Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-23T00:09:08.038Z Has data issue: false hasContentIssue false

The impact of schizophrenia and mood disorder risk alleles on emotional problems: investigating change from childhood to middle age

Published online by Cambridge University Press:  14 December 2017

Lucy Riglin*
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
Stephan Collishaw
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
Alexander Richards
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
Ajay K. Thapar
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
Frances Rice
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
Barbara Maughan
Affiliation:
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK
Michael C. O'Donovan
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
Anita Thapar*
Affiliation:
Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK
*
Author for correspondence: Lucy Riglin and Anita Thapar, E-mail: [email protected]; [email protected]
Author for correspondence: Lucy Riglin and Anita Thapar, E-mail: [email protected]; [email protected]

Abstract

Background

Previous studies find that both schizophrenia and mood disorder risk alleles contribute to adult depression and anxiety. Emotional problems (depression or anxiety) begin in childhood and show strong continuities into adult life; this suggests that symptoms are the manifestation of the same underlying liability across different ages. However, other findings suggest that there are developmental differences in the etiology of emotional problems at different ages. To our knowledge, no study has prospectively examined the impact of psychiatric risk alleles on emotional problems at different ages in the same individuals.

Methods

Data were analyzed using regression-based analyses in a prospective, population-based UK cohort (the National Child Development Study). Schizophrenia and major depressive disorder (MDD) polygenic risk scores (PRS) were derived from published Psychiatric Genomics Consortium genome-wide association studies. Emotional problems were assessed prospectively at six time points from age 7 to 42 years.

Results

Schizophrenia PRS were associated with emotional problems from childhood [age 7, OR 1.09 (1.03–1.15), p = 0.003] to mid-life [age 42, OR 1.10 (1.05–1.17), p < 0.001], while MDD PRS were associated with emotional problems only in adulthood [age 42, OR 1.06 (1.00–1.11), p = 0.034; age 7, OR 1.03 (0.98–1.09), p = 0.228].

Conclusions

Our prospective investigation suggests that early (childhood) emotional problems in the general population share genetic risk with schizophrenia, while later (adult) emotional problems also share genetic risk with MDD. The results suggest that the genetic architecture of depression/anxiety is not static across development.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alexopoulos, GS (2005) Depression in the elderly. The Lancet 365, 19611970.Google Scholar
Atherton, K, Fuller, E, Shepherd, P, Strachan, D and Power, C (2008) Loss and representativeness in a biomedical survey at age 45 years: 1958 British birth cohort. Journal of Epidemiology & Community Health 62, 216223.Google Scholar
Beesdo, K, Knappe, S and Pine, DS (2009) Anxiety and anxiety disorders in children and adolescents: developmental issues and implications for DSM-V. The Psychiatric Clinics of North America 32, 483524.Google Scholar
Brent, D and Maalouf, F (2015) Depressive disorders in childhood and adolescence. In Rutter's Child and Adolescent Psychiatry. Oxford, UK: John Wiley & Sons, Ltd., pp. 874892.Google Scholar
Collishaw, S, Goodman, R, Ford, T, Rabe-Hesketh, S and Pickles, A (2009) How far are associations between child, family and community factors and child psychopathology informant-specific and informant-general? Journal of Child Psychology and Psychiatry, and Allied Disciplines 50, 571580.Google Scholar
Cross-Disorder Group of the Psychiatric Genomics Consortium (2013) Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. The Lancet 381, 13711379.Google Scholar
Cuthbert, BN and Insel, TR (2013) Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC Medicine 11, 126.Google Scholar
Docherty, AR, Moscati, A, Dick, D, Savage, JE, Salvatore, JE, Cooke, M et al. (2017) Polygenic prediction of the phenome, across ancestry, in emerging adulthood. Psychological Medicine. https://doi.org/10.1017/S0033291717003312.Google Scholar
Gale, CR, Hagenaars, SP, Davies, G, Hill, WD, Liewald, DC, Cullen, B et al. (2016) Pleiotropy between neuroticism and physical and mental health: findings from 108 038 men and women in UK Biobank. Translational Psychiatry 6, e791.Google Scholar
Goodman, R, Iervolino, AC, Collishaw, S, Pickles, A and Maughan, B (2007) Seemingly minor changes to a questionnaire can make a big difference to mean scores: a cautionary tale. Social Psychiatry and Psychiatric Epidemiology 42, 322327.Google Scholar
Green, H, McGinnity, Á, Meltzer, H, Ford, T and Goodman, R (2005) Mental Health of Children and Young People in Great Britain, 2004. Basingstoke, UK: Palgrave Macmillan Basingstoke.Google Scholar
Hazell, P, O'Connell, D, Heathcote, D, Robertson, J and Henry, D (1995) Efficacy of tricyclic drugs in treating child and adolescent depression: a meta-analysis. BMJ 310, 897901.Google Scholar
Hyde, CL, Nagle, MW, Tian, C, Chen, X, Paciga, SA, Wendland, JR et al. (2016) Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nature Genetics 48, 10311036.Google Scholar
Insel, T, Cuthbert, B, Garvey, M, Heinssen, R and Pine, DS (2010) Research domain criteria (RDoC): toward a New classification framework for Re. The American Journal of Psychiatry 167, 7.Google Scholar
Jones, HJ, Stergiakouli, E, Tansey, KE, Hubbard, L, Heron, J, Cannon, M et al. (2016) Phenotypic manifestation of genetic risk for schizophrenia during adolescence in the general population. JAMA Psychiatry 73, 221228.Google Scholar
Kendler, KS (2016) The schizophrenia polygenic risk score: to what does it predispose in adolescence? JAMA Psychiatry 73, 193194.Google Scholar
Kessler, RC, Avenevoli, S and Merikangas, KR (2001) Mood disorders in children and adolescents: an epidemiologic perspective. Biological Psychiatry 49, 10021014.Google Scholar
Kessler, RC, Berglund, P, Demler, O, Jin, R, Merikangas, KR and Walters, EE (2005) Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national comorbidity survey replication. Archives of General Psychiatry 62, 593602.Google Scholar
Lewinsohn, PM, Gotlib, IH, Lewinsohn, M, Seeley, JR and Allen, NB (1998) Gender differences in anxiety disorders and anxiety symptoms in adolescents. Journal of Abnormal Psychology 107, 109.Google Scholar
Martin, J, Tilling, K, Hubbard, L, Stergiakouli, E, Thapar, A, Smith, GD et al. (2016) Association of genetic risk for schizophrenia with nonparticipation over time in a population-based cohort study. American Journal of Epidemiology 183, 11491158.Google Scholar
Maughan, B and Collishaw, S (2015) Development and psychopathology: a life course perspective. In Thapar, A, Pine, DS, Leckman, JF, Scott, S, Snowling, MJ, Taylor, E (eds). Rutter's Child and Adolescent Psychiatry. Oxford, UK: John Wiley & Sons, Ltd., pp. 116.Google Scholar
McManus, S, Meltzer, H, Brugha, T, Bebbington, P and Jenkins, R (2009) Adult Psychiatric Morbidity in England, 2007: Results of A Household Survey. London, UK: The NHS Information Centre for health and social care.Google Scholar
Murray, CJ and Lopez, AD (1997) Alternative projections of mortality and disability by cause 1990–2020: global burden of disease study. The Lancet 349, 14981504.Google Scholar
Murray, CJL and Lopez, AD (2013) Measuring the global burden of disease. New England Journal of Medicine 369, 448457.Google Scholar
Nivard, MG, Gage, SH, Hottenga, JJ, van Beijsterveldt, CE, Abdellaoui, A, Bartels, M et al. (2017) Genetic overlap between schizophrenia and developmental psychopathology: longitudinal and multivariate polygenic risk prediction of common psychiatric traits during development. Schizophrenia Bulletin 43, 11971207.Google Scholar
Okbay, A, Baselmans, BM, De Neve, JE, Turley, P, Nivard, MG, Fontana, MA et al. (2016) Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nature Genetics 48, 624633.Google Scholar
Power, C and Elliott, J (2006) Cohort profile: 1958 British birth cohort (national child development study). International Journal of Epidemiology 35, 3441.Google Scholar
Power, RA, Tansey, KE, Buttenschøn, HN, Cohen-Woods, S, Bigdeli, T, Hall, LS et al. (2017) Genome-wide association for major depression through age at onset stratification. Biological Psychiatry 81, 325335.Google Scholar
Riglin, L, Collishaw, S, Richards, A, Thapar, A, Maughan, B, O'Donovan, M et al. (2017 a) Schizophrenia risk alleles and neurodevelopmental outcomes in childhood: a population-based cohort study. Lancet Psychiatry 4, 5762.Google Scholar
Riglin, L, Collishaw, S, Thapar, AK, Dalsgaard, S, Langley, K, Smith, GD et al. (2016) Association of genetic risk variants With attention-deficit/hyperactivity disorder trajectories in the general population. JAMA Psychiatry 73, 12851292.Google Scholar
Riglin, L, Eyre, O, Cooper, M, Collishaw, S, Martin, J, Langley, K et al. (2017 b) Investigating the genetic underpinnings of early-life irritability. Translational Psychiatry 7, e1241.Google Scholar
Ripke, S, Wray, NR, Lewis, CM, Hamilton, SP, Weissman, MM, Breen, G et al. (2013) A mega-analysis of genome-wide association studies for major depressive disorder. Molecular Psychiatry 18, 497511.Google Scholar
Rodgers, B, Pickles, A, Power, C, Collishaw, S and Maughan, B (1999) Validity of the malaise inventory in general population samples. Social Psychiatry and Psychiatric Epidemiology 34, 333341.Google Scholar
Rutter, M, Kim-Cohen, J and Maughan, B (2006) Continuities and discontinuities in psychopathology between childhood and adult life. Journal of Child Psychology and Psychiatry 47, 276295.Google Scholar
Rutter, M, Tizard, J and Whitmore, K (1970) Education, Health and Behaviour. London, UK: Longman Publishing Group.Google Scholar
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421427.Google Scholar
StataCorp (2013) Stata Statistical Software: Release 13. College Station, TX: StataCorp LP.Google Scholar
Thapar, A, Collishaw, S, Pine, DS and Thapar, AK (2012) Depression in adolescence. Lancet 379, 10561067.Google Scholar
Verduijn, J, Milaneschi, Y, Peyrot, WJ, Hottenga, JJ, Abdellaoui, A, de Geus, EJ et al. (2017) Using clinical characteristics to identify which patients with major depressive disorder have a higher genetic load for three psychiatric disorders. Biological Psychiatry 81, 316324.Google Scholar
Wolke, D, Waylen, A, Samara, M, Steer, C, Goodman, R, Ford, T et al. (2009) Selective drop-out in longitudinal studies and non-biased prediction of behaviour disorders. The British Journal of Psychiatry 195, 249256.Google Scholar
Supplementary material: File

Riglin et al. supplementary material

Tables S1-S6 and Figures S1-S3

Download Riglin et al. supplementary material(File)
File 61 KB