Three-and-a-Half-Factor Model? The Genetic and Environmental Structure of the CBCL/6–18 Internalizing Grouping

In the present article, multivariate genetic item analyses were employed to address questions regarding the ontology and the genetic and environmental etiology of the Anxious/Depressed, Withdrawn, and Somatic Complaints syndrome dimensions of the Internalizing grouping of the Child Behavior Checklist/6–18 (CBCL/6–18). Using common and independent pathway genetic factor modeling, it was examined whether these syndrome dimensions can be ascribed a realist ontology. Subsequently, the structures of the genetic and environmental influences giving rise to the observed symptom covariation were examined. Maternal ratings of a population-based sample of 17,511 Dutch twins of mean age 7.4 (SD = 0.4) on the items of the Internalizing grouping of the Dutch CBCL/6–18 were analyzed. Applications of common and independent pathway modeling demonstrated that the Internalizing syndrome dimensions may be better understood as a composite of unconstrained genetic and environmental influences than as causally relevant entities generating the observed symptom covariation. Furthermore, the results indicate a common genetic basis for anxiety, depression, and withdrawn behavior, with the distinction between these syndromes being driven by the individual-specific environment. Implications for the substantive interpretation of these syndrome dimensions are discussed.     

The Genetic Basis of Emotional Behavior: Has the Time Come for a Drosophila Model?

Abstract: The aim of this review was to summarize the studies potentially relevant to whether Drosophila can be used as a genetically tractable model to study the genetic and molecular basis of emotional behavior. Can these studies contribute to a better understanding of neural substrates of abnormal emotional states and specific neuropsychiatric illnesses, such as depression and anxiety?     

Genetic and Environmental Vulnerabilities Underlying Adolescent Substance Use and Problem Use: General or Specific?

Are genetic and environmental risks for adolescent substance use specific to individual substances or general across substance classes? We examined this question in 645 monozygotic twin pairs, 702 dizygotic twin pairs, 429 biological sibling pairs, and 96 adoptive (biologically unrelated) sibling pairs ascertained from community-based samples, and ranging in age from 12 to 18 years. Substance use patterns and symptoms were assessed using structured psychiatric interviews. Biometrical model fitting was carried out using age- and sex-specific thresholds for (a) repeated use and (b) problem use, defined as one or more DSM-IV symptoms of abuse or dependence. We hypothesized that problem use would be more heritable than use in adolescence, and that both genetic and environmental risks underlying tobacco, alcohol, and marijuana use and problem use would be significantly correlated. Results of univariate analyses suggested significant heritable factors for use and problem use for all substances with the exception of alcohol use. Shared environmental factors were important in all cases and special twin environmental factors were significant for tobacco use, tobacco problem use, and alcohol use. Multivariate analyses yielded significant genetic correlations between each of the substances (for both levels studied), and significant shared environmental correlations among use variables only. Our results suggest that tobacco, alcohol, and marijuana problem use are mediated by common genetic influences, but shared environmental influences may be more substance-specific for problem use.     

Genetic and Environmental Factors Affecting Self-Rated Health from Age 16–25: A Longitudinal Study of Finnish Twins

We analyzed genetic and environmental determinants of self-rated health and its change from adolescence to early adulthood. Questionnaires were mailed to Finnish twins born 1975–1979 at ages 16, 17, and, on average, 25 years of age (N = 2465 complete twin pairs). The data were analyzed using quantitative genetic methods for twin data by the Mx statistical package. Heritability of self-rated health was greatest at age 16 (63%, 95% confidence intervals (CI) 56–67%, men and women together) and declined steadily to age 25 (33%, 95% CI 25–41%). The residual variation was due to unshared environments. Health ratings at different ages were modestly correlated (r = 0.33–0.61). These correlations were mainly due to genetic factors, but unshared environment also contributed to them. An important challenge for further research is to identify environmental influences contributing to self-rated health independently of, or in interaction with, genetic factors. Edited by Peter McGuffin and John Hewitt     

Structure and function of Norrin in assembly and activation of a Frizzled 4–Lrp5/6 complex

Norrin is a cysteine-rich growth factor that is required for angiogenesis in the eye, ear, brain, and female reproductive organs. It functions as an atypical Wnt ligand by specifically binding to the Frizzled 4 (Fz4) receptor. Here we report the crystal structure of Norrin, which reveals a unique dimeric structure with each monomer adopting a conserved cystine knot fold. Functional studies demonstrate that the novel Norrin dimer interface is required for Fz4 activation. Furthermore, we demonstrate that Norrin contains separate binding sites for Fz4 and for the Wnt ligand coreceptor Lrp5 (low-density lipoprotein-related protein 5) or Lrp6. Instead of inducing Fz4 dimerization, Norrin induces the formation of a ternary complex with Fz4 and Lrp5/6 by binding to their respective extracellular domains. These results provide crucial insights into the assembly and activation of the Norrin–Fz4–Lrp5/6 signaling complex.     

Genetic causes of rare and common epilepsies: What should the epileptologist know?

In past decades, the identification of genes involved in epileptic disorders has grown exponentially. The pace of gene identification in epileptic disorders began to accelerate in the late 2000s, driven by new technologies such as molecular cytogenetics and next-generation sequencing (NGS). These technologies have also been applied to genetic diagnostics, with different configurations, such as gene panels, whole-exome sequencing and whole-genome sequencing. The clinician must be aware that any technology has its limitations and complementary techniques must still be used to establish a diagnosis for specific diseases. In addition, increasing the amount of genetic information available in a larger patient sample also increases the need for rigorous interpretation steps, when taking into account the clinical, electroclinical, and when available, functional data. Local, multidisciplinary discussions have proven valuable in difficult diagnostic situations, especially in cases where precision medicine is being considered. They also serve to improve genetic counseling in complex situations.In this article, we will briefly review the genetic basis of rare and common epilepsies, the current strategies used for molecular diagnosis, including their limitations, and some pitfalls for data interpretation, in the context of etiological diagnosis and genetic counseling.     

Are Different Individuals Sensitive to Different Environments? Individual Differences in Sensitivity to the Effects of the Parent,Peer and School Environment on Externalizing Behavior and its Genetic and Environmental Etiology

Behavior Genetics - Externalizing behavior is substantially affected by genetic effects, which are moderated by environmental exposures. However, little is known about whether these moderation...     

The Best and the Worst of Us?

Wood, Nezworski, Garb, and Lilienfeld provide a compelling critique of the norms developed by Exner for the Rorschach Comprehensive System. There does appear to be a systematic error that results in clinicians and researchers identifying pathology that may not in fact be present. Wood and his colleagues recommend that the Comprehensive System not be used in clinical or forensic work. The Rorschach is prone to excessive interpretation and should perhaps not have an appreciable or significant impact on the resolution of legal disputes. However, even Wood and Lilienfeld previously concluded that valid information can be obtained within a Rorschach protocol. The dispute over the Rorschach may be a flashpoint of a wider and more fundamental dispute within the profession.     

Structure–property relationships of a biopolymer network: The eggshell membrane

The eggshell membrane (ESM) is a biopolymer network that may have potential applications in biomedicine, but it also may reveal important details regarding the behaviour of biopolymer networks. In this paper, we have studied the mechanical and morphological properties of the ESM in order to reveal important structure–property relationships. Light optical microscopy and atomic force microscopy were used to assess the morphology of the ESM. The mechanical properties of membranes and individual fibres were studied by means of tensile tests and nanoindentation tests, respectively. The mechanical behaviour of ESM networks in different environmental conditions showed a non-linear and a linear regime. As for elastomers and other biopolymer systems, the non-linear regime was modelled by the Mooney–Rivlin relation. The Young’s modulus in the linear regime of the network was related to the Young’s modulus of the individual fibres using Gibson and Ashby analysis for cellular solids. The results of morphological characterization were used to relate the properties of individual fibres to the properties of the whole networks. This enabled us to predict the macroscopical properties of the network based on the properties of the individual fibres. It was found that the ESM networks behaved as both Mooney–Rivlin and Hookean materials in different environmental conditions. This study helps elucidate the properties of the biopolymer networks found in nature and describes important mechanical properties for the use of the ESM as a biomaterial.     

The response of the host microcirculation to bacterial sepsis: does the pathogen matter?

Sepsis results from the interaction between a host and an invading pathogen. The microcirculatory dysfunction is now considered central in the development of the often deadly multiple organ dysfunction syndrome in septic shock patients. The microcirculatory flow shutdown and flow shunting leading to oxygen demand and supply mismatch at the cellular level and the local activation of inflammatory pathways resulting from the leukocyte–endothelium interactions are both features of the sepsis-induced microcirculatory dysfunction. Although the host response through the inflammatory and immunologic response appears to be critical, there are also evidences that Gram-positive and Gram-negative bacteria can exert different effects at the microcirculatory level. In this review we discuss available data on the potential bacterial-specific microcirculatory alterations observed during sepsis.     

Racial/Ethnic and Social Inequities in Sleep Medicine: The Tip of the Iceberg?

Purpose

It is known that racial disparities exist in terms of disease prevalence and access to health care. However, the link between race/ethnicity and sleep quality is often under-recognized.