title: Heterogeneity of Psychosis Risk Within Individuals at Clinical High Risk: A Meta-analytical Stratification.
abstract: OBJECTIVE
  Individuals can be classified as being at clinical high risk (CHR) for psychosis if they meet at least one of the ultra-high-risk (UHR) inclusion criteria (brief limited intermittent psychotic symptoms [BLIPS] and/or attenuated psychotic symptoms [APS] and/or genetic risk and deterioration syndrome [GRD]) and/or basic symptoms [BS]. The meta-analytical risk of psychosis of these different subgroups is still unknown.
  
  
  OBJECTIVE
  To compare the risk of psychosis in CHR individuals who met at least one of the major inclusion criteria and in individuals not at CHR for psychosis (CHR-).
  
  
  METHODS
  Electronic databases (Web of Science, MEDLINE, Scopus) were searched until June 18, 2015, along with investigation of citations of previous publications and a manual search of the reference lists of retrieved articles.
  
  
  METHODS
  We included original follow-up studies of CHR individuals who reported the risk of psychosis classified according to the presence of any BLIPS, APS and GRD, APS alone, GRD alone, BS, and CHR-.
  
  
  METHODS
  Independent extraction by multiple observers and random-effects meta-analysis of proportions. Moderators were tested with meta-regression analyses (Bonferroni corrected). Heterogeneity was assessed with the I2 index. Sensitivity analyses tested robustness of results. Publication biases were assessed with funnel plots and the Egger test.
  
  
  METHODS
  The proportion of each subgroup with any psychotic disorder at 6, 12, 24, 36, and 48 or more months of follow-up.
  
  
  RESULTS
  Thirty-three independent studies comprising up to 4227 individuals were included. The meta-analytical proportion of individuals meeting each UHR subgroup at intake was: 0.85 APS (95%CI, 0.79-0.90), 0.1 BLIPS (95%CI, 0.06-0.14), and 0.05 GRD (95%CI, 0.03-0.07). There were no significant differences in psychosis risk at any time point between the APS and GRD and the APS-alone subgroups. There was a higher risk of psychosis in the any BLIPS greater than APS greater than GRD-alone subgroups at 24, 36, and 48 or more months of follow-up. There was no evidence that the GRD subgroup has a higher risk of psychosis than the CHR- subgroup. There were too few BS or BS and UHR studies to allow robust conclusions.
  
  
  CONCLUSIONS
  There is meta-analytical evidence that BLIPS represents separate risk subgroup compared with the APS. The GRD subgroup is infrequent and not associated with an increased risk of psychosis. Future studies are advised to stratify their findings across these different subgroups. The CHR guidelines should be updated to reflect these differences.
authors.affiliation: Institute of Psychiatry, Psychology, and Neuroscience, King's College, London, United Kingdom2OASIS Clinic, South London and Maudsley National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fusar-Poli
authors.affiliation: Institute of Psychiatry, Psychology, and Neuroscience, King's College, London, United Kingdom3Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cappucciati
authors.affiliation: University of Basel Psychiatric Clinics, Basel, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Borgwardt
authors.affiliation: Department of Psychiatry, Yale University, New Haven, Connecticut.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Woods
authors.affiliation: Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jean
authors.initials: J
authors.lastname: Addington
authors.affiliation: Orygen, the National Centre of Excellence in Youth Mental Health, and Centre for Youth Mental Health, the University of Melbourne, Parkville, Australia.
authors.forename: Barnaby
authors.initials: B
authors.lastname: Nelson
authors.affiliation: Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Dorien H
authors.initials: DH
authors.lastname: Nieman
authors.affiliation: Institute of Psychiatry, Psychology, and Neuroscience, King's College, London, United Kingdom.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Stahl
authors.affiliation: Institute of Psychiatry, Psychology, and Neuroscience, King's College, London, United Kingdom.
authors.forename: Grazia
authors.initials: G
authors.lastname: Rutigliano
authors.affiliation: University of Basel Psychiatric Clinics, Basel, Switzerland.
authors.forename: Anita
authors.initials: A
authors.lastname: Riecher-Rössler
authors.affiliation: University of Basel Psychiatric Clinics, Basel, Switzerland9Specialized Early Psychosis Outpatient Service for Adolescents and Young Adults, Department of Psychiatry, Bruderholz, Switzerland.
authors.forename: Andor E
authors.initials: AE
authors.lastname: Simon
authors.affiliation: Department of Neuropsychiatry, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Mizuno
authors.affiliation: Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Tae Young
authors.initials: TY
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jun Soo
authors.initials: JS
authors.lastname: Kwon
authors.affiliation: Kwai Chung Hospital, New Territories, Hong Kong, People's Republic of China.
authors.forename: May M L
authors.initials: MM
authors.lastname: Lam
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Jesus
authors.initials: J
authors.lastname: Perez
authors.affiliation: Nyiro Gyula Hospital, National Institute of Psychiatry and Addictions, Budapest, Hungary.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Keri
authors.affiliation: Orygen, the National Centre of Excellence in Youth Mental Health, and Centre for Youth Mental Health, the University of Melbourne, Parkville, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Amminger
authors.affiliation: Centre for Social Psychiatry, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Zurich, Switzerland.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Metzler
authors.affiliation: Centre for Social Psychiatry, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Zurich, Switzerland.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Kawohl
authors.affiliation: Centre for Social Psychiatry, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Zurich, Switzerland.
authors.forename: Wulf
authors.initials: W
authors.lastname: Rössler
authors.affiliation: Department of General Psychiatry, Institute of Mental Health, Singapore, Singapore.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, Corporacio Sanitaria Parc Tauli Sabadell, Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Labad
authors.affiliation: Department of Clinical Child and Adolescent Studies, Leiden University, Leiden, the Netherlands.
authors.forename: Tim
authors.initials: T
authors.lastname: Ziermans
authors.affiliation: Department of Psychiatry, Yonsei University College of Medicine, Severance Hospital, Seoul, South Korea.
authors.forename: Suk Kyoon
authors.initials: SK
authors.lastname: An
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chen-Chung
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Center for Psychiatric Research, Maine Medical Center, Portland, Maine22Departments of Psychiatry, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Woodberry
authors.affiliation: Psychiatry Department, University Hospital Farhat Hached, Sousse, Tunisia.
authors.forename: Amel
authors.initials: A
authors.lastname: Braham
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Corcoran
authors.affiliation: Orygen, the National Centre of Excellence in Youth Mental Health, and Centre for Youth Mental Health, the University of Melbourne, Parkville, Australia.
authors.forename: Patrick
authors.initials: P
authors.lastname: McGorry
authors.affiliation: Institute of Brain, Behaviour and Mental Health, University of Manchester, and Greater Manchester West National Health Service Mental Health Foundation Trust, Manchester, United Kingdom.
authors.forename: Alison R
authors.initials: AR
authors.lastname: Yung
authors.affiliation: Institute of Psychiatry, Psychology, and Neuroscience, King's College, London, United Kingdom.
authors.forename: Philip K
authors.initials: PK
authors.lastname: McGuire
mesh_terms: D006801:Humans; D011618:Psychotic Disorders / Q000145:classification*; D012306:Risk