Genome-wide association study of body mass index in 23 000 individuals with and without asthma.

BACKGROUND: Both asthma and obesity are complex disorders that are influenced by environmental and genetic factors. Shared genetic factors between asthma and obesity have been proposed to partly explain epidemiological findings of co-morbidity between these conditions. OBJECTIVE: To identify genetic variants that are associated with body mass index (BMI) in asthmatic children and adults, and to evaluate if there are differences between the genetics of BMI in asthmatics and healthy individuals. METHODS: In total, 19 studies contributed with genome-wide analysis study (GWAS) data from more than 23 000 individuals with predominantly European descent, of whom 8165 are asthmatics. RESULTS: We report associations between several DENND1B variants (P = 2.2 × 10(-7) for rs4915551) on chromosome 1q31 and BMI from a meta-analysis of GWAS data using 2691 asthmatic children (screening data). The top DENND1B single nucleotide polymorphisms(SNPs) were next evaluated in seven independent replication data sets comprising 2014 asthmatics, and rs4915551 was nominally replicated (P < 0.05) in two of the seven studies and of borderline significance in one (P = 0.059). However, strong evidence of effect heterogeneity was observed and overall, the association between rs4915551 and BMI was not significant in the total replication data set, P = 0.71. Using a random effects model, BMI was overall estimated to increase by 0.30 kg/m(2) (P = 0.01 for combined screening and replication data sets, N = 4705) per additional G allele of this DENND1BSNP. FTO was confirmed as an important gene for adult and childhood BMI regardless of asthma status. CONCLUSIONS AND CLINICAL RELEVANCE: DENND1B was recently identified as an asthma susceptibility gene in a GWAS on children, and here, we find evidence that DENND1B variants may also be associated with BMI in asthmatic children. However, the association was overall not replicated in the independent data sets and the heterogeneous effect of DENND1B points to complex associations with the studied diseases that deserve further study.

Genetic repositories for the study of major psychiatric conditions: what do we know about ethnic minorities' genetic vulnerability?

In spite of considerable efforts, no genes of major effect have been found across an entire diagnostic category in psychiatry. Possible reasons for this may include difficulties in defining the phenotype, the complex relationship between genotype and gene expression and population stratification. This last problem has often been managed by restricting genetic sampling to only one ethnic group. An unintended consequence of using this strategy is that the major repositories of genetic material for the study of psychiatric conditions in the United States suffer from a paucity of genetic samples from non-Caucasian groups. Thus, these groups are being relatively understudied in terms of the genetic antecedents to psychiatric disease. The authors provide solutions including the need to augment the representation of African-American, Latino and Asian-Americans among research participants; a more nuanced approach to identify ancestry; and the development of analytic and genetic strategies to handle the issue of ethnic heterogeneity in samples.

Substance use and behaviour disorders in Puerto Rican youth: a migrant family study.

BACKGROUND: Hispanics in the USA have higher rates of substance use disorders than similar ethnic groups residing in Latin American nations, and recent evidence suggests an increase in substance use among US Hispanic youth. This investigation examines the familial and societal correlates of this increase by comparing Puerto Rican families residing in the mainland USA and Puerto Rico. METHODS: Using migrant and controlled family study methods, 279 probands in San Juan and 236 probands in New Haven were recruited from treatment clinics and the general community to compose four diagnostic groups: drug abuse/dependence; alcohol abuse/dependence; psychiatric controls; unaffected controls. 806 biological offspring aged 12-17 were then directly interviewed. RESULTS: Total rates for alcohol use were greater among San Juan youth than their migrant counterparts. By contrast, US migrant adolescents were more likely to use cannabis. A strong association was observed between parental and child substance use at both sites, particularly for boys, and offspring of probands with drug use disorders were at greatest risk for substance use and related disorders. Familial aggregation patterns did not vary substantially by site. CONCLUSIONS: Despite societal influences on the magnitude and patterns of substance use in migrant youth, the consistent influence of parental disorders across sites reveals that the cross-generational transmission of substance use disorders in prior studies extends to Hispanic families and is an important factor to consider in the development of prevention strategies.

25 years of child and adult psychiatric epidemiology studies in Puerto Rico

A review of the psychiatric epidemiology studies of the adult and child population of Puerto Rico carried out in the last 25 years is presented and discussed. Puerto Rico has experienced a plethora of psychiatric epidemiology studies since the decade of the 80's, with 4 adult and 4 child population based studies. The overall results of these studies showed that island Puerto Ricans are not at greater risk for psychiatric disorders as compared to other US or international populations in spite of the fact that the island is besieged by many of the socio-demographic factors associated with high risk populations. If anything, it appears that important protective factors associated with good family relationships and the importance of the family in Hispanic families may be buffering island families from the development of addictive and antisocial disorders.

Prevalence and factors associated to sexual behavior in Puerto Rican adolescents

Sexual relations with intercourse (ASR-I) and high prevalence of teen pregnancies (19.2%, in 2002) among adolescents in Puerto Rico constitute a serious biopsychosocial problem. Studying the consequences and correlates of ASR-I in community and mental health samples of adolescents is important in designing and implementing sexual health programs. Randomized representative cross-sectional samples of male and female adolescents from 11-18 years old (N = 994 from the general community, N = 550 receiving mental health services) who had engaged in ASR-I were the subjects of this study. Demographic, family, and sexual data and the DISC-IV were collected from individual interviews. Logistic regression models, bivariate odds ratios, Chi-squares, and t tests were used in the statistical analysis. The mental health sample showed higher rates of ASR-I, lifetime reports of pregnancy and lower age of ASR-I onset for females. No gender difference in the prevalence of ASR-I was observed in both samples. Older adolescents from the community sample meeting psychiatric diagnosis criteria, and with lower parental monitoring, were more likely to engage in ASR-I, whereas in the mental health sample, adolescents with lower parental monitoring and parental involvement reported significantly more ASR-I. Prevalence of ASR-I and Risky Sexual Behavior (RSB) were almost identical. Adolescents with mental health disorders initiate and engage in ASR-I earlier and more frequently regardless of gender. Older adolescents are more likely to engage in ASR-I and parent-child relationships emerged as a highly relevant predictor of adolescent sexual behavior. The high correspondence between ASR-I and RSB has important clinical implications.

tRNase Z: the end is not in sight.

Although the enzyme tRNase Z has only recently been isolated, a plethora of data has already been acquired concerning the enzyme. tRNase Z is the endonuclease that catalyzes the removal of the tRNA 3' trailer, yielding the mature tRNA 3' end ready for CCA addition and aminoacylation. Another substrate cleaved by tRNase Z is the small chromogenic phosphodiester bis(p-nitrophenyl)phosphate (bpNPP), which is the smallest tRNase Z substrate known so far. Hitherto the biological function as tRNA 3'-end processing enzyme has been shown only in one prokaryotic and one eukaryotic organism, respectively. This review summarizes the present information concerning the two tRNase Z substrates pre-tRNA and bpNPP, as well as the metal requirements of tRNase Z enzymes.

Psychometric evaluation of the Spanish version of CONNECT: a measure of continuity of care in mental health services.

This article provides the results of the psychometric testing of the Spanish version of CONNECT(-S), a measure of continuity of care in mental health services. CONNECT-S is a multidimensional measure designed for use with seriously mentally ill respondents. Consisting of 12 scales and one single-item indicator, it addresses qualities of interaction in current relationships between mental health service providers and consumers in five conceptual domains: (1) practitioner knowledge of their clients, (2) creating flexibility, (3) practitioner availability, (4) practitioner co-ordination, and (5) smoothing transitions. One-hundred-and-fifty participants took part in the study. Participants were recruited from mental health outpatient clinics in both the Puerto Rican (n = 109) and the San Antonio (n = 41) samples. Internal consistency for scales in a combined site estimate ranged from 0.68 to 0.96. Test-retest reliability ranged from fair to substantial in all but one scale. Concurrent validity hypotheses based on a priori predictions were mostly supported. The Spanish translation and adaptation of CONNECT-S provided sound psychometric results across both sites. CONNECT-S addresses the gap in measurement of continuity of care for the two largest US Latino subgroups, Mexican Americans and Puerto Ricans; and provides an encouraging starting point for a measure that is both relevant and culturally sensitive.

Does managed mental health care reallocate resources to those with greater need for services?

Evidence points to the existence of two coexisting inefficiencies in mental health care resource allocation: those with need receive too limited or no care while those with no apparent need receive services. In addition to reducing costs, managed mental health care is expected to reallocate treatment resources to those with greater need for services. However, there are no empirical findings regarding this issue. This study tests whether managed mental health care has had a differential impact by level of need. Data consist of three waves of a community sample with a control group. The study finds that managed care has not succeeded in reallocating resources from the unlikely to the definite "needers."

Prevalence and correlates of DSM-IV substance use disorders in Puerto Rico

We report the basic findings of a survey aimed at estimating rates of substance disorders in a probability sample of 4,709 household residents aged 15 to 64 years old. Lifetime use of alcohol was reported by 77.2, and 10.7 reported ever using illicit drugs. Overall, 14.7 of the sample met criteria for a lifetime substance disorder, and 4.9 for a past year disorder. The rates of lifetime disorders were 13.1 for alcohol and 4.1 for illicit drug. Past year abuse/dependence was 4.3 for alcohol and 1.3 for illicit drugs. Alcohol use disorders were associated with male gender, higher family annual income, being employed, and being married. Illicit drug use disorders were associated with male gender and younger age. Only 13.0 of respondents with a past year disorder reported using services for their disorder. A program of continuous monitoring of substance using disorders is critical to establishing and monitoring effective policies

Test-retest reliability of the Spanish version of the Diagnostic Interview Schedule for Children (DISC-IV).

The test-retest reliability of the Spanish Diagnostic Interview Schedule for Children (DISC-IV) is presented. This version was developed in Puerto Rico in consultation with an international bilingual committee, sponsored by NIMH. The sample (N = 146) consisted of children recruited from outpatient mental health clinics and a drug residential treatment facility. Two different pairs of nonclinicians administered the DISC twice to the parent and child respondents. Results indicated fair to moderate agreement for parent reports on most diagnoses. Relatively similar agreement levels were observed for last month and last year time frames. Surprisingly, the inclusion of impairment as a criterion for diagnosis did not substantially change the pattern of results for specific disorders. Parents were more reliable when reporting on diagnoses of younger (4-10) than older children. Children 11-17 years old were reliable informants on disruptive and substance abuse/dependence disorders, but unreliable for anxiety and depressive disorders. Hence, parents were more reliable when reporting about anxiety and depressive disorders whereas children were more reliable than their parents when reporting about disruptive and substance disorders.

Changes in access to mental health care among the poor and nonpoor: results from the health care reform in Puerto Rico.

OBJECTIVES: Health care reforms associated with managed care may adversely affect the health care safety net for disadvantaged populations. This study compared changes in health care use among poor and nonpoor individuals enrolled in managed care. METHODS: Data from 3 waves of a random community sample were collected on approximately 3,000 adults. Changes in use of mental health services were assessed in a pretest-posttest, quasi-experimental design. RESULTS: Managed care increased use of specialty services among the nonpoor while maintaining the same level of use for the poor in the public sector. CONCLUSIONS: Reallocation of mental health services may be a result of expanding Medicaid eligibility.

Prevalence and correlates of substance use disorders among older adolescents in Puerto Rico and the United States: a cross-cultural comparison.

Although there are substantial data on adolescent substance use, little systematic research has studied the prevalence of adolescent substance disorders in general populations, let alone cultural differences in disorder prevalence. In this paper we report the prevalence and correlates of alcohol and drug use and disorder among older adolescents on Puerto Rico (PR) and in the United States (US). Data come from an island-wide survey of the PR general residential population (15-18 year old subsample, unweighted N=922) fielded in 1997, and from the National Comorbidity Survey of the US household population (15-18 year old subsample, unweighted N=641), fielded in 1991. Both surveys used a similar standardized interview based on the Composite International Diagnostic Interview (CIDI) to generate DSM-IV diagnoses. Bivariate analyses and logistic regression were used. The major findings are: (1) US youth report higher rates of lifetime alcohol and drug use and substance-related disorder than PR youth; (2) the transition to abuse or dependence occurs for one-third of US drinkers, one-fifth of drinkers in PR, and about one-half of the drug users in both US and PR; (3) there are marked variations across sites in the types of symptoms substance users are likely to experience; (4) with the exception of family income, most correlates operate similarly in both sub-samples; and (5) the majority of both US and PR youth with a past year substance use disorder did not report any service utilization in the past year.

The DISC Predictive Scales (DPS): efficiently screening for diagnoses.

OBJECTIVE: To derive and test a series of brief diagnosis-specific scales to identify subjects who are at high probability of meeting diagnostic criteria and those who may safely be spared more extensive diagnostic inquiry. METHOD: Secondary data analysis of a large epidemiological data set (n = 1,286) produced a series of gate and contingent items for each diagnosis. Findings were replicated in a second retrospective analysis from a residential care sample (n = 884). The DISC Predictive Scales (DPS) were then used prospectively as a self-report questionnaire in two studies, in which parents (n = 128) and/or adolescents (n = 208) had subsequent diagnostic interviewing with the Diagnostic Interview Schedule for Children or the Schedule for Affective Disorders and Schizophrenia for School-Age Children. RESULTS: All analyses showed that gate item selection was valid and that any missed cases were due solely to inconsistent reports on the same questions. Screening performance of the full scales was shown to be good, and substantial reductions in scale length were not associated with significant changes in discriminatory power. CONCLUSIONS: The DPS can accurately determine subjects who can safely be spared further diagnostic inquiry in any diagnostic area. This has the potential to speed up structured diagnostic interviewing considerably. The full DPS can be used to screen accurately for cases of specific DSM-III-R disorders.

The impact of managed care on the use of outpatient mental health and substance abuse services in Puerto Rico.

This paper estimates the impact of managed care on use of mental health services by residents of low-income areas in Puerto Rico. A quasi-experimental design evaluates the impact of a low capitation rate on a minority population using three waves of data from a random community sample. Results indicate that two years after introducing managed care, privatization of mental health services had minimal impact on use. Advocates had hoped health care reform would increase access in comparison to access seen within the public system, while opponents feared profit motives would lead to decreased access. Neither forecast turned out to be correct. The question remains as to how to improve access for the poor with low capitation rates.

Prevalence and correlates of DSM-IV substance use disorders in Puerto Rico.

We report the basic findings of a survey aimed at estimating rates of substance disorders in a probability sample of 4,709 household residents aged 15 to 64 years old. Lifetime use of alcohol was reported by 77.2%, and 10.7% reported ever using illicit drugs. Overall, 14.7% of the sample met criteria for a lifetime substance disorder, and 4.9% for a past year disorder. The rates of lifetime disorders were 13.1% for alcohol and 4.1% for illicit drug. Past year abuse/dependence was 4.3% for alcohol and 1.3% for illicit drugs. Alcohol use disorders were associated with male gender, higher family annual income, being employed, and being married. Illicit drug use disorders were associated with male gender and younger age. Only 13.0% of respondents with a past year disorder reported using services for their disorder. A program of continuous monitoring of substance using disorders is critical to establishing and monitoring effective policies.

Prevalence and correlates of antisocial behaviors among three ethnic groups.

Using data from the MECA Study, this report examines the prevalence of Conduct Disorder (CD), Oppositional Defiant Disorder (ODD), and various levels of antisocial behavior and their correlates among three ethnic groups: Hispanics, subdivided into Island Puerto Ricans and Mainland Hispanics; African Americans; and Mainland Non-Hispanic, Non-African Americans. Correlates considered include stressful life events, birth defects, low birth weight, learning difficulties, teen mothers, family environment, marital adjustment, social competence, parental monitoring, and family relationships. Logistic regression was used to determine the association of outcomes with individual correlates and of interaction terms with ethnicity. Differences between adjusted rates and observed rates of disorders and levels of antisocial behaviors are compared to estimate the extent to which each correlate explains the group differences in rates. Island Puerto Ricans had a lower prevalence of CD, ODD, and various levels of antisocial behavior than mainland Hispanics, African Americans, and non-Hispanic Whites. The lower prevalence appears to be associated with differences in the extent to which a number of these correlates are found on the island, the most salient being better family relations between the target children and their parents and siblings.

Age and gender differences in oppositional behavior and conduct problems: a cross-sectional household study of middle childhood and adolescence.

Behavior problems among youths cannot be understood without explaining their age and gender differences, but age and gender differences cannot be explained until they have been accurately described. In a household survey of 1,285 youths aged 9 to 17 years, there were no gender differences in oppositional behavior, but aggression, property offenses, and status offenses were more common among boys. Levels of oppositional behavior were greater at younger ages, aggression peaked near the middle of this age range, and property and status offenses were more prevalent at older ages. These findings are generally consistent with developmental models of conduct problems but are inconsistent with a recent model of gender differences and raise questions about the external validity of current taxonomies.

Childhood obsessive-compulsive disorder in the NIMH MECA study: parent versus child identification of cases. Methods for the Epidemiology of Child and Adolescent Mental Disorders.

Abstract-Because as many as 50% of obsessive-compulsive disorder (OCD) cases have had onset by age 15, interest in its detection in childhood is strong. Clinical experience indicates that children often try to keep their OCD secret and that parental report may give marked underestimates. The authors examined the prevalence of childhood OCD in the NIMH Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study, a four-site community survey which allowed comparison of both parent and child report of the child's OCD and related symptoms and disorders. OCD cases, based on structured interviews (DISC-2.3 with DSM-III-R criteria) with 1,285 caretaker-child pairs, were identified separately for parent and child (aged 9 through 17) informants from the MECA database. Cases were then examined for demographic characteristics, for obsessive-compulsive symptoms and other diagnoses reported in cases "missed" by one reporter, and for comorbid disorders. Of a total of 35 (2.7%) identified cases, four (0.3%) were identified by the parent and 32 (2.5%) were identified by the child, with only one overlapping case. In general, when OCD cases were "missed" by one reporter, that reporter did not substitute another disorder. These findings support clinical data that children with OCD often hide their illness and underscore the importance of child interviews for its detection.