Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-10T08:00:36.587Z Has data issue: false hasContentIssue false
  • English
  • Français

Evidence that polygenic risk for psychotic disorder is expressed in the domain of neurodevelopment, emotion regulation and attribution of salience

Published online by Cambridge University Press:  24 April 2017

J. van Os ,
Y. van der Steen ,
Md. A. Islam ,
S. Gülöksüz ,
B. P. Rutten ,
C. J. Simons  and
GROUP Investigators
J. van Os*
Affiliation:
Department of Psychiatry and Psychology, Maastricht University Medical Centre, Maastricht, The Netherlands Department of Psychosis Studies, King's College London, King's Health Partners, Institute of Psychiatry, London, UK
Y. van der Steen
Affiliation:
Department of Psychiatry and Psychology, Maastricht University Medical Centre, Maastricht, The Netherlands
Md. A. Islam
Affiliation:
University of Groningen, University Medical Center Groningen, University Center for Psychiatry, Groningen, The Netherlands
S. Gülöksüz
Affiliation:
Department of Psychiatry and Psychology, Maastricht University Medical Centre, Maastricht, The Netherlands
B. P. Rutten
Affiliation:
Department of Psychiatry and Psychology, Maastricht University Medical Centre, Maastricht, The Netherlands
C. J. Simons
Affiliation:
Department of Psychiatry and Psychology, Maastricht University Medical Centre, Maastricht, The Netherlands GGzE, Institute for Mental Health Care Eindhoven and De Kempen, Eindhoven, The Netherlands
*
*Address for correspondence: J. van Os, Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Centre Utrecht, Heidelberglaan 100, Utrecht, the Netherlands. (Email: vanosj@gmail.com)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

The liability-threshold model of psychosis risk predicts stronger phenotypic manifestation of the polygenic risk score (PRS) in the healthy relatives of patients, as compared with healthy comparison subjects.

Methods

First-degree relatives of patients with psychotic disorder (871 siblings and 812 parents) and healthy comparison subjects (n = 523) were interviewed three times in 6 years. Repeated measures of two psychosis phenotypes, the Community Assessment of Psychic Experiences (CAPE; self-report – subscales of positive, negative and depressive symptoms) and the Structured Interview for Schizotypy – Revised (SIS-R; clinical interview – subscales of positive and negative schizotypy), were examined for association with PRS. Interview-based lifetime rate of depressive and manic episodes were also examined, as was association with repeated measures of intelligence quotient (IQ).

Results

In the relatives, PRS was associated with CAPE/SIS-R total score (respectively, B = 0.12, 95% CI 0.02–0.22 and B = 0.11, 95% CI 0.02–0.20), the SIS-R positive subscale (B = 0.16, 95% CI 0.04–0.28), the CAPE depression subscale (B = 0.21, 95% CI 0.07–0.34), any lifetime affective episode (OR 3.1, 95% CI 1.04–9.3), but not with IQ (B = −1.8, 95% CI −8.0 to 4.4). In the controls, similar associations were apparent between PRS on the one hand and SIS-R total score, SIS-R positive, SIS-R negative, any lifetime affective episode and, in contrast, lower IQ (B = −8.5, 95% CI −15.5 to −1.6).

Conclusions

In non-ill people, polygenic risk for psychotic disorder is expressed pleiotropically in the domain of neurodevelopment, emotion regulation and attribution of salience. In subjects at elevated genetic risk, emerging expression of neurodevelopmental alterations may create floor effects, obscuring genetic associations.

Keywords

Depressiongeneticsneurodevelopmentschizophrenia
Type
Original Articles
Information
Psychological Medicine , Volume 47 , Issue 14 , October 2017 , pp. 2421 - 2437
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.)

Footnotes

†

See Appendix.

References

Aas, M, Steen, NE, Agartz, I, Aminoff, SR, Lorentzen, S, Sundet, K, Andreassen, OA, Melle, I (2012). Is cognitive impairment following early life stress in severe mental disorders based on specific or general cognitive functioning? Psychiatry Research 198, 495–500.Google Scholar
Addington, D, Addington, J, Maticka-Tyndale, E (1993). Assessing depression in schizophrenia: the Calgary Depression Scale. British Journal of Psychiatry Supplement 22, 39–44.Google Scholar
Addington, J, Cadenhead, KS, Cannon, TD, Cornblatt, B, McGlashan, TH, Perkins, DO, Seidman, LJ, Tsuang, M, Walker, EF, Woods, SW, Heinssen, R (2007). North American Prodrome Longitudinal Study: a collaborative multisite approach to prodromal schizophrenia research. Schizophrenia Bulletin 33, 665–672.Google Scholar
Agerbo, E, Sullivan, PF, Vilhjalmsson, BJ, Pedersen, CB, Mors, O, Borglum, AD, Hougaard, DM, Hollegaard, MV, Meier, S, Mattheisen, M, Ripke, S, Wray, NR, Mortensen, PB (2015). Polygenic risk score, parental socioeconomic status, family history of psychiatric disorders, and the risk for schizophrenia: a Danish population-based study and Meta-analysis. JAMA Psychiatry 72, 635–641.Google Scholar
American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Text Revision. American Psychiatric Association: Washington, DC.Google Scholar
Andreasen, NC (1982). Negative symptoms in schizophrenia. Definition and reliability. Archives of General Psychiatry 39, 784–788.CrossRefGoogle ScholarPubMed
Andreasen, NC, Flaum, M, Arndt, S (1992). The Comprehensive Assessment of Symptoms and History (CASH). An instrument for assessing diagnosis and psychopathology. Archives of General Psychiatry 49, 615–623.CrossRefGoogle ScholarPubMed
Blyler, CR, Gold, JM, Iannone, VN, Buchanan, RW (2000). Short form of the WAIS-III for use with patients with schizophrenia. Schizophrenia Research 46, 209–215.Google Scholar
Cardno, AG, Marshall, EJ, Coid, B, Macdonald, AM, Ribchester, TR, Davies, NJ, Venturi, P, Jones, LA, Lewis, SW, Sham, PC, Gottesman, Ii, Farmer, AE, McGuffin, P, Reveley, AM, Murray, RM (1999). Heritability estimates for psychotic disorders: the Maudsley twin psychosis series. Archives of General Psychiatry 56, 162–168.CrossRefGoogle ScholarPubMed
Cougnard, A, Marcelis, M, Myin-Germeys, I, De Graaf, R, Vollebergh, W, Krabbendam, L, Lieb, R, Wittchen, HU, Henquet, C, Spauwen, J, Van Os, J (2007). Does normal developmental expression of psychosis combine with environmental risk to cause persistence of psychosis? A psychosis proneness-persistence model. Psychological Medicine 37, 513–527.CrossRefGoogle ScholarPubMed
Cross-Disorder Group of the Psychiatric Genomics C, Genetic Risk Outcome of Psychosis C (2013). Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381, 1371–1379.Google Scholar
Cross-Disorder Group of the Psychiatric Genomics C, Lee, SH, Ripke, S, Neale, BM, Faraone, SV, Purcell, SM, Perlis, RH, Mowry, BJ, Thapar, A, Goddard, ME, Witte, JS, Absher, D, Agartz, I, Akil, H, Amin, F, Andreassen, OA, Anjorin, A, Anney, R, Anttila, V, Arking, DE, Asherson, P, Azevedo, MH, Backlund, L, Badner, JA, Bailey, AJ, Banaschewski, T, Barchas, JD, Barnes, MR, Barrett, TB, Bass, N, Battaglia, A, Bauer, M, Bayes, M, Bellivier, F, Bergen, SE, Berrettini, W, Betancur, C, Bettecken, T, Biederman, J, Binder, EB, Black, DW, Blackwood, DH, Bloss, CS, Boehnke, M, Boomsma, DI, Breen, G, Breuer, R, Bruggeman, R, Cormican, P, Buccola, NG, Buitelaar, JK, Bunney, WE, Buxbaum, JD, Byerley, WF, Byrne, EM, Caesar, S, Cahn, W, Cantor, RM, Casas, M, Chakravarti, A, Chambert, K, Choudhury, K, Cichon, S, Cloninger, CR, Collier, DA, Cook, EH, Coon, H, Cormand, B, Corvin, A, Coryell, WH, Craig, DW, Craig, IW, Crosbie, J, Cuccaro, ML, Curtis, D, Czamara, D, Datta, S, Dawson, G, Day, R, De Geus, EJ, Degenhardt, F, Djurovic, S, Donohoe, GJ, Doyle, AE, Duan, J, Dudbridge, F, Duketis, E, Ebstein, RP, Edenberg, HJ, Elia, J, Ennis, S, Etain, B, Fanous, A, Farmer, AE, Ferrier, IN, Flickinger, M, Fombonne, E, Foroud, T, Frank, J, Franke, B, Fraser, C, Freedman, R, Freimer, NB, Freitag, CM, Friedl, M, Frisen, L, Gallagher, L, Gejman, PV, Georgieva, L, Gershon, ES, Geschwind, DH, Giegling, I, Gill, M, Gordon, SD, Gordon-Smith, K, Green, EK, Greenwood, TA, Grice, DE, Gross, M, Grozeva, D, Guan, W, Gurling, H, De Haan, L, Haines, JL, Hakonarson, H, Hallmayer, J, Hamilton, SP, Hamshere, ML, Hansen, TF, Hartmann, AM, Hautzinger, M, Heath, AC, Henders, AK, Herms, S, Hickie, IB, Hipolito, M, Hoefels, S, Holmans, PA, Holsboer, F, Hoogendijk, WJ, Hottenga, JJ, Hultman, CM, Hus, V, Ingason, A, Ising, M, Jamain, S, Jones, EG, Jones, I, Jones, L, Tzeng, JY, Kahler, AK, Kahn, RS, Kandaswamy, R, Keller, MC, Kennedy, JL, Kenny, E, Kent, L, Kim, Y, Kirov, GK, Klauck, SM, Klei, L, Knowles, JA, Kohli, MA, Koller, DL, Konte, B, Korszun, A, Krabbendam, L, Krasucki, R, Kuntsi, J, Kwan, P, Landen, M, Langstrom, N, Lathrop, M, Lawrence, J, Lawson, WB, Leboyer, M, Ledbetter, DH, Lee, PH, Lencz, T, Lesch, KP, Levinson, DF, Lewis, CM, Li, J, Lichtenstein, P, Lieberman, JA, Lin, DY, Linszen, DH, Liu, C, Lohoff, FW, Loo, SK, Lord, C, Lowe, JK, Lucae, S, Macintyre, DJ, Madden, PA, Maestrini, E, Magnusson, PK, Mahon, PB, Maier, W, Malhotra, AK, Mane, SM, Martin, CL, Martin, NG, Mattheisen, M, Matthews, K, Mattingsdal, M, McCarroll, SA, McGhee, KA, McGough, JJ, McGrath, PJ, McGuffin, P, McInnis, MG, McIntosh, A, McKinney, R, McLean, AW, McMahon, FJ, McMahon, WM, McQuillin, A, Medeiros, H, Medland, SE, Meier, S, Melle, I, Meng, F, Meyer, J, Middeldorp, CM, Middleton, L, Milanova, V, Miranda, A, Monaco, AP, Montgomery, GW, Moran, JL, Moreno-De-Luca, D, Morken, G, Morris, DW, Morrow, EM, Moskvina, V, Muglia, P, Muhleisen, TW, Muir, WJ, Muller-Myhsok, B, Murtha, M, Myers, RM, Myin-Germeys, I, Neale, MC, Nelson, SF, Nievergelt, CM, Nikolov, I, Nimgaonkar, V, Nolen, WA, Nothen, MM, Nurnberger, JI, Nwulia, EA, Nyholt, DR, O'Dushlaine, C, Oades, RD, Olincy, A, Oliveira, G, Olsen, L, Ophoff, RA, Osby, U, Owen, MJ, Palotie, A, Parr, JR, Paterson, AD, Pato, CN, Pato, MT, Penninx, BW, Pergadia, ML, Pericak-Vance, MA, Pickard, BS, Pimm, J, Piven, J, Posthuma, D, Potash, JB, Poustka, F, Propping, P, Puri, V, Quested, DJ, Quinn, EM, Ramos-Quiroga, JA, Rasmussen, HB, Raychaudhuri, S, Rehnstrom, K, Reif, A, Ribases, M, Rice, JP, Rietschel, M, Roeder, K, Roeyers, H, Rossin, L, Rothenberger, A, Rouleau, G, Ruderfer, D, Rujescu, D, Sanders, AR, Sanders, SJ, Santangelo, SL, Sergeant, JA, Schachar, R, Schalling, M, Schatzberg, AF, Scheftner, WA, Schellenberg, GD, Scherer, SW, Schork, NJ, Schulze, TG, Schumacher, J, Schwarz, M, Scolnick, E, Scott, LJ, Shi, J, Shilling, PD, Shyn, SI, Silverman, JM, Slager, SL, Smalley, SL, Smit, JH, Smith, EN, Sonuga-Barke, EJ, St Clair, D, State, M, Steffens, M, Steinhausen, HC, Strauss, JS, Strohmaier, J, Stroup, TS, Sutcliffe, JS, Szatmari, P, Szelinger, S, Thirumalai, S, Thompson, RC, Todorov, AA, Tozzi, F, Treutlein, J, Uhr, M, Van Den Oord, EJ, Van Grootheest, G, Van Os, J, Vicente, AM, Vieland, VJ, Vincent, JB, Visscher, PM, Walsh, CA, Wassink, TH, Watson, SJ, Weissman, MM, Werge, T, Wienker, TF, Wijsman, EM, Willemsen, G, Williams, N, Willsey, AJ, Witt, SH, Xu, W, Young, AH, Yu, TW, Zammit, S, Zandi, PP, Zhang, P, Zitman, FG, Zollner, S, Devlin, B, Kelsoe, JR, Sklar, P, Daly, MJ, O'Donovan, MC, Craddock, N, Sullivan, PF, Smoller, JW, Kendler, KS, Wray, NR, International Inflammatory Bowel Disease Consortium CuminsCoGenetics C (2013). Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics 45, 984–994.Google Scholar
Dickinson, D, Iannone, VN, Wilk, CM, Gold, JM (2004). General and specific cognitive deficits in schizophrenia. Biological Psychiatry 55, 826–833.Google Scholar
Euesden, J, Lewis, CM, O'Reilly, PF (2015). PRSice: Polygenic Risk Score software. Bioinformatics 31, 1466–1468.CrossRefGoogle ScholarPubMed
Fowler, D, Hodgekins, J, Garety, P, Freeman, D, Kuipers, E, Dunn, G, Smith, B, Bebbington, PE (2012). Negative cognition, depressed mood, and paranoia: a longitudinal pathway analysis using structural equation modeling. Schizophrenia Bulletin 38, 1063–1073.CrossRefGoogle ScholarPubMed
Freeman, D, Garety, PA (1999). Worry, worry processes and dimensions of delusions: an exploratory investigation of a role for anxiety processes in the maintenance of delusional distress. Behavioural and Cognitive Psychotherapy 27, 47–62.Google Scholar
Freeman, D, Garety, PA (2003). Connecting neurosis and psychosis: the direct influence of emotion on delusions and hallucinations. Behaviour Research and Therapy 41, 923–947.CrossRefGoogle ScholarPubMed
Fusar-Poli, P, Nelson, B, Valmaggia, L, Yung, AR, McGuire, PK (2014). Comorbid depressive and anxiety disorders in 509 individuals with an at-risk mental state: impact on psychopathology and transition to psychosis. Schizophrenia Bulletin 40, 120–131.CrossRefGoogle ScholarPubMed
Garety, PA, Kuipers, E, Fowler, D, Freeman, D, Bebbington, PE (2001). A cognitive model of the positive symptoms of psychosis. Psychological Medicine 31, 189–195.CrossRefGoogle ScholarPubMed
Gould, F, Clarke, J, Heim, C, Harvey, PD, Majer, M, Nemeroff, CB (2012). The effects of child abuse and neglect on cognitive functioning in adulthood. Journal of Psychiatric Research 46, 500–506.Google Scholar
Guloksuz, S, Van Nierop, M, Lieb, R, Van Winkel, R, Wittchen, HU, Van Os, J (2015). Evidence that the presence of psychosis in non-psychotic disorder is environment-dependent and mediated by severity of non-psychotic psychopathology. Psychological Medicine 45, 2389–2401.CrossRefGoogle ScholarPubMed
Hafner, H, Loffler, W, Maurer, K, Hambrecht, M, An Der Heiden, W (1999). Depression, negative symptoms, social stagnation and social decline in the early course of schizophrenia. Acta Psychiatrica Scandinavica. Aug 100, 105–118.Google Scholar
Hanssen, M, Peeters, F, Krabbendam, L, Radstake, S, Verdoux, H, Van Os, J (2003). How psychotic are individuals with non-psychotic disorders? Social Psychiatry and Psychiatric Epidemiology 38, 149–154.CrossRefGoogle ScholarPubMed
Hatzimanolis, A, Bhatnagar, P, Moes, A, Wang, R, Roussos, P, Bitsios, P, Stefanis, CN, Pulver, AE, Arking, DE, Smyrnis, N, Stefanis, NC, Avramopoulos, D (2015). Common genetic variation and schizophrenia polygenic risk influence neurocognitive performance in young adulthood. American Journal of Medical Genetics B Neuropsychiatric Genetics 168b, 392–401.CrossRefGoogle ScholarPubMed
Hubbard, L, Tansey, KE, Rai, D, Jones, P, Ripke, S, Chambert, KD, Moran, JL, McCarroll, SA, Linden, DE, Owen, MJ, O'Donovan, MC, Walters, JT, Zammit, S (2016). Evidence of common genetic overlap between Schizophrenia and cognition. Schizophrenia Bulletin 42, 832–842.Google Scholar
Iyegbe, C, Campbell, D, Butler, A, Ajnakina, O, Sham, P (2014). The emerging molecular architecture of schizophrenia, polygenic risk scores and the clinical implications for GxE research. Social Psychiatry and Psychiatric Epidemiology 49, 169–182.Google Scholar
Jeppesen, P, Larsen, JT, Clemmensen, L, Munkholm, A, Rimvall, MK, Rask, CU, Van Os, J, Petersen, L, Skovgaard, AM (2015). The CCC2000 birth Cohort Study of register-based family history of mental disorders and psychotic experiences in offspring. Schizophrenia Bulletin 41, 1084–1094.Google Scholar
Jones, HJ, Stergiakouli, E, Tansey, KE, Hubbard, L, Heron, J, Cannon, M, Holmans, P, Lewis, G, Linden, DE, Jones, PB, Davey Smith, G, O'Donovan, MC, Owen, MJ, Walters, JT, Zammit, S (2016). Phenotypic manifestation of genetic risk for schizophrenia during adolescence in the general population. JAMA Psychiatry 73, 221–228.Google Scholar
Jones, P, Rodgers, B, Murray, R, Marmot, M (1994). Child development risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet 344, 1398–1402.CrossRefGoogle ScholarPubMed
Kelleher, I, Keeley, H, Corcoran, P, Lynch, F, Fitzpatrick, C, Devlin, N, Molloy, C, Roddy, S, Clarke, MC, Harley, M, Arseneault, L, Wasserman, C, Carli, V, Sarchiapone, M, Hoven, C, Wasserman, D, Cannon, M (2012). Clinicopathological significance of psychotic experiences in non-psychotic young people: evidence from four population-based studies. British Journal of Psychiatry 201, 26–32.Google Scholar
Kendler, KS, Lieberman, JA, Walsh, D (1989). The structured interview for Schizotypy (SIS): a preliminary report. Schizophrenia Bulletin 15, 559–571.Google Scholar
Kendler, KS, McGuire, M, Gruenberg, AM, O'Hare, A, Spellman, M, Walsh, D (1993). The Roscommon Family Study. III. Schizophrenia-related personality disorders in relatives. Archives of General Psychiatry 50, 781–788.Google Scholar
Konings, M, Bak, M, Hanssen, M, Van Os, J, Krabbendam, L (2006). Validity and reliability of the CAPE: a self-report instrument for the measurement of psychotic experiences in the general population. Acta Psychiatrica Scandinavica 114, 55–61.Google Scholar
Korver, N, Quee, PJ, Boos, HB, Simons, CJ, De Haan, L, Group Investigators (2012). Genetic Risk and Outcome of Psychosis (GROUP), a multi-site longitudinal cohort study focused on gene-environment interaction: objectives, sample characteristics, recruitment and assessment methods. International Journal of Methods in Psychiatric Research 21, 205–221.CrossRefGoogle Scholar
Linscott, RJ, Van Os, J (2013). An updated and conservative systematic review and meta-analysis of epidemiological evidence on psychotic experiences in children and adults: on the pathway from proneness to persistence to dimensional expression across mental disorders. Psychological Medicine 43, 1133–1149.Google Scholar
Lysaker, PH, Meyer, PS, Evans, JD, Clements, CA, Marks, KA (2001). Childhood sexual trauma and psychosocial functioning in adults with schizophrenia. Psychiatric Services 52, 1485–1488.CrossRefGoogle ScholarPubMed
Maguire, SA, Williams, B, Naughton, AM, Cowley, LE, Tempest, V, Mann, MK, Teague, M, Kemp, AM (2015). A systematic review of the emotional, behavioural and cognitive features exhibited by school-aged children experiencing neglect or emotional abuse. Child: Care, Health and Development 41, 641–653.CrossRefGoogle ScholarPubMed
Majer, M, Nater, UM, Lin, JM, Capuron, L, Reeves, WC (2010). Association of childhood trauma with cognitive function in healthy adults: a pilot study. BMC Neurology 10, 61.CrossRefGoogle ScholarPubMed
Marden, JR, Walter, S, Tchetgen Tchetgen, EJ, Kawachi, I, Glymour, MM (2014). Validation of a polygenic risk score for dementia in black and white individuals. Brain and Behavior 4, 687–697.Google Scholar
Mark, W, Toulopoulou, T (2016). Cognitive intermediate phenotype and genetic risk for psychosis. Current Opinion in Neurobiology 36, 23–30.CrossRefGoogle ScholarPubMed
McCarthy, S, Das, S, Kretzschmar, W, Delaneau, O, Wood, AR, Teumer, A, Kang, HM, Fuchsberger, C, Danecek, P, Sharp, K, Luo, Y, Sidore, C, Kwong, A, Timpson, N, Koskinen, S, Vrieze, S, Scott, LJ, Zhang, H, Mahajan, A, Veldink, J, Peters, U, Pato, C, Van Duijn, CM, Gillies, CE, Gandin, I, Mezzavilla, M, Gilly, A, Cocca, M, Traglia, M, Angius, A, Barrett, JC, Boomsma, D, Branham, K, Breen, G, Brummett, CM, Busonero, F, Campbell, H, Chan, A, Chen, S, Chew, E, Collins, FS, Corbin, LJ, Smith, GD, Dedoussis, G, Dorr, M, Farmaki, AE, Ferrucci, L, Forer, L, Fraser, RM, Gabriel, S, Levy, S, Groop, L, Harrison, T, Hattersley, A, Holmen, OL, Hveem, K, Kretzler, M, Lee, JC, McGue, M, Meitinger, T, Melzer, D, Min, JL, Mohlke, KL, Vincent, JB, Nauck, M, Nickerson, D, Palotie, A, Pato, M, Pirastu, N, McInnis, M, Richards, JB, Sala, C, Salomaa, V, Schlessinger, D, Schoenherr, S, Slagboom, PE, Small, K, Spector, T, Stambolian, D, Tuke, M, Tuomilehto, J, Van Den Berg, LH, Van Rheenen, W, Volker, U, Wijmenga, C, Toniolo, D, Zeggini, E, Gasparini, P, Sampson, MG, Wilson, JF, Frayling, T, De Bakker, PI, Swertz, MA, McCarroll, S, Kooperberg, C, Dekker, A, Altshuler, D, Willer, C, Iacono, W, Ripatti, S, Soranzo, N, Walter, K, Swaroop, A, Cucca, F, Anderson, CA, Myers, RM, Boehnke, M, McCarthy, MI, Durbin, R, Haplotype Reference Consortium (2016). A reference panel of 64 976 haplotypes for genotype imputation. Nature Genetics 48, 1279–1283.Google ScholarPubMed
McGue, M, Gottesman, Ii, Rao, DC (1983). The transmission of schizophrenia under a multifactorial threshold model. American Journal of Human Genetics 35, 1161–1178.Google Scholar
McMillan, KA, Enns, MW, Cox, BJ, Sareen, J (2009). Comorbidity of Axis I and II mental disorders with schizophrenia and psychotic disorders: findings from the National Epidemiologic Survey on Alcohol and Related Conditions. Canadian Journal of Psychiatry Revue Canadienne de Psychiatrie 54, 477–486.Google Scholar
Myin-Germeys, I, Van Os, J (2007). Stress-reactivity in psychosis: evidence for an affective pathway to psychosis. Clinical Psychology Review 27, 409–424.CrossRefGoogle ScholarPubMed
Nimh.Genetics.Initiative (1992). Family Interview for Genetic Studies (FIGS). National Institute of Mental Health: Rockville, Md.Google Scholar
Philip, NS, Sweet, LH, Tyrka, AR, Carpenter, SL, Albright, SE, Price, LH, Carpenter, LL (2016). Exposure to childhood trauma is associated with altered n-back activation and performance in healthy adults: implications for a commonly used working memory task. Brain Imaging Behavior 10, 124–135.Google Scholar
Price, AL, Patterson, NJ, Plenge, RM, Weinblatt, ME, Shadick, NA, Reich, D (2006). Principal components analysis corrects for stratification in genome-wide association studies. Nature Genetics 38, 904–909.Google Scholar
International Schizophrenia C, Purcell, SM, Wray, NR, Stone, JL, Visscher, PM, O'Donovan, MC, Sullivan, PF, Sklar, P (2009). Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460, 748–752.Google Scholar
Sahu, G, Malavade, K, Jacob, T (2016). Cognitive impairment in Schizophrenia: interplay of BDNF and childhood trauma? A review of literature. Psychiatric Quarterly 87, 559–569.CrossRefGoogle ScholarPubMed
Schizophrenia Working Group of the Psychiatric Genomics C (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421–427.Google Scholar
Selten, JP, Sijben, NE, Van Den Bosch, RJ, Omloo Visser, J, Warmerdam, H (1993). The subjective experience of negative symptoms: a self-rating scale. Comprehensive Psychiatry 34, 192–197.Google Scholar
Sieradzka, D, Power, RA, Freeman, D, Cardno, AG, McGuire, P, Plomin, R, Meaburn, EL, Dudbridge, F, Ronald, A (2014). Are genetic risk factors for psychosis also associated with dimension-specific psychotic experiences in adolescence? PLoS ONE 9, e94398.Google Scholar
Slade, M, Phelan, M, Thornicroft, G, Parkman, S (1996). The Camberwell Assessment of Need (CAN): comparison of assessments by staff and patients of the needs of the severely mentally ill. Social Psychiatry and Psychiatric Epidemiology 31, 109–113.Google Scholar
Statacorp (2015). STATA Statistical Software: Release 14. College Station: Texas.Google Scholar
Steinberg, S, De Jong, S, Andreassen, OA, Werge, T, Borglum, AD, Mors, O, Mortensen, PB, Gustafsson, O, Costas, J, Pietilainen, OP, Demontis, D, Papiol, S, Huttenlocher, J, Mattheisen, M, Breuer, R, Vassos, E, Giegling, I, Fraser, G, Walker, N, Tuulio-Henriksson, A, Suvisaari, J, Lonnqvist, J, Paunio, T, Agartz, I, Melle, I, Djurovic, S, Strengman, E, G.R.O.U.P., Jurgens, G, Glenthoj, B, Terenius, L, Hougaard, DM, Orntoft, T, Wiuf, C, Didriksen, M, Hollegaard, MV, Nordentoft, M, Van Winkel, R, Kenis, G, Abramova, L, Kaleda, V, Arrojo, M, Sanjuan, J, Arango, C, Sperling, S, Rossner, M, Ribolsi, M, Magni, V, Siracusano, A, Christiansen, C, Kiemeney, LA, Veldink, J, Van Den Berg, L, Ingason, A, Muglia, P, Murray, R, Nothen, MM, Sigurdsson, E, Petursson, H, Thorsteinsdottir, U, Kong, A, Rubino, IA, De Hert, M, Rethelyi, JM, Bitter, I, Jonsson, EG, Golimbet, V, Carracedo, A, Ehrenreich, H, Craddock, N, Owen, MJ, O'Donovan, MC, Ruggeri, M, Tosato, S, Peltonen, L, Ophoff, RA, Collier, DA, St Clair, D, Rietschel, M, Cichon, S, Stefansson, H, Rujescu, D, Stefansson, K (2011). Common variants at VRK2 and TCF4 conferring risk of schizophrenia. Human Molecular Genetics 20, 4076–4081.CrossRefGoogle ScholarPubMed
Stochl, J, Khandaker, GM, Lewis, G, Perez, J, Goodyer, IM, Zammit, S, Sullivan, S, Croudace, TJ, Jones, PB (2015). Mood, anxiety and psychotic phenomena measure a common psychopathological factor. Psychological Medicine 45, 1483–1493.Google Scholar
Svrakic, DM, Zorumski, CF, Svrakic, NM, Zwir, I, Cloninger, CR (2013). Risk architecture of schizophrenia: the role of epigenetics. Current Opinion in Psychiatry 26, 188–195.Google Scholar
Toulopoulou, T, Picchioni, M, Rijsdijk, F, Hua-Hall, M, Ettinger, U, Sham, P, Murray, R (2007). Substantial genetic overlap between neurocognition and schizophrenia: genetic modeling in twin samples. Archives of General Psychiatry 64, 1348–1355.Google Scholar
Tsuang, MT, Dempsey, GM (1979). Long-term outcome of major psychoses. II. Schizoaffective disorder compared with schizophrenia, affective disorders, and a surgical control group. Archives of General Psychiatry 36, 1302–1304.Google Scholar
Van Nierop, M, Viechtbauer, W, Gunther, N, Van Zelst, C, De Graaf, R, Ten Have, M, Van Dorsselaer, S, Bak, M, Genetic, R, Investigators OUOP, Van Winkel, R (2015). Childhood trauma is associated with a specific admixture of affective, anxiety, and psychosis symptoms cutting across traditional diagnostic boundaries. Psychological Medicine 45, 1277–1288.Google Scholar
Van Os, J (2016). Measures of psychosis proneness and genetic risk for schizophrenia. JAMA Psychiatry 73, 638.Google Scholar
Van Os, J, Kenis, G, Rutten, BP (2010). The environment and schizophrenia. Nature 468, 203–212.Google Scholar
Van Os, J, Marsman, A, Van Dam, D, Simons, CJ, Investigators, G (2017). Evidence that the impact of childhood Trauma on IQ is substantial in controls, moderate in siblings, and absent in patients with psychotic disorder. Schizophrenia Bulletin. doi: 10.1093/schbul/sbw177. [Epub ahead of print].Google Scholar
Van Os, J, Reininghaus, U (2016). Psychosis as a transdiagnostic and extended phenotype in the general population. World Psychiatry 15, 118–124.Google Scholar
Van Rossum, I, Dominguez, MD, Lieb, R, Wittchen, HU, Van Os, J (2011). Affective dysregulation and reality distortion: a 10-year prospective study of their association and clinical relevance. Schizophrenia Bulletin 37, 561–571.CrossRefGoogle ScholarPubMed
Varghese, D, Scott, J, Welham, J, Bor, W, Najman, J, O'Callaghan, M, Williams, G, McGrath, J (2011). Psychotic-like experiences in major depression and anxiety disorders: a population-based survey in young adults. Schizophrenia Bulletin 37, 389–393.Google Scholar
Velthorst, E, Levine, SZ, Henquet, C, De Haan, L, Van Os, J, Myin-Germeys, I, Reichenberg, A (2013). To cut a short test even shorter: reliability and validity of a brief assessment of intellectual ability in schizophrenia–a control-case family study. Cognitive Neuropsychiatry 18, 574–593.CrossRefGoogle Scholar
Verdoux, H, Van Os, J, Maurice-Tison, S, Gay, B, Salamon, R, Bourgeois, M-L (1999). Increased occurrence of depression in psychosis-prone subjects: A follow-up study in primary care settings. Comprehensive Psychiatry 40, 462–468.CrossRefGoogle ScholarPubMed
Vollema, MG, Ormel, J (2000). The reliability of the structured interview for schizotypy-revised. Schizophrenia Bulletin 26, 619–629.CrossRefGoogle ScholarPubMed
Wechsler, D (1997). WAIS-III: Wechsler Adult Intelligence Scale (3rd ed.) Administration and Scoring Manual. Psychological Corporation: San Antonio, TX.Google Scholar
Wigman, JT, Van Nierop, M, Vollebergh, WA, Lieb, R, Beesdo-Baum, K, Wittchen, HU, Van Os, J (2012). Evidence that psychotic symptoms are prevalent in disorders of anxiety and depression, impacting on illness onset, risk, and severity–implications for diagnosis and ultra-high risk research. Schizophrenia Bulletin 38, 247–257.Google Scholar
Wing, JK, Babor, T, Brugha, T, Burke, J, Cooper, JE, Giel, R, Jablenski, A, Regier, D, Sartorius, N (1990). SCAN. Schedules for clinical assessment in neuropsychiatry. Archives of General Psychiatry 47, 589–593.CrossRefGoogle ScholarPubMed
Wing, JK, Cooper, JE, Sartorius, N (1974). The Measurement and Classification of Psychiatric Symptoms. Cambridge University Press: London.Google Scholar
World Health Organisation (1992). WHO Coordinated Multi-Centre Study on the Course and Outcome of Schizophrenia. World Health Organisation: Geneva.Google Scholar
Zammit, S, Hamshere, M, Dwyer, S, Georgiva, L, Timpson, N, Moskvina, V, Richards, A, Evans, DM, Lewis, G, Jones, P, Owen, MJ, O'Donovan, MC (2014). A population-based study of genetic variation and psychotic experiences in adolescents. Schizophrenia Bulletin 40, 1254–1262.Google Scholar