central Research Register (DPCRR) including ICD-10 and ICD-8 diagnoses., Results: The numbers of patients with any preceding diagnoses amounted to 69.3% in BD and 76.6% in SZ with affective disorders (excluding BD) being the most frequent preceding diagnosis (46.6 vs. 28.0%), followed by psychoses (PSY) other than SZ (14.2 vs. 41.5%, p < .001), and substance use disorders (SUD) (16.1 vs. 26.9%, p < .001). Reactions to severe stress were equally frequent in both samples (26.3 vs. 26.6%) as were personality disorders (21.8 vs. 22.4%) and ADHD (4.2 vs. 3.5%), whereas rates of conduct disorders (1.7 vs. 3.1%) were rather low in both samples. Very few of the preceding diagnoses had their onset in childhood and adolescence. Overall patients with SZ had a minor but statistically significant earlier onset of any psychiatric disorder compared to BD (mean age: 23.3 vs. 22.5, p < .001). Regression analyses indicated that BD was associated with an increased risk of having experienced preceding affective disorders and ADHD, while SZ was associated with an increased risk of preceding substance use disorders, psychosis, anxiety disorders, and personality disorders., Conclusions: Specific developmental trajectories of preceding disorders were delineated for BD and SZ with affective disorders being more specific for BD and both SUD and PSY more specific to SZ. There are different patterns of vulnerability in terms of preceding diagnosis in young adults with BD and SZ.

Background: High rates of mental disorders have been found in detained juvenile offenders, whereas the role of psychopathology in non-detained offenders is less clear. Therefore, the present study compared psychopathology in male non-detained delinquent juveniles and two matched samples from the community and an adolescent psychiatric clinic., Methods: 125 male adolescents aged 11 to 19 years (m = 16.2 years, SD = 1.5 years) from an outpatient adolescent forensic clinic were compared to a community sample from the Zurich Adolescent Psychology and Psychopathology Study (ZAPPS) and a referred sample from a psychiatric clinic matched for age and nationality. All subjects responded to questionnaires measuring internalizing and externalizing problems, depressive symptoms and self-esteem., Results: The sample of non-detained juvenile offenders showed similar rates of self-reported internalizing and externalizing problems when compared to the community sample, whereas the clinic sample displayed an increased rate of various disturbances. Similar results were found also for self-esteem. In agreement with these findings, non-detained juvenile offenders less frequently had a psychiatric diagnosis after full clinical assessment when compared to the clinical sample. However, a diagnosis of conduct disorders and a lower IQ range was found more frequently in non-detained juvenile offenders. Offenders with serious delinquent acts and involving weapons showed higher depression scores than the rest of the offenders., Conclusion: In non-detained assessment situations before court examination, juvenile offenders present rather normal behaviour. Their lack of awareness of potential behavioural problems should be considered during assessment and treatment of this group of offenders.

Background: The current review analyzes the long-term outcome and prognosis of early onset schizophrenia based on previously published studies in 1980., Methods: A systematic search of articles published in the English-language literature after 1980 identified a total of 21 studies, which included 716 patients who were either suffering from early onset schizophrenia (EOS) or both EOS and other psychotic disorders (MIX). The authors of the current review scored the outcome as either "good," "moderate," or "poor." The mean age of onset in these studies was <18 years., Results: In general, the outcome in studies with EOS is worse than the outcome in MIX studies. Only 15.4% of the patients in EOS studies versus 19.6% of the patients in MIX studies experienced a "good" outcome. In contrast, 24.5% of the patients in EOS studies versus 33.6% in MIX studies experienced a "moderate" outcome, and 60.1% in EOS studies versus 46.8% in MIX studies experienced a "poor" outcome. The authors identified various significant effects on outcome. In EOS, the findings were significantly affected by sample attrition, indicating that in studies with a high dropout rate, fewer patients experienced a "moderate" outcome, and more patients experienced a "poor" outcome; however, the effect sizes were small. Furthermore, the effects were also small and more favourable for specific functioning measures, as opposed to more global measures, small to moderate in terms of worse outcomes for follow-up periods >10 years, small to moderate for more unfavourable outcomes in males, and small to large for worse outcomes in studies including patients diagnosed before 1970., Conclusions: In contrast to the adult manifestation, the early manifestation of schizophrenia in childhood and adolescence still carries a particularly poor prognosis. According to these aggregated data analyses, longer follow-up periods, male sex, and patients having been diagnosed before 1970 contribute predominantly to the rather poor course of EOS.

Background: The International Multi-centre ADHD Genetics (IMAGE) project with 11 participating centres from 7 European countries and Israel has collected a large behavioural and genetic database for present and future research. Behavioural data were collected from 1068 probands with ADHD and 1446 unselected siblings. The aim was to describe and analyse questionnaire data and IQ measures from all probands and siblings. In particular, to investigate the influence of age, gender, family status (proband vs. sibling), informant, and centres on sample homogeneity in psychopathological measures., Methods: Conners' Questionnaires, Strengths and Difficulties Questionnaires, and Wechsler Intelligence Scores were used to describe the phenotype of the sample. Data were analysed by use of robust statistical multi-way procedures., Results: Besides main effects of age, gender, informant, and centre, there were considerable interaction effects on questionnaire data. The larger differences between probands and siblings at home than at school may reflect contrast effects in the parents. Furthermore, there were marked gender by status effects on the ADHD symptom ratings with girls scoring one standard deviation higher than boys in the proband sample but lower than boys in the siblings sample. The multi-centre design is another important source of heterogeneity, particularly in the interaction with the family status. To a large extent the centres differed from each other with regard to differences between proband and sibling scores., Conclusions: When ADHD probands are diagnosed by use of fixed symptom counts, the severity of the disorder in the proband sample may markedly differ between boys and girls and across age, particularly in samples with a large age range. A multi-centre design carries the risk of considerable phenotypic differences between centres and, consequently, of additional heterogeneity of the sample even if standardized diagnostic procedures are used. These possible sources of variance should be counteracted in genetic analyses either by using age and gender adjusted diagnostic procedures and regional normative data or by adjusting for design artefacts by use of covariate statistics, by eliminating outliers, or by other methods suitable for reducing heterogeneity.

Background: The International Multi-centre ADHD Genetics (IMAGE) project with 11 participating centres from 7 European countries and Israel has collected a large behavioural and genetic database for present and future research. Behavioural data were collected from 1068 probands with the combined type of attention deficit/hyperactivity disorder (ADHD-CT) and 1446 'unselected' siblings. The aim was to analyse the IMAGE sample with respect to demographic features (gender, age, family status, and recruiting centres) and psychopathological characteristics (diagnostic subtype, symptom frequencies, age at symptom detection, and comorbidities). A particular focus was on the effects of the study design and the diagnostic procedure on the homogeneity of the sample in terms of symptom-based behavioural data, and potential consequences for further analyses based on these data., Methods: Diagnosis was based on the Parental Account of Childhood Symptoms (PACS) interview and the DSM-IV items of the Conners' teacher questionnaire. Demographics of the full sample and the homogeneity of a subsample (all probands) were analysed by using robust statistical procedures which were adjusted for unequal sample sizes and skewed distributions. These procedures included multi-way analyses based on trimmed means and winsorised variances as well as bootstrapping., Results: Age and proband/sibling ratios differed between participating centres. There was no significant difference in the distribution of gender between centres. There was a significant interaction between age and centre for number of inattentive, but not number of hyperactive symptoms. Higher ADHD symptom frequencies were reported by parents than teachers. The diagnostic symptoms differed from each other in their frequencies. The face-to-face interview was more sensitive than the questionnaire. The differentiation between ADHD-CT probands and unaffected siblings was mainly due to differences in hyperactive/impulsive symptoms., Conclusions: Despite a symptom-based standardized inclusion procedure according to DSM-IV criteria with defined symptom thresholds, centres may differ markedly in probands' ADHD symptom frequencies. Both the diagnostic procedure and the multi-centre design influence the behavioural characteristics of a sample and, thus, may bias statistical analyses, particularly in genetic or neurobehavioral studies.

Background: The present study investigated the impact of divergent instructions and response cost on strategic cognitive control in children with ADHD., Methods: Children with ADHD (N = 34), combined subtype, and control children (N = 34) performed a series of self-paced computerized visual search tasks. The tasks varied by verbal instructions: after a baseline task, children were either instructed to work as fast as possible (speed instruction) or as accurately as possible (accuracy instruction). In addition, tasks were performed with and without response cost., Results: Both groups modulated latencies and errors according to instructions in a comparable way, except for latency in the accuracy - instruction without response cost, where control children showed a larger increase of response time. Response cost did not affect the modulation of response style in children with ADHD to a larger extent than in controls. However, with instructions group differences related to target criteria became clearly more accentuated compared to baseline but disappeared when response cost was added., Conclusions: Delay aversion theory and motivational or state regulation models may account for different aspects of the results. Modifications related to task presentation, such as the emphasis put on different details in the verbal instruction, may lead to divergent results when comparing performances of children with ADHD and control children on a self-paced task.

Background: Low serotonergic (5-HT) activity correlates with increased impulsive-aggressive behavior, while the opposite association may apply to cognitive impulsiveness. Both types of impulsivity are associated with attention-deficit/hyperactivity disorder (ADHD), and genes of functional significance for the 5-HT system are implicated in this disorder. Here we demonstrate the separation of aggressive and cognitive components of impulsivity from symptom ratings and test their association with 5-HT and functionally related genes using a family-based association test (FBAT-PC)., Methods: Our sample consisted of 1180 offspring from 607 families from the International Multicenter ADHD Genetics (IMAGE) study. Impulsive symptoms were assessed using the long forms of the Conners and the Strengths and Difficulties parent and teacher questionnaires. Factor analysis showed that the symptoms aggregated into parent- and teacher-rated behavioral and cognitive impulsivity. We then selected 582 single nucleotide polymorphisms (SNPs) from 14 genes directly or indirectly related to 5-HT function. Associations between these SNPs and the behavioral/cognitive groupings of impulsive symptoms were evaluated using the FBAT-PC approach., Results: In the FBAT-PC analysis for cognitive impulsivity 2 SNPs from the gene encoding phenylethanolamine N-methyltransferase (PNMT, the rate-limiting enzyme for adrenalin synthesis) attained corrected gene-wide significance. Nominal significance was shown for 12 SNPs from BDNF, DRD1, HTR1E, HTR2A, HTR3B, DAT1/SLC6A3, and TPH2 genes replicating reported associations with ADHD. For overt aggressive impulsivity nominal significance was shown for 6 SNPs from BDNF, DRD4, HTR1E, PNMT, and TPH2 genes that have also been reported to be associated with ADHD. Associations for cognitive impulsivity with a SERT/SLC6A4 variant (STin2: 12 repeats) and aggressive behavioral impulsivity with a DRD4 variant (exon 3: 3 repeats) are also described., Discussion: A genetic influence on monoaminergic involvement in impulsivity shown by children with ADHD was found. There were trends for separate and overlapping influences on impulsive-aggressive behavior and cognitive impulsivity, where an association with PNMT (and arousal mechanisms affected by its activity) was more clearly involved in the latter. Serotonergic and dopaminergic mechanisms were implicated in both forms of impulsivity with a wider range of serotonergic mechanisms (each with a small effect) potentially influencing cognitive impulsivity. These preliminary results should be followed up with an examination of environmental influences and associations with performance on tests of impulsivity in the laboratory.

Introduction: The present review describes the different variants of Fetal Alcohol Spectrum Disorders (FASD) as a consequence of maternal alcohol abuse during pregnancy. According to international findings, some 3000 to 4000 affected newborns may be expected annually in Germany. Detection of these individuals in clinical practice is insufficient., Method: Selective review of the literature and report of own findings based on longitudinal studies., Results: Key features of FASD are short stature, microcephaly, various dysmorphic features, in severe cases amongst others consisting of congenital heart disease and dysplasias of the skeleton and urogenital system, varying degrees of developmental delay including mental retardation, and a positive history of maternal alcohol abuse during pregnancy. Longitudinal studies in young adulthood show that independent of the severity of FASD the key features remain associated with limitations of an independent life-style., Discussion: Pathogenesis of FASD is not sufficiently clear and there is no causal treatment. Thus, besides prevention and information, early diagnosis, installation of fostering or adoption, and intensive psychosocial care including selection of appropriate schooling, occupational counselling and supportive care in adulthood are mandatory.

Background: Surprisingly little is known about the frequency, stability, and correlates of school fear and truancy based on self-reported data of adolescents., Methods: Self-reported school fear and truancy were studied in a total of N = 834 subjects of the community-based Zurich Adolescent Psychology and Psychopathology Study (ZAPPS) at two times with an average age of thirteen and sixteen years. Group definitions were based on two behavioural items of the Youth Self-Report (YSR). Comparisons included a control group without indicators of school fear or truancy. The three groups were compared across questionnaires measuring emotional and behavioural problems, life-events, self-related cognitions, perceived parental behaviour, and perceived school environment., Results: The frequency of self-reported school fear decreased over time (6.9 vs. 3.6%) whereas there was an increase in truancy (5.0 vs. 18.4%). Subjects with school fear displayed a pattern of associated internalizing problems and truants were characterized by associated delinquent behaviour. Among other associated psychosocial features, the distress coming from the perceived school environment in students with school fear is most noteworthy., Conclusion: These findings from a community study show that school fear and truancy are frequent and display different developmental trajectories. Furthermore, previous results are corroborated which are based on smaller and selected clinical samples indicating that the two groups display distinct types of school-related behaviour.

As part of the International Multi-centre ADHD Genetics project we completed an affected sibling pair study of 142 narrowly defined Diagnostic and Statistical Manual of Mental Disorders, fourth edition combined type attention deficit hyperactivity disorder (ADHD) proband-sibling pairs. No linkage was observed on the most established ADHD-linked genomic regions of 5p and 17p. We found suggestive linkage signals on chromosomes 9 and 16, respectively, with the highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (log of the odds, LOD=3.1) overlapping data published from the previous UCLA (University of California, Los Angeles) (LOD>1, approximately 95 cM) and Dutch (LOD>1, approximately 100 cM) studies. The second highest peak in this study was on chromosome 9q22 at 90 cM (LOD=2.13); both the previous UCLA and German studies also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93 cM; German LOD=0.68 at 100 cM). The overlap of these two main peaks with previous findings suggests that loci linked to ADHD may lie within these regions. Meta-analysis or reanalysis of the raw data of all the available ADHD linkage scan data may help to clarify whether these represent true linked loci.

The offspring of mothers with epilepsy are considered to be at developmental risk during pregnancy from: (1) generalized maternal seizures (hypoxia); (2) teratogenicity of antiepileptic drugs (AEDs); and (3) adverse socio-familial conditions associated with having a chronically sick mother. Sixty-seven children of mothers with epilepsy and 49 children from non-affected mothers, matched for control variables, were followed from birth to adolescence (53 males, 63 females; mean age 14y 2mo, range 10-20y). Prediction of intellectual performance of these children during adolescence was calculated from the following variables: maternal generalized seizures, prenatal exposure to AEDs, and quality of family stimulation (HOME Inventory) assessed in children at 2 years of age. Children who were prenatally exposed to AEDs achieved lower IQs than control children at adolescence. This effect was moderately significant for children who had been exposed to monotherapy (6 IQ points lower), but was considerable in those exposed to polytherapy (12 IQ points lower). Generalized seizures during pregnancy, observed in half the mothers, did not exacerbate this effect. Relative to prenatal risk status, the quality of the family environment had varied effects on intellectual development. Children with prenatal risks appeared to be more vulnerable to environmental disadvantage than control children, but they also showed longer-lasting effects of environmental support.

Background: Few studies have analyzed the frequency of alcohol use across time from adolescence to young adulthood and its outcome in young adulthood. A Swiss longitudinal multilevel assessment project using various measures of psychopathology and psychosocial variables allowed for the study of the frequency and correlates of alcohol use so that this developmental trajectory may be better understood., Method: Alcohol use was studied by a questionnaire in a cohort of N = 593 subjects who had been assessed at three times between adolescence and young adulthood within the Zurich Psychology and Psychopathology Study (ZAPPS). Other assessment included questionnaire data measuring emotional and behavioural problems, life events, coping style, self-related cognitions, perceived parenting style and school environment, and size and efficiency of the social network., Results: The increase of alcohol use from early adolescence to young adulthood showed only a few sex-specific differences in terms of the amount of alcohol consumption and the motives to drink. In late adolescence and young adulthood, males had a higher amount of alcohol consumption and were more frequently looking for drunkenness and feeling high. Males also experienced more negative consequences of alcohol use. A subgroup of heavy or problem drinkers showed a large range of emotional and behavioural problems and further indicators of impaired psychosocial functioning both in late adolescence and young adulthood., Conclusion: This Swiss community survey documents that alcohol use is problematic in a sizeable proportion of youth and goes hand in hand with a large number of psychosocial problems.

Developmental dyslexia is defined as a disorder of learning to read. It is thus critical to examine the neural processes that impair learning to read during the early phase of reading acquisition, before compensatory mechanisms are adapted by older readers with dyslexia. Using electroencephalography-based event-related imaging, we investigated how tuning of visual activity for print advances in the same children before and after initial reading training in school. The focus was on a fast, coarse form of visual tuning for print, measured as an increase of the occipito-temporal N1 response at 150-270 ms in the event-related potential (ERP) to words compared to symbol strings. The results demonstrate that the initial development of reading skills and visual tuning for print progressed more slowly in those children who became dyslexic than in their control peers. Print-specific tuning in 2nd grade strongly distinguished dyslexic children from controls. It was maximal in the inferior occipito-temporal cortex, left-lateralized in controls, and reduced in dyslexic children. The results suggest that delayed initial visual tuning for print critically contributes to the development of dyslexia.

Background: The study of the continuity, psychosocial correlates, and prediction of problematic substance use (PSU) across time from adolescence to young adulthood., Methods: Substance use was studied in a cohort of N = 593 subjects who had been assessed at three times between adolescence and young adulthood within the Zurich Psychology and Psychopathology Study (ZAPPS). Based on the frequency of tobacco, alcohol, and cannabis consumption, groups with PSU were defined at each of the three measurement points in time and compared to the rest of the sample. Comparisons included questionnaire data regarding emotional and behavioural problems, life events, coping style, self-related cognitions, perceived parenting style, perceived school environment, and size and efficiency of the social network., Results: The size of the groups with PSU increased continuously across time. The cross-sectional correlates of PSU were characterized by a similar pattern that included higher scores for externalizing behaviour, and both number and negative impact of life events across all three times. At time 1 and 2 subjects with PSU also experienced less favourable parenting styles and school environments. Longitudinally, PSU in young adulthood was predicted most strongly and persistently by previous risk status, externalizing problems and male gender., Conclusion: Problematic substance use is a major problem in youth. Its contributing pattern of associated and predictive psychosocial variables can be identified in the community.

Background: Although several promising studies on neurofeedback training in Attention Deficit/Hyperactivity Disorder (ADHD) have been performed in recent years, the specificity of positive treatment effects continues to be challenged., Methods: To evaluate the specificity of a neurofeedback training of slow cortical potentials, a twofold strategy was pursued: First, the efficacy of neurofeedback training was compared to a group training program for children with ADHD. Secondly, the extent of improvements observed in the neurofeedback group in relation to successful regulation of cortical activation was examined. Parents and teachers rated children's behaviour and executive functions before and after treatment. In addition, children underwent neuropsychological testing before and after training., Results: According to parents' and teachers' ratings, children of the neurofeedback training group improved more than children who had participated in a group therapy program, particularly in attention and cognition related domains. On neuropsychological measures children of both groups showed similar improvements. However, only about half of the neurofeedback group learned to regulate cortical activation during a transfer condition without direct feedback. Behavioural improvements of this subgroup were moderately related to neurofeedback training performance, whereas effective parental support accounted better for some advantages of neurofeedback training compared to group therapy according to parents' and teachers' ratings., Conclusion: There is a specific training effect of neurofeedback of slow cortical potentials due to enhanced cortical control. However, non-specific factors, such as parental support, may also contribute to the positive behavioural effects induced by the neurofeedback training.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.

A sample of 12 children (seven males, five females; mean age 6 years 7 months, SD 2 years 6 months, range 2 years 4 months to 12 years 1 month) with moderate-to-severe foetal alcohol syndrome (FAS) and another sample of 26 children (12 males, 14 females; mean age of 6 years 2 months SD 2 years 10 months, range 2 years 6 months to 12 years 8 months) with mild FAS or foetal alcohol effects (FAE) as well as a sample of 15 age- and sex-matched control children with unspecific intellectual disability were compared using the Developmental Behaviour Checklist (DBC). There were significant differences (p=0.01) between the groups on five of six subscales of the DBC with controls scoring lower on the disruptive, self-absorbed, anxiety, antisocial behaviour, and communication disturbance scales. The DBC profiles of the two foetal alcohol exposed groups did not differ from each other. It is concluded that quantitative behaviour measurement provides insights into specific behavioural phenotypes of FAS/FAE.

In order to classify attention-deficit-hyperactivity disorder (ADHD) in 11-year-old children, the role of specific attentional and motor deficits was examined. Participants comprised 22 children with ADHD (19 male, 3 female; median age 11 years, range 8.8 to 13.5 years) and 20 control children (17 male, 3 female; median age 10.6 years, range 8.2 to 12.6 years). Neuromotor assessment indicated that while both groups needed more time to complete finger compared to hand movements, this increase was more pronounced in children with ADHD. Reaction-time testing with continuous-force recording identified both motor and attentional deficits in children with ADHD. Longer intervals between force onset and force peak, and higher rate of responses with multiple force peaks (particularly in the bilateral condition) revealed specific deficits in the speed and quality of their motor output. Increase in errors and variability of force onsets indicated attentional deficits. Prediction analysis indicated that force-onset variability contributed significantly to group classification which was 85.7% correct. Neither neuromotor assessment nor specific motor deficits contributed significantly to classification, indicating that pure motor-speed measures play a minor role in characterizing ADHD in this age range.

Thirty-two dwarfed children and adolescents were studied clinically, by laboratory assessment, by a battery of psychological tests and a structured interview. Growth hormone deficiency was present in 16 cases, but in the remaining 16 cases there was no endocrine disease. Dwarfed children differed from nornal controls in perception, and a specific personality pattern emerged in the dwarfed children. The effects of age, sex, and socioeconomic status on personality traits were similar for dwarfs as for controls. Intelligence and personality variable were similar in dwarfs with and without endocrine disease. However, symptoms of the psychoendocrine syndrome, namely appetite and thirst disturbances, hypersensitivities, and impulse reduction, were more frequently seen among hypopituitary dwarfs. Social and coping behaviour was impaired in the majority of dwarfs. It is concluded that psychological disturbance occuring inchildren of small stature is a response to being small and is not attributable to any endocrine effect.