The endophenotype concept in psychiatric genetics

The idea that some phenotypes bear a closer relationship to the biological processes that give rise to psychiatric illness than diagnostic categories has attracted considerable interest. Much effort has been devoted to finding such endophenotypes, partly because it is believed that the genetic basis of endophenotypes will be easier to analyse than that of psychiatric disease. This belief depends in part on the assumption that the effect sizes of genetic loci contributing to endophenotypes are larger than those contributing to disease susceptibility, hence increasing the chance that genetic linkage and association tests will detect them. We examine this assumption by applying meta-analytical techniques to genetic association studies of endophenotypes. We find that the genetic effect sizes of the loci examined to date are no larger than those reported for other phenotypes. A review of the genetic architecture of traits in model organisms also provides no support for the view that the effect sizes of loci contributing to phenotypes closer to the biological basis of disease is any larger than those contributing to disease itself. While endophenotype measures may afford greater reliability, it should not be assumed that they will also demonstrate simpler genetic architecture

Effects of acute alcohol consumption and processing of emotion in faces:Implications for understanding alcohol-related aggression

The negative consequences of chronic alcohol abuse are well known, but heavy episodic consumption ("binge drinking") is also associated with significant personal and societal harms. Aggressive tendencies are increased after alcohol but the mechanisms underlying these changes are not fully understood. While effects on behavioural control are likely to be important, other effects may be involved given the widespread action of alcohol. Altered processing of social signals is associated with changes in social behaviours, including aggression, but until recently there has been little research investigating the effects of acute alcohol consumption on these outcomes. Recent work investigating the effects of acute alcohol on emotional face processing has suggested reduced sensitivity to submissive signals (sad faces) and increased perceptual bias towards provocative signals (angry faces) after alcohol consumption, which may play a role in alcohol-related aggression. Here we discuss a putative mechanism that may explain how alcohol consumption influences emotional processing and subsequent aggressive responding, via disruption of OFC-amygdala connectivity. While the importance of emotional processing on social behaviours is well established, research into acute alcohol consumption and emotional processing is still in its infancy. Further research is needed and we outline a research agenda to address gaps in the literature

Triangulating meta-analyses:the example of the serotonin transporter gene, stressful life events and major depression

BACKGROUND: Meta-analysis is intended as a tool for the objective synthesis of evidence across a literature, in order to obtain the best evidence as to whether or not an association or effect is robust. However, as the use of meta-analysis has proliferated it has become increasingly clear that the results of a meta-analysis can be critically sensitive to methodological and analytical choices, so that different meta-analyses on the same topic can arrive at quite different conclusions. RESULTS: We demonstrate the variability in results of different meta-analyses on the same topic, using the example of the literature on the putative moderating effect of 5-HTTLPR genotype on the association between stressful life events and major depression. We also extend on previous work by including a P-curve analysis of studies from this literature, drawn from a previous meta-analysis, in an attempt to resolve the discrepant conclusions arrived at by previous meta-analyses. CONCLUSIONS: We highlight the divergent conclusions that can be reached when different methodological and analytical choices are taken, and argue that triangulating evidence using multiple evidence synthesis methods is preferable where possible, and that every effort should be made for meta-analyses to be as unbiased as possible (e.g., conducted by methodologists or as part of an adversarial collaboration between authors from opposing camps). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40359-016-0129-0) contains supplementary material, which is available to authorized users