Family history of depression is associated with younger age of onset in patients with recurrent depression

Tozzi, Federica; Prokopenko, Inga; Perry, Julia; Kennedy, James L.; McCarthy, Alun D.; Holsboer, Florian; Berrettini, Wade H.; Middleton, Lefkos; Chilcoat, Howard D.; Muglia, Pierandrea

doi:10.1017/s0033291707002681

Cited by 59 publications

(50 citation statements)

References 44 publications

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“…While some negative findings have been reported [reviewed in Sullivan et al, 2000], most studies suggest an inverse relationship between AAO and familial risk, with the greatest risk observed in those under 30 years old. Two large clinical studies suggest that a family history of MDD is associated with an AAO of between 20 and 25 [Nierenberg et al, 2007;Tozzi et al, 2008]. In line with this, Lyons et al [1998] reported that while the heritability of early onset (<30) MDD was substantial (h 2 ¼ 0.70), estimates for later onset MDD (>30) were considerably lower (h 2 ¼ 0.10).…”

Section: Introductionmentioning

confidence: 83%

“…The replication cohort consisted of two studies based in Munich, Germany: The Munich Antidepressant Response Signature (MARS) study [Ising et al, 2009;Kohli et al, 2011] and a clinical cohort of individuals collected in Munich [Tozzi et al, 2008]. The MARS study included 551 cases and 542 controls, and was designed as a pharmacogenetic study to monitor treatment response.…”

Section: Replicationmentioning

confidence: 99%

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Dissecting the Genetic Heterogeneity of Depression Through Age at Onset

Power

Keers

et al. 2012

American J of Med Genetics Pt B

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Genome-wide studies in major depression have identified few replicated associations, potentially due to heterogeneity within the disorder. Several studies have suggested that age at onset (AAO) can distinguish sub-types of depression with specific heritable components. This paper investigates the role of AAO in the genetic susceptibility for depression using genome-wide association data on 2,746 cases and 1,594 screened controls from the RADIANT studies, with replication performed in 1,471 cases and 1,403 controls from two Munich studies. Three methods were used to analyze AAO: First a time-to-event analysis with controls censored, secondly comparing controls to case-subsets defined using AAO cut-offs, and lastly analyzing AAO as a quantitative trait. In the time-to-event analysis three SNPs reached suggestive significance (P < 5E-06), overlapping with the original case-control analysis of this study. In a case-control analysis using AAO thresholds, SNPs in 10 genomic regions showed suggestive association though again none reached genome-wide significance. Lastly, case-only analysis of AAO as a quantitative trait resulted in 5 SNPs reaching suggestive significance. Sex specific analysis was performed as a secondary analysis, yielding one SNP reaching genome-wide significance in early-onset males. No SNPs achieved significance in the replication study after correction for multiple testing. Analysis of AAO as a quantitative trait did suggest that, across all SNPs, common genetic variants explained a large proportion of the variance (51%, P = 0.04). This study provides the first focussed analysis of the genetic contribution to AAO in depression, and establishes a statistical framework that can be applied to a quantitative trait underlying any disorder.

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Section: Introductionmentioning

confidence: 83%

Section: Replicationmentioning

confidence: 99%

Dissecting the Genetic Heterogeneity of Depression Through Age at Onset

Power

Keers

et al. 2012

American J of Med Genetics Pt B

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“…PGC would allow identifying SNPs of small effect and also testing, with reasonable power, the presence of genetic risk factors that predispose to MDD subtypes and to relevant symptom dimensions. Our study ascertained MDD cases with recurrent episodes reducing to some degree the substantial heterogeneity that exist for MDD; additional evidences however suggest that other clinical variables as severity 12 and age at onset 15,22 that appear to define more heritable phenotypes, should be considered for future analysis.…”

Section: Discussionmentioning

confidence: 99%

“…21 Approximately 26% of cases (n = 262) showed presence of at least one anxiety symptom during their worst episode as assessed by the SCAN interview. The anxiety symptoms considered were the presence of general rating of anxiety, general rating of phobia, free-floating anxiety or anxious foreboding with autonomic symptoms (see Tozzi et al, 2008 for more details on symptom selection). 22 Within patients with these anxiety symptoms 51% had a formal diagnosis of anxiety disorders (including generalized anxiety disorder, panic disorder with or without agoraphobia, social and specific phobia) according to DSM-IV.…”

Section: Subjectsmentioning

confidence: 99%

“…The anxiety symptoms considered were the presence of general rating of anxiety, general rating of phobia, free-floating anxiety or anxious foreboding with autonomic symptoms (see Tozzi et al, 2008 for more details on symptom selection). 22 Within patients with these anxiety symptoms 51% had a formal diagnosis of anxiety disorders (including generalized anxiety disorder, panic disorder with or without agoraphobia, social and specific phobia) according to DSM-IV. The SCAN interview did not assess axis II disorders so we cannot exclude the presence of personality disorders among our cases.…”

Section: Subjectsmentioning

confidence: 99%

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Genome-wide association study of recurrent major depressive disorder in two European case–control cohorts

et al. 2008

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Major depressive disorder (MDD) is a highly prevalent disorder with substantial heritability. Heritability has been shown to be substantial and higher in the variant of MDD characterized by recurrent episodes of depression. Genetic studies have thus far failed to identify clear and consistent evidence of genetic risk factors for MDD. We conducted a genome-wide association study (GWAS) in two independent datasets. The first GWAS was performed on 1022 recurrent MDD patients and 1000 controls genotyped on the Illumina 550 platform. The second was conducted on 492 recurrent MDD patients and 1052 controls selected from a population-based collection, genotyped on the Affymetrix 5.0 platform. Neither GWAS identified any SNP that achieved GWAS significance. We obtained imputed genotypes at the Illumina loci for the individuals genotyped on the Affymetrix platform, and performed a meta-analysis of the two GWASs for this common set of approximately half a million SNPs. The meta-analysis did not yield genome-wide significant results either. The results from our study suggest that SNPs with substantial odds ratio are unlikely to exist for MDD, at least in our datasets and among the relatively common SNPs genotyped or tagged by the half-million-loci arrays. Meta-analysis of larger datasets is warranted to identify SNPs with smaller effects or with rarer allele frequencies that contribute to the risk of MDD.

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Predictive Value of Family History on Severity of Illness

Milne¹,

Caspi²,

Harrington³

et al. 2009

Arch Gen Psychiatry

139

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Context If family history is associated with clinical features that are thought to index seriousness of disorder, this could inform clinicians predicting patients’ prognosis and researchers selecting cases for genetic studies. Although tests of associations between family history and clinical features are numerous for depression, such tests are relatively lacking for other disorders. Objective To test the hypothesis that family history is associated with 4 clinical indexes of disorder (recurrence, impairment, service use, and age at onset) in relation to 4 psychiatric disorders (major depressive episode, anxiety disorder, alcohol dependence, and drug dependence). Design Prospective longitudinal cohort study. Setting New Zealand. Participants A total of 981 members of the 1972 to 1973 Dunedin Study birth cohort (96% retention). Main Outcome Measures For each disorder, family history scores were calculated as the proportion of affected family members from data on 3 generations of the participants’ families. Data collected prospectively at the study’s repeated assessments (ages 11–32 years) were used to assess recurrence, impairment, and age at onset; data collected by means of a life history calendar at age 32 years were used to assess service use. Results Family history was associated with the presence of all 4 disorder types. In addition, family history was associated with a more recurrent course for all 4 disorders (but not significantly for women with depression), worse impairment, and greater service use. Family history was not associated with younger age at onset for any disorder. Conclusions Associations between family history of a disorder and clinical features of that disorder in probands showed consistent direction of effects across depression, anxiety disorder, alcohol dependence, and drug dependence. For these disorder types, family history is useful for determining patients’ clinical prognosis and for selecting cases for genetic studies.

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Family history of depression is associated with younger age of onset in patients with recurrent depression

Abstract: FH of depression contributes to the onset of depression at a younger age and may affect the clinical features of the illness.

Cited by 59 publications

References 44 publications

Dissecting the Genetic Heterogeneity of Depression Through Age at Onset

Dissecting the Genetic Heterogeneity of Depression Through Age at Onset

Genome-wide association study of recurrent major depressive disorder in two European case–control cohorts

Predictive Value of Family History on Severity of Illness

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