We propose a taxonomy of psychopathology based on patterns of shared causal influences identified in a review of multivariate behavior genetic studies that distinguish genetic and environmental influences that are either common to multiple dimensions of psychopathology or unique to each dimension. At the phenotypic level, first-order dimensions are defined by correlations among symptoms; correlations among first-order dimensions similarly define higher-order domains (e.g., internalizing or externalizing psychopathology). We hypothesize that the robust phenotypic correlations among first-order dimensions reflect a hierarchy of increasingly specific etiologic influences. Some nonspecific etiologic factors increase risk for all first-order dimensions of psychopathology to varying degrees through a general factor of psychopathology. Other nonspecific etiologic factors increase risk only for all first-order dimensions within a more specific higher-order domain. Furthermore, each first-order dimension has its own unique causal influences. Genetic and environmental influences common to family members tend to be nonspecific, whereas environmental influences unique to each individual are more dimension-specific. We posit that these causal influences on psychopathology are moderated by sex and developmental processes. This causal taxonomy also provides a novel framework for understanding the heterogeneity of each first-order dimension: Different persons exhibiting similar symptoms may be influenced by different combinations of etiologic influences from each of the 3 levels of the etiologic hierarchy. Furthermore, we relate the proposed causal taxonomy to transdimensional psychobiological processes, which also impact the heterogeneity of each psychopathology dimension. This causal taxonomy implies the need for changes in strategies for studying the etiology, psychobiology, prevention, and treatment of psychopathology. (PsycINFO Database Record

A hierarchical causal taxonomy of psychopathology across the life span.

ObjectiveDeveloping categorical diagnoses that have biological meaning within the clinical phenotype of psychosis (schizophrenia, schizoaffective disorder, and bipolar I disorder with psychosis) is as important for developing targeted treatments as for nosological goals. The Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) was formed to examine a broad array of intermediate phenotypes across psychotic disorders and to test the hypothesis that intermediate phenotype characteristics are homogeneous within phenomenologically derived DSM-IV diagnoses.MethodThe consortium recruited 933 stable probands with schizophrenia, schizoaffective disorder, or psychotic bipolar I disorder, 1,055 of their first-degree relatives, and 459 healthy comparison subjects for clinical characterization and dense phenotyping. Clinical, psychosocial, and family characteristics were contrasted.ResultsAll proband groups showed lower psychosocial functioning than the relatives or comparison group. On average, schizophr...

https://ajp.psychiatryonline.org/doi/pdf/10.1176/appi.ajp.2013.12101339

Clinical Phenotypes of Psychosis in the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP)

The genetics of schizophrenia has been approached utilizing a variety of methods. One emerging strategy is the use of endophenotypes in order to understand and identify the functional importance of genetically transmitted, brain-based deficits across schizophrenia kindreds. The endophenotype strategy is a topic of this issue of Schizophrenia Bulletin. Endophenotypes are quantitative, heritable, trait-related deficits typically assessed by laboratory-based methods rather than clinical observation. Endophenotypes are seen as closer to genetic variation than are clinical symptoms of schizophrenia, and are therefore closely linked to heritable risk factors. There has been a broad expansion of opportunities available to psychiatric neuroscientists who use the endophenotype strategy to understand the genetic basis of schizophrenia. In this context, genetic variation such as single nucleotide polymorphisms (SNPs) induces abnormalities in endophenotypic domains such as neurocognition, neurodevelopment, metabolism, and neurophysiology. This article discusses the challenges that abound in genetic research of schizophrenia, including issues in ascertainment, epistasis, ethnic diversity, and the potentially normalizing effects of second-generation antipsychotic medications on neurocognitive and neurophysiological measures. Robust strategies for meeting these challenges are discussed in this review and the subsequent articles in this issue. This article summarizes conceptual advances and progress in the measurement and use of endophenotypes in schizophrenia that form the basis of the multisite National Institute of Mental Health Consortium on the Genetics of Schizophrenia. The endophenotype strategy offers powerful and exciting opportunities to understand the genetically conferred neurobiological vulnerabilities and possible new strong inference and molecularly based treatments for schizophrenia.

/pdf/deconstructing-schizophrenia-an-overview-of-the-use-of-3id6897pb6.pdf

Deconstructing Schizophrenia: An Overview of the Use of Endophenotypes in Order to Understand a Complex Disorder

Neurocognition in first-episode schizophrenia: a meta-analytic review

Background: Smoking and depression are both leading causes of disability, mortality and morbidity around the world. Using epidemiologic data to study the association between depression and the severity, course, and persistence of smoking in the general population is important for understanding the scope of the problem of smoking among people with depression. Objectives: The current paper aims to critically review existing epidemiologic research on the smoking behaviors of persons with depressive symptoms and disorders and to identify gaps in the literature that warrant further study. Methods: Literature searches of Medline and EMBASE were used to identify articles that analyzed epidemiologic data and examined an aspect of smoking behavior in persons with depressive symptoms or disorders. Six hundred ninety-three abstracts were reviewed and 45 studies met all of the inclusion criteria to be included in the review. Results: Persons with depression, compared to those without depression, are more like...

Depression and cigarette smoking behavior: A critical review of population-based studies

Smoking and depression are significant public health problems with multiple etiological dimensions and outcomes. Although each condition is important by itself, they are important because they often potentiate each other. Consequently, it is also essential to understand the nature their relationship. This representative review focuses on the genetic etiology of the relationship in the context of reviewing first the epidemiology of depression and smoking, and then by exploring behavioral and molecular genetic studies, and other psychiatric and medical comorbidities. At this point, epidemiological evidence for a relationship between depression and smoking/nicotine dependence is compelling. Although behavioral genetic results differ somewhat by gender and in accordance with specific definitions of depression and smoking variables, recent studies show converging evidence for common genetic factors underlying the relationship, often in addition to non-shared environmental factors. The search for underlying genes and genetic mechanisms is at an early stage, but shows promising candidate genes and genetic approaches for future studies.

Genetics of smoking and depression

Group and site differences on the California Verbal Learning Test in persons with schizophrenia and their first-degree relatives: Findings from the Consortium on the Genetics of Schizophrenia (COGS)

Alison R. Thomas

Papers

Genetics of smoking and depression

Group and site differences on the California Verbal Learning Test in persons with schizophrenia and their first-degree relatives: Findings from the Consortium on the Genetics of Schizophrenia (COGS)