Low peripheral mitochondrial DNA copy number during manic episodes of bipolar disorders is associated with disease severity and inflammation

Angrand, Loïc; Boukouaci, Wahid; Lajnef, Mohamed; Richard, Jean Romain; Andreazza, Ana Cristina; Wu, Chieng Lien; Bouassida, Jihène; Rafik, Ismail; Foiselle, Marianne; Mezouad, Esma; Naamoune, Soumia; Chami, Leila; Mihoub, Ons; Salah, Samir; Benchaaben, Arij; Corvoisier, Philippe Le; Barau, Caroline; Costes, Bruno; Yolken, Robert H.; Crépeaux, Guillemette; Leboyer, Marion; Tamouza, Ryad

doi:10.1016/j.bbi.2021.09.003

Cited by 23 publications

(17 citation statements)

References 72 publications

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“…The decreased mtDNA CN has also been reported in the postmortem hippocampus of BD patients [ 43 ]. Interestingly, peripheral mtDNA CN showed a marked decrease in both SZ [ 36 , 44 , 45 ] and BD [ 35 , 46 – 48 ], in contrast to our postmortem DLPFC mtDNA CN marked increase. This discrepancy might be because the brain tissue has a higher bioenergetics profile than peripheral tissue.…”

Section: Discussioncontrasting

confidence: 90%

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Mitochondria DNA copy number, mitochondria DNA total somatic deletions, Complex I activity, synapse number, and synaptic mitochondria number are altered in schizophrenia and bipolar disorder

et al. 2022

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Mitochondrial dysfunction is a neurobiological phenomenon implicated in the pathophysiology of schizophrenia and bipolar disorder that can synergistically affect synaptic neurotransmission. We hypothesized that schizophrenia and bipolar disorder share molecular alterations at the mitochondrial and synaptic levels. Mitochondria DNA (mtDNA) copy number (CN), mtDNA common deletion (CD), mtDNA total deletion, complex I activity, synapse number, and synaptic mitochondria number were studied in the postmortem human dorsolateral prefrontal cortex (DLPFC), superior temporal gyrus (STG), primary visual cortex (V1), and nucleus accumbens (NAc) of controls (CON), and subjects with schizophrenia (SZ), and bipolar disorder (BD). The results showed (i) the mtDNA CN is significantly higher in DLPFC of both SZ and BD, decreased in the STG of BD, and unaltered in V1 and NAc of both SZ and BD; (ii) the mtDNA CD is significantly higher in DLPFC of BD while unaltered in STG, V1, and NAc of both SZ and BD; (iii) The total deletion burden is significantly higher in DLPFC in both SZ and BD while unaltered in STG, V1, and NAc of SZ and BD; (iv) Complex I activity is significantly lower in DLPFC of both SZ and BD, which is driven by the presence of medications, with no alteration in STG, V1, and NAc. In addition, complex I protein concentration, by ELISA, was decreased across three cortical regions of SZ and BD subjects; (v) The number of synapses is decreased in DLPFC of both SZ and BD, while the synaptic mitochondria number was significantly lower in female SZ and female BD compared to female controls. Overall, these findings will pave the way to understand better the pathophysiology of schizophrenia and bipolar disorder for therapeutic interventions.

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Section: Discussioncontrasting

confidence: 90%

“…Decreased peripheral mtDNA CN has been reported in SZ and BD [ 35 , 36 ]. Peripheral mtDNA CN has also been shown to decrease with aging, although brain tissue mtDNA CN showed no age-related changes [ 37 , 38 ].…”

Section: Resultsmentioning

confidence: 99%

Mitochondria DNA copy number, mitochondria DNA total somatic deletions, Complex I activity, synapse number, and synaptic mitochondria number are altered in schizophrenia and bipolar disorder

et al. 2022

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“…The decreased mtDNA CN has also been reported in postmortem hippocampus of BD patients [27]. Interestingly, peripheral mtDNA CN showed marked decrease in both SZ [21,28,29] and BD [20,30–32] while our postmortem DLPFC mtDNA CN showed marked increase. This discrepancy might be because the brain tissue has higher bioenergetics profile compared to peripheral tissue.…”

Section: Discussionsupporting

confidence: 82%

“…Different tissues have various bioenergetics profiles which makes mtDNA copy number (CN) vary in a tissue-specific (and sometimes age-dependent) manner. Decreased peripheral mtDNA CN has been reported in SZ and BD [20, 21]. Peripheral mtDNA CN has also been shown to decrease with aging, although brain tissue mtDNA CN showed no age-related changes [22, 23].…”

Section: Resultsmentioning

confidence: 99%

mtDNA copy number, mtDNA total somatic deletions, Complex I activity, synapse number and synaptic mitochondria number are altered in schizophrenia and bipolar disorder

Das

Hjelm

Galke

et al. 2022

Preprint

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Mitochondrial dysfunction is a neurobiological phenomenon implicated in the pathophysiology of schizophrenia and bipolar disorder that can synergistically affect synaptic neurotransmission. We hypothesized that schizophrenia and bipolar disorder share molecular alterations at the mitochondrial and synaptic level: mtDNA copy number (CN), mtDNA common deletion (CD), mtDNA total deletion, complex I activity, synapse number, and synaptic mitochondria number. These mitochondrial parameters were studied in dorsolateral prefrontal cortex (DLPFC), superior temporal gyrus (STG), primary visual cortex (V1), and nucleus accumbens (NAc) of 44 controls (CON), 27 schizophrenia (SZ), and 26 bipolar disorder (BD) subjects. The results showed- (i) the mtDNA CN is significantly higher in DLPFC of both SZ and BD, decreased in the STG of BD, and unaltered in V1 and NAc of both SZ and BD; (ii) the mtDNA CD is significantly higher in DLPFC of BD while unaltered in STG, V1 and NAc of both SZ and BD; (iii) The total deletion burden is significantly higher in DLPFC in both SZ and BD while unaltered in STG, V1, and NAc of SZ and BD; (iv) Complex I activity is significantly lower in DLPFC of both SZ and BD with no alteration in STG, V1 and NAc. (v) The number of synapses is decreased in DLPFC of both SZ and BD, while the synaptic mitochondria number was significantly lower in female SZ and female BD compared to female controls. Overall, these findings will pave the way to better understand the pathophysiology of schizophrenia and bipolar disorder for therapeutic interventions.

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“…For instance, a reduction in peripheral blood mtDNA-CN was correlated with the development of multiple sclerosis [ 30 ]. Lower peripheral mtDNA-CN was also associated with adverse clinical outcomes in peritoneal dialysis patients [ 43 ] as well as with the severity and inflammation in bipolar disorder [ 44 ]. Moreover, reduced mtDNA-CN has been shown to precede the development of type 2 diabetes [ 45 ] and observed in the early stages of neurodegenerative disorders including multiple sclerosis [ 30 ], Parkinson’s disease [ 46 ] and Alzheimer’s disease [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Leukocyte mitochondrial DNA copy number is a potential non-invasive biomarker for psoriasis

2022

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Abnormalities in the mitochondria have been linked to psoriasis, a chronic immune-mediated inflammatory skin disease. The mitochondrial DNA (mtDNA) is present in thousands of copies per cell and altered mtDNA copy number (mtDNA-CN), a common indicator of mitochondrial function, has been proposed as a biomarker for several diseases including autoimmune diseases. In this case–control study, we investigated whether the mtDNA-CN is related to psoriasis, correlates with the disease duration and severity, and can serve as a disease biomarker. Relative mtDNA-CN as compared with nuclear DNA was measured by a quantitative real-time polymerase chain reaction in peripheral blood buffy coat samples from 56 patients with psoriasis and 44 healthy controls. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the value of mtDNA-CN as a biomarker. We found that the mtDNA-CN was significantly decreased in patients with psoriasis compared to healthy controls (93.6±5.3 vs. 205±71; P = 0.04). Sub-group analyses with stratification of patients based on disease duration under or over 10 years and disease severity indicated that the mtDNA-CN was significantly lower in patients with longer disease duration (74±4.3 in disease duration >10 years vs. 79±8.3 in disease duration <10 years, P = 0.009), and higher disease severity (72±4.3 in moderate-to-severe index vs. 88.3 ± 6 in mild index, P = 0.017). Moreover, the mtDNA-CN was negatively correlated with the disease duration and disease severity (r = -0.36, P = 0.006; r = -0.41, P = 0.003 respectively). The ROC analysis of mtDNA-CN showed an area under the curve (AUC) of 0.84 (95% confidence interval: 0.69–0.98; P = 0.002) for differentiating patients from healthy controls. Our study suggests that low mtDNA-CN may be an early abnormality in psoriasis and associates with the disease progression. Our study also suggests that mtDNA-CN may be a novel blood-based biomarker for the early detection of psoriasis.

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Low peripheral mitochondrial DNA copy number during manic episodes of bipolar disorders is associated with disease severity and inflammation

Cited by 23 publications

References 72 publications

Mitochondria DNA copy number, mitochondria DNA total somatic deletions, Complex I activity, synapse number, and synaptic mitochondria number are altered in schizophrenia and bipolar disorder

Mitochondria DNA copy number, mitochondria DNA total somatic deletions, Complex I activity, synapse number, and synaptic mitochondria number are altered in schizophrenia and bipolar disorder

mtDNA copy number, mtDNA total somatic deletions, Complex I activity, synapse number and synaptic mitochondria number are altered in schizophrenia and bipolar disorder

Leukocyte mitochondrial DNA copy number is a potential non-invasive biomarker for psoriasis

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