TY - JOUR

T1 - Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis

AU - Haas, Shalaila S.

AU - Ge, Ruiyang

AU - Agartz, Ingrid

AU - Amminger, G. Paul

AU - Andreassen, Ole A.

AU - Bachman, Peter

AU - Baeza, Inmaculada

AU - Choi, Sunah

AU - Colibazzi, Tiziano

AU - Cropley, Vanessa L.

AU - De La Fuente-Sandoval, Camilo

AU - Ebdrup, Bjørn H.

AU - Fortea, Adriana

AU - Fusar-Poli, Paolo

AU - Glenthøj, Birte Yding

AU - Glenthøj, Louise Birkedal

AU - Haut, Kristen M.

AU - Hayes, Rebecca A.

AU - Heekeren, Karsten

AU - Hooker, Christine I.

AU - Hwang, Wu Jeong

AU - Jahanshad, Neda

AU - Kaess, Michael

AU - Kasai, Kiyoto

AU - Katagiri, Naoyuki

AU - Kim, Minah

AU - Kindler, Jochen

AU - Koike, Shinsuke

AU - Kristensen, Tina D.

AU - Kwon, Jun Soo

AU - Lawrie, Stephen M.

AU - Lebedeva, Irina

AU - Lee, Jimmy

AU - Lemmers-Jansen, Imke L.J.

AU - Lin, Ashleigh

AU - Ma, Xiaoqian

AU - Mathalon, Daniel H.

AU - McGuire, Philip

AU - Michel, Chantal

AU - Mizrahi, Romina

AU - Mizuno, Masafumi

AU - Møller, Paul

AU - Mora-Durán, Ricardo

AU - Nelson, Barnaby

AU - Nemoto, Takahiro

AU - Nordentoft, Merete

AU - Nordholm, Dorte

AU - Omelchenko, Maria A.

AU - Pantelis, Christos

AU - Pariente, Jose C.

AU - Raghava, Jayachandra M.

AU - Reyes-Madrigal, Francisco

AU - Røssberg, Jan I.

AU - Rössler, Wulf

AU - Salisbury, Dean F.

AU - Sasabayashi, Daiki

AU - Schall, Ulrich

AU - Smigielski, Lukasz

AU - Sugranyes, Gisela

AU - Suzuki, Michio

AU - Takahashi, Tsutomu

AU - Tamnes, Christian K.

AU - Theodoridou, Anastasia

AU - Thomopoulos, Sophia I.

AU - Thompson, Paul M.

AU - Tomyshev, Alexander S.

AU - Uhlhaas, Peter J.

AU - Værnes, Tor G.

AU - Van Amelsvoort, Therese A.M.J.

AU - Van Erp, Theo G.M.

AU - Waltz, James A.

AU - Wenneberg, Christina

AU - Westlye, Lars T.

AU - Wood, Stephen J.

AU - Zhou, Juan H.

AU - Hernaus, Dennis

AU - Jalbrzikowski, Maria

AU - Kahn, René S.

AU - Corcoran, Cheryl M.

AU - Frangou, Sophia

N1 - Publisher Copyright: © 2024 American Medical Association. All rights reserved.

PY - 2024

Y1 - 2024

N2 - Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective: 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. Design, Setting, and Participants: This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)-derived regional measures of 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. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. Main Outcomes and Measures: 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. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z < -1.96) or supranormal (z > 1.96) scores. Results: Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the mean (SD) age was 22.32 (4.95) years. 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 or supranormal 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 (β = -0.08; 95% CI, -0.13 to -0.02; P =.02 for false discovery rate) and IQ (β = 0.09; 95% CI, 0.02-0.15; P =.02 for false discovery rate). Conclusions and Relevance: In this case-control study, findings suggest that macroscale neuromorphometric measures may not provide an adequate explanation of psychosis risk.

AB - Importance: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. Objective: 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. Design, Setting, and Participants: This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)-derived regional measures of 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. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. Main Outcomes and Measures: 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. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z < -1.96) or supranormal (z > 1.96) scores. Results: Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the mean (SD) age was 22.32 (4.95) years. 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 or supranormal 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 (β = -0.08; 95% CI, -0.13 to -0.02; P =.02 for false discovery rate) and IQ (β = 0.09; 95% CI, 0.02-0.15; P =.02 for false discovery rate). Conclusions and Relevance: In this case-control study, findings suggest that macroscale neuromorphometric measures may not provide an adequate explanation of psychosis risk.

U2 - 10.1001/jamapsychiatry.2023.3850

DO - 10.1001/jamapsychiatry.2023.3850

M3 - Journal article

C2 - 37819650

AN - SCOPUS:85181018589

VL - 81

SP - 77

EP - 88

JO - JAMA Psychiatry

JF - JAMA Psychiatry

SN - 2168-622X

IS - 1

ER -