R Blakey1, S Ranlund1, E Zartaloudi1, W Cahn2, S Calafato1, M Colizzi3, B Crespo-Facorro4, C Daniel1, Á Díez-Revuelta1, M Di Forti3, C Iyegbe3, A Jablensky5, R Jones1, M-H Hall6, R Kahn2, L Kalaydjieva7, E Kravariti3, K Lin3, C McDonald8, A M McIntosh9, M Picchioni3, J Powell3, A Presman1, D Rujescu10, K Schulze3, M Shaikh11, J H Thygesen1, T Toulopoulou3, N Van Haren2, J Van Os12, M Walshe1, R M Murray3, E Bramon1. 1. Division of Psychiatry,University College London,London,UK. 2. Department of Psychiatry,Brain Centre Rudolf Magnus,University Medical Center Utrecht,Utrecht,The Netherlands. 3. Institute of Psychiatry Psychology and Neuroscience at King's College London and South London and Maudsley NHS Foundation Trust,London,UK. 4. CIBERSAM,Centro Investigación Biomédica en Red Salud Mental,Madrid,Spain. 5. Centre for Clinical Research in Neuropsychiatry,The University of Western Australia,Perth,Western Australia,Australia. 6. Psychology Research Laboratory,Harvard Medical School,McLean Hospital,Belmont, MA,USA. 7. Harry Perkins Institute of Medical Research and Centre for Medical Research,The University of Western Australia,Perth,Australia. 8. Department of Psychiatry,Clinical Science Institute,National University of Ireland Galway,Ireland. 9. Division of Psychiatry,University of Edinburgh,Royal Edinburgh Hospital,Edinburgh,UK. 10. Department of Psychiatry,Ludwig-Maximilians University of Munich,Munich,Germany. 11. North East London Foundation Trust,London,UK. 12. Department of Psychiatry and Psychology,Maastricht University Medical Centre,EURON,Maastricht,The Netherlands.
Abstract
BACKGROUND: A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related. METHODS: This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes. RESULTS: The P300 amplitude and latency were not associated (regression coef. -0.06, 95% CI -0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10-0.28, p 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships. CONCLUSIONS: The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.
BACKGROUND: A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related. METHODS: This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes. RESULTS: The P300 amplitude and latency were not associated (regression coef. -0.06, 95% CI -0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10-0.28, p 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships. CONCLUSIONS: The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.
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