Gamma-aminobutyric acid (GABA) levels in the midcingulate cortex and clozapine response in patients with treatment-resistant schizophrenia: A proton magnetic resonance spectroscopy (1H-MRS) study

被引：19

作者：

Ueno, Fumihiko ^{[1
,2
,3
]}

Nakajima, Shinichiro ^{[1
,2
]}

Iwata, Yusuke ^{[4
]}

Honda, Shiori ^{[2
]}

Torres-Carmona, Edgardo ^{[1
,5
]}

Mar, Wanna ^{[1
]}

Tsugawa, Sakiko ^{[2
]}

Truong, Peter ^{[1
]}

Plitman, Eric ^{[3
]}

Noda, Yoshihiro ^{[2
]}

Mimura, Masaru ^{[2
]}

Sailasuta, Napapon ^{[6
]}

Mikkelsen, Mark ^{[7
]}

Edden, Richard A. E. ^{[8
,9
]}

De Luca, Vincenzo ^{[3
,5
,10
]}

Remington, Gary ^{[3
,5
,10
]}

Gerretsen, Philip ^{[1
,3
,5
,10
]}

Graff-Guerrero, Ariel ^{[1
,3
,5
,10
]}

机构：

[1] Ctr Addict & Mental Hlth CAMH, Brain Hlth Imaging Ctr, Toronto, ON, Canada

[2] Keio Univ, Dept Neuropsychiat, Sch Med, Tokyo, Japan

[3] Univ Toronto, Dept Psychiat, Toronto, ON, Canada

[4] Univ Yamanashi, Dept Neuropsychiat, Fac Med, Chuo, Japan

[5] Univ Toronto, Inst Med Sci, Toronto, ON, Canada

[6] Univ Hawaii, Dept Trop Med, Honolulu, HI 96822 USA

[7] Weill Cornell Med, Dept Radiol, New York, NY USA

[8] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA

[9] Kennedy Krieger Inst, FM Kirby Res Ctr Funct Brain Imaging, Baltimore, MD USA

[10] CAMH, Campbell Family Mental Hlth Res Inst, Toronto, ON, Canada

来源：

PSYCHIATRY AND CLINICAL NEUROSCIENCES | 2022年 / 76卷 / 11期

关键词：

1H-MRS; Clozapine; GABA; MEGA-PRESS; treatment-resistant schizophrenia; ANTIPSYCHOTIC TREATMENT; IN-VIVO; GLUTAMATE; VALIDATION; PSYCHOSIS; PRESS; SCALE; MINI;

D O I：

10.1111/pcn.13463

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background Gamma-Aminobutyric Acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. GABAergic dysfunction has been implicated in the pathophysiology of schizophrenia. Clozapine, the only approved drug for treatment-resistant schizophrenia (TRS), involves the GABAergic system as one of its targets. However, no studies have investigated the relationship between brain GABA levels, as measured by proton magnetic resonance spectroscopy (H-1-MRS), and clozapine response in patients with TRS. Methods This study enrolled patients with TRS who did not respond to clozapine (ultra-resistant schizophrenia: URS) and who responded to clozapine (non-URS), patients with schizophrenia who responded to first-line antipsychotics (first-line responders: FLR), and healthy controls (HCs). We measured GABA levels in the midcingulate cortex (MCC) using 3T H-1-MRS and compared these levels among the groups. The associations between GABA levels and symptom severity were also explored within the patient groups. Results A total of 98 participants (URS: n = 22; non-URS: n = 25; FLR: n = 16; HCs: n = 35) completed the study. We found overall group differences in MCC GABA levels (F(3,86) = 3.25, P = 0.04). Specifically, patients with URS showed higher GABA levels compared to those with non-URS (F(1,52) = 8.40, P = 0.03, Cohen's d = 0.84). MCC GABA levels showed no associations with any of the symptom severity scores within each group or the entire patient group. Conclusion Our study is the first to report elevated GABA levels in the MCC in patients with schizophrenia resistant to clozapine treatment compared with those responsive to clozapine. Longitudinal studies are required to evaluate if GABA levels are a suitable biomarker to predict clozapine resistance.

引用

页码：587 / 594

页数：8

共 40 条

[11] Gannet: A Batch-Processing Tool for the Quantitative Analysis of Gamma-Aminobutyric Acid-Edited MR Spectroscopy Spectra [J].