J I Nurnberger

..The 2005 Molecular Psychiatry Meeting was held from 6 to 8 February 2005 at the Treasure Mountain Inn in Park City, Utah...

..Data from the collaborative study were used to test three phenotypes (comorbid alcoholism and depression, alcoholism or depression, and depression) for genetic linkage...

..We also assessed the aggregation of other psychiatric disorders in the same sample to identify areas of possible shared genetic vulnerability...

..As the neurobiology of replicated candidate genes is considered, models of potentially relevant biological pathways may be constructed...

..A convincing demonstration for a susceptibility gene will probably require a mixture of case- control studies, family-based association methods, and pathophysiologic studies...

..The childhood precursors of adult bipolar disorder (BP) are still a matter of controversy...

..Nighttime levels of corticotropin and cortisol were also examined as potential trait vulnerability markers...

..Interest continues to center on 6p 24-22 for schizophrenia. Another area of possible linkage to both schizophrenia and bipolar disorder exists at 6q 21-22. Neither of these areas maybe considered confirmed at this time...

..The 11th Annual Molecular Psychiatry Meeting was held from 8 to 10 February 2004, at the Treasure Mountain Inn in Park City, Utah. The meeting was hosted by Bill Byerley, University of California, Irvine...

..CFG analysis of the gene expression changes identified a series of novel candidate genes and blood biomarkers for bipolar disorder, alcoholism, and stress reactivity...

..Alcoholism and substance dependence frequently co-occur. Accordingly, we evaluated the familial transmission of alcohol, marijuana, and cocaine dependence and habitual smoking in the Collaborative Study on the Genetics of Alcoholism...

..Our studies suggest that blood biomarkers may offer an unexpectedly informative window into brain functioning and disease state...

..05) with that reported for the period of wheel running activity in seven C x B RI strains (Schwartz, W.J., and Zimmerman, P., J. Neurosci. 10:3685 1990)...

..Lastly, we describe a prototype of how such testing could be used to categorize disease risk in individuals and aid personalized medicine approaches, in psychiatry and beyond...

..1 and 1.4 for the two regions on chromosome 2. These results are consistent with linkage, but do not provide definitive evidence. We are currently creating a denser map in these regions and have begun genotyping a second sample in COGA...

..Although some linkage findings may be false positives, the results could help prioritize the search for rare variants using whole exome or genome sequencing...

..A previous study reported linkage to chromosomes 1, 2, and 7 in a large data set that consisted of 105 families, each with at least three alcoholic members...

..These become prime targets for hypothesis driven follow-up studies, new drug development and personalized medicine approaches...

..Thus, several regions showed modest evidence for linkage to bipolar disorder in this initial genomic scan of these chromosomes, including broad regions near previous reports of possible linkage...

..There was also a conjunction with a locus determined from QTL analysis of the previously reported tau of wheel running activity in seven CXB RI strains (Schwartz and Zimmerman, 1990)...

..For wheel-running period, the chromosome-wide surveys identified QTL on chromosomes 2 and 13 and one highly suggestive QTL on proximal chromosome 1. The results are compared to other published studies of QTL of circadian period...

..The CFG approach may also be particularly useful for identification of blood biomarkers of the illness...

..Other pathways are new potential targets for drug development. Lastly, a comparison with our earlier work on bipolar disorder illuminates the significant molecular overlap between schizophrenia and bipolar disorder...

..There also was no evidence for unequal transmission of DRD2 alleles for the phenotypes "ever smoker" or comorbid alcohol dependence and habitual smoking. This study does not support linkage of the DRD2 with smoking...

..Other chromosomal regions with lod scores over 1.50 for at least one Model Included chromosomes 8 (Model III), 16 (Model III), and 20 (Model I). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:18-23, 2000..

..There was no association with other genes in the GABAA cluster on chromosome 4 with illicit drug dependence...

..It also reveals the significant genetic overlap with other major psychiatric disorder domains, suggesting the need for improved nosology...

..The goal of this study was to examine the association of this variant with cocaine dependence...

..Collectively, results of this study and the literature suggest that enhanced NE function in the LC of C57 mice is associated with their susceptibility to stress-induced behavioral depression...

..The host was Bill Byerley (University of California, Irvine, California, USA), and the meeting was supported by Janssen Pharmaceutica and the Department of Psychiatry, University of California, Irvine, California, USA...

..Alcohol dependence is a complex disease, and although linkage and candidate gene studies have identified several genes associated with the risk for alcoholism, these explain only a portion of the risk...

..This indel is, therefore, a functional regulatory variation likely to explain at least part of the association of OPRK1 with alcohol dependence...

..11 and 1.16. Further dissection of the alcoholism phenotype, to disentangle the influence of comorbid substance-use disorders, will be a next step in identifying genetic variants associated with alcohol dependence...

..Pharmacological studies have provided evidence that the administration of NK3R agonists attenuates the intake of alcohol and NK3R can also mediate the acute and chronic behavioral effects of cocaine...

..The purpose of this study was to investigate the effectiveness of zonisamide in the treatment of bipolar depression...

..Additional studies suggest that cocaine may affect NPY expression...

..04-0.05). Secondary analyses suggested that two adjacent SNPs in intron 1 of OPRL1 were marginally associated with opioid dependence (P = 0.05); none of the SNPs in PNOC were associated with opioid dependence...

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..Thus, variations in NFKB1 appear to affect the risk for alcoholism, particularly contributing to an earlier onset of the disease...

..In conjunction with a higher reactivity to its rewarding effects, they may able to ingest enough of this nonspecific drug for a strong hedonic and addictive effect to occur...

..This article explores how this genetic risk factor interacts with marital status, another factor previously shown to be associated with the risk for alcohol dependence...

..Maternal transmissions provided no evidence for association. These data are consistent with an association between the expressed alleles in the GABA(A)-gene cluster on chromosome 15 and alcoholism that is modulated by genetic imprinting...

..Growing evidence suggests that BDNF is involved in the pathophysiology of mood disorders...

..05) and rs806380 (P = 0.009)]. Haplotype analyses revealed the association to be largely driven by the SNP rs806380. These results suggest a role for the cannabinoid receptor 1 gene in cannabis dependence...

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..We conclude with suggestions for strategies that may help clarify the genetic bases of this complex illness...

..There is considerable debate surrounding the effective measurement of DSM-IV symptoms used to assess manic disorders in epidemiological samples...

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..The goal of this study was to identify predictors of problematic young adult alcohol use...

..These findings provide strong evidence that variants within or close to the CHRM2 locus influence risk for two common psychiatric disorders...

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..These initial results suggest that APP may play an important role in the early development of the rat brain and the alcohol-preferring trait may influence APP processing in the developing brain...

..CONCLUSIONS: The results indicate that a distinction between independent and alcohol-induced mood disorders in alcoholics with a history of suicide attempts may be useful...

..05 and P < 0.01. These data suggest that at least one locus located on mouse chromosome 17 near or between 6 and 13 cM from the centromere influences HACU in the striatum and possibly the frontal cortex and hippocampus of the mouse...

..The aim of this study was to examine the abbreviated Desires for Alcohol Questionnaire (DAQ) with respect to component structure and concurrent validity...

..This suggests that a gene or genes on chromosome 1 may predispose some people to alcoholism and others to depression (which may be alcohol induced)...

..Samples collected have been shown to produce usable DNA after shipment through conventional mail. The DNA produced by rapid elution of these swabs in chaotropic buffers is, however, of limited quality and low purity...

..Our aim is to map chromosomal regions that harbor loci that increase susceptibility to bipolar disorder...

..We sought to determine if postpartum mood symptoms and depressive episodes exhibit familial aggregation in bipolar I pedigrees...

..These families were recruited as part of the Collaborative Study on the Genetics of Alcoholism (COGA)...

..10), on chromosomes 2p, 3q, and 8q. This study, which is based on the largest linkage sample for bipolar disorder analyzed to date, indicates that several genes contribute to bipolar disorder...

..Finally, there is also evidence of an area on chromosome 2 that may reflect a common genetic vulnerability locus to both habitual smoking and alcohol dependence...

..Phenomena in the bipolar spectrum, including rapid cycling, cyclothymia, and affective instability of borderline personality, may be important markers of etiologic heterogeneity. Rapid switching of mood may be central to these phenomena...

..The authors investigated whether comorbidity of bipolar disorder and panic disorder is associated with rapid mood switching in families with a high rate of bipolar disorder...

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..These findings underscore the importance of considering parental comorbid psychopathology when examining the relationship between parental alcoholism and offspring adjustment...

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..This study attempts to characterize clinical correlates, familial aggregation, and genetic linkage in subjects with these features...

..0 on chromosome 2 (3.2, 234 cM), 10 (2.4 and 2.6 at 60 cM and 116 cM) and 13 (2.1 at 64 cM). These regions may harbor genes that contribute to the biological basis of alcohol and drug dependence...

..Our results establish genomewide significant linkage to BP on chromosomes 6q and 8q, which provides solid information to guide future gene-finding efforts that rely on fine-mapping and association approaches...

..A major criterion to validate diagnoses is stability over time...

..Application of conditional analyses is potentially useful in larger sample collections to identify susceptibility genes of modest influence that may not be identified in a genome-wide scan aimed to identify single gene effects...

..This study examines the relationship between parental substance use consequences and adolescent psychological problems by gender of the adolescent and gender of the parent...

..It is also unclear whether psychiatric comorbidity in AD subjects accounts for additional variance in frontal asymmetry, beyond a diagnosis of AD alone...

..However, the effects of this genotype on measures of stress sensitivity are poorly understood. Therefore, this study examined whether 5-HTTLPR genotype was associated with negative information processing biases in early childhood...

..We note that meta-analysis can sometimes provide support for linkage but cannot disprove linkage in any candidate region...

..We hypothesized that symptoms would correlate with each other across a woman's reproductive life span in both major depression (MDD) and bipolar I disorder (BP)...

..Furthermore, investigators should consider the specific disorder(s) being investigated and the ages of the children being studied when determining whether to include parent reports as part of study design...

..38, which exceeds standard criteria for suggestive linkage, and a corresponding parametric HLOD score of 2.98. The combined analysis did not provide further support for linkage to 4q32 and 4q35...

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..Implications of the findings for future research on BPD vulnerability are described...

..Previous research indicates that the serotonin transporter promoter region polymorphism is a candidate gene for such traits...

..The ethical implications of this research will be studied by examining the effects of participation and the effect on self-esteem due to high- risk status. ..

..Analysis of the existing sib pair families plus this large set of cases and controls should permit the confirmation of several vulnerability genes during this grant period. ..

..Genotypes will be shared with a consortium of investigators studying linkage in bipolar illness. Cell lines and interview data will be made freely available to the scientific community. ..

..The ethical implications of this research will be studied by examining the effects of participation and the effect on self-esteem due to high- risk status. ..