Nature and nurture in neuropsychiatric genetics: Where do we stand?

Department of Psychiatry, Virginia Institute of Psychiatric and Behavioral Genetics, Richmond 23298, USA.
Dialogues in clinical neuroscience 03/2010; 12(1):7-23.
Source: PubMed

ABSTRACT Both genetic and nongenetic risk factors, as well as interactions and correlations between them, are thought to contribute to the etiology of psychiatric and behavioral phenotypes. Genetic epidemiology consistently supports the involvement of genes in liability. Molecular genetic studies have been less successful in identifying liability genes, but recent progress suggests that a number of specific genes contributing to risk have been identified. Collectively, the results are complex and inconsistent, with a single common DNA variant in any gene influencing risk across human populations. Few specific genetic variants influencing risk have been unambiguously identified, Contemporary approaches, however hold great promise to further elucidate liability genes and variants, as well as their potential inter-relationships with each other and with the environment. We will review the fields of genetic epidemiology and molecular genetics, providing examples from the literature to illustrate the key concepts emerging from this work.

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Available from: Brien Patrick Riley, Aug 25, 2015
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    • "The number of recent claims by social scientists to have discovered a statistically significant association between a particular common gene variant—either on its own or in conjunction with a particular environment—and complex, politically relevant behaviors warrants careful evaluation. This evaluation is particularly needed because the search for genes that could predict prevalent and devastating behavioral phenotypes such as schizophrenia and autism, not to mention global killers such as diabetes and hypertension, has to date been unsuccessful (Dick, Riley, and Kendler 2010; Franke, Neale, and Faraone 2009; Plomin and Davis 2009; Talmud et al. 2010). The purpose of this article is to undertake such an evaluation. "
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    ABSTRACT: Political scientists are making increasing use of the methodologies of behavior genetics in an attempt to uncover whether or not political behavior is heritable, as well as the specific genotypes that might act as predisposing factors for—or predictors of—political “phenotypes.” Noteworthy among the latter are a series of candidate gene association studies in which researchers claim to have discovered one or two common genetic variants that predict such behaviors as voting and political orientation. We critically examine the candidate gene association study methodology by considering, as a representative example, the recent study by Fowler and Dawes according to which “two genes predict voter turnout.” In addition to demonstrating, on the basis of the data set employed by Fowler and Dawes, that two genes do not predict voter turnout, we consider a number of difficulties, both methodological and genetic, that beset the use of gene association studies, both candidate and genome-wide, in the social and behavioral sciences.
    American Political Science Review 02/2012; 106(01). DOI:10.1017/S0003055411000554 · 3.93 Impact Factor
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    • "Its cost to society in terms of health care demands and lost productivity is well documented (Rice 2009), as are the personal stories of lifelong anguish and suffering among SZ patients and their families. While both genetic and epigenetic factors are associated with a risk for developing this disorder (Dick et al. 2010), the etiology and pathophysiology of SZ remain incompletely understood. More than 50 years after the introduction of drugs that target its symptoms, the standard medications for SZ are at best modestly effective. "
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    ABSTRACT: Current antipsychotic medications do little to improve real-life function in most schizophrenia patients. A dispassionate view of the dispersed and variable neuropathology of schizophrenia strongly suggests that it is not currently, and may never be, correctable with drugs. In contrast, several forms of cognitive therapy have been demonstrated to have modest but lasting positive effects on cognition, symptoms, and functional outcomes in schizophrenia patients. To date, attempts to improve clinical outcomes in schizophrenia by adding pro-cognitive drugs to antipsychotic regimens have had limited success, but we propose that a more promising strategy would be to pair drugs that enhance specific neurocognitive functions with cognitive therapies that challenge and reinforce those functions. By using medications that engage spared neural resources in the service of cognitive interventions, it might be possible to significantly enhance the efficacy of cognitive therapies. We review and suggest several laboratory measures that might detect potential pro-neurocognitive effects of drugs in individual patients, using a "test dose" design, aided by specific biomarkers predicting an individual's drug sensitivity. Lastly, we argue that drug classes viewed as "counter-intuitive" based on existing models for the pathophysiology of schizophrenia-including pro-catecholaminergic and NMDA-antagonistic drugs-might be important candidate "pro-cognitive therapy" drugs.
    Handbook of experimental pharmacology 01/2012; 213(213):81-111. DOI:10.1007/978-3-642-25758-2_4
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    • "It has proven difficult to identify genes that predispose to schizophrenia (Sullivan, 2005; Crow, 2008; Sanders et al., 2008; Sullivan, 2008a; Sullivan, 2008b; Need et al., 2009; Dick et al., 2010; Gejman et al., 2010), and many explanations for the missing heritability have been suggested (Manolio et al., 2009; Gershon et al., 2011). Thus it is not surprising that our SNP-wise analyses did not alter the excess risk associated with familial history of psychiatric disorder — in particular when taking a resolution of only 547,071 SNPs and a sample size of only 739 cases and 800 controls into account. "
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    ABSTRACT: Epidemiological studies indicate that having any family member with schizophrenia increases the risk of schizophrenia in the probands. However, genome-wide association studies (GWAS) have accounted for little of this variation. The aim of this study was to use a population-based sample to explore the influence of single-nucleotide polymorphisms (SNPs) on the excess schizophrenia risk in offspring of parents with a psychotic, bipolar affective or other psychiatric disorder. A nested case-control study with 739 cases with schizophrenia and 800 controls. Their parents and siblings. Information from national health registers and GWAS data from the national neonatal biobank. Offspring schizophrenia risk was elevated in those whose mother, father or siblings had been diagnosed with schizophrenia or related psychosis, bipolar affective disorder or any other psychiatric disorder. The rate ratio was 9.31 (3.85; 22.44) in offspring whose 1st degree relative was diagnosed with schizophrenia. This rate ranged between 8.31 and 11.34 when adjusted for each SNP individually and shrank to 8.23 (3.13; 21.64) when adjusted for 25% of the SNP-variation in candidate genes. The percentage of the excess risk associated with a family history of schizophrenia mediated through genome-wide SNP-variation ranged between -6.1%(-17.0%;2.6%) and 4.1%(-3.9%;15.2%). Analogous results were seen for each parent and for histories of bipolar affective and other psychiatric diagnoses. The excess risk of schizophrenia in offspring of parents who have a psychotic, bipolar affective or other psychiatric disorder is not currently explained by the SNP variation included in this study in accordance with findings from published genetic studies.
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