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The Cavan-Monaghan First Episode Psychosis Study (CAMFEPS): arbitrary diagnostic boundaries across the gene–environment interface and within evolving models of care

Published online by Cambridge University Press:  12 April 2019

John L. Waddington*
Affiliation:
Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland Cavan-Monaghan Mental Health Service, St. Davnet’s Hospital, Monaghan, Ireland Jiangsu Key Laboratory of Translational Research & Therapy for Neuropsychiatric Disorders and Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, China
Vincent Russell
Affiliation:
Cavan-Monaghan Mental Health Service, Cavan General Hospital, Cavan, Ireland Department of Psychiatry, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont, Dublin, Ireland
*
*Address for correspondence: John L. Waddington, Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland. (Email: [email protected])

Abstract

As research into psychotic illness evolves along established lines, insights are emerging that deviate from those lines and challenge more fundamentally our understanding. On the background of a new generation of studies on first-episode psychosis, investigations across the gene–environment interface and the intersection with ‘normal’ human mentation heighten these concerns. Using findings from the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS) as an exemplar, we here review the complexity of these challenges from the perspective of this real-world setting. They range from trans-diagnostic epidemiology and clinical characterisation, through molecular genetics, social milieu, developmental pathobiology and functional outcome across arbitrary diagnostic boundaries, to the evidence base for early intervention and more radical conceptualisations and structures for provision of mental health care.

Type
Review Article
Copyright
© College of Psychiatrists of Ireland 2019 

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References

Anderson, AE, Marder, S, Reise, SP, Savitz, A, Salvadore, G, Fu, DJ, Li, Q, Turkoz, I, Han, C, Bilder, RM (2018). Bifactor modeling of the Positive and Negative Syndrome Scale: generalized psychosis spans schizoaffective, bipolar and schizophrenia diagnoses. Schizophrenia Bulletin 44, 12041216. doi: 10.1093/schbul/sbx163.CrossRefGoogle ScholarPubMed
Arango, C, Diaz-Caneja, CM, McGorry, PD, Rapoport, J, Sommer, IE, Vorstman, JA, McDaid, D, Marion, O, Serrano-Drozdowskyj, E, Freedman, R, Carpenter, WT (2018). Preventive strategies for mental health. Lancet Psychiatry 5, 591604.CrossRefGoogle ScholarPubMed
Baldwin, P, Browne, D, Scully, PJ, Quinn, JF, Morgan, MG, Kinsella, A, Owens, JM, Russell, V, O’Callaghan, E, Waddington, JL (2005). Epidemiology of first-episode psychosis: illustrating the challenges across diagnostic boundaries through the Cavan/Monaghan study at 8 years. Schizophrenia Bulletin 31, 624638.CrossRefGoogle Scholar
Barch, DM, Bustillo, J, Gaebel, W, Gur, R, Heckers, S, Malaspina, D, Owen, MJ, Schultz, S, Tandon, R, Tsuang, M, van Os, J, Carpenter, W (2013). Logic and justification for dimensional assessment of symptoms and related phenomena in psychosis: relevance to DSM-5. Schizophrenia Research 150, 3135.CrossRefGoogle ScholarPubMed
Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium (2018). Genomic dissection of bipolar disorder and schizophrenia, including 28 subphenotypes. Cell 173, 17051715.CrossRefGoogle Scholar
Birnbaum, R, Weinberger, DR (2017). Genetic insights into the neurodevelopmental origins of schizophrenia. Nature Reviews Neuroscience 18, 727740.CrossRefGoogle ScholarPubMed
Birur, B, Kraguljac, NV, Shelton, RC, Lahti, AC (2017). Brain structure, function, and neurochemistry in schizophrenia and bipolar disorder—a systematic review of the magnetic resonance neuroimaging literature. NPJ Schizophrenia 3, 15 doi: 10.1038/s41537-017-0013-9.CrossRefGoogle ScholarPubMed
Bortolato, B, Kohler, CA, Evangelou, E, Leon-Caballero, J, Solmi, M, Stubbs, B, Belbasis, L, Pacchiarotti, I, Kessing, LV, Berk, M, Vieta, E, Carvalho, AF (2017). Systematic assessment of environmental risk factors for bipolar disorder: an umbrella review of systematic reviews and meta-analyses. Bipolar Disorders 19, 8496.CrossRefGoogle ScholarPubMed
Brainstorm Consortium (2018). Analysis of shared heritability in common disorders of the brain. Science 360, pii: eaap8757. doi: 10.1126/science.aap8757.CrossRefGoogle Scholar
Brown, AS (2011). The environment and susceptibility to schizophrenia. Progress in Neurobiology 93, 2358.CrossRefGoogle Scholar
Browne, S, Clarke, M, Gervin, M, Waddington, JL, Larkin, C, O’Callaghan, E (2000). Determinants of quality of life at first presentation with schizophrenia. British Journal of Psychiatry 176, 173176.CrossRefGoogle ScholarPubMed
Cardno, AG, Owen, MJ (2014). Genetic relationship between schizophrenia, bipolar disorder, and schizoaffective disorder. Schizophrenia Bulletin 40, 504515.CrossRefGoogle Scholar
Carpenter, WT (2018). Clinical high risk controversies and challenges for the experts. Schizophrenia Bulletin 44, 223225.CrossRefGoogle Scholar
Castillejos, MC, Martin-Perez, C, Moreno-Kustner, B (2018). A systematic review and meta-analysis of the incidence of psychotic disorders: the distribution of rates and the influence of gender, urbanicity, immigration and socio-economic level. Psychological Medicine 48, 21012115. doi: 10.1017/S0033291718000235.CrossRefGoogle Scholar
Clarke, M, McDonough, CM, Doyle, R, Waddington, JL (2016). Are we really impacting duration of untreated psychosis and does it matter? Longitudinal perspectives on early intervention from the Irish public health services. Psychiatric Clinics of North America 39, 175186.CrossRefGoogle ScholarPubMed
Correll, CU, Galling, B, Pawar, A, Krivko, A, Bonetto, C, Ruggeri, M, et al. (2018). Comparison of early intervention services vs treatment as usual for early-phase psychosis: A systematic review, meta-analysis and meta-regression. JAMA Psychiatry 75, 555565.CrossRefGoogle ScholarPubMed
Craddock, N, Owen, MJ (2010). The Kraepelinian dichotomy – going, going… but still not gone. British Journal of Psychiatry 196, 9295.CrossRefGoogle Scholar
Craddock, N, Sklar, P (2013). Genetics of bipolar disorder. Lancet 381, 16541662.CrossRefGoogle ScholarPubMed
Cross-Disorder Group of the Psychiatric Genomics Consortium (2013a). Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381, 13711379.CrossRefGoogle Scholar
Cross-Disorder Group of the Psychiatric Genomics Consortium (2013b). Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics 45, 984994.CrossRefGoogle Scholar
Davies, C, Cipriani, A, Ioannidis, JPA, Radua, J, Stahl, D, Provenzani, U, McGuire, P, Fusar-Poli, P (2018). Lack of evidence to favor specific preventive interventions in psychosis: a network meta-analysis. World Psychiatry 17, 196209.CrossRefGoogle ScholarPubMed
Davis, J, Eyre, H, Jacka, FN, Dodd, S, Dean, O, McEwen, S, Debnath, M, McGrath, J, Maes, M, Amminger, P, McGorry, PD, Pantelis, C, Berk, M (2016). A review of vulnerability and risks for schizophrenia: beyond the two hit hypothesis. Neuroscience & Biobehavioral Reviews 65, 185194.CrossRefGoogle ScholarPubMed
Demjaha, A, MacCabe, JH, Murray, RM (2012). How genes and environmental factors determine the different neurodevelopmental trajectories of schizophrenia and bipolar disorder. Schizophrenia Bulletin 38, 209214.CrossRefGoogle ScholarPubMed
Domschke, K (2013). Clinical and molecular genetics of psychotic depression. Schizophrenia Bulletin 39, 766775.CrossRefGoogle ScholarPubMed
European Network of National Networks Studying Gene-Environment Interactions in Schizophrenia (2014). Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations. Schizophrenia Bulletin 40, 729736.CrossRefGoogle Scholar
Fusar-Poli, P, Borgwardt, S, Bechdolf, A, Addington, J, Riecher-Rössler, A, Schultze-Lutter, F, et al. (2013). The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA Psychiatry 70, 107120.CrossRefGoogle ScholarPubMed
Fusar-Poli, P, Cappucciati, M, Rutigliano, G, Heslin, M, Stahl, D, Brittenden, Z, Caverzasi, E, McGuire, P, Carpenter, WT (2016). Diagnostic stability of ICD/DSM first episode psychosis diagnoses: meta-analysis. Schizophrenia Bulletin 42, 13951406.CrossRefGoogle ScholarPubMed
Hennessy, RJ, Baldwin, PA, Browne, DJ, Kinsella, A, Waddington, JL (2007). Three-dimensional laser surface imaging and geometric morphometrics resolve frontonasal dysmorphology in schizophrenia. Biological Psychiatry 61, 11871194.CrossRefGoogle Scholar
Hennessy, RJ, Baldwin, PA, Browne, DJ, Kinsella, A, Waddington, JL (2010). Frontonasal dysmorphology in bipolar disorder by 3D laser surface imaging and geometric morphometrics: comparisons with schizophrenia. Schizophrenia Research 122, 6371.CrossRefGoogle ScholarPubMed
Hilker, R, Helenius, D, Fagerlund, B, Skytthe, A, Christensen, K, Werge, TM, Nordentoft, M, Glenthoj, B (2017). Heritability of schizophrenia and schizophrenia spectrum based on the nationwide Danish twin register. Biological Psychiatry 83, 492498.CrossRefGoogle ScholarPubMed
Howes, OD, McCutcheon, R, Owen, MJ, Murray, RM (2017). The role of genes, stress, and dopamine in the development of schizophrenia. Biological Psychiatry 81, 920.CrossRefGoogle ScholarPubMed
Howes, OD, Murray, RM (2014). Schizophrenia: an integrated sociodevelopmental-cognitive model. Lancet 383, 16771687.CrossRefGoogle ScholarPubMed
Kahn, RS, Sommer, IE, Murray, RM, Meyer-Lindenberg, A, Weinberger, DR, Cannon, TD, O’Donovan, M, Correll, CU, Kane, JM, van Os, J, Insel, TR (2015). Schizophrenia. Nature Reviews Disease Primers 1, 15067. doi: 10.1038/nrdp.2015.67.CrossRefGoogle ScholarPubMed
Kelly, BD, O’Callaghan, E, Waddington, JL, Feeney, L, Browne, S, Scully, PJ, Clarke, M, Quinn, JF, McTigue, O, Morgan, MG, Kinsella, A, Larkin, C (2010). Schizophrenia and the city: a review of literature and prospective study of psychosis and urbanicity in Ireland. Schizophrenia Research 116, 7589.CrossRefGoogle ScholarPubMed
Keshavan, MS, Schooler, NR (1992). First-episode studies in schizophrenia: criteria and characterization. Schizophrenia Bulletin 18, 491513.CrossRefGoogle ScholarPubMed
Kingston, T, Scully, PJ, Browne, D, Baldwin, PA, Kinsella, A, O’Callaghan, E, Waddington, JL (2018). Functional outcome and service engagement inn major depressive disorder with psychotic features: comparisons with schizophrenia, schizoaffective disorder and bipolar disorder in a 6-year follow-up of the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS). CNS Neuroscience & Therapeutics 24, 633640.CrossRefGoogle Scholar
Kingston, T, Scully, PJ, Browne, D, Baldwin, P, Kinsella, A, Russell, V, O’Callaghan, E, Waddington, JL (2013). Diagnostic trajectory, interplay and convergence/divergence across all 12 DSM-IV psychotic diagnoses: 6-year follow-up of the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS). Psychological Medicine 43, 25232533.CrossRefGoogle Scholar
Kirch, DG, Lieberman, JA, Matthews, SM (1992). First-episode psychosis. Schizophrenia Bulletin 18, 177178.CrossRefGoogle ScholarPubMed
Kirkbride, JB, Errazuriz, A, Croudace, TJ, Morgan, C, Jackson, D, Boydell, J, Murray, RM, Jones, PB (2012). Incidence of schizophrenia and other psychoses in England, 1950-2009: a systematic review and meta-analyses. PLOS One 7, e31660. doi: 10.1371/journal.pone.0031660.CrossRefGoogle ScholarPubMed
Lally, J, Ajnakina, O, Stubbs, B, Cullinane, M, Murphy, KC, Gaughran, F, Murray, RM (2017). Remission and recovery from first-episode psychosis in adults: systematic review and meta-analysis of long-term outcome studies. British Journal of Psychiatry 211, 350358.CrossRefGoogle ScholarPubMed
Marcucio, R, Hallgrimsson, B, Young, NM (2015). Facial morphogenesis: physical and molecular interactions between the brain and face. Current Topics in Developmental Biology 115, 299320.CrossRefGoogle Scholar
Marcucio, RS, Young, NM, Hu, D, Hallgrimsson, B (2011). Mechanisms that underlie co-variation of the brain and face. Genesis 49, 177189.CrossRefGoogle Scholar
McCauley, M, Rooney, S, Clarke, C, Carey, T, Owens, J (2003). Home-based treatment in Monaghan: the first two years. Irish Journal of Psychological Medicine 20, 1114.CrossRefGoogle ScholarPubMed
McGorry, PD, Hartmann, JA, Spooner, R, Nelson, B (2018). Beyond the “at risk mental state” concept: transitioning to transdiagnostic psychiatry. World Psychiatry 17, 133142.CrossRefGoogle ScholarPubMed
McGrath, JJ (2005). Myths and truths about schizophrenia epidemiology. Acta Psychiatrica Scandinavica 111, 411.CrossRefGoogle ScholarPubMed
Millan, MJ, Andrieux, A, Bartzokis, G, Cadenhead, K, Dazzan, P, Fusar-Poli, P, et al. (2016). Altering the course of schizophrenia: progress and perspectives. Nature Reviews Drug Discovery 15, 485515.CrossRefGoogle Scholar
Million, T, Grossman, S, Meagher, S (2004). Masters of the Mind: Exploring the Story of Mental Illness from Ancient Times to the New Millennium. John Wiley: Hoboken, NJ.Google Scholar
Murray, RM, Bhavsar, V, Tripoli, G, Howes, O (2017). 30 years on: How the neurodevelopmental hypothesis of schizophrenia morphed into the developmental risk factor model of psychosis. Schizophrenia Bulletin 43, 11901196.CrossRefGoogle Scholar
Nwachukwu, I, Nkire, N, Russell, V (2014). Profile and activities of a rural home-based treatment service in Ireland. International Journal of Psychiatry in Clinical Practice 18, 125130.CrossRefGoogle ScholarPubMed
Nkire, N, Sardinha, S, Nwosu, B, McDonough, CM, De Coteau, PA, Duffy, I, Waddington, JL, Russell, V (2015). Evaluation of knowledge and attitudes among primary care physicians in Cavan-Monaghan as ‘gatekeepers-in-waiting’ for the introduction of Carepath for Overcoming Psychosis Early (COPE). Early Intervention in Psychiatry 9, 141150.CrossRefGoogle Scholar
O’Donoghue, B, Roche, E, Lane, A (2016). Neighbourhood level social deprivation and the risk of psychotic disorders: a systematic review. Social Psychiatry and Psychiatric Epidemiology 51, 941950.CrossRefGoogle ScholarPubMed
Oliver, D, Davies, C, Crossland, G, Lim, S, Gifford, G, McGuire, P, Fusar-Poli, P (2018). Can we reduce the duration of untreated psychosis? A systematic review and meta-analysis of controlled intervention studies. Schizophrenia Bulletin 44, 13621372. doi: 10.1093/schbul/sbx166.CrossRefGoogle Scholar
Omer, S, Finnegan, M, Pringle, DG, Kinsella, A, Fearon, P, Russell, V, O’Callaghan, E, Waddington, JL (2016). Socioeconomic status at birth and risk for first episode psychosis in rural Ireland: eliminating the features of urbanicity in the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS). Schizophrenia Research 173, 8489.CrossRefGoogle Scholar
Omer, S, Kirkbride, JB, Pringle, DG, Russell, V, O’Callaghan, E, Waddington, JL (2014). Neighbourhood-level socio-environmental factors and incidence of first episode psychosis by place at onset in rural Ireland: the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS). Schizophrenia Research 152, 152157.CrossRefGoogle Scholar
Owen, MJ (2014). New approaches to psychiatric diagnostic classification. Neuron 84, 564571.CrossRefGoogle ScholarPubMed
Owen, MJ, Sawa, A, Mortensen, PB (2016). Schizophrenia. Lancet 388, 8697.CrossRefGoogle ScholarPubMed
Owoeye, O, Kingston, T, Scully, PJ, Baldwin, P, Browne, D, Kinsella, A, Russell, V, O’Callaghan, E, Waddington, JL (2013). Epidemiological and clinical characterization following a first psychotic episode in major depressive disorder: comparisons with schizophrenia and bipolar I disorder in the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS). Schizophrenia Bulletin 39, 756765.CrossRefGoogle Scholar
Parellada, M, Gomez-Vallejo, S, Burdeus, M, Arango, C (2017). Developmental differences between schizophrenia and bipolar disorder. Schizophrenia Bulletin 43, 11761189.CrossRefGoogle ScholarPubMed
Pearlson, GD (2015). Etiologic, phenomenologic, and endophenotypic overlap of schizophrenia and bipolar disorder. Annual Review of Clinical Psychology 11, 251281.CrossRefGoogle ScholarPubMed
Radua, J, Ramella-Cravaro, V, Ioannidis, JPA, Reichenberg, A, Phiphopthatsanee, N, Amir, T, Yenn Thoo, H, Oliver, D, Davies, C, Morgan, C, McGuire, P, Murray, RM, Fusar-Poli, P (2018) What causes schizophrenia? An umbrella review of risk and protective factors. World Psychiatry 17, 4966.CrossRefGoogle ScholarPubMed
Ram, R, Bromet, EJ, Eaton, WW, Pato, C, Schwartz, JE (1992). The natural course of schizophrenia: a review of first admission studies. Schizophrenia Bulletin 18, 185207.CrossRefGoogle ScholarPubMed
Renwick, L, Gavin, B, McGlade, N, Lacey, P, Goggins, R, Jackson, D, Turner, N, Foley, S, McWilliams, S, Behan, C, Lawlor, E, Cullen, W, O’Callaghan, E (2008). Early intervention service for psychosis: views from primary care. Early Intervention in Psychiatry 2, 285290.CrossRefGoogle ScholarPubMed
Russell, V, Nkire, N, Kingston, T, Waddington, JL (2019). Forging successful partnerships in psychosis research: lessons from the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS). Irish Journal of Psychological Medicine (in press).CrossRefGoogle Scholar
Santesteban-Echarri, O, Paino, M, Rice, S, Gonzalez-Blanch, C, McGorry, P, Gleeson, J, Alvarez-Jimenez, M (2017). Predictors of functional recovery in first-episode psychosis: a systematic review and meta-analysis of longitudinal studies. Clinical Psychology Reviews 58, 5975.CrossRefGoogle ScholarPubMed
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421427.CrossRefGoogle Scholar
Sullivan, PF, Agrawal, A, Bulik, CM, Andreassen, OA, Borglum, AD, Breen, G, Cichon, S, Edenberg, HJ, Faraone, SV, Gelernter, J, Mathews, CA, Nievergelt, CM, Smoller, JW, O’Donovan, MC, Psychiatric Genomics Consortium (2018). Psychiatric genomics: an update and agenda. American Journal of Psychiatry 175, 1527.CrossRefGoogle ScholarPubMed
Tost, H, Meyer-Lindenberg, A (2012). Puzzling over schizophrenia: schizophrenia, social environment and the brain. Nature Medicine 18, 211213.CrossRefGoogle Scholar
Van der Werf, M, Hanssen, M, Kohler, S, Verkaaik, M, Verhey, FR, RISE Investigators, van Winkel, R, van Os, J, Allardyce, J (2014). Systematic review and collaborative recalculation of 133693 incident cases of schizophrenia. Psychological Medicine 44, 916.CrossRefGoogle ScholarPubMed
van Os, J, Kapur, S (2009). Schizophrenia. Lancet 374, 635645.CrossRefGoogle ScholarPubMed
van Os, J, Reininghaus, U (2016). Psychosis as a transdiagnostic and extended phenotype in the general population. World Psychiatry 15, 118124.CrossRefGoogle ScholarPubMed
Vieta, E, Berk, M, Scxhulze, TG, Carvalho, AF, Suppes, T, Calabrese, JR, Gao, K, Miskowiak, KW, Grande, I (2018). Bipolar disorders. Nature Reviews Disease Primers 4, 18008. doi: 10.1038/nrdp.2018.8.CrossRefGoogle ScholarPubMed
Waddington, JL, Brown, AS, Schaefer, CA, Goetz, RR, Bresnahan, M, Susser, ES (2008). Congenital anomalies and early functional impairments in a prospective birth cohort: risk of schizophrenia-spectrum disorder in adulthood. British Journal of Psychiatry 192, 264267.CrossRefGoogle Scholar
Waddington, JL, Buckley, PF (2013). Psychotic depression: an underappreciated window to explore the dimensionality and pathobiology of psychosis. Schizophrenia Bulletin 39, 754755.CrossRefGoogle Scholar
Waddington, JL, Hennessy, RJ, O’Tuathaigh, CMP, Owoeye, O, Russell, V (2012). Schizophrenia and the lifetime trajectory of psychotic illness: developmental neuroscience and pathobiology. In The Origins of Schizophrenia (ed. Brown, A. S. and Harrison, P. H.), pp. 321. Columbia University Press: New York.Google Scholar
Waddington, JL, Larkin, C (1993). A new developmental epidemiology of schizophrenia: the HRB Schizophrenia Research Unit, 1991-92, and contemporary perspectives of the disease. Irish Journal of Psychological Medicine 10, 5659.CrossRefGoogle Scholar
Waddington, JL, Kingston, T, Nkire, N, Russell, V (2019). Major depressive disorder with psychotic features: confronting and resolving the dimensional challenge. In Psychotic Disorders: Comprehensive Conceptualization and Treatments (ed. van Os, J., Tamminga, C. A., Ivleva, E. I. and Reininghaus, U.). Oxford University Press: Oxford. (in press)Google Scholar
Weinberger, DR (2017). Future of days past: neurodevelopment and schizophrenia. Schizophrenia Bulletin 43, 11641168.CrossRefGoogle Scholar
Xu, T, Chan, RCK, Compton, MT (2011). Minor physical anomalies in patients with schizophrenia, unaffected first-degree relatives, and healthy controls: a meta-analysis. PLoS ONE 6, e24129.CrossRefGoogle ScholarPubMed
Zhen, XC, Waddington, JL (2018). Emerging and evolving concepts in the pathobiology and treatment of psychosis. CNS Neuroscience & Therapeutics 24, 583585.CrossRefGoogle ScholarPubMed