Advertisement

Psychosis Risk and Development: What Do We Know From Population-Based Studies?

  • Eva Mennigen
    Affiliations
    Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California

    Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
    Search for articles by this author
  • Carrie E. Bearden
    Correspondence
    Address correspondence to Carrie E. Bearden, Ph.D., UCLA Semel Institute for Neuroscience & Human Behavior, 760 Westwood Plaza, Los Angeles, CA 90095.
    Affiliations
    Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California

    Department of Psychology, University of California, Los Angeles, Los Angeles, California
    Search for articles by this author
Published:December 20, 2019DOI:https://doi.org/10.1016/j.biopsych.2019.12.014

      Abstract

      Recent years have seen an advent in population-based studies in children, adolescents, and adults that examine the prevalence, etiology, and developmental trajectories of diverse subclinical psychopathological symptoms that pose a risk for the later development of severe mental illnesses. It is increasingly recognized that most categorically defined psychiatric disorders occur on a spectrum or continuum, show high heterogeneity and symptom overlap, and share genetic and environmental risk factors. We discuss neurodevelopmental underpinnings of psychosis spectrum symptoms and review brain morphometric and functional alterations as well as genetic liability for psychosis in individuals experiencing psychotic symptoms (PSs) in the general population. With regard to brain structure and function, findings of qualitatively similar alterations in individuals experiencing subthreshold PSs and individuals with overt psychotic disorders support the notion of a psychosis continuum. However, genetic and epidemiological studies have emphasized the overlap of PSs and other psychiatric illnesses. In particular, PSs during adolescence appear to be a nonspecific precursor of different psychopathological outcomes. Given the evidence presented in this review, we argue that findings from population-based studies are appropriate to guide policy-making to further emphasize public health efforts. Broadly accessible mental health programs are promising to make a difference in the field of adolescent mental health. However, the specific efficacy of these programs warrants further study, and caution is advised to not overpathologize potentially transient occurrence of mental health problems.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Guloksuz S.
        • van Os J.
        The slow death of the concept of schizophrenia and the painful birth of the psychosis spectrum.
        Psychol Med. 2018; 48: 229-244
        • Curtis D.
        • Derks E.M.
        Letter to the Editor: Schizophrenia does not represent the extreme of a normally distributed trait.
        Psychol Med. 2018; 48: 521-522
        • Hartmann J.A.
        • Nelson B.
        • Ratheesh A.
        • Treen D.
        • McGorry P.D.
        At-risk studies and clinical antecedents of psychosis, bipolar disorder and depression: A scoping review in the context of clinical staging.
        Psychol Med. 2019; 49: 177-189
        • Kounali D.
        • Zammit S.
        • Wiles N.
        • Sullivan S.
        • Cannon M.
        • Stochl J.
        • et al.
        Common versus psychopathology-specific risk factors for psychotic experiences and depression during adolescence.
        Psychol Med. 2014; 44: 2557-2566
        • Marquand A.F.
        • Kia S.M.
        • Zabihi M.
        • Wolfers T.
        • Buitelaar J.K.
        • Beckmann C.F.
        Conceptualizing mental disorders as deviations from normative functioning [published correction appears in Mol Psychiatry 2019;24:1565].
        Mol Psychiatry. 2019; 24: 1415-1424
        • Beer M.D.
        The dichotomies: Psychosis/neurosis and functional/organic: A historical perspective.
        Hist Psychiatry. 1996; 7: 231-255
        • David A.S.
        Why we need more debate on whether psychotic symptoms lie on a continuum with normality.
        Psychol Med. 2010; 40: 1935-1942
        • Strauss J.S.
        Hallucinations and delusions as points on continua function: Rating scale evidence.
        Arch Gen Psychiatry. 1969; 21: 581-586
        • van Os J.
        • Linscott R.J.
        • Myin-Germeys I.
        • Delespaul P.
        • Krabbendam L.
        A systematic review and meta-analysis of the psychosis continuum: Evidence for a psychosis proneness–persistence–impairment model of psychotic disorder.
        Psychol Med. 2009; 39: 179-195
        • Linscott R.J.
        • van Os J.
        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.
        Psychol Med. 2013; 43: 1133-1149
        • Marder S.R.
        • Galderisi S.
        The current conceptualization of negative symptoms in schizophrenia.
        World Psychiatry. 2017; 16: 14-24
        • Kotov R.
        • Foti D.
        • Li K.
        • Bromet E.J.
        • Hajcak G.
        • Ruggero C.J.
        Validating dimensions of psychosis symptomatology: Neural correlates and 20-year outcomes.
        J Abnorm Psychol. 2016; 125: 1103-1119
        • McGorry P.D.
        • Hickie I.B.
        • Yung A.R.
        • Pantelis C.
        • Jackson H.J.
        Clinical staging of psychiatric disorders: A heuristic framework for choosing earlier, safer and more effective interventions.
        Aust N Z J Psychiatry. 2006; 40: 616-622
        • McGlashan T.H.
        • Miller T.J.
        • Woods S.W.
        • Hoffman R.E.
        • Davidson L.
        Instrument for the assessment of prodromal symptoms and states.
        in: Miller T. Mednick S.A. McGlashan T.H. Libiger J. Johannessen J.O. Early Intervention in Psychotic Disorders. Springer Netherlands, Dordrecht2001: 135-149
        • Cannon T.D.
        • Cadenhead K.
        • Cornblatt B.
        • Woods S.W.
        • Addington J.
        • Walker E.
        • et al.
        Prediction of psychosis in youth at high clinical risk: A multisite longitudinal study in North America.
        Arch Gen Psychiatry. 2008; 65: 28-37
        • Fusar-Poli P.
        • Bonoldi I.
        • Yung A.R.
        • Borgwardt S.
        • Kempton M.J.
        • Valmaggia L.
        • et al.
        Predicting psychosis: Meta-analysis of transition outcomes in individuals at high clinical risk.
        Arch Gen Psychiatry. 2012; 69: 220-229
        • Arango C.
        • Díaz-Caneja C.M.
        • McGorry P.D.
        • Rapoport J.
        • Sommer I.E.
        • Vorstman J.A.
        • et al.
        Preventive strategies for mental health.
        Lancet Psychiatry. 2018; 5: 591-604
        • Schultze-Lutter F.
        • Michel C.
        • Schmidt S.J.
        • Schimmelmann B.G.
        • Maric N.P.
        • Salokangas R.K.R.
        • et al.
        EPA guidance on the early detection of clinical high risk states of psychoses.
        Eur Psychiatry. 2015; 30: 405-416
        • van Os J.
        • Guloksuz S.
        A critique of the “ultra-high risk” and “transition” paradigm.
        World Psychiatry. 2017; 16: 200-206
        • Fusar-Poli P.
        • Rutigliano G.
        • Stahl D.
        • Davies C.
        • De Micheli A.
        • Ramella-Cravaro V.
        • et al.
        Long-term validity of the At Risk Mental State (ARMS) for predicting psychotic and non-psychotic mental disorders.
        Eur Psychiatry. 2017; 42: 49-54
        • Woods S.W.
        • Powers A.R.
        • Taylor J.H.
        • Davidson C.A.
        • Johannesen J.K.
        • Addington J.
        • et al.
        Lack of diagnostic pluripotentiality in patients at clinical high risk for psychosis: Specificity of comorbidity persistence and search for pluripotential subgroups.
        Schizophr Bull. 2018; 44: 254-263
        • McGrath J.J.
        • Saha S.
        • Al-Hamzawi A.O.
        • Alonso J.
        • Andrade L.
        • Borges G.
        • et al.
        Age of onset and lifetime projected risk of psychotic experiences: Cross-national data from the World Mental Health Survey.
        Schizophr Bull. 2016; 42: 933-941
        • Mollon J.
        • David A.S.
        • Morgan C.
        • Frissa S.
        • Glahn D.
        • Pilecka I.
        • et al.
        Psychotic experiences and neuropsychological functioning in a population-based sample.
        JAMA Psychiatry. 2016; 73: 129-138
        • Alonso J.
        • Saha S.
        • Lim C.C.W.
        • Aguilar-Gaxiola S.
        • Al-Hamzawi A.
        • Benjet C.
        • et al.
        The association between psychotic experiences and health-related quality of life: A cross-national analysis based on World Mental Health Surveys.
        Schizophr Res. 2018; 201: 46-53
        • Yates K.
        • Lång U.
        • Cederlöf M.
        • Boland F.
        • Taylor P.
        • Cannon M.
        • et al.
        Association of psychotic experiences with subsequent risk of suicidal ideation, suicide attempts, and suicide deaths: A systematic review and meta-analysis of longitudinal population studies.
        JAMA Psychiatry. 2019; 76: 180-189
        • Degenhardt L.
        • Saha S.
        • Lim C.C.W.
        • Aguilar-Gaxiola S.
        • Al-Hamzawi A.
        • Alonso J.
        • et al.
        The associations between psychotic experiences and substance use and substance use disorders: Findings from the World Health Organization World Mental Health surveys.
        Addiction. 2018; 113: 924-934
        • Navarro-Mateu F.
        • Alonso J.
        • Lim C.C.W.
        • Saha S.
        • Aguilar-Gaxiola S.
        • Al-Hamzawi A.
        • et al.
        The association between psychotic experiences and disability: Results from the WHO World Mental Health Surveys.
        Acta Psychiatr Scand. 2017; 136: 74-84
        • Cornblatt B.A.
        • Carrión R.E.
        • Addington J.
        • Seidman L.
        • Walker E.F.
        • Cannon T.D.
        • et al.
        Risk factors for psychosis: Impaired social and role functioning.
        Schizophr Bull. 2012; 38: 1247-1257
        • Barber A.D.
        • Lindquist M.A.
        • DeRosse P.
        • Karlsgodt K.H.
        Dynamic functional connectivity states reflecting psychotic-like experiences.
        Biol Psychiatry Cogn Neurosci Neuroimaging. 2018; 3: 443-453
        • DeRosse P.
        • Ikuta T.
        • Karlsgodt K.H.
        • Peters B.D.
        • Gopin C.B.
        • Szeszko P.R.
        • Malhotra A.K.
        White matter abnormalities associated with subsyndromal psychotic-like symptoms predict later social competence in children and adolescents.
        Schizophr Bull. 2017; 43: 152-159
        • Satterthwaite T.D.
        • Vandekar S.N.
        • Wolf D.H.
        • Bassett D.S.
        • Ruparel K.
        • Shehzad Z.
        • et al.
        Connectome-wide network analysis of youth with psychosis-spectrum symptoms.
        Mol Psychiatry. 2015; 20: 1508-1515
        • Satterthwaite T.D.
        • Wolf D.H.
        • Calkins M.E.
        • Vandekar S.N.
        • Erus G.
        • Ruparel K.
        • et al.
        Structural brain abnormalities in youth with psychosis spectrum symptoms.
        JAMA Psychiatry. 2016; 73: 515-524
        • Wolf D.H.
        • Satterthwaite T.D.
        • Calkins M.E.
        • Ruparel K.
        • Elliott M.A.
        • Hopson R.D.
        • et al.
        Functional neuroimaging abnormalities in youth with psychosis spectrum symptoms.
        JAMA Psychiatry. 2015; 72: 456-465
        • Roalf D.R.
        • Quarmley M.
        • Calkins M.E.
        • Satterthwaite T.D.
        • Ruparel K.
        • Elliott M.A.
        • et al.
        Temporal lobe volume decrements in psychosis spectrum youths.
        Schizophr Bull. 2017; 43: 601-610
        • Fisher H.L.
        • Caspi A.
        • Poulton R.
        • Meier M.H.
        • Houts R.
        • Harrington H.
        • et al.
        Specificity of childhood psychotic symptoms for predicting schizophrenia by 38 years of age: A birth cohort study.
        Psychol Med. 2013; 43: 2077-2086
        • McGrath J.J.
        • Saha S.
        • Al-Hamzawi A.
        • Andrade L.
        • Benjet C.
        • Bromet E.J.
        • et al.
        The bi-directional associations between psychotic experiences and DSM-IV mental disorders.
        Am J Psychiatry. 2016; 173: 997-1006
        • Nivard M.G.
        • Gage S.H.
        • Hottenga J.J.
        • van Beijsterveldt C.E.M.
        • Abdellaoui A.
        • Bartels M.
        • et al.
        Genetic overlap between schizophrenia and developmental psychopathology: Longitudinal and multivariate polygenic risk prediction of common psychiatric traits during development.
        Schizophr Bull. 2017; 43: 1197-1207
        • Jones H.J.
        • Heron J.
        • Hammerton G.
        • Stochl J.
        • Jones P.B.
        • Cannon M.
        • et al.
        Investigating the genetic architecture of general and specific psychopathology in adolescence.
        Transl Psychiatry. 2018; 8: 145
        • Calkins M.E.
        • Moore T.M.
        • Satterthwaite T.D.
        • Wolf D.H.
        • Turetsky B.I.
        • Roalf D.R.
        • et al.
        Persistence of psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort: A prospective two-year follow-up.
        World Psychiatry. 2017; 16: 62-76
        • Healy C.
        • Gordon A.A.
        • Coughlan H.
        • Clarke M.
        • Kelleher I.
        • Cannon M.
        Do childhood psychotic experiences improve the prediction of adolescent psychopathology? A longitudinal population-based study.
        Early Interv Psychiatry. 2019; 13: 1245-1251
        • White T.
        Subclinical psychiatric symptoms and the brain: What can developmental population neuroimaging bring to the table?.
        J Am Acad Child Adolesc Psychiatry. 2015; 54: 797-798
        • Yung A.R.
        • Phillips L.J.
        • Yuen H.P.
        • McGorry P.D.
        Risk factors for psychosis in an ultra high-risk group: Psychopathology and clinical features.
        Schizophr Res. 2004; 67: 131-142
        • Rasic D.
        • Hajek T.
        • Alda M.
        • Uher R.
        Risk of mental illness in offspring of parents with schizophrenia, bipolar disorder, and major depressive disorder: A meta-analysis of family high-risk studies.
        Schizophr Bull. 2014; 40: 28-38
        • Radoeva P.D.
        22q11.2 deletion syndrome: Characterization of psychosis spectrum and future directions.
        Biol Psychiatry. 2017; 82: e5-e7
        • Tang S.X.
        • Moore T.M.
        • Calkins M.E.
        • Yi J.J.
        • Savitt A.
        • Kohler C.G.
        • et al.
        The psychosis spectrum in 22q11.2 deletion syndrome is comparable to that of nondeleted youths.
        Biol Psychiatry. 2017; 82: 17-25
        • Pignon B.
        • Schürhoff F.
        • Szöke A.
        • Geoffroy P.A.
        • Jardri R.
        • Roelandt J.L.
        • et al.
        Sociodemographic and clinical correlates of psychotic symptoms in the general population: Findings from the MHGP survey.
        Schizophr Res. 2018; 193: 336-342
        • World Health Organization
        Prevention of Mental Disorders: Effective Interventions And Policy Options: Summary Report/A Report of the World Health Organization Dept. of Mental Health and Substance Abuse; in Collaboration With the Prevention Research Centre of the Universities of Nijmegen and Maastricht.
        World Health Organization, Geneva2004
        • Poulton R.
        • Caspi A.
        • Moffitt T.E.
        • Cannon M.
        • Murray R.
        • Harrington H.
        Children’s self-reported psychotic symptoms and adult schizophreniform disorder: A 15-year longitudinal study.
        Arch Gen Psychiatry. 2000; 57: 1053-1058
        • Costello E.J.
        • Edelbrock C.S.
        • Costello A.J.
        Validity of the NIMH Diagnostic Interview Schedule for Children: A comparison between psychiatric and pediatric referrals.
        J Abnorm Child Psychol. 1985; 13: 579-595
        • Niarchou M.
        • Zammit S.
        • Lewis G.
        The Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort as a resource for studying psychopathology in childhood and adolescence: A summary of findings for depression and psychosis.
        Soc Psychiatry Psychiatr Epidemiol. 2015; 50: 1017-1027
        • Sullivan S.A.
        • Wiles N.
        • Kounali D.
        • Lewis G.
        • Heron J.
        • Cannon M.
        • et al.
        Longitudinal associations between adolescent psychotic experiences and depressive symptoms.
        PLoS One. 2014; 9e105758
        • Horwood J.
        • Salvi G.
        • Thomas K.
        • Duffy L.
        • Gunnell D.
        • Hollis C.
        • et al.
        IQ and non-clinical psychotic symptoms in 12-year-olds: Results from the ALSPAC birth cohort.
        Br J Psychiatry. 2008; 193: 185-191
        • Cannon T.D.
        • Yu C.
        • Addington J.
        • Bearden C.E.
        • Cadenhead K.S.
        • Cornblatt B.A.
        • et al.
        An individualized risk calculator for research in prodromal psychosis.
        Am J Psychiatry. 2016; 173: 980-988
        • Lin A.
        • Wood S.J.
        • Nelson B.
        • Beavan A.
        • McGorry P.
        • Yung A.R.
        Outcomes of nontransitioned cases in a sample at ultra-high risk for psychosis.
        Am J Psychiatry. 2015; 172: 249-258
        • Bolhuis K.
        • Koopman-Verhoeff M.E.
        • Blanken L.M.E.
        • Cibrev D.
        • Jaddoe V.W.V.
        • Verhulst F.C.
        • et al.
        Psychotic-like experiences in pre-adolescence: What precedes the antecedent symptoms of severe mental illness?.
        Acta Psychiatr Scand. 2018; 138: 15-25
        • Kooijman M.N.
        • Kruithof C.J.
        • van Duijn C.M.
        • Duijts L.
        • Franco O.H.
        • van IJzendoorn M.H.
        • et al.
        The Generation R Study: Design and cohort update 2017.
        Eur J Epidemiol. 2016; 31: 1243-1264
        • Edelbrock C.
        • Costello A.J.
        • Dulcan M.K.
        • Conover N.C.
        • Kala R.
        Parent-child agreement on child psychiatric symptoms assessed via structured interview.
        J Child Psychol Psychiatry. 1986; 27: 181-190
        • De Los Reyes A.
        • Kazdin A.E.
        Informant discrepancies in the assessment of childhood psychopathology: A critical review, theoretical framework, and recommendations for further study.
        Psychol Bull. 2005; 131: 483-509
        • Shakoor S.
        • McGuire P.
        • Cardno A.G.
        • Freeman D.
        • Ronald A.
        A twin study exploring the association between childhood emotional and behaviour problems and specific psychotic experiences in a community sample of adolescents.
        J Child Psychol Psychiatry. 2018; 59: 565-573
        • Dolphin L.
        • Dooley B.
        • Fitzgerald A.
        Prevalence and correlates of psychotic like experiences in a nationally representative community sample of adolescents in Ireland.
        Schizophr Res. 2015; 169: 241-247
        • Nusslock R.
        • Miller G.E.
        Early-life adversity and physical and emotional health across the lifespan: A neuroimmune network hypothesis.
        Biol Psychiatry. 2016; 80: 23-32
        • Callaghan B.L.
        • Tottenham N.
        The stress acceleration hypothesis: Effects of early-life adversity on emotion circuits and behavior.
        Curr Opin Behav Sci. 2016; 7: 76-81
        • McGrath J.J.
        • McLaughlin K.A.
        • Saha S.
        • Aguilar-Gaxiola S.
        • Al-Hamzawi A.
        • Alonso J.
        • et al.
        The association between childhood adversities and subsequent first onset of psychotic experiences: A cross-national analysis of 23 998 respondents from 17 countries.
        Psychol Med. 2017; 47: 1230-1245
        • van Os J.
        • Bak M.
        • Hanssen M.
        • Bijl R.V.
        • de Graaf R.
        • Verdoux H.
        Cannabis use and psychosis: A longitudinal population-based study.
        Am J Epidemiol. 2002; 156: 319-327
        • Marconi A.
        • Di Forti M.
        • Lewis C.M.
        • Murray R.M.
        • Vassos E.
        Meta-analysis of the association between the level of cannabis use and risk of psychosis.
        Schizophr Bull. 2016; 42: 1262-1269
        • Gage S.H.
        • Hickman M.
        • Zammit S.
        Association between cannabis and psychosis: Epidemiologic evidence.
        Biol Psychiatry. 2016; 79: 549-556
        • The International Schizophrenia Consortium
        Common polygenic variation contributes to risk of schizophrenia and bipolar disorder.
        Nature. 2009; 460: 748-752
        • Ripke S.
        • Neale B.M.
        • Corvin A.
        • Walters J.T.R.
        • Farh K.H.
        • et al.
        • Schizophrenia Working Group of the Psychiatric Genomics Consortium
        Biological insights from 108 schizophrenia-associated genetic loci.
        Nature. 2014; 511: 421-427
        • Anttila V.
        • Bulik-Sullivan B.
        • Finucane H.K.
        • Walters R.K.
        • Bras J.
        • et al.
        • Brainstorm Consortium
        Analysis of shared heritability in common disorders of the brain.
        Science. 2018; 360
        • Jones H.J.
        • Stergiakouli E.
        • Tansey K.E.
        • Hubbard L.
        • Heron J.
        • Cannon M.
        • et al.
        Phenotypic manifestation of genetic risk for schizophrenia during adolescence in the general population.
        JAMA Psychiatry. 2016; 73: 221-228
        • Riglin L.
        • Collishaw S.
        • Richards A.
        • Thapar A.K.
        • Maughan B.
        • O’Donovan M.C.
        • Thapar A.
        Schizophrenia risk alleles and neurodevelopmental outcomes in childhood: A population-based cohort study.
        Lancet Psychiatry. 2017; 4: 57-62
        • Haworth C.M.A.
        • Davis O.S.P.
        • Plomin R.
        Twins Early Development Study (TEDS): A genetically sensitive investigation of cognitive and behavioral development from childhood to young adulthood.
        Twin Res Hum Genet. 2013; 16: 117-125
        • Anckarsäter H.
        • Lundström S.
        • Kollberg L.
        • Kerekes N.
        • Palm C.
        • Carlström E.
        • et al.
        The Child and Adolescent Twin Study in Sweden (CATSS).
        Twin Res Hum Genet. 2011; 14: 495-508
        • Pain O.
        • Dudbridge F.
        • Cardno A.G.
        • Freeman D.
        • Lu Y.
        • Lundstrom S.
        • et al.
        Genome-wide analysis of adolescent psychotic-like experiences shows genetic overlap with psychiatric disorders.
        Am J Med Genet B Neuropsychiatr Genet. 2018; 177: 416-425
        • Olde Loohuis L.
        • Mennigen E.
        • Ori A.
        • Perkins D.
        • Robinson E.
        • Addington J.
        • et al.
        Genetic and clinical analyses of psychosis spectrum symptoms in a large multi-ethnic youth cohort reveal significant link with ADHD.
        bioRxiv. 2019;
        • Singh T.
        • Walters J.T.R.
        • Johnstone M.
        • Curtis D.
        • Suvisaari J.
        • Torniainen M.
        • et al.
        The contribution of rare variants to risk of schizophrenia in individuals with and without intellectual disability.
        Nat Genet. 2017; 49: 1167-1173
        • Genovese G.
        • Fromer M.
        • Stahl E.A.
        • Ruderfer D.M.
        • Chambert K.
        • Landén M.
        • et al.
        Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia.
        Nat Neurosci. 2016; 19: 1433-1441
        • Martin A.R.
        • Kanai M.
        • Kamatani Y.
        • Okada Y.
        • Neale B.M.
        • Daly M.J.
        Clinical use of current polygenic risk scores may exacerbate health disparities.
        Nat Genet. 2019; 51: 584-591
        • Torkamani A.
        • Wineinger N.E.
        • Topol E.J.
        The personal and clinical utility of polygenic risk scores.
        Nat Rev Genet. 2018; 19: 581-590
        • Satterthwaite T.D.
        • Elliott M.A.
        • Ruparel K.
        • Loughead J.
        • Prabhakaran K.
        • Calkins M.E.
        • et al.
        Neuroimaging of the Philadelphia Neurodevelopmental Cohort.
        Neuroimage. 2014; 86: 544-553
        • Volkow N.D.
        • Koob G.F.
        • Croyle R.T.
        • Bianchi D.W.
        • Gordon J.A.
        • Koroshetz W.J.
        • et al.
        The conception of the ABCD study: From substance use to a broad NIH collaboration.
        Dev Cogn Neurosci. 2018; 32: 4-7
        • Calkins M.E.
        • Merikangas K.R.
        • Moore T.M.
        • Burstein M.
        • Behr M.A.
        • Satterthwaite T.D.
        • et al.
        The Philadelphia Neurodevelopmental Cohort: Constructing a deep phenotyping collaborative.
        J Child Psychol Psychiatry. 2015; 56: 1356-1369
        • Nenadic I.
        • Dietzek M.
        • Schönfeld N.
        • Lorenz C.
        • Gussew A.
        • Reichenbach J.R.
        • et al.
        Brain structure in people at ultra-high risk of psychosis, patients with first-episode schizophrenia, and healthy controls: A VBM study.
        Schizophr Res. 2015; 161: 169-176
        • Meisenzahl E.M.
        • Koutsouleris N.
        • Bottlender R.
        • Scheuerecker J.
        • Jäger M.
        • Teipel S.J.
        • et al.
        Structural brain alterations at different stages of schizophrenia: A voxel-based morphometric study.
        Schizophr Res. 2008; 104: 44-60
        • Jalbrzikowski M.
        • Freedman D.
        • Hegarty C.E.
        • Mennigen E.
        • Karlsgodt K.H.
        • Olde Loohuis L.M.
        • et al.
        Structural brain alterations in youth with psychosis and bipolar spectrum symptoms.
        J Am Acad Child Adolesc Psychiatry. 2019; 58: 1079-1091
        • Haijma S.V.
        • Van Haren N.
        • Cahn W.
        • Koolschijn P.C.M.P.
        • Hulshoff Pol H.E.
        • Kahn R.S.
        Brain volumes in schizophrenia: A meta-analysis in over 18,000 subjects.
        Schizophr Bull. 2013; 39: 1129-1138
        • Hegarty C.E.
        • Jolles D.D.
        • Mennigen E.
        • Jalbrzikowski M.
        • Bearden C.E.
        • Karlsgodt K.H.
        Disruptions in white matter maturation and mediation of cognitive development in youths on the psychosis spectrum.
        Biol Psychiatry Cogn Neurosci Neuroimaging. 2019; 4: 423-433
        • Glahn D.C.
        • Ragland J.D.
        • Abramoff A.
        • Barrett J.
        • Laird A.R.
        • Bearden C.E.
        • Velligan D.I.
        Beyond hypofrontality: A quantitative meta-analysis of functional neuroimaging studies of working memory in schizophrenia.
        Hum Brain Mapp. 2005; 25: 60-69
        • Green M.F.
        • Horan W.P.
        • Lee J.
        Social cognition in schizophrenia.
        Nat Rev Neurosci. 2015; 16: 620-631
        • Papanastasiou E.
        • Mouchlianitis E.
        • Joyce D.W.
        • McGuire P.
        • Banaschewski T.
        • Bokde A.L.W.
        Examination of the neural basis of psychoticlike experiences in adolescence during reward processing.
        JAMA Psychiatry. 2018; 75: 1043-1051
        • Karcher N.R.
        • O’Brien K.J.
        • Kandala S.
        • Barch D.M.
        Resting-state functional connectivity and psychotic-like experiences in childhood: Results from the Adolescent Brain Cognitive Development Study.
        Biol Psychiatry. 2019; 86: 7-15
        • Whitfield-Gabrieli S.
        • Thermenos H.W.
        • Milanovic S.
        • Tsuang M.T.
        • Faraone S.V.
        • McCarley R.W.
        • et al.
        Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia.
        Proc Natl Acad Sci U S A. 2009; 106: 1279-1284
        • Pankow A.
        • Deserno L.
        • Walter M.
        • Fydrich T.
        • Bermpohl F.
        • Schlagenhauf F.
        • Heinz A.
        Reduced default mode network connectivity in schizophrenia patients.
        Schizophr Res. 2015; 165: 90-93
        • Xia C.H.
        • Ma Z.
        • Ciric R.
        • Gu S.
        • Betzel R.F.
        • Kaczkurkin A.N.
        • et al.
        Linked dimensions of psychopathology and connectivity in functional brain networks.
        Nat Commun. 2018; 9: 3003
        • Mennigen E.
        • Jolles D.D.
        • Hegarty C.E.
        • Gupta M.
        • Jalbrzikowski M.
        • Olde Loohuis L.M.
        • et al.
        State-dependent functional dysconnectivity in youth with psychosis spectrum symptoms.
        Schizophr Bull. 2020; 46: 408-421
        • Sheffield J.M.
        • Kandala S.
        • Burgess G.C.
        • Harms M.P.
        • Barch D.M.
        Cingulo-opercular network efficiency mediates the association between psychotic-like experiences and cognitive ability in the general population.
        Biol Psychiatry Cogn Neurosci Neuroimaging. 2016; 1: 498-506
        • Damaraju E.
        • Allen E.A.
        • Belger A.
        • Ford J.M.
        • McEwen S.
        • Mathalon D.H.
        • et al.
        Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia.
        Neuroimage Clin. 2014; 5: 298-308
        • Chung Y.
        • Addington J.
        • Bearden C.E.
        • Cadenhead K.
        • Cornblatt B.
        • Mathalon D.H.
        • et al.
        Use of machine learning to determine deviance in neuroanatomical maturity associated with future psychosis in youths at clinically high risk.
        JAMA Psychiatry. 2018; 75: 960-968
        • McGorry P.
        • Trethowan J.
        • Rickwood D.
        Creating headspace for integrated youth mental health care.
        World Psychiatry. 2019; 18: 140-141
        • Stafford M.R.
        • Jackson H.
        • Mayo-Wilson E.
        • Morrison A.P.
        • Kendall T.
        Early interventions to prevent psychosis: Systematic review and meta-analysis.
        BMJ. 2013; 346: f185
        • Millan M.J.
        • Andrieux A.
        • Bartzokis G.
        • Cadenhead K.
        • Dazzan P.
        • Fusar-Poli P.
        • et al.
        Altering the course of schizophrenia: Progress and perspectives.
        Nat Rev Drug Discov. 2016; 15: 485-515
        • Ricciardi A.
        • McAllister V.
        • Dazzan P.
        Is early intervention in psychosis effective?.
        Epidemiol Psychiatr Sci. 2008; 17: 227-235
        • McCrone P.
        • Knapp M.
        Economic evaluation of early intervention services.
        Br J Psychiatry. 2007; 191: s19-s22
        • Mihalopoulos C.
        • Harris M.
        • Henry L.
        • Harrigan S.
        • McGorry P.
        Is early intervention in psychosis cost-effective over the long term?.
        Schizophr Bull. 2009; 35: 909-918
        • Miklowitz D.J.
        • O’Brien M.P.
        • Schlosser D.A.
        • Addington J.
        • Candan K.A.
        • Marshall C.
        • et al.
        Family-focused treatment for adolescents and young adults at high risk for psychosis: Results of a randomized trial.
        J Am Acad Child Adolesc Psychiatry. 2014; 53: 848-858
        • Hutton P.
        • Taylor P.J.
        Cognitive behavioural therapy for psychosis prevention: A systematic review and meta-analysis.
        Psychol Med. 2014; 44: 449-468
        • Schmidt S.J.
        • Schultze-Lutter F.
        • Schimmelmann B.G.
        • Maric N.P.
        • Salokangas R.K.R.
        • Riecher-Rössler A.
        • et al.
        EPA guidance on the early intervention in clinical high risk states of psychoses.
        Eur Psychiatry. 2015; 30: 388-404
        • McLaughlin K.A.
        • DeCross S.N.
        • Jovanovic T.
        • Tottenham N.
        Mechanisms linking childhood adversity with psychopathology: Learning as an intervention target.
        Behav Res Ther. 2019; 118: 101-109
        • Eldreth D.
        • Hardin M.G.
        • Pavletic N.
        • Ernst M.
        Adolescent transformations of behavioral and neural processes as potential targets for prevention.
        Prev Sci. 2013; 14: 257-266
        • Loewy R.L.
        • Pearson R.
        • Vinogradov S.
        • Bearden C.E.
        • Cannon T.D.
        Psychosis risk screening with the Prodromal Questionnaire–Brief Version (PQ-B).
        Schizophr Res. 2011; 129: 42-46
        • Fusar-Poli P.
        • Byrne M.
        • Badger S.
        • Valmaggia L.R.
        • McGuire P.K.
        Outreach and Support in South London (OASIS), 2001–2011: Ten years of early diagnosis and treatment for young individuals at high clinical risk for psychosis.
        Eur Psychiatry. 2013; 28: 315-326
        • Rickwood D.J.
        • Mazzer K.R.
        • Telford N.R.
        • Parker A.G.
        • Tanti C.J.
        • McGorry P.D.
        Changes in psychological distress and psychosocial functioning in young people visiting Headspace centres for mental health problems.
        Med J Aust. 2015; 202: 537-542
        • Bassilios B.
        • Telford N.
        • Rickwood D.
        • Spittal M.J.
        • Pirkis J.
        Complementary primary mental health programs for young people in Australia: Access to Allied Psychological Services (ATAPS) and Headspace.
        Int J Ment Health Syst. 2017; 11: 19
        • Sampogna G.
        • Bakolis I.
        • Evans-Lacko S.
        • Robinson E.
        • Thornicroft G.
        • Henderson C.
        The impact of social marketing campaigns on reducing mental health stigma: Results from the 2009–2014 Time to Change programme.
        Eur Psychiatry. 2017; 40: 116-122
        • Thornicroft G.
        • Mehta N.
        • Clement S.
        • Evans-Lacko S.
        • Doherty M.
        • Rose D.
        • et al.
        Evidence for effective interventions to reduce mental-health-related stigma and discrimination.
        Lancet. 2016; 387: 1123-1132
        • Robinson E.J.
        • Henderson C.
        Public knowledge, attitudes, social distance and reporting contact with people with mental illness 2009–2017.
        Psychol Med. 2019; 49: 2717-2726
        • O’Keeffe L.
        • O’Reilly A.
        • O’Brien G.
        • Buckley R.
        • Illback R.
        Description and outcome evaluation of Jigsaw: An emergent Irish mental health early intervention programme for young people.
        Irish J Psychol Med. 2015; 32: 71-77
        • Wolke D.
        • Lereya S.T.
        • Fisher H.L.
        • Lewis G.
        • Zammit S.
        • et al.
        Bullying in elementary school and psychotic experiences at 18 years: A longitudinal, population-based cohort study.
        Psychol Med. 2014; 44: 2199-2211
        • Hielscher E.
        • DeVylder J.
        • Connell M.
        • Hasking P.
        • Martin G.
        • Scott J.G.
        • et al.
        Investigating the role of hallucinatory experiences in the transition from suicidal thoughts to attempts.
        Acta Psychiatr Scand. 2020; 141: 241-253
        • Wittchen H.U.
        Reliability and validity studies of the WHO-Composite International Diagnostic Interview (CIDI): A critical review.
        J Psychiatr Res. 1994; 28: 57-84
        • Bijl R.V.
        • van Zessen G.
        • Ravelli A.
        • de Rijk C.
        • Langendoen Y.
        The Netherlands Mental Health Survey and Incidence Study (NEMESIS): Objectives and design.
        Soc Psychiatry Psychiatr Epidemiol. 1988; 33: 581-586
        • Bijl R.V.
        • Ravelli A.
        • van Zessen G.
        Prevalence of psychiatric disorder in the general population: Results of The Netherlands Mental Health Survey and Incidence Study (NEMESIS).
        Soc Psychiatry Psychiatr Epidemiol. 1998; 33: 587-595
        • Crush E.
        • Arseneault L.
        • Moffitt T.E.
        • Danese A.
        • Caspi A.
        • Jaffee S.R.
        • et al.
        Protective factors for psychotic experiences amongst adolescents exposed to multiple forms of victimization.
        J Psychiatr Res. 2018; 104: 32-38
        • Dooley B.
        • Fitzgerald A.
        Methodology on the My World Survey (MWS): A unique window into the world of adolescents in Ireland.
        Early Interv Psychiatry. 2013; 7: 12-22
        • Oliver B.R.
        • Plomin R.
        Twins’ Early Development Study (TEDS): A multivariate, longitudinal genetic investigation of language, cognition and behavior problems from childhood through adolescence.
        Twin Res Hum Genet. 2007; 10: 96-105
        • Törn P.
        • Pettersson E.
        • Lichtenstein P.
        • Anckarsäter H.
        • Lundström S.
        • Hellner Gumpert C.
        • et al.
        Childhood neurodevelopmental problems and adolescent bully victimization: population-based, prospective twin study in Sweden.
        Eur Child Adolesc Psychiatry. 2015; 24: 1049-1459
        • Satterthwaite T.D.
        • Connolly J.J.
        • Ruparel K.
        • Calkins M.E.
        • Jackson C.
        • Elliott M.A.
        • et al.
        The Philadelphia Neurodevelopmental Cohort: A publicly available resource for the study of normal and abnormal brain development in youth.
        Neuroimage. 2016; 124: 1115-1119
        • Hagler Jr, D.J.
        • Hatton S.
        • Cornejo M.D.
        • Makowski C.
        • Fair D.A.
        • Dick A.S.
        • et al.
        Image processing and analysis methods for the Adolescent Brain Cognitive Development Study.
        Neuroimage. 2019; 202: 116091
        • Somerville L.H.
        • Bookheimer S.Y.
        • Buckner R.L.
        • Burgess G.C.
        • Curtiss S.W.
        • Dapretto M.
        • et al.
        The Lifespan Human Connectome Project in Development: A large-scale study of brain connectivity development in 5-21 year olds.
        Neuroimage. 2018; 183: 456-468
        • Schumann G.
        • Loth E.
        • Banaschewski T.
        • Barbot A.
        • Barker G.
        • Büchel C.
        • et al.
        The IMAGEN study: reinforcement-related behaviour in normal brain function and psychopathology.
        Mol Psychiatry. 2010; 15: 1128-1139
        • Jaddoe V.W.
        • van Duijn C.M.
        • Franco O.H.
        • van der Heijden A.J.
        • van Iizendoorn M.H.
        • de Jongste J.C.
        • et al.
        The Generation R Study: Design and cohort update 2012.
        Eur J Epidemiol. 2012; 27: 739-756
        • Gradie M.I.
        • Jorde L.B.
        • Bouchard G.
        Genetic structure of the Saguenay, 1852-1911: Evidence from migration and isonymy matrices.
        Am J Phys Anthropol. 1988; 77: 321-333
        • Nooner K.B.
        • Colcombe S.J.
        • Tobe R.H.
        • Mennes M.
        • Benedict M.M.
        • Moreno A.L.
        • et al.
        The NKI-Rockland Sample: A model for accelerating the pace of discovery science in psychiatry.
        Front Neurosci. 2012; 6: 152