Skip to main content

Advertisement

Log in

Quantification of total mitochondrial DNA and mitochondrial common deletion in the frontal cortex of patients with schizophrenia and bipolar disorder

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

Data published during the last decade are suggestive of a role for mitochondrial dysfunction in the pathogenesis of schizophrenia, bipolar disorder and other psychiatric diseases. In order to determine if the mitochondrial deficits reported in the literature are caused by abnormalities in the mitochondrial DNA of psychiatric patients, we quantified mitochondrial DNA (mtDNA) levels and the 5 kb common mitochondrial deletion (CD) in postmortem frontal cortex tissue. The mitochondrial CD and mtDNA levels were measured in tissue obtained from the frontal cortex (Brodmann Area 46) of 144 individuals (45 patients with schizophrenia, 40 patients with bipolar disorder, 44 controls, and 15 patients with major depression). These variables were measured using newly developed SYBR green and TaqMan real time PCR assays.

Both the TaqMan and the SYBR green assays gave similar results. There was no statistically significant difference for the quantity of the common mitochondrial deletion between controls and patients. We also did not detect a difference in the mtDNA levels amongst the diagnosis groups. There were statistically significant differences for the evaluated parameters for smokers, schizophrenic patients on antipsychotic drugs at time of death, and bipolar patients with antidepressant use and alcohol abuse. Based on this study and other reports, we conclude that neither the common mitochondrial deletion nor changes in mitochondrial DNA levels are likely to account for the mitochondrial changes associated with bipolar disorder or schizophrenia. The effect of premortem agonal factors and medication on mitochondrial dysfunction still needs further elucidation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • CA Altar LW Jurata V Charles A Lemire P Liu Y Bukhman et al. (2005) ArticleTitleDeficient hippocampal neuron expression of proteasome, ubiquitin, and mitochondrial genes in multiple schizophrenia cohorts Biol Psychiatry 58 85–96 Occurrence Handle16038679 Occurrence Handle10.1016/j.biopsych.2005.03.031 Occurrence Handle1:CAS:528:DC%2BD2MXmsVWrsb8%3D

    Article  PubMed  CAS  Google Scholar 

  • HJ Bandelt YG Yao T Kivisild (2005) ArticleTitleMitochondrial genes and schizophrenia Schizophr Res 72 267–269 Occurrence Handle15560971 Occurrence Handle10.1016/j.schres.2004.05.003

    Article  PubMed  Google Scholar 

  • MF Beal (2005) ArticleTitleMitochondria take center stage in aging and neurodegeneration Ann Neurol 58 495–505 Occurrence Handle16178023 Occurrence Handle10.1002/ana.20624 Occurrence Handle1:CAS:528:DC%2BD2MXhtFGrs7fE

    Article  PubMed  CAS  Google Scholar 

  • A Bender KJ Krishnan CM Morris GA Taylor AK Reeve RH Perry E Jaros JS Hersheson J Betts T Klopstock RW Taylor DM Turnbull (2006) ArticleTitleHigh levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson’s disease Nat Genet 38 515–517 Occurrence Handle16604074 Occurrence Handle10.1038/ng1769 Occurrence Handle1:CAS:528:DC%2BD28XjvVGksbs%3D

    Article  PubMed  CAS  Google Scholar 

  • AG Bruce AM Bakke ME Thouless TM Rose (2005) ArticleTitleDevelopment of a real-time QPCR assay for the detection of RV2 lineage-specific rhadinoviruses in macaques and baboons Virol J 2 2 Occurrence Handle15634356 Occurrence Handle10.1186/1743-422X-2-2 Occurrence Handle1:CAS:528:DC%2BD2MXjsVaitbk%3D

    Article  PubMed  CAS  Google Scholar 

  • L Cavelier EE Jazin I Eriksson J Prince U Bave L Oreland et al. (1995) ArticleTitleDecreased cytochrome-c oxidase activity and lack of age-related accumulation of mitochondrial DNA deletions in the brains of schizophrenics Genomics 29 217–224 Occurrence Handle8530074 Occurrence Handle10.1006/geno.1995.1234 Occurrence Handle1:CAS:528:DyaK2MXotF2hurc%3D

    Article  PubMed  CAS  Google Scholar 

  • M Corral-Debrinski T Horton MT Lott JM Shoffner MF Beal DC Wallace (1992) ArticleTitleMitochondrial DNA deletions in human brain: regional variability and increase with advanced age Nat Genet 2 324–329 Occurrence Handle1303288 Occurrence Handle10.1038/ng1292-324 Occurrence Handle1:CAS:528:DyaK3sXnvVGntQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • SR Dager SD Friedman et al. (2004) ArticleTitleBrain metabolic alterations in medication-free patients with bipolar disorder Arch Gen Psychiatry 61 450–458 Occurrence Handle15123489 Occurrence Handle10.1001/archpsyc.61.5.450 Occurrence Handle1:CAS:528:DC%2BD2cXkslektbg%3D

    Article  PubMed  CAS  Google Scholar 

  • S Dimauro G Davidzon (2005) ArticleTitleMitochondrial DNA and disease Ann Med 37 222–232 Occurrence Handle16019721 Occurrence Handle10.1080/07853890510007368 Occurrence Handle1:CAS:528:DC%2BD2MXkt1Skt7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • H Fukuzako (2001) ArticleTitleNeurochemical investigation of the schizophrenic brain by in vivo phosphorus magnetic resonance spectroscopy World J Biol Psychiatry 2 70–82 Occurrence Handle12587188 Occurrence Handle1:STN:280:DC%2BD3s%2Fns1yktg%3D%3D Occurrence Handle10.3109/15622970109027496

    Article  PubMed  CAS  Google Scholar 

  • K Iwamoto M Bundo T Kato (2005) ArticleTitleAltered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis Hum Mol Genet 14 241–253 Occurrence Handle15563509 Occurrence Handle10.1093/hmg/ddi022 Occurrence Handle1:CAS:528:DC%2BD2MXitFGksw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • C Kakiuchi M Ishiwata M Kametani C Nelson K Iwamoto T Kato (2005) ArticleTitleQuantitative analysis of mitochondrial DNA deletions in the brains of patients with bipolar disorder and schizophrenia Int J Neuropsychopharmacol 8 515–522 Occurrence Handle16202181 Occurrence Handle10.1017/S1461145705005213 Occurrence Handle1:CAS:528:DC%2BD2MXhtVKls7jN

    Article  PubMed  CAS  Google Scholar 

  • T Kato S Takahashi et al. (1993) ArticleTitleAlterations in brain phosphorous metabolism in bipolar disorder detected by in vivo 31P and 7Li magnetic resonance spectroscopy J Affect Disord 27 53–59 Occurrence Handle8432961 Occurrence Handle10.1016/0165-0327(93)90097-4 Occurrence Handle1:STN:280:DyaK3s7mtlCruw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • T Kato OC Stine et al. (1997) ArticleTitleIncreased levels of a mitochondrial DNA deletion in the brain of patients with bipolar disorder Biol Psychiatry 42 871–875 Occurrence Handle9359971 Occurrence Handle10.1016/S0006-3223(97)00012-7 Occurrence Handle1:STN:280:DyaK1c%2FisVaksA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • AA Kazuno K Munakata K Mori M Tanaka S Nanko H Kunugi et al. (2005) ArticleTitleMitochondrial DNA sequence analysis of patients with ‘atypical psychosis’ Psychiatry Clin Neurosci 59 497–503 Occurrence Handle16048457 Occurrence Handle10.1111/j.1440-1819.2005.01404.x Occurrence Handle1:CAS:528:DC%2BD2MXps1Krs7c%3D

    Article  PubMed  CAS  Google Scholar 

  • MS Keshavan JA Stanley JW Pettegrew (2000) ArticleTitleMagnetic resonance spectroscopy in schizophrenia: methodological issues and findings-part II Biol Psychiatry 48 369–380 Occurrence Handle10978720 Occurrence Handle10.1016/S0006-3223(00)00940-9 Occurrence Handle1:CAS:528:DC%2BD3cXmtF2qsrk%3D

    Article  PubMed  CAS  Google Scholar 

  • C Konradi M Eaton ML MacDonald J Walsh FM Benes S Heckers (2004) ArticleTitleMolecular evidence for mitochondrial dysfunction in bipolar disorder Arch Gen Psychiatry 61 300–308 Occurrence Handle14993118 Occurrence Handle10.1001/archpsyc.61.3.300 Occurrence Handle1:CAS:528:DC%2BD2cXislylurY%3D

    Article  PubMed  CAS  Google Scholar 

  • Y Kraytsberg E Kudryavtseva AC McKee C Geula NW Kowall K Khrapko (2006) ArticleTitleMitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons Nat Genet 38 518–520 Occurrence Handle16604072 Occurrence Handle10.1038/ng1778 Occurrence Handle1:CAS:528:DC%2BD28XjvVGktr0%3D

    Article  PubMed  CAS  Google Scholar 

  • JZ Li MP Vawter et al. (2004) ArticleTitleSystematic changes in gene expression in postmortem human brains associated with tissue pH and terminal medical conditions Hum Mol Genet 13 609–616 Occurrence Handle14734628 Occurrence Handle10.1093/hmg/ddh065 Occurrence Handle1:CAS:528:DC%2BD2cXhs12ktL4%3D

    Article  PubMed  CAS  Google Scholar 

  • C Mawrin E Kirches K Dietzmann (2003) ArticleTitleSingle-cell analysis of mtDNA in amyotrophic lateral sclerosis: towards the characterization of individual neurons in neurodegenerative disorders Pathol Res Pract 199 415–418 Occurrence Handle12924443 Occurrence Handle10.1078/0344-0338-00439 Occurrence Handle1:CAS:528:DC%2BD3sXot1Sjtbc%3D

    Article  PubMed  CAS  Google Scholar 

  • C Mawrin E Kirches G Krause FR Wiedemann CK Vorwerk B Bogerts et al. (2004a) ArticleTitleSingle-cell analysis of mtDNA deletion levels in sporadic amyotrophic lateral sclerosis Neuroreport 15 939–943 Occurrence Handle10.1097/00001756-200404290-00002 Occurrence Handle1:CAS:528:DC%2BD2cXkvFajurw%3D

    Article  CAS  Google Scholar 

  • C Mawrin E Kirches G Krause R Schneider-Stock B Bogerts CK Vorwerk et al. (2004b) ArticleTitleRegion-specific analysis of mitochondrial DNA deletions in neurodegenerative disorders in humans Neurosci Lett 357 111–114 Occurrence Handle10.1016/j.neulet.2003.11.073 Occurrence Handle1:CAS:528:DC%2BD2cXhsVKhtrg%3D

    Article  CAS  Google Scholar 

  • S Prabakaran JE Swatton MM Ryan SJ Huffaker JT Huang JL Griffin et al. (2004) ArticleTitleMitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress Mol Psychiatry 9 684–697 Occurrence Handle15098003 Occurrence Handle10.1038/sj.mp.4001532 Occurrence Handle1:CAS:528:DC%2BD2cXltFWntLs%3D

    Article  PubMed  CAS  Google Scholar 

  • JA Prince MS Yassin L Oreland (1997) ArticleTitleNormalization of cytochrome-c oxidase activity in the rat brain by neuroleptics after chronic treatment with PCP or methamphetamine Neuropharmacology 36 1665–1678 Occurrence Handle9517438 Occurrence Handle10.1016/S0028-3908(97)00152-4 Occurrence Handle1:CAS:528:DyaK1cXhsFCns78%3D

    Article  PubMed  CAS  Google Scholar 

  • JA Prince K Blennow CG Gottfries I Karlsson L Oreland (1999) ArticleTitleMitochondrial function is differentially altered in the basal ganglia of chronic schizophrenics Neuropsychopharmacology 21 372–379 Occurrence Handle10457534 Occurrence Handle10.1016/S0893-133X(99)00016-0 Occurrence Handle1:STN:280:DyaK1MzosF2rtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • J Sambrook DW Russell (2001) Molecular cloning: a laboratory manual EditionNumberThird Cold Spring Laboratory Press Cold Spring Harbor

    Google Scholar 

  • S Schoeler R Szibor FN Gellerich T Wartmann C Mawrin K Dietzmann et al. (2005) ArticleTitleMitochondrial DNA deletions sensitize cells to apoptosis at low heteroplasmy levels Biochem Biophys Res Commun 332 43–49 Occurrence Handle15896297 Occurrence Handle10.1016/j.bbrc.2005.04.086 Occurrence Handle1:CAS:528:DC%2BD2MXkt1OjtLg%3D

    Article  PubMed  CAS  Google Scholar 

  • OC Stine SU Luu et al. (1993) ArticleTitleThe possible association between affective disorder and partially deleted mitochondrial DNA Biol Psychiatry 33 141–142 Occurrence Handle8439606 Occurrence Handle10.1016/0006-3223(93)90317-7 Occurrence Handle1:CAS:528:DyaK3sXitFSltbw%3D

    Article  PubMed  CAS  Google Scholar 

  • RW Taylor DM Turnbull (2005) ArticleTitleMitochondrial DNA mutations in human disease Nat Rev Genet 6 389–402 Occurrence Handle15861210 Occurrence Handle10.1038/nrg1606 Occurrence Handle1:CAS:528:DC%2BD2MXjs1OksLY%3D

    Article  PubMed  CAS  Google Scholar 

  • H Tomita MP Vawter et al. (2004) ArticleTitleEffect of agonal and postmortem factors on gene expression profile: quality control in microarray analyses of postmortem human brain Biol Psychiatry 55 346–352 Occurrence Handle14960286 Occurrence Handle10.1016/j.biopsych.2003.10.013 Occurrence Handle1:CAS:528:DC%2BD2cXhtFWhsbo%3D

    Article  PubMed  CAS  Google Scholar 

  • EF Torrey M Webster M Knable N Johnston RH Yolken (2000) ArticleTitleThe Stanley foundation brain collection and neuropathology consortium Schizophr Res 44 151–155 Occurrence Handle10913747 Occurrence Handle10.1016/S0920-9964(99)00192-9 Occurrence Handle1:STN:280:DC%2BD3cvlsVKgtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • MP Vawter H Tomita et al. (2006) ArticleTitleMitochondrial-related gene expression changes are sensitive to agonal-pH state: implications for brain disorders Mol Psychiatry 11 663–679 Occurrence Handle10.1038/sj.mp.4001830 Occurrence Handle1:CAS:528:DC%2BD28XmtFyrt7s%3D

    Article  CAS  Google Scholar 

  • HP Volz R Rzanny G Rossger G Hubner I Kreitschmann-Andermahr WA Kaiser et al. (1997) ArticleTitleDecreased energy demanding processes in the frontal lobes of schizophrenics due to neuroleptics? A 31P-magneto-resonance spectroscopic study Psychiatry Res 76 123–129 Occurrence Handle9522404 Occurrence Handle10.1016/S0925-4927(97)00047-4 Occurrence Handle1:CAS:528:DyaK1cXhvVyqu7o%3D

    Article  PubMed  CAS  Google Scholar 

  • DC Wallace (1994) ArticleTitleMitochondrial DNA sequence variation in human evolution and disease Proc Natl Acad Sci USA 91 8739–8746 Occurrence Handle8090716 Occurrence Handle10.1073/pnas.91.19.8739 Occurrence Handle1:CAS:528:DyaK2cXlvFKqsbc%3D

    Article  PubMed  CAS  Google Scholar 

  • DC Wallace (1999) ArticleTitleMitochondrial diseases in man and mouse Science 283 1482–1488 Occurrence Handle10066162 Occurrence Handle10.1126/science.283.5407.1482 Occurrence Handle1:CAS:528:DyaK1MXhs1ygurk%3D

    Article  PubMed  CAS  Google Scholar 

  • SA Whatley D Curti RM Marchbanks (1996) ArticleTitleMitochondrial involvement in schizophrenia and other functional psychoses Neurochem Res 21 995–1004 Occurrence Handle8897462 Occurrence Handle10.1007/BF02532409 Occurrence Handle1:CAS:528:DyaK28Xmt12hu7g%3D

    Article  PubMed  CAS  Google Scholar 

  • M Zeviani S Di Donato (2004) ArticleTitleMitochondrial disorders Brain 127 2153–2172 Occurrence Handle15358637 Occurrence Handle10.1093/brain/awh259

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

First two authors contributed equally to this paper

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sabunciyan, S., Kirches, E., Krause, G. et al. Quantification of total mitochondrial DNA and mitochondrial common deletion in the frontal cortex of patients with schizophrenia and bipolar disorder. J Neural Transm 114, 665–674 (2007). https://doi.org/10.1007/s00702-006-0581-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-006-0581-8

Navigation