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The Lausanne–Geneva cohort study of offspring of parents with mood disorders: methodology, findings, current sample characteristics, and perspectives

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Abstract

Purpose

Studies focusing on the offspring of affected parents utilize the well-established familial aggregation of mood disorders as a powerful tool for the identification of risk factors, early clinical manifestations, and prodromes of mood disorders in these offspring. The major goals of the Lausanne–Geneva mood cohort study are to: (1) assess the familial aggregation of bipolar and unipolar mood disorders; (2) prospectively identify risk factors for mood disorders as well as their early signs and prodromes; (3) identify their endophenotypes including cognitive features, alterations in brain structure, HPA-axis dysregulation, and abnormalities of the circadian rhythm of activity.

Methods

Probands with bipolar disorders, major depressive disorder, and controls with at least one child aged from 4 to 17.9 years at study intake, their offspring, as well as their spouses are invited to take part in follow-up assessments at predetermined ages of the offspring. Direct semi-structured diagnostic interviews have been used for all participants. Probands, spouses, and adult offspring also undergo neurocognitive testing, anthropomorphic measures and biochemical exams, structural Magnetic Resonance Imaging, as well as objective assessments of physical activity using accelerometers in combination with ecological momentary assessments.

Results

Currently, our study has up to seven follow-up assessments extending over a period of 20 years. There are 214 probands and 389 offspring with one direct interview before age 18 as well as a second assessment over follow-up. Data on 236 co-parents are also available from whom 55% have been directly interviewed. First publications support the specificity of the familial aggregation of BPD and the strong influence of an early onset of the parental BPD, which amplifies the risk of developing this disorder in offspring.

Conclusions

Information from clinical, biological, cognitive, and behavioral measures, based on contemporary knowledge, should further enhance our understanding of mood disorder psychopathology, its consequences, and underlying mechanisms.

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Acknowledgements

The authors would like to express their gratitude to the participants and to the collaborators who contributed to the coordination of the study and the collection of data. Special thanks to Prof. Pierre-François Leyvraz, Dr. Nicolas Favarger, and Prof. Daniel Egloff from the Orthopedic Department in Lausanne, as well as to Prof. Pierre Hoffmeyer from the Orthopedic Department in Geneva for their help with the recruitment of the comparison participants of this study.

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Authors and Affiliations

  1. Department of Psychiatry, University Hospital of Lausanne, Site de Cery, Prilly, 1008, Lausanne, Switzerland

    Caroline L. Vandeleur, Marie-Pierre F. Strippoli, Enrique Castelao, Mehdi Gholam-Rezaee, Pierre Marquet & Martin Preisig

  2. Department of Mental Health and Psychiatry, University Hospital of Geneva, Geneva, Switzerland

    François Ferrero & Jean-Michel Aubry

Authors
  1. Caroline L. Vandeleur
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  2. Marie-Pierre F. Strippoli
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  3. Enrique Castelao
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  4. Mehdi Gholam-Rezaee
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  5. François Ferrero
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  6. Pierre Marquet
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  7. Jean-Michel Aubry
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  8. Martin Preisig
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Corresponding author

Correspondence to Caroline L. Vandeleur.

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Role of funding sources

This research was and is supported by five grants from the Swiss National Foundation (SNF: #3200-040677, #32003B-105969, and #32003B-118326 to F. Ferrero; #3200-049746 and #3200-061974 to M. Preisig), two grants for a national research project “The Synaptic Bases of Mental Diseases” (#125759 and #158776 to P. Magistretti) financed by the Swiss National Foundation, and a Grant from GlaxoSmithKline Clinical Genetics. The funders had no involvement in any aspect of this study.

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

The study protocols at the baseline and follow-up assessments were approved by the review board of the University Hospital of Lausanne and have, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

All participants gave written informed consent for their participation prior to the assessments and parents provided informed consent for the participation of their children younger than 18 years.

Appendix: List of peer-reviewed publications from the Lausanne–Geneva family study and high-risk cohort to date

Appendix: List of peer-reviewed publications from the Lausanne–Geneva family study and high-risk cohort to date

Papers from the family study (1–34)

Dafflon M, Decosterd LA, Biollaz J, Preisig M, Dufour H, Buclin T (1999) Trace lithium in mood disorders. J Affect Disord 541(2):199–203.

Preisig M, Bellivier F, Fenton BT, Baud P, Berney A, Courtet P et al (2000) Association between bipolar disorder and monoamine oxidase A gene polymorphisms: results of a multicenter study. Am J Psychiatry 1576:948–955.

Bellivier F, Golmard JL, Rietschel M, Schulze TG, Malafosse A, Preisig M et al (2003) Age at onset in bipolar-I affective disorder: further evidence for three subgroups. Am J Psychiatry 1605:999–1001.

Etain B, Rousseva A, Roy I, Henry C, Malafosse A, Buresi C et al (2004) Lack of association between 5HT2A receptor gene haplotype, bipolar disorder and its clinical subtypes in a West European sample. Am J Med Genet B Neuropsychiatr Genet 129B1:29–33. doi:10.1002/ajmg.b.30055.

Farmer A, Breen G, Brewster S, Craddock N, Gill M, Korszun A et al (2004) The Depression Network (DeNT) Study: methodology and sociodemographic characteristics of the first 470 affected sibling pairs from a large multi-site linkage genetic study. BMC Psychiatry 4:42. doi:10.1186/1471-244X-4-42.

Korszun A, Moskvina V, Brewster S, Craddock N, Ferrero F, Gill M et al (2004) Familiality of symptom dimensions in depression. Arch Gen Psychiatry 615:468–474. doi:10.1001/archpsyc.61.5.468.

McGuffin P, Knight J, Breen G, Brewster S, Boyd PR, Craddock N et al (2005) Whole genome linkage scan of recurrent depressive disorder from the depression network study. Hum Mol Genet 1422:3337–3345. doi:10.1093/hmg/ddi363.

Etain B, Mathieu F, Rietschel M, Maier W, Albus M, McKeon P et al (2006) Genome-wide scan for genes involved in bipolar affective disorder in 70 European families ascertained through a bipolar type I early-onset proband: supportive evidence for linkage at 3p14. Mol Psychiatry 117:685–694. doi:10.1038/sj.mp.4001815.

Tosic M, Ott J, Barral S, Bovet P, Deppen P, Gheorghita F et al (2006) Schizophrenia and oxidative stress: glutamate cysteine ligase modifier as a susceptibility gene. Am J Hum Genet 793:586–592. doi:10.1086/507566.

Gysin R, Kraftsik R, Sandell J, Bovet P, Chappuis C, Conus P et al (2007) Impaired glutathione synthesis in schizophrenia: convergent genetic and functional evidence. Proc Natl Acad Sci USA 10,442:16,621–16,626. doi:10.1073/pnas.0706778104.

Perroud N, Baud P, Preisig M, Etain B, Bellivier F, Favre S et al (2007) Social phobia is associated with suicide attempt history in bipolar inpatients. Bipolar Disord 97:713–721. doi:10.1111/j.1399-5618.2007.00471.x.

Crettol S, Besson J, Croquette-Krokar M, Hammig R, Gothuey I, Monnat M et al (2008) Association of dopamine and opioid receptor genetic polymorphisms with response to methadone maintenance treatment. Prog Neuropsychopharmacol Biol Psychiatry 327:1722–1727. doi:10.1016/j.pnpbp.2008.07.009.

Moskvina V, Farmer A, Jones IR, Brewster S, Ferrero F, Gill M et al (2008) Sex differences in symptom patterns of recurrent major depression in siblings. Depress Anxiety 256:527–534. doi:10.1002/da.20372.

Rougemont-Buecking A, Rothen S, Jeanpretre N, Lustenberger Y, Vandeleur CL, Ferrero F et al (2008) Inter-informant agreement on diagnoses and prevalence estimates of anxiety disorders: direct interview versus family history method. Psychiatry Res 1571-3:211–223. doi:10.1016/j.psychres.2006.04.022.

Vandeleur CL, Rothen S, Jeanpretre N, Lustenberger Y, Gamma F, Ayer E et al (2008) Inter-informant agreement and prevalence estimates for substance use disorders: direct interview versus family history method. Drug Alcohol Depend 921(3):9–19. doi:10.1016/j.drugalcdep.2007.05.023.

Vincze I, Perroud N, Buresi C, Baud P, Bellivier F, Etain B et al (2008) Association between brain-derived neurotrophic factor gene and a severe form of bipolar disorder, but no interaction with the serotonin transporter gene. Bipolar Disord 105:580–587. doi:10.1111/j.1399-5618.2008.00603.x.

Ball HA, Samaan Z, Brewster S, Craddock N, Gill M, Korszun A et al (2009) Depression, migraine with aura and migraine without aura: their familiality and interrelatedness. Cephalalgia 298:848–854. doi:10.1111/j.1468-2982.2008.01808.x.

Butler AW, Breen G, Tozzi F, Craddock N, Gill M, Korszun A et al (2010) A genomewide linkage study on suicidality in major depressive disorder confirms evidence for linkage to 2p12. Am J Med Genet B Neuropsychiatr Genet 153B8:1465–1473. doi:10.1002/ajmg.b.31127.

Mathieu F, Dizier MH, Etain B, Jamain S, Rietschel M, Maier W et al (2010) European collaborative study of early-onset bipolar disorder: Evidence for genetic heterogeneity on 2q14 according to age at onset. Am J Med Genet B Neuropsychiatr Genet 153B8:1425–1433. doi:10.1002/ajmg.b.31121.

Breen G, Webb BT, Butler AW, van den Oord EJ, Tozzi F, Craddock N et al (2011) A genome-wide significant linkage for severe depression on chromosome 3: the depression network study. Am J Psychiatry 1688:840–847. doi:10.1176/appi.ajp.2011.10091342.

Gysin R, Kraftsik R, Boulat O, Bovet P, Conus P, Comte-Krieger E et al (2011) Genetic dysregulation of glutathione synthesis predicts alteration of plasma thiol redox status in schizophrenia. Antioxid Redox Signal 157:2003–2010. doi:10.1089/ars.2010.3463.

Oneda B, Crettol S, Bochud M, Besson J, Croquette-Krokar M, Hammig R et al (2011) beta-Arrestin2 influences the response to methadone in opioid-dependent patients. Pharmacogenomics J 114:258–266. doi:10.1038/tpj.2010.37.

Schosser A, Butler AW, Ising M, Perroud N, Uher R, Ng MY et al (2011) Genomewide association scan of suicidal thoughts and behavior in major depression. PLoS One 67:e20690. doi:10.1371/journal.pone.0020690.

Power RA, Keers R, Ng MY, Butler AW, Uher R, Cohen-Woods S et al (2012) Dissecting the genetic heterogeneity of depression through age at onset. Am J Med Genet B Neuropsychiatr Genet 159B7:859–868. doi:10.1002/ajmg.b.32093.

Rucker JJ, Breen G, Pinto D, Pedroso I, Lewis CM, Cohen-Woods S et al (2013) Genome-wide association analysis of copy number variation in recurrent depressive disorder. Mol Psychiatry 182:183–189. doi:10.1038/mp.2011.144.

Schosser A, Butler AW, Uher R, Ng MY, Cohen-Woods S, Craddock N et al (2013) Genome-wide association study of co-occurring anxiety in major depression. World J Biol Psychiatry 148:611–621. doi:10.3109/15622975.2013.782107.

Ferentinos P, Rivera M, Ising M, Spain SL, Cohen-Woods S, Butler AW et al (2014) Investigating the genetic variation underlying episodicity in major depressive disorder: suggestive evidence for a bipolar contribution. J Affect Disord 155:81–89. doi:10.1016/j.jad.2013.10.027.

Hung CF, Rivera M, Craddock N, Owen MJ, Gill M, Korszun A et al (2014) Relationship between obesity and the risk of clinically significant depression: Mendelian randomisation study. Br J Psychiatry 2051:24–28. doi:10.1192/bjp.bp.113.130419.

Mullins N, Perroud N, Uher R, Butler AW, Cohen-Woods S, Rivera M et al (2014) Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: a genome-wide association and polygenic scoring study. Am J Med Genet B Neuropsychiatr Genet 165B5:428–437. doi:10.1002/ajmg.b.32247.

Vandeleur CL, Merikangas KR, Strippoli MP, Castelao E, Preisig M (2014) Specificity of psychosis, mania and major depression in a contemporary family study. Mol Psychiatry 192:209–213. doi:10.1038/mp.2013.132.

Ferentinos P, Koukounari A, Power R, Rivera M, Uher R, Craddock N et al (2015) Familiality and SNP heritability of age at onset and episodicity in major depressive disorder. Psychol Med 4510:2215–2225. doi:10.1017/S0033291715000215.

Vandeleur CL, Rothen S, Lustenberger Y, Glaus J, Castelao E, Preisig M (2015) Inter-informant agreement and prevalence estimates for mood syndromes: Direct interview versus family history method. J Affect Disord 171C:120–127. doi:10.1016/j.jad.2014.08.048.

Golmard JL, Scott J, Etain B, Preisig M, Aubry JM, Henry C et al (2016) Using admixture analysis to examine birth-cohort effects on age at onset of bipolar disorder. Acta Psychiatr Scand 1333:205–213. doi:10.1111/acps.12478.

Rucker JJ, Tansey KE, Rivera M, Pinto D, Cohen-Woods S, Uher R et al (2016) Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder. Biol Psychiatry 794:329–336. doi:10.1016/j.biopsych.2015.02.025.

Papers from the high-risk cohort (35–39)

Rothen S, Vandeleur CL, Lustenberger Y, Jeanpretre N, Ayer E, Fornerod D et al (2009) Personality traits in children of parents with unipolar and bipolar mood disorders. J Affect Disord 1131(2):133–141. doi:10.1016/j.jad.2008.05.013.

Rothen S, Vandeleur CL, Lustenberger Y, Jeanpretre N, Ayer E, Gamma F et al (2009) Parent–child agreement and prevalence estimates of diagnoses in childhood: direct interview versus family history method. Int J Methods Psychiatr Res 182:96–109. doi:10.1002/mpr.281.

Vandeleur C, Rothen S, Gholam-Rezaee M, Castelao E, Vidal S, Favre S et al (2012) Mental disorders in offspring of parents with bipolar and major depressive disorders. Bipolar Disord 146:641–653. doi:10.1111/j.1399-5618.2012.01048.x.

Vidal SI, Vandeleur C, Rothen S, Gholam-Rezaee M, Castelao E, Halfon O et al (2012) Risk of mental disorders in children of parents with alcohol or heroin dependence: a controlled high-risk study. Eur Addict Res 185:253–264. doi:10.1159/000337328.

Preisig M, Strippoli MP, Castelao E, Merikangas KR, Gholam-Rezaee M, Marquet P et al (2016) The specificity of the familial aggregation of early-onset bipolar disorder: A controlled 10-year follow-up study of offspring of parents with mood disorders. J Affect Disord 190:26–33. doi:10.1016/j.jad.2015.10.005.

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Vandeleur, C.L., Strippoli, MP.F., Castelao, E. et al. The Lausanne–Geneva cohort study of offspring of parents with mood disorders: methodology, findings, current sample characteristics, and perspectives. Soc Psychiatry Psychiatr Epidemiol 52, 1041–1058 (2017). https://doi.org/10.1007/s00127-017-1382-0

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