Brain metabolite levels in remitted psychotic depression with consideration of effects of antipsychotic medication,Brain Imaging and Behavior

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Brain metabolite levels in remitted psychotic depression with consideration of effects of antipsychotic medication
Brain Imaging and Behavior ( IF 2.4 ) Pub Date : 2023-11-02 , DOI: 10.1007/s11682-023-00807-0
Hideaki Tani _{1,

2} , Iska Moxon-Emre ₁ , Natalie J Forde _{1,

3} , Nicholas H Neufeld ₁ , Kathleen S Bingham ₄ , Ellen M Whyte ₅ , Barnett S Meyers ₆ , George S Alexopoulos ₆ , Matthew J Hoptman _{7,

8} , Anthony J Rothschild ₉ , Hiroyuki Uchida ₂ , Alastair J Flint ₄ , Benoit H Mulsant ₁ , Aristotle N Voineskos ₁

Affiliation

Centre for Addiction and Mental Health and Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada.
Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan.
Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
University Health Network and Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada.
Department of Psychiatry, University of Pittsburgh School of Medicine and UPMC Western Psychiatric Hospital, Pittsburgh, PA, USA.
Department of Psychiatry, Weill Medical College of Cornell University and New York Presbyterian Hospital, White Plains, NY, USA.
Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
Department of Psychiatry, New York University School of Medicine, New York, NY, USA.
University of Massachusetts Medical School and UMass Memorial Health Care, Worcester, MA, USA.

Background

The neurobiology of psychotic depression is not well understood and can be confounded by antipsychotics. Magnetic resonance spectroscopy (MRS) is an ideal tool to measure brain metabolites non-invasively. We cross-sectionally assessed brain metabolites in patients with remitted psychotic depression and controls. We also longitudinally assessed the effects of olanzapine versus placebo on brain metabolites.

Methods

Following remission, patients with psychotic depression were randomized to continue sertraline + olanzapine (n = 15) or switched to sertraline + placebo (n = 18), at which point they completed an MRS scan. Patients completed a second scan either 36 weeks later, relapse, or discontinuation. Where water-scaled metabolite levels were obtained and a Point-RESolved Spectroscopy sequence was utilized, choline, myo-inositol, glutamate + glutamine (Glx), N-acetylaspartate, and creatine were measured in the left dorsolateral prefrontal cortex (L-DLPFC) and dorsal anterior cingulate cortex (dACC). An ANCOVA was used to compare metabolites between patients (n = 40) and controls (n = 46). A linear mixed-model was used to compare olanzapine versus placebo groups.

Results

Cross-sectionally, patients (compared to controls) had higher myo-inositol (standardized mean difference [SMD] = 0.84; 95%CI = 0.25–1.44; p = 0.005) in the dACC but not different Glx, choline, N-acetylaspartate, and creatine. Longitudinally, patients randomized to placebo (compared to olanzapine) showed a significantly greater change with a reduction of creatine (SMD = 1.51; 95%CI = 0.71–2.31; p = 0.0002) in the dACC but not glutamate + glutamine, choline, myo-inositol, and N-acetylaspartate.

Conclusions

Patients with remitted psychotic depression have higher myo-inositol than controls. Olanzapine may maintain creatine levels. Future studies are needed to further disentangle the mechanisms of action of olanzapine.

中文翻译：

考虑抗精神病药物的影响，缓解精神病性抑郁症的脑代谢水平

背景

精神病性抑郁症的神经生物学尚不清楚，并且可能被抗精神病药物所混淆。磁共振波谱（MRS）是非侵入性测量大脑代谢物的理想工具。我们对精神病性抑郁症缓解患者和对照组的脑代谢进行了横断面评估。我们还纵向评估了奥氮平与安慰剂对脑代谢物的影响。

方法

缓解后，精神病性抑郁症患者被随机分配继续服用舍曲林 + 奥氮平 ( n = 15) 或改用舍曲林 + 安慰剂 ( n = 18)，此时他们完成了 MRS 扫描。患者在 36 周后完成第二次扫描，要么复发，要么停药。在获得水标代谢物水平并利用点解析光谱序列的情况下，在左背外侧前额皮质 (L-DLPFC) 中测量胆碱、肌醇、谷氨酸 + 谷氨酰胺 (Glx)、 N-乙酰天冬氨酸和肌酸和背侧前扣带皮层（dACC）。使用 ANCOVA 比较患者 ( n = 40) 和对照组 ( n = 46) 之间的代谢物。使用线性混合模型来比较奥氮平组与安慰剂组。

结果

横断面来看，患者（与对照组相比）dACC 中的肌醇较高（标准化平均差 [SMD] = 0.84；95%CI = 0.25–1.44； p = 0.005），但 Glx、胆碱、 N-乙酰天冬氨酸没有不同。和肌酸。纵向上，随机接受安慰剂的患者（与奥氮平相比）显示出显着更大的变化，dACC 中肌酸减少（SMD = 1.51；95%CI = 0.71–2.31； p = 0.0002），但谷氨酸 + 谷氨酰胺、胆碱、肌酸没有减少。 -肌醇和N-乙酰天冬氨酸。