Chouinard Virginie-Anne, Kim Sang-Young, Valeri Linda, Yuksel Cagri, Ryan Kyle P, Chouinard Guy, Cohen Bruce M, Du Fei, Öngür Dost
Psychotic Disorders Division, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Psychotic Disorders Division, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Schizophr Res. 2017 Sep;187:11-16. doi: 10.1016/j.schres.2017.02.024. Epub 2017 Mar 1.
Brain bioenergetic anomalies and redox dysregulation have been implicated in the pathophysiology of psychotic disorders. The present study examined brain energy-related metabolites and the balance between nicotinamide adenine dinucleotide metabolites (oxidized NAD+ and reduced NADH) using P-magnetic resonance spectroscopy (P-MRS) in unaffected siblings, compared to first episode psychosis (FEP) patients and healthy controls.
21 unaffected siblings, 32 FEP patients (including schizophrenia spectrum and affective psychoses), and 21 controls underwent P-MRS in the frontal lobe (6×6×4cm) on a 4T MR scanner, using custom-designed dual-tuned surface coil with outer volume suppression. Brain parenchymal pH and steady-state metabolite ratios of high energy phosphate compounds were measured. NAD+ and NADH levels were determined using a P-MRS fitting algorithm. 13 unaffected sibling-patient pairs were related; other patients and siblings were unrelated. ANCOVA analyses were used to examine P-MRS measures, with age and gender as covariates.
The phosphocreatine/adenosine triphosphate ratio was significantly reduced in both unaffected siblings and FEP patients, compared to controls. NAD+/NADH ratio was significantly reduced in patients compared to siblings and controls, with siblings showing a reduction in NAD+/NADH compared to controls that was not statistically significant. Compared to patients and controls, siblings showed significantly reduced levels of NAD+. Siblings did not differ from patients or controls on brain pH.
Our results indicate that unaffected siblings show some, but not all the same abnormalities in brain energy metabolites and redox state as FEP patients. Thus, P-MRS studies may identify factors related both to risk and expression of psychosis.
脑生物能量异常和氧化还原失调与精神障碍的病理生理学有关。本研究使用磷磁共振波谱（P-MRS）检测了未患病的同胞、首发精神病（FEP）患者和健康对照者大脑中与能量相关的代谢物以及烟酰胺腺嘌呤二核苷酸代谢物（氧化型NAD⁺和还原型NADH）之间的平衡。
21名未患病的同胞、32名FEP患者（包括精神分裂症谱系和情感性精神病患者）以及21名对照者在4T磁共振成像扫描仪上，使用定制设计的带有外容积抑制的双调谐表面线圈，在额叶（6×6×4cm）进行P-MRS检查。测量脑实质pH值和高能磷酸化合物的稳态代谢物比率。使用P-MRS拟合算法测定NAD⁺和NADH水平。13对未患病的同胞-患者对具有亲属关系；其他患者和同胞无亲属关系。采用协方差分析（ANCOVA）来检验P-MRS测量结果，将年龄和性别作为协变量。
与对照组相比，未患病的同胞和FEP患者的磷酸肌酸/三磷酸腺苷比率均显著降低。与同胞和对照组相比，患者的NAD⁺/NADH比率显著降低，同胞的NAD⁺/NADH比率与对照组相比有所降低，但差异无统计学意义。与患者和对照组相比，同胞的NAD⁺水平显著降低。同胞在脑pH值方面与患者或对照组无差异。
我们的结果表明，未患病的同胞在脑能量代谢物和氧化还原状态方面表现出一些但并非所有与FEP患者相同的异常。因此，P-MRS研究可能会识别出与精神病风险和表达相关的因素。
