Genetics and intermediate phenotypes of the schizophrenia—bipolar disorder boundary

Ivleva, Elena I.; Morris, David W.; Moates, Amanda F.; Suppes, Trisha; Thaker, Gunvant K.; Tamminga, Carol A.

doi:10.1016/j.neubiorev.2009.11.022

Cited by 137 publications

(123 citation statements)

References 478 publications

Supporting

Mentioning

109

Contrasting

Unclassified

Order By: Relevance

“…[18][19][20]44,45 Protocadherins and other cadherins have also been studied as candidate risk genes, but generally in small samples (o100 patients) of schizophrenia, bipolar disorder and OCD patients. [46][47][48][49][50][51][52][53][54][55] In addition, some cadherins have been specifically identified in genome-wide association scans of ADHD, addiction and neuroticism personality features. [56][57][58] Of related interest, variants in CDH2 and other cadherins have been widely found to CDH2 variants in OCD and TD PR Moya et al be associated with various cancers 16,59,60 and, specifically, upregulated CDH2 has been associated with transepithelial spreading of melanoma and pancreatic cancer together with rapid recurrence of cancer.…”

Section: Resultsmentioning

confidence: 99%

Rare missense neuronal cadherin gene (CDH2) variants in specific obsessive-compulsive disorder and Tourette disorder phenotypes

et al. 2013

View full text Add to dashboard Cite

The recent finding that the neuronal cadherin gene CDH2 confers a highly significant risk for canine compulsive disorder led us to investigate whether missense variants within the human ortholog CDH2 are associated with altered susceptibility to obsessive-compulsive disorder (OCD), Tourette disorder (TD) and related disorders. Exon resequencing of CDH2 in 320 individuals identified four non-synonymous single-nucleotide variants, which were subsequently genotyped in OCD probands, Tourette disorder probands and relatives, and healthy controls (total N ¼ 1161). None of the four variants was significantly associated with either OCD or TD. One variant, N706S, was found only in the OCD/TD groups, but not in controls. By examining clinical data, we found there were significant TD-related phenotype differences between those OCD probands with and without the N845S variant with regard to the co-occurrence of TD (Fisher's exact test P ¼ 0.014, OR ¼ 6.03). Both N706S and N845S variants conferred reduced CDH2 protein expression in transfected cells. Although our data provide no overall support for association of CDH2 rare variants in these disorders considered as single entities, the clinical features and severity of probands carrying the uncommon non-synonymous variants suggest that CDH2, along with other cadherin and cell adhesion genes, is an interesting gene to pursue as a plausible contributor to OCD, TD and related disorders with repetitive behaviors, including autism spectrum disorders.

show abstract

Section: Resultsmentioning

confidence: 99%

Rare missense neuronal cadherin gene (CDH2) variants in specific obsessive-compulsive disorder and Tourette disorder phenotypes

et al. 2013

View full text Add to dashboard Cite

show abstract

“…1 This is opposed to the traditional view of the 2 most prominent psychotic disorders, schizophrenia and bipolar disorder, being categorical entities. 2 Optimal methods for categorizing psychotic illnesses remain uncertain given the lack of biology-based diagnostic criteria.…”

Section: Introductionmentioning

confidence: 94%

Smooth Pursuit Eye Movement, Prepulse Inhibition, and Auditory Paired Stimuli Processing Endophenotypes Across the Schizophrenia-Bipolar Disorder Psychosis Dimension

Ivleva

Moates

Hamm

et al. 2013

Schizophrenia Bulletin

Self Cite

View full text Add to dashboard Cite

Background: This study examined smooth pursuit eye movement (SPEM), prepulse inhibition (PPI), and auditory event-related potentials (ERP) to paired stimuli as putative endophenotypes of psychosis across the schizophrenia-bipolar disorder dimension. Methods: Sixty-four schizophrenia probands (SZP), 40 psychotic bipolar I disorder probands (BDP), 31 relatives of SZP (SZR), 26 relatives of BDP (BDR), and 53 healthy controls (HC) were tested. Standard clinical characterization, SPEM, PPI, and ERP measures were administered. Results: There were no differences between either SZP and BDP or SZR and BDR on any of the SPEM, PPI, or ERP measure. Compared with HC, SZP and BDP had lower SPEM maintenance and predictive pursuit gain and ERP theta/ alpha and beta magnitudes to the initial stimulus. PPI did not differ between the psychosis probands and HC. Compared with HC, SZR and BDR had lower predictive pursuit gain and ERP theta/alpha and beta magnitudes to the first stimulus with differences ranging from a significant to a trend level. Neither active symptoms severity nor concomitant medications were associated with neurophysiological outcomes. SPEM, PPI, and ERP scores had low intercorrelations. Conclusion: These findings support SPEM predictive pursuit and lower frequency auditory ERP activity in a paired stimuli paradigm as putative endophenotypes of psychosis common to SZ and BD probands and relatives. PPI did not differ between the psychosis probands and HC. Future studies in larger scale psychosis family samples targeting putative psychosis endophenotypes and underlying molecular and genetic mediators may aid in the development of biology-based diagnostic definitions.

show abstract

“…For example, in a recent large-scale genomewide association study, Purcell and colleagues of the International Schizophrenia Consortium (2009) reported that at least one-third of the variance in schizophrenia liability could be explained by a polygenic model involving thousands of commonly occurring alleles. Polygenic models suggest that the genetic liability may manifest as individual differences in specific neural circuits, producing observable neurocognitive intermediate phenotypes (Gottesman & Gould, 2003 ;Meyer-Lindenberg & Weinberger, 2006 ;Braff et al 2007 ;Ivleva et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Face emotion recognition is related to individual differences in psychosis-proneness

Germine

Hooker

2010

Psychol. Med.

View full text Add to dashboard Cite

Background. Deficits in face emotion recognition (FER) in schizophrenia are well documented, and have been proposed as a potential intermediate phenotype for schizophrenia liability. However, research on the relationship between psychosis vulnerability and FER has mixed findings and methodological limitations. Moreover, no study has yet characterized the relationship between FER ability and level of psychosis-proneness. If FER ability varies continuously with psychosis-proneness, this suggests a relationship between FER and polygenic risk factors.Method. We tested two large internet samples to see whether psychometric psychosis-proneness, as measured by the Schizotypal Personality Questionnaire-Brief (SPQ-B), is related to differences in face emotion identification and discrimination or other face processing abilities.Results. Experiment 1 (n=2332) showed that psychosis-proneness predicts face emotion identification ability but not face gender identification ability. Experiment 2 (n=1514) demonstrated that psychosis-proneness also predicts performance on face emotion but not face identity discrimination. The tasks in Experiment 2 used identical stimuli and task parameters, differing only in emotion/identity judgment. Notably, the relationships demonstrated in Experiments 1 and 2 persisted even when individuals with the highest psychosis-proneness levels (the putative highrisk group) were excluded from analysis.Conclusions. Our data suggest that FER ability is related to individual differences in psychosis-like characteristics in the normal population, and that these differences cannot be accounted for by differences in face processing and/or visual perception. Our results suggest that FER may provide a useful candidate intermediate phenotype.

show abstract

Genetics and intermediate phenotypes of the schizophrenia—bipolar disorder boundary

Cited by 137 publications

References 478 publications

Rare missense neuronal cadherin gene (CDH2) variants in specific obsessive-compulsive disorder and Tourette disorder phenotypes

Rare missense neuronal cadherin gene (CDH2) variants in specific obsessive-compulsive disorder and Tourette disorder phenotypes

Smooth Pursuit Eye Movement, Prepulse Inhibition, and Auditory Paired Stimuli Processing Endophenotypes Across the Schizophrenia-Bipolar Disorder Psychosis Dimension

Face emotion recognition is related to individual differences in psychosis-proneness

Contact Info

Product

Resources

About