Functional alterations of two salience-related systems jointly and independently contribute to psychosis
Year: 2021
Type: preprint
Study design: Observational Study
Abstract: Background and hypothesis Salience is a critical mechanism for animal survival. Aberrant salience is essentially implicated in psychosis, involving the midbrain–striatum–hippocampus and the anterior cingulate cortex (ACC)–insula salience network (SN) systems. However, whether these two systems jointly or independently contribute to psychosis traits, staging, and state remains unknown. Study design Eight scanners at seven institutions recruited 209 subjects with psychosis at the ultra-high-risk (UHR), first-episode (FEP), and chronic (ChrP) stages and 279 matched healthy controls (HC). Resting-state functional MRI data, which were intensively denoised and scanner effect-removed, revealed the two systems comprising five networks: midbrain-thalamic and striatal parts of the basal ganglia network (BGN-MbThal and BGN-Str), the medial temporal lobe network (MTLN), and the ACC and insular parts of the SN (SN-ACC and SN-Ins). Group differences, correlations with positive symptoms, and effects of medication/psychosis type of the networks were investigated in each psychosis stage. Study results Connectivity within the SN-ACC was reduced in UHR compared to HC (p<0.05, family-wise-error [FWE] corrected) and in the FEP and ChrP stages at liberal thresholds, with effect sizes of UHR>FEP>ChrP. FEP showed reduced connectivity within the BGN-MbThal, increased brain-state instability among the five networks, and positive correlations between positive symptoms and connectivity within and between the MTLN (all p<0.05, FWE). The correlation was stronger in unmedicated than in medicated, and in affective than in non-affective psychosis patients (p<0.05, FWE). Conclusions The results provide a novel concept that the two salience mechanisms work in an integrated and separate manner in psychosis.
Source: medRxiv
Authors: Jun Miyata, Toby Winton-Brown, Thomas Sedlak, Toshihiko Aso, Nicola Cascella, Jennifer Coughlin, Nicolas A. Crossley, Emrah Duezel, Takahiro Ezaki, Masaki Fukunaga, Carolyn Howell, Masanori Isobe, Kouhei Kamiya, Kiyoto Kasai, Takanori Kochiyama, Shinsuke Koike, Akira Kunimatsu, Naoki Masuda, Susumu Mori, Yasuo Mori, Toshiya Murai, Kiyotaka Nemoto, Frederick Nucifora, Kazutaka Ohi, Naohiro Okada, Yuki Sakai, Nobukatsu Sawamoto, Tsutomu Takahashi, Shinichi Urayama, Yoshiyuki Watanabe, Crystal C. Watkins, Hidenaga Yamamori, Yuka Yasuda, Ryota Hashimoto, Hidehiko Takahashi, Akira Sawa, Philip McGuire
Institutions: King's College London, Kyoto University, Johns Hopkins University, RIKEN Center for Biosystems Dynamics Research, Pontificia Universidad Católica de Chile, University College London, The University of Tokyo, National Institute for Physiological Sciences, Toho University Omori Medical Center, Advanced Telecommunications Research Institute International, Mita Hospital, University at Buffalo, State University of New York, University of Tsukuba, Kanazawa Medical University, Gifu University, University of Toyama, Shiga University of Medical Science, National Center of Neurology and Psychiatry, Osaka Hospital, Japan Community Healthcare Organization, National Institute of Mental Health, The University of Osaka, Tokyo Medical and Dental University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3203418304