TY - JOUR
T1 - Associations between psychosis endophenotypes across brain functional, structural, and cognitive domains
AU - Blakey, R.
AU - Ranlund, Siri
AU - Zartaloudi, E.
AU - Cahn, W.
AU - Calafato, Stella
AU - Colizzi, M.
AU - Crespo-Facorro, Benedicto
AU - Daniel, C.
AU - Díez-Revuelta,
AU - di Forti, M.
AU - Iyegbe, Conrad
AU - Jablensky, Assen
AU - Jones, R.
AU - Hall, M.-H.
AU - Kahn, R.
AU - Kalaydjieva, Luba
AU - Kravariti, Eugenia
AU - Lin, K.
AU - McDonald, C.
AU - McIntosh, Andrew M.
AU - Picchioni, M.
AU - Powell, J.
AU - Presman, A.
AU - Rujescu, D.
AU - Schulze, K.
AU - Shaikh, Muddassir M uhammad
AU - Thygesen, Johan H.
AU - Toulopoulou, T
AU - Van Haren, N.
AU - Van Os, J.
AU - Walshe, M.
AU - Murray, Robin M.
AU - Bramon, E.
PY - 2018/6/1
Y1 - 2018/6/1
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Brain/physiopathology
KW - Case-Control Studies
KW - Electrophysiology
KW - Endophenotypes
KW - Event-Related Potentials, P300
KW - Female
KW - Humans
KW - Linear Models
KW - Magnetic Resonance Imaging
KW - Male
KW - Middle Aged
KW - Nerve Net/physiopathology
KW - Neuropsychological Tests
KW - Psychotic Disorders/physiopathology
KW - Young Adult
UR - http://www.scopus.com/inward/record.url?scp=85033404019&partnerID=8YFLogxK
U2 - 10.1017/S0033291717002860
DO - 10.1017/S0033291717002860
M3 - Article
C2 - 29094675
AN - SCOPUS:85033404019
SN - 0033-2917
VL - 48
SP - 1325
EP - 1340
JO - Psychological Medicine
JF - Psychological Medicine
IS - 8
ER -