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Cannabis is the most widely used illicit drug in the world. It is well established that substance abuse comorbidity i.a. cannabis use is much higher among patients with Schizophrenia (SCZ) and Bipolar Disorders (BD) than in the general population. However, the relationship between risk of SCZ, BD and cannabis use has not been completely understood so far. Previous studies have revealed that a genetic predisposition to SCZ might be associated with increased use of cannabis in healthy individuals. Given this relationship, we intended to study whether polygenic risk scores (PRS) for SCZ predict cannabis use in patients with SCZ and BD. In addition, we want to test whether BD PRS or Cannabis (CAN) PRS have an impact on cannabis use in these two subgroups. The present study included the USA GAIN/TGEN sample (1.150 BD patients) and the German KFO/PsyCourse cohort (433 SCZ and 327 BD patients) (www.kfo241.de; www.PsyCourse.de). Information on ever/never use of cannabis was available in these samples. PRS were calculated as follows: For each SNP contributing to the PRS, the number of risk variants carried by an individual was multiplied by the logarithm of the odds ratio for that particular variant. The resulting values were summed up in an additive fashion obtaining a weighted individual estimate of the SCZ genetic burden in each individual at different p-value thresholds. The most recent summary statistics on SCZ GWAS (Ripke et al., 2014), BD GWAS (Hou et al., 2016) and Cannabis use (Sherva et al., 2016) were used to ascertain risk variants, their P-values, and associated odds ratios for the respective disorders. SCZ PRS were associated (P<0.05) with cannabis use in the GAIN/TGEN sample of BD patients in all P-value thresholds tested ranging from P=0.04 until P=1. A larger genetic burden was associated with a higher risk to use cannabis. The R2 change explained by PRS ranged from 0.5% to 1.15%. These effects of SCZ PRS were replicated in the BD patients from the KFO/PsyCourse cohort (P-value threshold 0.0001, R2 change=1.94%, P-value=0.020). No effects were observed in the SCZ patients from this replication cohort. Likewise, no associations were observed between BD PRS and CAN PRS in any of the subsamples in this study. First results suggest that individuals with BD and an increased polygenic risk for SCZ are more likely to use cannabis. The association between BD and cannabis use might be not simply one of an environmental risk factor, but rather involves gene–environment interaction, as individuals choose and shape their own environment according on their own innate preferences. [ABSTRACT FROM AUTHOR]

For more than half a decade, lithium has been successfully used to treat bipolar disorder. Worldwide, it is considered the first-line mood stabilizer. Apart from its proven antimanic and prophylactic effects, considerable evidence also suggests an antisuicidal effect in affective disorders. Lithium is also effectively used to augment antidepressant drugs in the treatment of refractory major depressive episodes and prevent relapses in recurrent unipolar depression. In contrast to many psychiatric drugs, lithium has outlasted various pharmacotherapeutic 'fashions', and remains an indispensable element in contemporary psychopharmacology. Nevertheless, data from pharmacogenetic studies of lithium are comparatively sparse, and these studies are generally characterized by small sample sizes and varying definitions of response. Here, we present an international effort to elucidate the genetic underpinnings of lithium response in bipolar disorder. Following an initiative by the International Group for the Study of Lithium-Treated Patients (www.IGSLI.org) and the Unit on the Genetic Basis of Mood and Anxiety Disorders at the National Institute of Mental Health,lithium researchers from around the world have formed the Consortium on Lithium Genetics (www.ConLiGen.org) to establish the largest sample to date for genome-wide studies of lithium response in bipolar disorder, currently comprising more than 1,200 patients characterized for response to lithium treatment. A stringent phenotype definition of response is one of the hallmarks of this collaboration. ConLiGen invites all lithium researchers to join its efforts., (Copyright 2010 S. Karger AG, Basel.)

Objective: The purpose of this study was to assemble and validate a database of phenotypic variables that were collected from families with bipolar disorder as a resource for genetic and other biological studies., Method: Participants were ascertained for two bipolar disorder genetic linkage studies: the University of Chicago, Johns Hopkins, and National Institute of Mental Health (NIMH) Intramural Program (CHIP) Collaboration and the NIMH Genetics Initiative project. All participants underwent detailed, phenotypic assessment with either the Schedule for Affective Disorders and Schizophrenia-Lifetime Version or one of four versions of the Diagnostic Interview for Genetic Studies. Clinicians reviewed the interview items and derived variable definitions that were used to extract data from the original datasets. The combined data were subjected to range and logic assessments, and a subset was re-verified against the original data. Inconsistent data and variables that were deemed unreliable were excluded. Several of the resulting variables were characterized in the total cohort and tested for familial clustering, heritability, and statistical power in genetic linkage and association studies., Results: The combined database of phenotypic variables contained 197 variables on 5,721 subjects in 1,177 families. Deoxyribonucleic acid (DNA) samples are available for 5,373 of these subjects. The clinical presentation of bipolar disorder varied markedly. Most subjects suffered from serious and often disabling illness. Many phenotypic variables are strongly familial, and some quantitative variables are highly heritable. The cohort assembled in this study offers substantial power to carry out genetic linkage and association studies that use specific clinical features as covariates or as primary phenotypes., Conclusions: This is the largest database of phenotypic variables yet assembled for bipolar disorder, and it is now available to the research community. Researchers and clinicians can use this database to explore the connections between phenomenology and genetics in a cohort that is adequately powered to detect even modest genetic effects in bipolar disorder.

Background: We have reported genetic linkage between bipolar disorder and markers on chromosome 6q16.3-22.1 in the National Institute of Mental Health Genetics Initiative wave 3 pedigrees. Here we test for: 1) robustness of the linkage to differing analysis methods, genotyping error, and gender-specific maps; 2) parent-of-origin effects; and 3) interaction with markers within the schizophrenia linkage region on chromosome 6p., Methods: Members of 245 families ascertained through a sibling pair affected with bipolar I or schizoaffective-bipolar disorder were genotyped with 18 markers spanning chromosome 6. Nonparametric linkage analysis was performed., Results: Linkage to 6q is robust to analysis method, gender-specific map differences, and genotyping error. The locus confers a 1.4-fold increased risk. Affected siblings share the maternal more often than the paternal chromosome (p =.006), which could reflect a maternal parent-of-origin effect. There is a positive correlation between family-specific linkage scores on 6q and those on 6p22.2 (r =.26; p <.0001). Linkage analysis for each locus conditioned on evidence of linkage to the other increases the evidence for linkage at both loci (p <.0005). Logarithm of the odds (LOD) scores increased from 2.26 to 5.42 on 6q and from.35 to 2.26 on 6p22.2., Conclusions: These results support linkage of bipolar disorder to 6q, uncover a maternal parent-of-origin effect, and demonstrate an interaction of this locus with one on chromosome 6p22.2, previously linked only to schizophrenia.