TY - JOUR
T1 - Decreased cortical gyrification and surface area in the left medial parietal cortex in patients with treatment-resistant and ultratreatment-resistant schizophrenia
AU - Kitajima, Kazutoshi
AU - Tamura, Shunsuke
AU - Sasabayashi, Daiki
AU - Nakajima, Shinichiro
AU - Iwata, Yusuke
AU - Ueno, Fumihiko
AU - Takai, Yoshifumi
AU - Takahashi, Junichi
AU - Caravaggio, Fernando
AU - Mar, Wanna
AU - Torres-Carmona, Edgardo
AU - Noda, Yoshihiro
AU - Gerretsen, Philip
AU - Luca, Vincenzo de
AU - Mimura, Masaru
AU - Hirano, Shogo
AU - Nakao, Tomohiro
AU - Onitsuka, Toshiaki
AU - Remington, Gary
AU - Graff-Guerrero, Ariel
AU - Hirano, Yoji
N1 - Funding Information:
The authors would like to thank all participants who participated in the current study and Itta Nakamura for his support. This study was supported by JSPS KAKENHI grant numbers JP18K15509 (D.S.), 18H02755 (S.N.), JP20K12572 (T.M.), JP20KK0193 (Y.H.), JP18K07604 (Y.H.), JP19H00630 (Y.H.), JP19H03579 (Y.H.), JP21H02851 (Y.H.), 20K22286 (S.T.), and 21K13753 (S.T.); AMED grant numbers JP20dm0207069 (T.O.) and JP19dm0107124h0004 (Y.H.); SIRS Research Fund Award (Y.H.); Ontario Mental Health Foundation Type A grant (A.G.G.) and by Canadian Institutes of Health Research (grant numbers MOP‐142493 (A.G.G., P.G., G.R.) and MOP‐141968 (A.G.G.).
Funding Information:
G.R. has received grants from HLS Therapeutics, Inc. F.U. has received grants from Nakatani Foundation. S.N. has received grants from Japan Research Foundation for Clinical Pharmacology, Naito Foundation, Takeda Science Foundation, Uehara Memorial Foundation, and Daiichi Sankyo Scholarship Donation Program within the past 3 years.
Publisher Copyright:
© 2022 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.
PY - 2023/1
Y1 - 2023/1
N2 - Aim: Validating the vulnerabilities and pathologies underlying treatment-resistant schizophrenia (TRS) is an important challenge in optimizing treatment. Gyrification and surface area (SA), reflecting neurodevelopmental features, have been linked to genetic vulnerability to schizophrenia. The aim of this study was to identify gyrification and SA abnormalities specific to TRS. Methods: We analyzed 3T magnetic resonance imaging findings of 24 healthy controls (HCs), 20 responders to first-line antipsychotics (FL-Resp), and 41 patients with TRS, including 19 clozapine responders (CLZ-Resp) and 22 FL- and clozapine-resistant patients (patients with ultratreatment-resistant schizophrenia [URS]). The local gyrification index (LGI) and associated SA were analyzed across groups. Diagnostic accuracy was verified by receiver operating characteristic curve analysis. Results: Both CLZ-Resp and URS had lower LGI values than HCs (P = 0.041, Hedges g [gH] = 0.75; P = 0.013, gH = 0.96) and FL-Resp (P = 0.007, gH = 1.00; P = 0.002, gH = 1.31) in the left medial parietal cortex (Lt-MPC). In addition, both CLZ-Resp and URS had lower SA in the Lt-MPC than FL-Resp (P < 0.001, gH = 1.22; P < 0.001, gH = 1.75). LGI and SA were positively correlated in non-TRS (FL-Resp) (ρ = 0.64, P = 0.008) and TRS (CLZ-Resp + URS) (ρ = 0.60, P < 0.001). The areas under the receiver operating characteristic curve for non-TRS versus TRS with LGI and SA in the Lt-MPC were 0.79 and 0.85, respectively. SA in the Lt-MPC was inversely correlated with negative symptoms (ρ = −0.40, P = 0.018) and clozapine plasma levels (ρ = −0.35, P = 0.042) in TRS. Conclusion: LGI and SA in the Lt-MPC, a functional hub in the default-mode network, were abnormally reduced in TRS compared with non-TRS. Thus, altered LGI and SA in the Lt-MPC might be structural features associated with genetic vulnerability to TRS.
AB - Aim: Validating the vulnerabilities and pathologies underlying treatment-resistant schizophrenia (TRS) is an important challenge in optimizing treatment. Gyrification and surface area (SA), reflecting neurodevelopmental features, have been linked to genetic vulnerability to schizophrenia. The aim of this study was to identify gyrification and SA abnormalities specific to TRS. Methods: We analyzed 3T magnetic resonance imaging findings of 24 healthy controls (HCs), 20 responders to first-line antipsychotics (FL-Resp), and 41 patients with TRS, including 19 clozapine responders (CLZ-Resp) and 22 FL- and clozapine-resistant patients (patients with ultratreatment-resistant schizophrenia [URS]). The local gyrification index (LGI) and associated SA were analyzed across groups. Diagnostic accuracy was verified by receiver operating characteristic curve analysis. Results: Both CLZ-Resp and URS had lower LGI values than HCs (P = 0.041, Hedges g [gH] = 0.75; P = 0.013, gH = 0.96) and FL-Resp (P = 0.007, gH = 1.00; P = 0.002, gH = 1.31) in the left medial parietal cortex (Lt-MPC). In addition, both CLZ-Resp and URS had lower SA in the Lt-MPC than FL-Resp (P < 0.001, gH = 1.22; P < 0.001, gH = 1.75). LGI and SA were positively correlated in non-TRS (FL-Resp) (ρ = 0.64, P = 0.008) and TRS (CLZ-Resp + URS) (ρ = 0.60, P < 0.001). The areas under the receiver operating characteristic curve for non-TRS versus TRS with LGI and SA in the Lt-MPC were 0.79 and 0.85, respectively. SA in the Lt-MPC was inversely correlated with negative symptoms (ρ = −0.40, P = 0.018) and clozapine plasma levels (ρ = −0.35, P = 0.042) in TRS. Conclusion: LGI and SA in the Lt-MPC, a functional hub in the default-mode network, were abnormally reduced in TRS compared with non-TRS. Thus, altered LGI and SA in the Lt-MPC might be structural features associated with genetic vulnerability to TRS.
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U2 - 10.1111/pcn.13482
DO - 10.1111/pcn.13482
M3 - Article
C2 - 36165228
AN - SCOPUS:85140961300
SN - 1323-1316
VL - 77
SP - 2
EP - 11
JO - Psychiatry and clinical neurosciences
JF - Psychiatry and clinical neurosciences
IS - 1
ER -
