Decrease in gamma-band auditory steady-state response in patients with treatment-resistant schizophrenia.

BACKGROUND

Thirty percent of patients with schizophrenia do not respond to non-clozapine antipsychotics and are termed treatment-resistant schizophrenia (TRS). The 40-Hz auditory steady-state response (ASSR) is a well-known to be reduced in patients with schizophrenia compared to healthy controls (HCs), suggesting impaired gamma oscillation in schizophrenia. Given no ASSR study on TRS, we aimed to examine the neurophysiological basis of TRS employing 40-Hz ASSR paradigm.

METHOD

We compared ASSR measures among HCs, patients with non-TRS, and patients with TRS. TRS criteria were defined by a score of 4 or higher on two items of the Positive and Negative Syndrome Scale (PANSS) positive symptoms despite standard antipsychotic treatment. Participants were examined for ASSR with 40-Hz click-train stimulus, and then time-frequency analysis was performed to calculate evoked power and phase-locking factor (PLF) of 40-Hz ASSR.

RESULTS

A total of 79 participants were included: 27 patients with TRS (PANSS = 92.6 ± 15.8); 27 patients with non-TRS (PANSS = 63.3 ± 14.7); and 25 HCs. Evoked power in 40-Hz ASSR was lower in the TRS group than in the HC group (F

CONCLUSION

These results suggest that glutamatergic and GABAergic neurophysiological dysfunctions are involved in the pathophysiology of TRS. Our findings warrant more comprehensive and longitudinal studies for deep phenotyping of TRS.

Informations de copyright

Copyright © 2023. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of competing interest Y.N. has received a Grant-in-Aid for Scientific Research (B) (21H02813) from the Japan Society for the Promotion of Science (JSPS), research grants from Japan Agency for Medical Research and Development (AMED), investigator-initiated clinical study grants from Teijin Pharma Ltd., and Inter Reha Co., Ltd. He also receives research grants from Japan Health Foundation, Meiji Yasuda Mental Health Foundation, Mitsui Life Social Welfare Foundation, Takeda Science Foundation, SENSHIN Medical Research Foundation, Health Science Center Foundation, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Taiju Life Social Welfare Foundation, and Daiichi Sankyo Scholarship Donation Program. He has received speaker's honoraria from Dainippon Sumitomo Pharma, Mochida Pharmaceutical Co., Ltd., Yoshitomiyakuhin Co., Ltd., Qol Co., Ltd., Teijin Pharma Ltd., and Takeda Pharmaceutical Co., Ltd. within the past five years. He also receives equipment-in-kind support for an investigator-initiated study from Magventure Inc., Inter Reha Co., Ltd., Brainbox Ltd., and Miyuki Giken Co., Ltd. SN has received grants from Japan Society for the Promotion of Science (18H02755), Japan Agency for Medical Research and development (AMED), Japan Research Foundation for Clinical Pharmacology, Naito Foundation, Takeda Science Foundation, Uehara Memorial Foundation, and Daiichi Sankyo Scholarship Donation Program within the past three years. SN has also received research support, manuscript fees or speaker's honoraria from Dainippon Sumitomo Pharma, Meiji-Seika Pharma, Otsuka Pharmaceutical, Shionogi, and Yoshitomi Yakuhin within the past three years. M.M. has received speaker's honoraria from Biogen Japan, Byer Pharmaceutical, Daiichi Sankyo, Dainippon-Sumitomo Pharma, Demant Japan, Eisai, Eli Lilly, Fuji Film RI Pharma, Hisamitsu Pharmaceutical, H.U. Frontier, Janssen Pharmaceutical, Mochida Pharmaceutical, MSD, Mylan EPD, Nippon Chemipher, Novartis Pharma, Ono Yakuhin, Otsuka Pharmaceutical, Pfizer, Shionogi, Takeda Yakuhin, Teijin Pharma, and Viatris within the past three years. Also, he received grants from Daiichi Sankyo, Eisai, Fronteo, Shionogi, Takeda, Tanabe Mitsubishi and Tsumura within the past three years outside the submitted work. Y.H. has received grants from Grants-in-Aid for Scientific Research B (JP21H02851) and Fund for the Promotion of Joint International Research (Fostering Joint International Research (B)) (JP20KK0193) from JSPS and SIRS Research Fund Award from Schizophrenia International Research Society. S.F. has received a Grant-in-Aid for Grants-in-Aid for Scientific Research B (20H04092) from JSPS and research grants from Keio University Academic Development Funds. H.U. has received grants from Daiichi Sankyo, Eisai, Mochida, Otsuka, and Sumitomo Dainippon Pharma; speaker's fees from Eisai, Janssen, Lundbeck, Meiji Seika Pharma, Otsuka, and Sumitomo Dainippon Pharma; and advisory board fees from Lundbeck, Sumitomo Pharma and Boehringer Ingelheim Japan. N.A. has received a Grant-in-Aid for Early-Career Scientists (JP19K17070) and Meiji Yasuda Mental Health Foundation. K.O. has received a Grant from Inokashira Hospital Research Foundation.