The Philadelphia Neurodevelopmental Cohort: constructing a deep phenotyping collaborative

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Abstract

An integrative multidisciplinary approach is required to elucidate the multiple factors that shape neurodevelopmental trajectories of mental disorders. The Philadelphia Neurodevelopmental Cohort (PNC), funded by the National Institute of Mental Health Grand Opportunity (GO) mechanism of the American Recovery and Reinvestment Act, was designed to characterize clinical and neurobehavioral phenotypes of genotyped youths. Data generated, which are recently available through the NIMH Database of Genotypes and Phenotypes (dbGaP), have garnered considerable interest. We provide an overview of PNC recruitment and clinical assessment methods to allow informed use and interpretation of the PNC resource by the scientific community. We also evaluate the structure of the assessment tools and their criterion validity.

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The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women.

Kenneth Kendler, Carol Prescott, John Myers … (2003)

Patterns of comorbidity suggest that the common psychiatric and substance use syndromes may be divisible into 2 broad groups of internalizing and externalizing disorders. We do not know how genetic and environmental risk factors contribute to this pattern of comorbidity or whether the etiologic structure of these groups differ in men and women. Lifetime diagnoses for 10 psychiatric syndromes were obtained at a personal interview in more than 5600 members of male-male and female-female twin pairs ascertained from a population-based registry. Multivariate twin modeling was performed using the program Mx. We first fit models to the following 7 syndromes: major depression, generalized anxiety disorder, phobia, alcohol dependence, drug abuse/dependence, adult antisocial behavior, and conduct disorder. The full model, which could be constrained to equality in male and female subjects, identified 2 genetic factors. The first had strongest loadings on alcohol dependence, drug abuse/dependence, adult antisocial behavior, and conduct disorder; the second, on major depression, generalized anxiety disorder, and phobia. Alcohol dependence and drug abuse/dependence had substantial disorder-specific genetic risk factors. Shared environmental factors were most pronounced for conduct disorder and adult antisocial behavior. No clear internalizing/externalizing structure was seen for the unique environmental common factors. We then fit models to 5 internalizing syndromes. The full model, which could also be constrained to equality in men and women, revealed one genetic factor loading most heavily on major depression and generalized anxiety disorder and another loading most strongly on animal and situational phobia. The underlying structure of the genetic and environmental risk factors for the common psychiatric and drug abuse disorders in men and women is very similar. Genetic risk factors predispose to 2 broad groups of internalizing and externalizing disorders. Within the internalizing disorders, 2 genetic factors are seen that predispose to disorders dominated by anxious-misery and fear. Substance use disorders have disorder-specific genetic risks. The externalizing disorders of conduct disorder and adult antisocial behavior are significantly influenced by the shared environment. The pattern of lifetime comorbidity of common psychiatric and substance use disorders results largely from the effects of genetic risk factors.

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Validation of a self-administered instrument to assess stage of adolescent development.

N Morris, J Udry (1980)

Drawings were made from Tanner's photographs illustrating five stages of development each for male genitalia, testicular size, male pubic hair, female breasts, and female pubic hair. Forty-seven females and forty-eight males aged 12-16 years indicated on questionnaires which stage they were most like, and answered other questions related to their physical development. Afterwards they were examined by physicians who had not seen their answers. Pearson correlation coefficients were 0.6 or above for the physician's observations compared with the adolescents' answers for the drawings, with the exception of testicular size. Answers to questions concerning amount of underarm hair and general development also yielded high correlations.

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Prevalence of psychotic symptoms in childhood and adolescence: a systematic review and meta-analysis of population-based studies.

Justin D. Connor, Cynthia Harley, I Kelleher … (2012)

Psychotic symptoms occur more frequently in the general population than psychotic disorder and index risk for psychopathology. Multiple studies have reported on the prevalence of these symptoms using self-report questionnaires or clinical interviews but there is a lack of consensus about the prevalence of psychotic symptoms among children and adolescents. We conducted a systematic review of all published literature on psychotic symptom prevalence in two age groups, children aged 9-12 years and adolescents aged 13-18 years, searching through electronic databases PubMed, Ovid Medline, PsycINFO and EMBASE up to June 2011, and extracted prevalence rates. We identified 19 population studies that reported on psychotic symptom prevalence among children and adolescents. The median prevalence of psychotic symptoms was 17% among children aged 9-12 years and 7.5% among adolescents aged 13-18 years. Psychotic symptoms are relatively common in young people, especially in childhood. Prevalence is higher in younger (9-12 years) compared to older (13-18 years) children.