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

  • J. van Os (a1) (a2), Y. van der Steen (a1), Md. A. Islam (a3), S. Gülöksüz (a1), B. P. Rutten (a1), C. J. Simons (a1) (a4) and GROUP Investigators...
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.

Copyright
Corresponding author
*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)
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References
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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, 495500.
Addington D, Addington J, Maticka-Tyndale E (1993). Assessing depression in schizophrenia: the Calgary Depression Scale. British Journal of Psychiatry Supplement 22, 3944.
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, 665672.
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, 635641.
American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Text Revision. American Psychiatric Association: Washington, DC.
Andreasen NC (1982). Negative symptoms in schizophrenia. Definition and reliability. Archives of General Psychiatry 39, 784788.
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, 615623.
Blyler CR, Gold JM, Iannone VN, Buchanan RW (2000). Short form of the WAIS-III for use with patients with schizophrenia. Schizophrenia Research 46, 209215.
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, 162168.
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, 513527.
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, 13711379.
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, 984994.
Dickinson D, Iannone VN, Wilk CM, Gold JM (2004). General and specific cognitive deficits in schizophrenia. Biological Psychiatry 55, 826833.
Euesden J, Lewis CM, O'Reilly PF (2015). PRSice: Polygenic Risk Score software. Bioinformatics 31, 14661468.
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, 10631073.
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, 4762.
Freeman D, Garety PA (2003). Connecting neurosis and psychosis: the direct influence of emotion on delusions and hallucinations. Behaviour Research and Therapy 41, 923947.
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, 120131.
Garety PA, Kuipers E, Fowler D, Freeman D, Bebbington PE (2001). A cognitive model of the positive symptoms of psychosis. Psychological Medicine 31, 189195.
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, 500506.
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, 23892401.
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, 105118.
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, 149154.
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, 392401.
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, 832842.
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, 169182.
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, 10841094.
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, 221228.
Jones P, Rodgers B, Murray R, Marmot M (1994). Child development risk factors for adult schizophrenia in the British 1946 birth cohort. Lancet 344, 13981402.
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, 2632.
Kendler KS, Lieberman JA, Walsh D (1989). The structured interview for Schizotypy (SIS): a preliminary report. Schizophrenia Bulletin 15, 559571.
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, 781788.
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, 5561.
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, 205221.
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, 11331149.
Lysaker PH, Meyer PS, Evans JD, Clements CA, Marks KA (2001). Childhood sexual trauma and psychosocial functioning in adults with schizophrenia. Psychiatric Services 52, 14851488.
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, 641653.
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.
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, 687697.
Mark W, Toulopoulou T (2016). Cognitive intermediate phenotype and genetic risk for psychosis. Current Opinion in Neurobiology 36, 2330.
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, 12791283.
McGue M, Gottesman Ii, Rao DC (1983). The transmission of schizophrenia under a multifactorial threshold model. American Journal of Human Genetics 35, 11611178.
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, 477486.
Myin-Germeys I, Van Os J (2007). Stress-reactivity in psychosis: evidence for an affective pathway to psychosis. Clinical Psychology Review 27, 409424.
Nimh.Genetics.Initiative (1992). Family Interview for Genetic Studies (FIGS). National Institute of Mental Health: Rockville, Md.
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, 124135.
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, 904909.
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, 748752.
Sahu G, Malavade K, Jacob T (2016). Cognitive impairment in Schizophrenia: interplay of BDNF and childhood trauma? A review of literature. Psychiatric Quarterly 87, 559569.
Schizophrenia Working Group of the Psychiatric Genomics C (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421427.
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, 192197.
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.
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, 109113.
Statacorp (2015). STATA Statistical Software: Release 14. College Station: Texas.
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, 40764081.
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, 14831493.
Svrakic DM, Zorumski CF, Svrakic NM, Zwir I, Cloninger CR (2013). Risk architecture of schizophrenia: the role of epigenetics. Current Opinion in Psychiatry 26, 188195.
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, 13481355.
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, 13021304.
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, 12771288.
Van Os J (2016). Measures of psychosis proneness and genetic risk for schizophrenia. JAMA Psychiatry 73, 638.
Van Os J, Kenis G, Rutten BP (2010). The environment and schizophrenia. Nature 468, 203212.
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].
Van Os J, Reininghaus U (2016). Psychosis as a transdiagnostic and extended phenotype in the general population. World Psychiatry 15, 118124.
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, 561571.
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, 389393.
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, 574593.
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, 462468.
Vollema MG, Ormel J (2000). The reliability of the structured interview for schizotypy-revised. Schizophrenia Bulletin 26, 619629.
Wechsler D (1997). WAIS-III: Wechsler Adult Intelligence Scale (3rd ed.) Administration and Scoring Manual. Psychological Corporation: San Antonio, TX.
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, 247257.
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, 589593.
Wing JK, Cooper JE, Sartorius N (1974). The Measurement and Classification of Psychiatric Symptoms. Cambridge University Press: London.
World Health Organisation (1992). WHO Coordinated Multi-Centre Study on the Course and Outcome of Schizophrenia. World Health Organisation: Geneva.
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, 12541262.
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