클리닉소개

THE SEOUL YOUTH CLINIC

연구 및 치료성과

Thinner cortex is associated with psychosis onset in individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group mega-analysis
Journal
medRxiv
Author
Maria Jalbrzikowski, Rebecca A Hayes, Stephen J Wood, Dorte Nordholm, Juan H Zhou, Paolo Fusar-Poli, Peter J Uhlhaas, Tsutomu Takahashi, Gisela Sugranyes, Yoo Bin Kwak, Daniel H Mathalon, Naoyuki Katagiri, Christine I Hooker, Lukasz Smigielski, Tiziano Co
Year
2021

Abstract

Importance The ENIGMA clinical high risk for psychosis (CHR) initiative, the largest pooled CHR-neuroimaging sample to date, aims to discover robust neurobiological markers of psychosis risk in a sample with known heterogeneous outcomes.

Objective We investigated baseline structural neuroimaging differences between CHR subjects and healthy controls (HC), and between CHR participants who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-). We assessed associations with age by group and conversion status, and similarities between the patterns of effect size maps for psychosis conversion and those found in other large-scale psychosis studies.

Design, Setting, and Participants Baseline T1-weighted MRI data were pooled from 31 international sites participating in the ENIGMA CHR Working Group. MRI scans were processed using harmonized protocols and analyzed within a mega- and meta-analysis framework from January-October 2020.

Main Outcome(s) and Measure(s) Measures of regional cortical thickness (CT), surface area (SA), and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR, HC) and conversion status (CHR-PS+, CHR-PS-, HC).

Results The final dataset consisted of 3,169 participants (CHR=1,792, HC=1,377, age range: 9.5 to 39.8 years, 45% female). Using longitudinal clinical information, we identified CHR-PS+ (N=253) and CHR-PS-(N=1,234). CHR exhibited widespread thinner cortex compared to HC (average d=-0.125, range: −0.09 to −0.17), but not SA or subcortical volume. Thinner cortex in the fusiform, superior temporal, and paracentral regions was associated with psychosis conversion (average d=-0.22). Age showed a stronger negative association with left fusiform and left paracentral CT in HC, compared to CHR-PS+. Regional CT psychosis conversion effect sizes resembled patterns of CT alterations observed in other ENIGMA studies of psychosis.

Conclusions and Relevance We provide evidence for widespread subtle CT reductions in CHR. The pattern of regions displaying greater CT alterations in CHR-PS+ were similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread CT disruptions coupled with abnormal age associations in CHR may point to disruptions in postnatal brain developmental processes.

Question How do baseline brain morphometric features relate to later psychosis conversion in individuals at clinical high risk (CHR)?

Findings In the largest coordinated international analysis to date, reduced baseline cortical thickness, but not cortical surface area or subcortical volume, was more pronounced in CHR, in a manner highly consistent with thinner cortex in established psychosis. Regions that displayed greater cortical thinning in future psychosis converters additionally displayed abnormal associations with age.

Meaning CHR status and later transition to psychosis is robustly associated with reduced cortical thickness. Abnormal age associations and specificity to cortical thickness may point to aberrant postnatal brain development in CHR, including pruning and myelination.



Maria Jalbrzikowski, Rebecca A Hayes, Stephen J Wood, Dorte Nordholm, Juan H Zhou, Paolo Fusar-Poli, Peter J Uhlhaas, Tsutomu Takahashi, Gisela Sugranyes, Yoo Bin Kwak, Daniel H Mathalon, Naoyuki Katagiri, Christine I Hooker, Lukasz Smigielski, Tiziano Colibazzi, Esther Via, Jinsong Tang, Shinsuke Koike, Paul E Rasser, Chantal Michel, Irina Lebedeva, Wenche ten Velden Hegelstad, Camilo de la Fuente-Sandoval, James A Waltz, Romina RM Mizrahi, Cheryl Corcoran, Franz Resch, Christian K Tamnes, Shalaila S Haas, Imke LJ Lemmers-Jansen, Ingrid Agartz, Paul Allen, Ole A Andreassen, Kimberley Atkinson, Peter Bachman, Inmaculada Baeza, Helen Baldwin, Cali F Bartholomeusz, Kolbjørn S Brønnick, Sabrina Catalano, Michael WL Chee, Xiaogang Chen, Kang Ik K Cho, Rebecca E Cooper, Vanessa L Cropley, Bjørn H Ebdrup, Adriana Fortea, Louise B Glenthøj, Birte Y Glenthøj, Lieuwe de Haan, Holly K Hamilton, Mathew A Harris, Kristen M Haut, Ying He, Karsten Heekeren, Andreas Heinz, Daniela Hubl, Wu Jeong Hwang, Michael Kaess, Kiyoto Kasai, Minah Kim, Jochen Kindler, Mallory J Klaunig, Tina D Kristensen, Jun Soo Kwon, Stephen M Lawrie, Jimmy Lee, León-Ortiz Pablo, Ashleigh Lin, Rachel L Loewy, Xiaoqian Ma, Patrick McGorry, Philip McGuire, Masafumi Mizuno, Møller Paul, Tomas Moncada-Habib, Barnaby Nelson, Takahiro Nemoto, Merete Nordentoft, Maria A Omelchenko, Ketil Oppedal, Lijun Ouyang, Christos Pantelis, Jose C Pariente, Jayachandra Raghava, Francisco Reyes-Madrigal, Brian J Roach, Wulf Rössler, Dean F Salisbury, Daiki Sasabayashi, Ulrich Schall, Jason Schiffman, Florian Schlagenhauf, Andre Schmidt, Mikkel E Sørensen, Michio Suzuki, Anastasia Theodoridou, Alexander S Tomyshev, Dennis Velakoulis, Gloria D Venegoni, Sophia Vinogradov, Christina Wenneberg, Lars T Westlye, Hidenori Yamasue, Liu Yuan, Alison R Yung, Thérèse AMJ van Amelsvoort, Jessica A Turner, Theo GM van Erp, Paul M Thompson, Dennis Hernaus, Abadia Dolz