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Brain bioenergetics and redox state measured by 31P magnetic resonance spectroscopy in unaffected siblings of patients with psychotic disorders.

ABSTRACT: 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 31P-magnetic resonance spectroscopy (31P-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 31P-MRS in the frontal lobe (6×6×4cm3) 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 31P-MRS fitting algorithm. 13 unaffected sibling-patient pairs were related; other patients and siblings were unrelated. ANCOVA analyses were used to examine 31P-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, 31P-MRS studies may identify factors related both to risk and expression of psychosis.

SUBMITTER: Chouinard VA

PROVIDER: S-EPMC5581291 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Brain bioenergetics and redox state measured by <sup>31</sup>P magnetic resonance spectroscopy in unaffected siblings of patients with psychotic disorders.

Chouinard Virginie-Anne VA Kim Sang-Young SY Valeri Linda L Yuksel Cagri C Ryan Kyle P KP Chouinard Guy G Cohen Bruce M BM Du Fei F Öngür Dost D

Schizophrenia research 20170301

<h4>Background</h4>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 <sup>31</sup>P-magnetic resonance spectroscopy (<sup>31</sup>P-MRS) in unaffected siblings, compared to first episode psychosis (FEP) patients and healthy controls.<h4>Methods</h4>21 unaffect ...[more]

PMID: 28258794

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Project description:BACKGROUND:Altered structural network-connectivity has been reported in psychotic disorder but whether these alterations are associated with genetic vulnerability, and/or with phenotypic variation, has been less well examined. This study examined i) whether differences in network-connectivity exist between patients with psychotic disorder, siblings of patients with psychotic disorder and controls, and ii) whether network-connectivity alterations vary with (subclinical) symptomatology. METHODS:Network-connectivity measures (global efficiency (GE), density, local efficiency (LE), clustering coefficient (CC)) were derived from diffusion weighted imaging (DWI) and were compared between 85 patients with psychotic disorder, 93 siblings without psychotic disorder and 80 healthy comparison subjects using multilevel regression models. In patients, associations between Positive and Negative Syndrome Scale (PANSS) symptoms and topological measures were examined. In addition, interactions between subclinical psychopathology and sibling/healthy comparison subject status were examined in models of topological measures. RESULTS:While there was no main effect of group with respect to GE, density, LE and CC, siblings had a significantly higher CC compared to patients (B = 0.0039, p = .002). In patients, none of the PANSS symptom domains were significantly associated with any of the four network-connectivity measures. The two-way interaction between group and SIR-r positive score in the model of LE was significant (χ2 = 6.24, p = .01, df = 1). In the model of CC, the interactions between group and respectively SIS-r positive (χ2 = 5.59, p = .02, df = 1) and negative symptom scores (χ2 = 4.71, p = .03, df = 1) were significant. Stratified analysis showed that, in siblings, decreased LE and CC was significantly associated with increased SIS-r positive scores (LE: B = -0.0049, p = .003, CC: B = -0.0066, p = .01) and that decreased CC was significantly associated with increased SIS-r negative scores (B = -0.012, p = .003). There were no significant interactions between group and SIS-r scores in the models of GE and density. CONCLUSION:The findings indicate absence of structural network-connectivity alterations in individuals with psychotic disorder and in individuals at higher than average genetic risk for psychotic disorder, in comparison with healthy subjects. The differential subclinical symptom-network connectivity associations in siblings with respect to controls may be a sign of psychosis vulnerability in the siblings.

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Dataset Information

Brain bioenergetics and redox state measured by 31P magnetic resonance spectroscopy in unaffected siblings of patients with psychotic disorders.

Publications

Brain bioenergetics and redox state measured by <sup>31</sup>P magnetic resonance spectroscopy in unaffected siblings of patients with psychotic disorders.

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