Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

T his study compared parents' ratings of behavioral and emotional problems on the Child Behavior Checklist (Achenbach, 1991;Achenbach & Rescorla, 2001) for general population samples of children ages 6 to 16 from 31 societies (N = 55,508). Effect sizes for society ranged from .03 to .14. Effect sizes for gender were ≤ .01, with girls generally scoring higher on Internalizing problems and boys generally scoring higher on Externalizing problems. Effect sizes for age were ≤ .01 and varied across types of problems.Total Problems scores for 19 of 31 societies were within 1 SD of the overall mean of 22.5. Bisociety correlations for mean item scores averaged .74. The findings indicate that parents' reports of children's problems were similar in many ways across highly diverse societies. Nonetheless, effect sizes for society were larger than those for gender and age,indicating the need to take account of multicultural variations in parents' reports of children's problems.Children of immigrant parents constitute increasing proportions of populations served by mental health, educational, medical, and welfare systems in many societies. In addition, assessment of needs for child mental health services is a significant public health goal around the world. To meet these challenges for assessment of behavioral and emotional problems in diverse societies, there is a need for instruments that are easily administered, scored, and interpreted by a wide range of practitioners and researchers and that demonstrate multicultural robustness. Multicultural robustness is established through systematic research demonstrating that an instrument performs similarly across many societies in terms of features such as reliability, internal consistency, factor structure, scale scores, and associations of scores with age and gender (Geisinger, 1994).In the early stages of multicultural research, mental health specialists in a society often evaluate instruments developed in other societies for use in their own. If an instrument is in a foreign language, a translated version is created, and then an independent back-translation into the original language is done to verify that the translation captures the meaning of the original. Ideally, researchers then collect data using the instrument with a large general population sample. When data are available from many societies, they can be analyzed together to compare variations between societies and within societies. Establishing the multicultural robustness of an instrument is thus an incremental process using an etic approach to research, whereby the same standardized assessment instrument is used in different societies. This contrasts with an emic approach to research, whereby the meanings of the constructs under study are explored within each society.

There is a growing need for multicultural collaboration in child mental health services, training, and research. To facilitate such collaboration, this study tested the 8-syndrome structure of the Child Behavior Checklist (CBCL) in 30 societies. Parents' CBCL ratings of 58,051 6- to 18-year-olds were subjected to confirmatory factor analyses, which were conducted separately for each society. Societies represented Asia; Africa; Australia; the Caribbean; Eastern, Western, Southern, and Northern Europe; the Middle East; and North America. Fit indices strongly supported the correlated 8-syndrome structure in each of 30 societies. The results support use of the syndromes in diverse societies.

As a basis for theories of psychopathology, clinical psychology and related disciplines need sound taxonomies that are generalizable across diverse populations. To test the generalizability of a statistically derived 8-syndrome taxonomic model for youth psychopathology, confirmatory factor analyses (CFAs) were performed on the Youth Self-Report (T. M. Achenbach & L. A. Rescorla, 2001) completed by 30,243 youths 11-18 years old from 23 societies. The 8-syndrome taxonomic model met criteria for good fit to the data from each society. This was consistent with findings for the parent-completed Child Behavior Checklist (Achenbach & Rescorla, 2001) and the teacher-completed Teacher's Report Form (Achenbach & Rescorla, 2001) from many societies. Separate CFAs by gender and age group supported the 8-syndrome model for boys and girls and for younger and older youths within individual societies. The findings provide initial support for the taxonomic generalizability of the 8-syndrome model across very diverse societies, both genders, and 2 age groups.

In this study, the authors compared ratings of behavioral and emotional problems and positive qualities on the Youth Self-Report (T. M. Achenbach & L. A. Rescorla, 2001) by adolescents in general population samples from 24 countries (N = 27,206). For problem scales, country effect sizes (ESs) ranged from 3% to 9%, whereas those for gender and age ranged from less than 1% to 2%. Scores were significantly higher for girls than for boys on Internalizing Problems and significantly higher for boys than for girls on Externalizing Problems. Bicountry correlations for mean problem item scores averaged .69. For Total Problems, 17 of 24 countries scored within one standard deviation of the overall mean of 35.3. In the 19 countries for which parent ratings were also available, the mean of 20.5 for parent ratings was far lower than the self-report mean of 34.0 in the same 19 countries (d = 2.5). Results indicate considerable consistency across 24 countries in adolescents' self-reported problems but less consistency for positive qualities.

We used population sample data from 25 societies to answer the following questions: (a) How consistently across societies do adolescents report more problems than their parents report about them? (b) Do levels of parent-adolescent agreement vary among societies for different kinds of problems? (c) How well do parents and adolescents in different societies agree on problem item ratings? (d) How much do parent-adolescent dyads within each society vary in agreement on item ratings? (e) How well do parent-adolescent dyads within each society agree on the adolescent's deviance status? We used five methods to test cross-informant agreement for ratings obtained from 27,861 adolescents ages 11 to 18 and their parents. Youth Self-Report (YSR) mean scores were significantly higher than Child Behavior Checklist (CBCL) mean scores for all problem scales in almost all societies, but the magnitude of the YSR-CBCL discrepancy varied across societies. Cross-informant correlations for problem scale scores varied more across societies than across types of problems. Across societies, parents and adolescents tended to rate the same items as low, medium, or high, but within-dyad parent-adolescent item agreement varied widely in every society. In all societies, both parental noncorroboration of self-reported deviance and adolescent noncorroboration of parent-reported deviance were common. Results indicated many multicultural consistencies but also some important differences in parent-adolescent cross-informant agreement. Our findings provide valuable normative baselines against which to compare multicultural findings for clinical samples.

Parent-teacher cross-informant agreement, although usually modest, may provide important clinical information. Using data for 27,962 children from 21 societies, we asked the following: (a) Do parents report more problems than teachers, and does this vary by society, age, gender, or type of problem? (b) Does parent-teacher agreement vary across different problem scales or across societies? (c) How well do parents and teachers in different societies agree on problem item ratings? (d) How much do parent-teacher dyads in different societies vary in within-dyad agreement on problem items? (e) How well do parents and teachers in 21 societies agree on whether the child's problem level exceeds a deviance threshold? We used five methods to test agreement for Child Behavior Checklist (CBCL) and Teacher's Report Form (TRF) ratings. CBCL scores were higher than TRF scores on most scales, but the informant differences varied in magnitude across the societies studied. Cross-informant correlations for problem scale scores varied moderately across societies studied and were significantly higher for Externalizing than Internalizing problems. Parents and teachers tended to rate the same items as low, medium, or high, but within-dyad item agreement varied widely in every society studied. In all societies studied, both parental noncorroboration of teacher-reported deviance and teacher noncorroboration of parent-reported deviance were common. Our findings underscore the importance of obtaining information from parents and teachers when evaluating and treating children, highlight the need to use multiple methods of quantifying cross-informant agreement, and provide comprehensive baselines for patterns of parent-teacher agreement across 21 societies.

SUMMARY Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (<1% frequency) copy-number variants (CNVs) using SNP microarray data. We observed an enrichment of global CNV burden that was prominent for large (>1 Mb), singleton events (OR=2.28, 95%CI [1.39–3.79], p=1.2×10−3) and known, pathogenic CNVs (OR=3.03 [1.85–5.07], p=1.5×10−5). We also identified two individual, genome-wide significant loci, each conferring a substantial increase in TS risk (NRXN1 deletions, OR=20.3, 95%CI [2.6–156.2]; CNTN6 duplications, OR=10.1, 95% CI [2.3–45.4]). Approximately 1% of TS cases carry one of these CNVs, indicating that rare structural variation contributes significantly to the genetic architecture of TS.