Brain cytochrome-c-oxidase as a marker of mitochondrial function: a pilot study in major depression using NIRS
| Autor: | J. John Mann, Elizabeth M. Sublette, Lisa Holper, Patrick J. Brown, Martin J. Lan, Ainsley K. Burke |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male medicine.medical_specialty Population Pilot Projects Article Electron Transport Complex IV 03 medical and health sciences Young Adult 0302 clinical medicine Internal medicine medicine Humans Bipolar disorder education Inner mitochondrial membrane Major depressive episode Aged Aged 80 and over education.field_of_study Brain Mapping Depressive Disorder Major Spectroscopy Near-Infrared business.industry Brain Middle Aged medicine.disease 030227 psychiatry Mitochondria Psychiatry and Mental health Clinical Psychology Endocrinology Cerebral blood flow Mood disorders Biomarker (medicine) Major depressive disorder Female medicine.symptom business 030217 neurology & neurosurgery Biomarkers |
| Zdroj: | Depress Anxiety |
| Popis: | Background Brain mitochondrial dysfunction is implicated in the pathophysiology of mood disorders. Brain cytochrome‐c‐oxidase (COX) activity is associated with the mitochondrial function. Near‐infrared spectroscopy (NIRS) noninvasively measures oxidized COX (oxCOX) and tissue oxygenation index (TOI) reflecting cerebral blood flow and oxygenation. Methods oxCOX and TOI were assessed in prefrontal cortex (Fp1/2, Brodmann area 10) in patients in a major depressive episode (N = 13) with major depressive disorder (MDD; N = 7) and bipolar disorder (BD; N = 6) compared with the controls (N = 10). One patient with MDD and all the patients with BD were taking medications. Computational modeling estimated oxCOX and TOI related indices of mitochondrial function and cerebral blood flow, respectively. Results oxCOX was lower in patients than controls (p = .014) correlating inversely with depression severity (r = −.72; p = .006), driven primarily by lower oxCOX in BD compared with the controls. Computationally modeled mitochondrial parameters of the electron transport chain, such as the nicotinamide adenine dinucleotide ratio (NAD+/NADH; p = .001) and the proton leak rate across the inner mitochondrial membrane (klk2; p = .008), were also lower in patients and correlated inversely with depression severity. No such effects were found for TOI. Conclusions In this pilot study, oxCOX and related mitochondrial parameters assessed by NIRS indicate an abnormal cerebral metabolic state in mood disorders proportional to depression severity, potentially providing a biomarker of antidepressant effect. Because the effect was driven by the medicated BD group, findings need to be evaluated in a larger, medication‐free population. |
| Databáze: | OpenAIRE |
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