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Background. Electrophysiological endophenotypes are far less explored in bipolar disorder as compared to schizophrenia. No previous twin study of event-related potentials (ERPs) in bipolar illness has been reported. This study uses a twin design and advanced genetic model fitting analyses aiming to (1) assess and quantify the relationship of a range of ERP components with bipolar disorder with psychotic features, and (2) examine the source of the relationship (due to genetic or environmental factors). Method. P300, P50 suppression and mismatch negativity (MMN) were recorded in 10 discordant monozygotic (MZ) bipolar twin pairs, six concordant MZ bipolar twin pairs and 78 control twin pairs. Statistical analyses were based on structural equation modelling. Results. Bipolar disorder was significantly associated with smaller P300 amplitude and decreased P50 suppression. Genetic correlations were the main source of the associations, estimated to be x0 . 33 for P300 amplitude and 0 . 46 for P50 ratio. Individual-specific environmental influences were not significant. MMN and P300 latency were not associated with the illness. Conclusions. The results provide supporting evidence that P300 amplitude and P50 suppression ratio are ERP endophenotypes for bipolar disorder.

Context For more than a century, it has been uncertain whether or not the major diagnostic categories of psychosis—schizophrenia and bipolar disorder—are distinct disease entities with specific genetic causes and neuroanatomical substrates. Objective To investigate the relationship between genetic risk and structural variation throughout the entire brain in patients and their unaffected relatives sampled from multiply affected families with schizophrenia or bipolar disorder. Design Analysis of the association between genetic risk and variation in tissue volume on magnetic resonance images. Setting Psychiatric research center. Participants Subjects comprised 25 patients with schizophrenia, 36 of their unaffected first-degree relatives, 37 patients with bipolar 1 disorder who experienced psychotic symptoms during illness exacerbation, and 50 of their unaffected first-degree relatives. Main Outcome Measures We used computational morphometric techniques to map significant associations between a continuous measure of genetic liability for each subject and variation in gray or white matter volume. Results Genetic risk for schizophrenia was specifically associated with distributed gray matter volume deficits in the bilateral fronto-striato-thalamic and left lateral temporal regions, whereas genetic risk for bipolar disorder was specifically associated with gray matter deficits only in the right anterior cingulate gyrus and ventral striatum. A generic association between genetic risk for both disorders and white matter volume reduction in the left frontal and temporoparietal regions was consistent with left frontotemporal disconnectivity as a genetically controlled brain structural abnormality common to both psychotic disorders. Conclusions Genetic risks for schizophrenia and bipolar disorder are associated with specific gray matter but generic white matter endophenotypes. Thus, Emil Kraepelin’s pivotal distinction was neither wholly right nor wholly wrong: the 2 major psychoses show both distinctive and similar patterns of brain structural abnormality related to variable genetic risk.

To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense. © 2012 Nature America, Inc. All rights reserved.

P300 wave anomalies correlate with genetic risk for schizophrenia and constitute a plausible endophenotype for the disease. The COMT gene is thought to influence cognitive performance and to be a susceptibility gene for schizophrenia. Unlike two previous studies, we found no significant influence of the COMT gene on P300 amplitude or latency in 189 individuals examined. The well-supported role of the COMT gene both in dopamine catabolism as well as in prefrontal cognition makes a strong theoretical case for the influence of COMT Val158Met polymorphism on P300 endophenotypes. However, the available neurophysiologic evidence suggests that any such association, if present, must be very subtle.

Understanding the etiology of schizophrenia has been a considerable challenge. The neurodevelopmental hypothesis has held sway in recent years, focusing our attention on biological causes acting in early life. Much evidence supports this hypothesis and risk factors operating in early life (e.g., obstetric complications) have been shown to be associated with the later development of schizophrenia. Indicators of abnormal neurodevelopment that characterize individuals vulnerable to later developing schizophrenia have also been identified. For example, as a group, children who will later develop schizophrenia subtly differ from their peers in terms of their motor, cognitive, and social functioning. However, there is much that cannot be explained in purely neurodevelopmental terms. There is growing evidence of associations between the risk of schizophrenia and factors such as drug misuse, ethnicity/migration, life events, and urbanicity. A multifactorial model of causation that encompasses biological, social, and psychological elements is arguably both a better representation of current research findings and a more appropriate model for clinical practice.

Several components of event-related potentials--P50 suppression, P300 amplitude and latency, and mismatch negativity--have been proposed as potential endophenotypes for schizophrenia on the basis of family studies. The present study used a twin design to estimate the extent of genetic overlap between these indices and the liability to schizophrenia.The authors measured mismatch negativity, P300, and P50 suppression in 16 monozygotic twin pairs concordant for schizophrenia, nine monozygotic twin pairs discordant for schizophrenia, and 78 healthy comparison twin pairs. The study design was based on a power calculation. Structural equation modeling was used to quantify the genetic and environmental contributions to the phenotypic covariance between schizophrenia and each of the event-related potential indices.Significant phenotypic correlation with schizophrenia was found for each of the event-related potential components. Genetic factors were the main source of the phenotypic correlations. P50 suppression had the greatest genetic correlation with schizophrenia, followed by P300 amplitude, P300 latency, and mismatch negativity.All four event-related potential indices are potentially valid endophenotypes for schizophrenia, but P50 suppression and P300 amplitude show the closest genetic relationship to schizophrenia.