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Comprehensive gene-based association study of a chromosome 20 linked region implicates novel risk loci for depressive symptoms in psychotic illness.

ABSTRACT: Prior genomewide scans of schizophrenia support evidence of linkage to regions of chromosome 20. However, association analyses have yet to provide support for any etiologically relevant variants.We analyzed 2988 LD-tagging single nucleotide polymorphisms (SNPs) in 327 genes on chromosome 20, to test for association with schizophrenia in 270 Irish high-density families (ISHDSF, N?=?270 families, 1408 subjects). These SNPs were genotyped using an Illumina iSelect genotyping array which employs the Infinium assay. Given a previous report of novel linkage with chromosome 20p using latent classes of psychotic illness in this sample, association analysis was also conducted for each of five factor-derived scores based on the Operational Criteria Checklist for Psychotic Illness (delusions, hallucinations, mania, depression, and negative symptoms). Tests of association were conducted using the PDTPHASE and QPDTPHASE packages of UNPHASED. Empirical estimates of gene-wise significance were obtained by adaptive permutation of a) the smallest observed P-value and b) the threshold-truncated product of P-values for each locus.While no single variant was significant after LD-corrected Bonferroni-correction, our gene-dropping analyses identified loci which exceeded empirical significance criteria for both gene-based tests. Namely, R3HDML and C20orf39 are significantly associated with depressive symptoms of schizophrenia (P(emp)<2×10??) based on the minimum P-value and truncated-product methods, respectively.Using a gene-based approach to family-based association, R3HDML and C20orf39 were found to be significantly associated with clinical dimensions of schizophrenia. These findings demonstrate the efficacy of gene-based analysis and support previous evidence that chromosome 20 may harbor schizophrenia susceptibility or modifier loci.

SUBMITTER: Bigdeli TB

PROVIDER: S-EPMC3248394 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Comprehensive gene-based association study of a chromosome 20 linked region implicates novel risk loci for depressive symptoms in psychotic illness.

Bigdeli T Bernard TB Maher Brion S BS Zhao Zhongming Z Oord Edwin J C G van den EJ Thiselton Dawn L DL Sun Jingchun J Webb Bradley T BT Amdur Richard L RL Wormley Brandon B O'Neill Francis A FA Walsh Dermot D Riley Brien P BP Kendler Kenneth S KS Fanous Ayman H AH

PloS one 20111229 12

<h4>Background</h4>Prior genomewide scans of schizophrenia support evidence of linkage to regions of chromosome 20. However, association analyses have yet to provide support for any etiologically relevant variants.<h4>Methods</h4>We analyzed 2988 LD-tagging single nucleotide polymorphisms (SNPs) in 327 genes on chromosome 20, to test for association with schizophrenia in 270 Irish high-density families (ISHDSF, N = 270 families, 1408 subjects). These SNPs were genotyped using an Illumina iSelect ...[more]

PMID: 22220189

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Project description:BackgroundDepression is the most prevalent mental health problem. The need for effective treatments for depression far outstrips the availability of trained mental health professionals. Smartphones and other widely available technologies are increasingly being leveraged to deliver treatments for depression. Whether there are patient characteristics that affect the potency of smartphone interventions for depression is not well understood.ObjectiveThis study aimed to evaluate whether patient characteristics including clinical diagnosis, depression severity, psychosis status, and current use of antidepressant medications impact the effects of an evidence-based smartphone intervention on depressive symptoms.MethodsData were collected as part of a 2-arm randomized controlled trial comparing a multimodal smartphone intervention called FOCUS with a clinic-based intervention. Here, we report on 82 participants assigned to 12 weeks of FOCUS treatment. We conducted assessments of depressive symptoms using the Beck Depression Inventory-second edition (BDI-II) at baseline, postintervention (3 months), and follow-up (6 months). We tested for differences in the amount of improvement in BDI-II scores from baseline to posttreatment and 6-month follow-up between each of the following patient subgroups using 2 (group) × 2 (time) mixed effects models: diagnosis (ie, schizophrenia spectrum disorder vs bipolar disorder vs major depressive disorder), depression severity (ie, minimal-mild vs moderate-severe depression), psychosis status (ie, presence vs absence of psychotic symptoms), and antidepressant use (ie, taking antidepressants vs not taking antidepressants).ResultsThe majority of participants were male (60%, 49/82), African American (65%, 53/82), and middle-aged (mean age 49 years), with a high school education or lower (62%, 51/82). There were no differences in patient demographics across the variables that were used to stratify the analyses. There was a significant group × time interaction for baseline depression severity (F1,76.8=5.26, P=.02 [posttreatment] and F1,77.4=6.56, P=.01 [6-month follow-up]). Participants with moderate or severe depression had significant improvements (t42=3.20, P=.003 [posttreatment] and t42=4.20, P<.001 [6-month follow-up]), but participants with minimal or mild depression did not (t31=0.20, P=.84 [posttreatment] and t30=0.43, P=.67 [6-month follow-up]). There were no significant group × time interactions for diagnosis, psychosis status, or antidepressant medication use. Participants with minimal or mild depression had negligible nonsignificant improvements (<1 point on the BDI-II). Reduction in depression in all other groups was larger (range 1.7-6.5 points on the BDI-II).ConclusionsOur results suggest that FOCUS can be deployed to treat moderate to severe depressive symptoms among people with schizophrenia spectrum disorders, bipolar disorder, and major depressive disorder, in concert with antidepressant medications or without them, in both people with and without active psychotic symptoms. The study results are consistent with research on transdiagnostic models in psychotherapy and extend our knowledge about the potential of transdiagnostic mobile health.Trial registrationClinicalTrials.gov NCT02421965; http://clinicaltrials.gov/ct2/show/NCT02421965 (Archived by WebCite at http://www.webcitation.org/76pyDlvAS).

Project description:BackgroundEvidence exists that maternal depression in the perinatal period has an adverse effect on a range of early childhood outcomes and increases the risk of offspring depression during adolescence. However, the association between maternal depression during the perinatal period and offspring psychotic experiences has not been investigated. We aimed to investigate whether there is an association between maternal antenatal or postnatal depression and offspring psychotic experiences at 18 years of age.MethodsThis longitudinal study used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective birth cohort, which recruited 14 541 pregnant women with an estimated delivery date between April 1, 1991, and Dec 31, 1992. Perinatal depression was measured using the Edinburgh Postnatal Depression Scale (EPDS); offspring psychotic experiences at 18 years of age were measured using the Psychosis-Like Symptom Interview. Offspring of mothers with complete data on maternal perinatal depression measures, and complete data on outcome (psychotic experiences) and confounding variables were included in the main analysis. For the main analysis, we used logistic regression to examine the associations between maternal depression (antenatal and postnatal) and offspring psychotic experiences at the age of 18 years. We used biprobit regression to model the association between maternal antenatal depression and the two offspring outcomes (psychotic experiences and depression) at 18 years of age jointly.Findings3067 offspring for whom data were available on maternal perinatal depression and offspring psychotic experiences aged 18 years were included in analyses. Maternal antenatal depressive symptoms were associated with offspring psychotic experiences at 18 years of age, with an unadjusted odds ratio (OR) of 1·38 (95% CI 1·18-1·61, p=0·0001) and after adjustment for confounders, an OR of 1·26 (1·06-1·49, p=0·0074). Maternal antenatal depressive symptoms were associated with both offspring psychotic experiences at the age of 18 years (n=2830, OR for a 5-point increase in EPDS score: 1·32 [95% CI 1·16-1·51], p<0·0001) and offspring depression at 18 years (OR for a 5-point increase in EPDS score: 1·18 [1·03-1·34], p=0·016). From joint modelling, there was no evidence that the association between maternal antenatal depression and offspring psychotic experiences differed in strength compared with offspring depression (p=0·19).InterpretationThe offspring of mothers who experience depression in the perinatal period are more likely to report psychotic experiences at 18 years of age. If the association is found to be causal, it would strengthen the case for identifying and treating maternal depression during and after pregnancy.FundingUK Medical Research Council and the Wellcome Trust.

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Comprehensive gene-based association study of a chromosome 20 linked region implicates novel risk loci for depressive symptoms in psychotic illness.

Publications

Comprehensive gene-based association study of a chromosome 20 linked region implicates novel risk loci for depressive symptoms in psychotic illness.

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