N-acetylcysteine in a Double-Blind Randomized Placebo-Controlled Trial: Toward Biomarker-Guided Treatment in Early Psychosis

被引：121

作者：

Conus, Philippe ^{[1
]}

Seidman, Larry J. ^{[2
]}

Fournier, Margot ^{[3
]}

Xin, Lijing ^{[4
]}

Cleusix, Martine ^{[3
]}

Baumann, Philipp S. ^{[1
,3
]}

Ferrari, Carina ^{[3
]}

Cousins, Ann ^{[2
]}

Alameda, Luis ^{[1
,3
]}

Gholam-Rezaee, Mehdi ^{[1
]}

Golay, Philippe ^{[1
]}

Jenni, Raoul ^{[3
]}

Woo, T. -U. Wilson ^{[2
,5
]}

Keshavan, Matcheri S. ^{[2
]}

Eap, Chin B. ^{[6
,7
]}

Wojcik, Joanne ^{[2
]}

Cuenod, Michel ^{[3
]}

Buclin, Thierry ^{[8
]}

Gruetter, Rolf ^{[9
]}

Do, Kim Q. ^{[3
]}

机构：

[1] Lausanne Univ Hosp CHUV, Dept Psychiat, TIPP Treatment & Early Intervent Psychosis Progra, Serv Gen Psychiat, Lausanne, Switzerland

[2] Harvard Med Sch, Massachusetts Mental Hlth Ctr, Beth Israel Deaconess Med Ctr, Publ Psychiat Div,Dept Psychiat, Boston, MA USA

[3] Lausanne Univ Hosp CHUV, Dept Psychiat, Ctr Psychiat Neurosci, Lausanne, Switzerland

[4] Ecole Polytech Fed Lausanne, Ctr Biomed Imaging CIBM, Anim Imaging & Technol Core AIT, Lausanne, Switzerland

[5] Harvard Med Sch, McLean Hosp, Dept Psychiat, Belmont, MA USA

[6] Lausanne Univ Hosp CHUV, Dept Psychiat, Unit Pharmacogenet & Clin Psychopharmacol, Lausanne, Switzerland

[7] Univ Geneva, Univ Lausanne, Sch Pharmaceut Sci, Geneva, Switzerland

[8] Lausanne Univ Hosp CHUV, Div Clin Pharmacol, Lausanne, Switzerland

[9] Ecole Polytech Fed Lausanne, Lab Funct & Metab Imaging, Lausanne, Switzerland

来源：

SCHIZOPHRENIA BULLETIN | 2018年 / 44卷 / 02期

基金：

瑞士国家科学基金会;

关键词：

glutathione; glutathione peroxidase; schizophrenia; MRS; prefrontal cortex; neurocognition; CONSENSUS COGNITIVE BATTERY; OXIDATIVE STRESS; NEGATIVE SYMPTOMS; 1ST-EPISODE SCHIZOPHRENIA; PHARMACOLOGICAL-TREATMENT; NEUROCOGNITIVE DEFICITS; GLUTATHIONE PRECURSOR; CEREBROSPINAL-FLUID; PREFRONTAL CORTEX; ACETYL-CYSTEINE;

D O I：

10.1093/schbul/sbx093

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

Biomarker-guided treatments are needed in psychiatry, and previous data suggest oxidative stress may be a target in schizophrenia. A previous add-on trial with the antioxidant N-acetylcysteine (NAC) led to negative symptom reductions in chronic patients. We aim to study NAC's impact on symptoms and neurocognition in early psychosis (EP) and to explore whether glutathione (GSH)/redox markers could represent valid biomarkers to guide treatment. In a double-blind, randomized, placebo-controlled trial in 63 EP patients, we assessed the effect of NAC supplementation (2700 mg/day, 6 months) on PANSS, neurocognition, and redox markers (brain GSH [GSH(mPFC)], blood cells GSH levels [GSH(BC)], GSH peroxidase activity [GPx(BC)]). No changes in negative or positive symptoms or functional outcome were observed with NAC, but significant improvements were found in favor of NAC on neurocognition (processing speed). NAC also led to increases of GSH(mPFC) by 23% (P =.005) and GSH(BC) by 19% (P =.05). In patients with high-baseline GPx(BC) compared to low-baseline GPx(BC), subgroup explorations revealed a link between changes of positive symptoms and changes of redox status with NAC. In conclusion, NAC supplementation in a limited sample of EP patients did not improve negative symptoms, which were at modest baseline levels. However, NAC led to some neurocognitive improvements and an increase in brain GSH levels, indicating good target engagement. Blood GPx activity, a redox peripheral index associated with brain GSH levels, could help identify a subgroup of patients who improve their positive symptoms with NAC. Thus, future trials with antioxidants in EP should consider biomarkerguided treatment.

引用

页码：317 / 327

页数：11

共 57 条

[1] Antipsychotic Dose Equivalents and Dose-Years: A Standardized Method for Comparing Exposure to Different Drugs [J].