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Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis


 The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder.

 This case-control study used cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group, with additional contributions from Kiyoto Kasai, Shinsuke Koike and their colleagues at the University of Tokyo. For each regional morphometric measure, deviation scores were computed as z scores indexing the degree of deviation from their normative means from a healthy reference population. Average deviation scores (ADS) were also calculated for regional CT, SA, and SV measures and globally across all measures. The results showed that individuals with CHR-P and healthy individuals overlapped in the distributions of the observed values, regional z scores, and all ADS values. For any given region, the proportion of individuals with CHR-P who had infranormal (z < −1.96) or supranormal (z > 1.96) values was low (up to 153 individuals [<11.42%]) and similar to that of healthy individuals (<115 individuals [<9.30%]). Individuals with CHR-P who converted to a psychotic disorder had a higher percentage of infranormal values in temporal regions compared with those who did not convert (7.01% vs 1.38%) and healthy individuals (5.10% vs 0.89%). In the CHR-P group, only the ADS SA was associated with positive symptoms and IQ.

 These findings suggest that macroscale neuromorphometric measures may not provide an adequate explanation of psychosis risk.




Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis
DOI: 10.1001/jamapsychiatry.2023.3850


ENIGMA Clinical High Risk for Psychosis Working Group;
Haas SS, Ge R, Agartz I, Amminger GP, Andreassen OA, Bachman P, Baeza I, Choi S, Colibazzi T, Cropley VL, de la Fuente-Sandoval C, Ebdrup BH, Fortea A, Fusar-Poli P, Glenthøj BY, Glenthøj LB, Haut KM, Hayes RA, Heekeren K, Hooker CI, Hwang WJ, Jahanshad N, Kaess M, Kasai K, Katagiri N, Kim M, Kindler J, Koike S, Kristensen TD, Kwon JS, Lawrie SM, Lebedeva I, Lee J, Lemmers-Jansen ILJ, Lin A, Ma X, Mathalon DH, McGuire P, Michel C, Mizrahi R, Mizuno M, Møller P, Mora-Durán R, Nelson B, Nemoto T, Nordentoft M, Nordholm D, Omelchenko MA, Pantelis C, Pariente JC, Raghava JM, Reyes-Madrigal F, Røssberg JI, Rössler W, Salisbury DF, Sasabayashi D, Schall U, Smigielski L, Sugranyes G, Suzuki M, Takahashi T, Tamnes CK, Theodoridou A, Thomopoulos SI, Thompson PM, Tomyshev AS, Uhlhaas PJ, Værnes TG, van Amelsvoort TAMJ, van Erp TGM, Waltz JA, Wenneberg C, Westlye LT, Wood SJ, Zhou JH, Hernaus D, Jalbrzikowski M, Kahn RS, Corcoran CM, Frangou S.


      JAMA Psychiatry  2023 Oct 11: e233850.