Leukocyte mitochondrial DNA copy number in schizophrenia

Shivakumar, Venkataram; Rajasekaran, Ashwini; Subbanna, Manjula; Kalmady, Sunil V.; Venugopal, Deepthi; Agrawal, Rimjhim; Amaresha, Anekal C.; Agarwal, Sri Mahavir; Joseph, Boban; Narayanaswamy, Janardhanan C.; Debnath, Monojit; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N.

doi:10.1016/j.ajp.2020.102193

Cited by 15 publications

(13 citation statements)

References 54 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: 91%

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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: 91%

“…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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“…The same trends were reported for cell-free circulating MCN (ccf-MCN) in plasma, which has been proposed as a more accurate biomarker for mitochondrial disruption, with decreased (79) or increased (24) ccf-MCN. Only a few studies have looked for MCN in the blood of schizophrenic patients; they have found a slight decrease in MCN among patients when compared to the controls (80)(81)(82); although no difference in ccf-MCN was observed (79). Studies on mtDNA integrity, i.e., point mutation or deletion, are scant but the general trend shows increased mtDNA damage among patients with psychiatric disorders (25,27).…”

Section: Discussionmentioning

confidence: 99%

Mental Disorders Are Associated With Leukocytes Telomere Shortening Among People Who Inject Drugs

et al. 2022

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Premature biological aging, assessed by shorter telomere length (TL) and mitochondrial DNA (mtDNA) alterations, has been reported among people with major depressive disorders or psychotic disorders. However, these markers have never been assessed together among people who inject drugs (PWIDs), although mental disorders are highly prevalent in this population, which, in addition, is subject to other aggravating exposures. Diagnosis of mental disorders was performed by a psychiatrist using the Mini International Neuropsychiatric Interview test among active PWIDs in Haiphong, Vietnam. mtDNA copy number (MCN), mtDNA deletion, and TL were assessed by quantitative PCR and compared to those without any mental disorder. We next performed a multivariate analysis to identify risk factors associated with being diagnosed with a major depressive episode (MDE) or a psychotic syndrome (PS). In total, 130 and 136 PWIDs with and without psychiatric conditions were analyzed. Among PWIDs with mental disorders, 110 and 74 were diagnosed with MDE and PS, respectively. TL attrition was significantly associated with hepatitis C virus-infected PWIDs with MDE or PS (adjusted odds ratio [OR]: 0.53 [0.36; 0.80] and 0.59 [0.39; 0.88], respectively). TL attrition was even stronger when PWIDs cumulated at least two episodes of major depressive disorders. On the other hand, no difference was observed in mtDNA alterations between groups. The telomeric age difference with drug users without a diagnosis of psychiatric condition was estimated during 4.2–12.8 years according to the number of MDEs, making this group more prone to age-related diseases.

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Leukocyte mitochondrial DNA copy number in schizophrenia

Cited by 15 publications

References 54 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

Mental Disorders Are Associated With Leukocytes Telomere Shortening Among People Who Inject Drugs

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