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The other, forgotten genome: mitochondrial DNA and mental disorders

Molecular Psychiatry volume 6, pages 625–633 (2001)Cite this article

Abstract

This paper summarizes recent research on mitochondrial DNA (mtDNA)—which might be described as the ‘other, forgotten genome’. Recent studies suggest the possible pathophysiological significance of mtDNA in schizophrenia and neurodegenerative and mood disorders. Decreased activity of the mitochondrial electron transport chain has been implicated in both Parkinson's and Alzheimer's disease and while age-related accumulation of mtDNA deletions has been suggested as a possible cause, there is no concrete evidence that particular mtDNA polymorphisms are responsible. In schizophrenia, the activity and/or mRNA expression of complex IV are involved, but the direction of the alteration is not the same and there is no evidence linking schizophrenia with mtDNA. In bipolar disorder, there is some evidence of parent-of-origin effects and association with mtDNA polymorphisms but further investigation is needed to elucidate the role of mtDNA in mental disorders.

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References

  1. Anderson S, Bankier AT, Barrel BG, de Bruijn MHL, Coulson AR, Drouin J et al. Sequence and organization of the human mitochondrial genome Nature 1981 290: 457–465

    Article  CAS  PubMed  Google Scholar 

  2. Holt IJ, Harding AE, Morgan-Hughes JA . Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies Nature 1988 331: 717–719

    Article  CAS  PubMed  Google Scholar 

  3. Goto Y, Nonaka I, Horai S . A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies Nature 1990 348: 651–653

    Article  CAS  PubMed  Google Scholar 

  4. Scheffler IE . Mitochondria Wiley-Liss: New York 1999

    Google Scholar 

  5. Beal MF, Howell N, Bodis-Wollner I . Mitochondria and free radicals. In: Beal MF (ed). Neurodegenerative Diseases Wiley-Liss: New York 1997

    Google Scholar 

  6. Babcock DF, Hille B . Mitochondrial oversight of cellular Ca2+ signaling Curr Opin Neurobiol 1998 8: 398–404

    CAS  PubMed  Google Scholar 

  7. Moudy AM, Handran SD, Goldberg MP, Ruffin N, Karl I, Kranz-Eble P et al. Abnormal calcium homeostasis and mitochondrial polarization in a human encephalomyopathy Proc Acad Sci USA 1995 92: 729–733

    CAS  Google Scholar 

  8. Brini M, Pinton P, King MP, Davidson M, Schon EA, Rizzuto R . A calcium signaling defect in the pathogenesis of a mitochondrial DNA inherited oxidative phosphorylation deficiency Nature Med 1999 5: 951–954

    CAS  PubMed  Google Scholar 

  9. Marzuki S, Noer AS, Lertrit P, Thyagarajan D, Kapsa R, Utthanaphol P et al. Normal variants of human mitochondrial DNA and translation products: the building of a reference data base Hum Genet 1991 88: 139–145

    CAS  PubMed  Google Scholar 

  10. Horai S . Mitochondrial genetics. In: Nonaka I, Goto Y (eds) Mitochondrial Disease Igakushoin: Tokyo 1997 52–73

    Google Scholar 

  11. King MP, Attardi G . Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation Science 1989 246: 500–503

    CAS  PubMed  Google Scholar 

  12. Ito S, Ohta S, Nishimaki K, Kagawa Y, Soma R, Kuno SY et al. Functional integrity of mitochondrial genomes in human platelets and autopsied brain tissues from elderly patients with Alzheimer's disease Proc Natl Acad Sci USA 1999 96: 2099–2103

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Kadowaki T, Kadowaki H, Mori Y, Tobe K, Sakuta R, Suzuki Y et al. A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA New England J Med 1994 330: 962–968

    CAS  Google Scholar 

  14. Kogelnik AM, Lott MT, Brown MD, Navathe SB, Wallace DC . MITOMAP: a human mitochondrial genome database—1998 update Nucleic Acids Res 1998 26: 112–115

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Ozawa T, Hayakawa M, Katsumata K, Yoneda M, Ikebe S, Mizuno Y . Fragile mitochondrial DNA: the missing link in the apoptotic neuronal cell death in Parkinson's disease Biochem Biophys Res Commun 1997 235: 158–161

    CAS  PubMed  Google Scholar 

  16. Kosel S, Egensperger R, Schnopp NM, Graeber MB . The ‘common deletion’ is not increased in Parkinsonian substantia nigra as shown by competitive polymerase chain reaction Mov Disord 1997 12: 639–645

    CAS  PubMed  Google Scholar 

  17. Bonilla E, Tanji K, Hirano M, Vu TH, DiMauro S, Schon EA . Mitochondrial involvement in Alzheimer's disease Biochim Biophys Acta 1999 1410: 171–182

    CAS  PubMed  Google Scholar 

  18. Fukuyama R, Hatanpaa K, Rapoport SI, Chandrasekaran K . Gene expression of ND4, a subunit of complex I of oxidative phosphorylation in mitochondria, is decreased in temporal cortex of brains of Alzheimer's disease patients Brain Res 1996 713: 290–293

    CAS  PubMed  Google Scholar 

  19. Lin FH, Lin R, Wisniewski HM, Hwang YW, Grundke-Iqbal I, Healy-Louie G et al. Detection of point mutations in codon 331 of mitochondrial NADH dehydrogenase subunit 2 in Alzheimer's brains Biochem Biophys Res Commun 1992 182: 238–246

    CAS  PubMed  Google Scholar 

  20. Shoffner JM, Brown MD, Torroni A, Lott MT, Cabell MF, Mirra SS et al. Mitochondrial DNA variants observed in Alzheimer disease and Parkinson disease patients Genomics 1993 17: 171–184

    CAS  PubMed  Google Scholar 

  21. Hutchin T, Cortopassi G . A mitochondrial DNA clone is associated with increased risk for Alzheimer disease Proc Natl Acad Sci USA 1995 92: 6892–6895

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Egensperger R, Kosel S, Schnopp NM, Mehraein P, Graeber MB . Association of the mitochondrial tRNA(A4336G) mutation with Alzheimer's and Parkinson's diseases Neuropathol Appl Neurobiol 1997 23: 315–321

    CAS  PubMed  Google Scholar 

  23. Petruzzella V, Chen X, Schon EA . Is a point mutation in the mitochondrial ND2 gene associated with Alzheimer's disease Biochem Biophys Res Commun 1992 186: 491–497

    CAS  PubMed  Google Scholar 

  24. Kosel S, Egensperger R, Mehraein P, Graeber MB . No association of mutations at nucleotide 5460 of mitochondrial NADH dehydrogenase with Alzheimer's disease Biochem Biophys Res Commun 1994 203: 745–749

    CAS  PubMed  Google Scholar 

  25. Janetzky B, Schmid C, Bischof F, Frolich L, Gsell W, Kalaria RN et al. Investigations on the point mutations at nt 5460 of the mtDNA in different neurodegenerative and neuromuscular diseases Eur Neurol 1996 36: 149–153

    CAS  PubMed  Google Scholar 

  26. Wragg MA, Talbot CJ, Morris JC, Lendon CL, Goate AM . No association found between Alzheimer's disease and a mitochondrial tRNA glutamine gene variant Neurosci Lett 1995 201: 107–110

    CAS  PubMed  Google Scholar 

  27. Tanno Y, Okuizumi K, Tsuji S . mtDNA polymorphisms in Japanese sporadic Alzheimer's disease Neurobiol Aging 1998 19 (Suppl 1): S47–S51

    Google Scholar 

  28. Hutchin TP, Heath PR, Pearson RC, Sinclair AJ . Mitochondrial DNA mutations in Alzheimer's disease Biochem Biophys Res Commun 1997 241: 221–225

    CAS  PubMed  Google Scholar 

  29. Davis RE, Miller S, Herrnstadt C, Ghosh SS, Fahy E, Shinobu LA et al. Mutations in mitochondrial cytochrome c oxidase genes segregate with late-onset Alzheimer disease Proc Natl Acad Sci USA 1997 94: 4526–4531

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Hirano M, Shtilbans A, Mayeux R, Davidson MM, DiMauro S, Knowles JA et al. Apparent mtDNA heteroplasmy in Alzheimer's disease patients and in normals due to PCR amplification of nucleus-embedded mtDNA pseudogenes Proc Natl Acad Sci USA 1997 94: 14894–14899

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Wallace DC, Stugard C, Murdock D, Schurr T, Brown MD . Ancient mtDNA sequences in the human nuclear genome: a potential source of errors in identifying pathogenic mutations Proc Natl Acad Sci USA 1997 94: 14900–14905

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Davis JN II, Parker WD Jr . Evidence that two reports of mtDNA cytochrome c oxidase ‘mutations’ in Alzheimer's disease are based on nDNA pseudogenes of recent evolutionary origin Biochem Biophys Res Commun 1998 244: 877–883

    PubMed  Google Scholar 

  33. Sawa A, Wiegand GW, Cooper J, Margolis RL, Sharp AH, Lawler JF Jr et al. Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization Nature Med 1999 10: 1194–1198

    Google Scholar 

  34. Swerdlow RH, Parks JK, Cassarino DS, Trimmer PA, Miller SW, Maguire DJ et al. Mitochondria in sporadic amyotrophic lateral sclerosis Exp Neurol 1998 153: 135–142

    CAS  PubMed  Google Scholar 

  35. Swerdlow RH, Parks JK, Cassarino DS, Shilling AT, Bennett JP Jr, Harrison MB et al. Characterization of cybrid cell lines containing mtDNA from Huntington's disease patients Biochem Biophys Res Commun 1999 261: 701–704

    CAS  PubMed  Google Scholar 

  36. Sheehan JP, Swerdlow RH, Miller SW, Davis RE, Parks JK, Parker WD et al. Calcium homeostasis and reactive oxygen species production in cells transformed by mitochondria from individuals with sporadic Alzheimer's disease J Neurosci 1997 17: 4612–4622

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Sheehan JP, Swerdlow RH, Parker WD, Miller SW, Davis RE, Tuttle JB . Altered calcium homeostasis in cells transformed by mitochondria from individuals with Parkinson's disease J Neurochem 1997 68: 1221–1233

    CAS  PubMed  Google Scholar 

  38. Linnane AW, Marzuki S, Ozawa T, Tanaka M . Mitochondrial DNA mutations as an important contributor to aging and degenerative diseases Lancet 1989 1: 642–645

    CAS  PubMed  Google Scholar 

  39. Corral-Debrinski M, Horton T, Lott MT, Shoffner JM, Beal MF, Wallace DC . Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age Nature Genet 1992 2: 324–329

    CAS  PubMed  Google Scholar 

  40. Michikawa Y, Mazzucchelli F, Bresolin N, Scarlato G, Attardi G . Aging-dependent large accumulation of point mutations in the human mtDNA control region for replication Science 1999 286: 774–779

    CAS  PubMed  Google Scholar 

  41. Tanaka M, Gong JS, Zhang J, Yoneda M, Yagi K . Mitochondrial genotype associated with longevity Lancet 1998 351: 185–186

    CAS  PubMed  Google Scholar 

  42. De Benedictis G, Rose G, Carrieri G, De Luca M, Falcone E, Passarino G et al. Mitochondrial DNA inherited variants are associated with successful aging and longevity in humans FASEB J 1999 13: 1532–1536

    CAS  PubMed  Google Scholar 

  43. Kegeles LS, Humaran TJ, Mann JJ . In vivo neurochemistry of the brain in schizophrenia as revealed by magnetic resonance spectroscopy Biol Psychiatry 1998 44: 382–398

    CAS  PubMed  Google Scholar 

  44. Shimizu A, Kurachi M, Yamaguchi N, Torii H, Isaki K . Morbidity risk of schizophrenia to parents and siblings of schizophrenic patients Jpn J Psychiatry Neurol 1987 41: 65–70

    CAS  PubMed  Google Scholar 

  45. Goldstein JM, Faraone SV, Chen WJ, Tolomiczencko GS, Tsuang MT . Sex differences in the familial transmission of schizophrenia Br J Psychiatry 1990 156: 819–826

    CAS  PubMed  Google Scholar 

  46. Wolyniec PS, Pulver AE, McGrath JA, Tam D . Schizophrenia gender and familial risk J Psychiatr Res 1992 26: 17–27

    CAS  PubMed  Google Scholar 

  47. Swerdlow RH, Binder D, Parker WD . Risk factors for schizophrenia N Engl J Med 1999 341: 371–372, discussion 372

    CAS  PubMed  Google Scholar 

  48. Morgan-Hughes JA, Hayes DJ, Clark JB, Landon DN, Swash M, Stark RJ et al. Mitochondrial encephalomyopathies: biochemical studies in two cases revealing defects in the respiratory chain Brain 1982 105: 553–582

    PubMed  Google Scholar 

  49. Pavlakis SG, Phillips PC, DiMauro S, De Vivo DC, Rowland LP . Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes: a distinctive clinical syndrome Ann Neurol 1984 16: 481–488

    CAS  PubMed  Google Scholar 

  50. Fusegi M, Gomibuchi T, Mizusawa H, Iwamoto H . A case report of MELAAS; on various psychiatric symptoms as acute exogenous reaction type Seihin Igaku (Clin Psychiatry) 1992 34: 703–710

    Google Scholar 

  51. Ueda Y, Motomura N, Nanomura Y, Okamura T, Yoneda H, Sakai T . A case of mitochondrial encephalomyopathy (MELAS) with the psychotic features Seishin Igaku (Clin Psychiatry) 1992 34: 711–716

    Google Scholar 

  52. Ishitsu T, Matsuda I, Kitano A, Shimoji A, Kimura H . Familial cases of mitochondria cytopathy Clin Neurol 1987 27: 983–989

    CAS  Google Scholar 

  53. Suzuki T, Koizumi J et al. Mitochondrial encephalopathy (MELAS) with mental disorder. CT, MRI, and SPECT findings Neuroradiology 1990 32: 74

    CAS  PubMed  Google Scholar 

  54. Yamazaki M, Igarashi H, Hamamoto M, Miyazaki T, Nonaka I . A case of mitochondrial encephalopathy with schizophrenic psychosis, dementia and neuroleptic malignant syndrome Clin Neurol 1991 31: 1219–1223

    CAS  Google Scholar 

  55. Thomeer EC, Verhoeven WM, van de Vlasakker CJ, Klompenhouwer JL . Psychiatric symptoms in MELAS; a case report [letter] J Neurol Neurosurg Psychiatry 1998 64: 692–693

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Amemiya S, Hamamoto M, Goto Y, Komaki H, Nishino I, Nonaka I et al. Psychosis and progressing dementia: presenting features of a mitochondriopathy Neurology 2000 55: 600–601

    CAS  PubMed  Google Scholar 

  57. Prayson RA, Wang N . Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome: an autopsy report Arch Pathol Lab Med 1998 122: 978–981

    CAS  PubMed  Google Scholar 

  58. Odawara M, Isaka M, Tada K, Mizusawa H, Yamashita K . Diabetes mellitus associated with mitochondrial myopathy and schizophrenia: a possible link between diabetes mellitus and schizophrenia Diabet Med 1997 14: 503

    CAS  PubMed  Google Scholar 

  59. Inagaki T, Ishino H, Seno H, Ohguni S, Tanaka J, Kato Y . Psychiatric symptoms in a patient with diabetes mellitus associated with point mutation in mitochondria DNA Biol Psychiatry 1997 42: 1067–1069

    CAS  PubMed  Google Scholar 

  60. Odawara M, Arinami T, Tachi Y, Hamaguchi H, Toru Michio, Yamashita K . Absence of association between a mitochondrial DNA mutation at nucleotide position 3243 and schizophrenia in Japanese Hum Genet 1998 102: 708–709

    CAS  PubMed  Google Scholar 

  61. Whatley SA, Curti D, Marchbanks RM . Mitochondrial involvement in schizophrenia and other functional psychoses Neurochem Res 1996 21: 995–1004

    CAS  PubMed  Google Scholar 

  62. Whatley SA, Curti D, Das Gupta F . Superoxide, neuroleptics and the ubiquinone and cytochrome b5 reductases in brain and lymphocytes from normals and schizophrenic patients Mol Psychiatry 1998 3: 227–237

    CAS  PubMed  Google Scholar 

  63. Mulcrone J, Whatley SA, Ferrier IN, Marchbanks RM . A study of altered gene expression in frontal cortex from schizophrenic patients using differential screening Schizophr Res 1995 14: 203–213

    CAS  PubMed  Google Scholar 

  64. Cavelier L, Jazin EE, Eriksson I, Prince J, Bave U, Oreland L et al. Decreased cytochrome-c oxidase activity and lack of age-related accumulation of mitochondrial DNA deletions in the brains of schizophrenics Genomics 1995 29: 217–224

    CAS  PubMed  Google Scholar 

  65. Prince JA, Yassin MS, Oreland L . Neuroleptic-induced mitochondrial enzyme alterations in the rat brain J Pharmacol Exp Ther 1997 280: 261–267

    CAS  PubMed  Google Scholar 

  66. Prince JA, Yassin MS, Oreland L . Normalization of cytochrome-c oxidase activity in the rat brain by neuroleptics after chronic treatment with PCP or methamphetamine Neuropharmacology 1997 36: 1665–1678

    CAS  PubMed  Google Scholar 

  67. Prince JA, Blennow K, Gottfries CG, Karlsson I, Oreland L . Mitochondrial function is differentially altered in the basal ganglia of chronic schizophrenics Neuropsychopharmacology 1999 21: 372–379

    CAS  PubMed  Google Scholar 

  68. Prince JA, Harro J, Blennow K, Gottfries CG, Oreland L . Putamen mitochondrial energy metabolism is highly correlated to emotional and intellectual impairment in schizophrenics Neuropsychopharmacology 2000 22: 284–292

    CAS  PubMed  Google Scholar 

  69. Kung L, Roberts RC . Mitochondrial pathology in human schizophrenic striatum: a postmortem ultrastructural study Synapse 1999 31: 67–75

    CAS  PubMed  Google Scholar 

  70. Kolomeets NS, Uranova NA . Synaptic contacts in schizophrenia: studies using immunocytochemical identification of dopaminergic neurons Neurosci Behav Physiol 1999 29: 217–221

    CAS  PubMed  Google Scholar 

  71. Lindholm E, Cavelier L, Howell WM, Eriksson I, Jalonen P, Adolfsson R et al. Mitochondrial sequence variants in patients with schizophrenia Eur J Hum Genet 1997 5: 406–412

    CAS  PubMed  Google Scholar 

  72. Gentry KM, Nimgaonkar VL . Mitochondrial DNA variants in schizophrenia: association studies Psychiatr Genet 2000 10: 27–31

    CAS  PubMed  Google Scholar 

  73. Altshuler LL, Curran JG, Hauser P, Mintz J, Denicoff K, Post R . T2 hyperintensities in bipolar disorder; magnetic resonance imaging comparison and literature meta-analysis Am J Psychiatry 1995 152: 1139–1144

    CAS  PubMed  Google Scholar 

  74. Barkovich AJ, Good WV, Koch TK, Berg BO . Mitochondrial disorders: analysis of their clinical and imaging characteristics AJNR Am J Neuroradiol 1998 14: 1119–1137

    Google Scholar 

  75. Kato T, Takahashi S, Shioiri T, Inubushi T . Alterations in brain phosphorous metabolism in bipolar disorder detected by in vivo31P and 7Li magnetic resonance spectroscopy J Affect Disord 1993 27: 53–60

    CAS  PubMed  Google Scholar 

  76. Kato T, Murashita J, Kamiya A, Shioiri T, Kato N, Inubushi T . Decreased brain intracellular pH measured by 31P-MRS in bipolar disorder: a confirmation in drug-free patients and correlation with white matter hyperintensity Eur Arch Psychiatry Clin Neurosci 1998 248: 301–306

    CAS  PubMed  Google Scholar 

  77. Kato T, Takahashi S, Shioiri T, Murashita J, Hamakawa H, Inubuhshi T . Reduction of brain phosphocreatine in bipolar II disorder detected by phosphorus-31 magnetic resonance spectroscopy J Affect Disord 1994 31: 125–133

    CAS  PubMed  Google Scholar 

  78. Volz HP, Rzanny R, Riehemann S, May S, Hegewald H, Preussler B et al. 31P magnetic resonance spectroscopy in the frontal lobe of major depressed patients Eur Arch Psychiatry Clin Neurosci 1998 248: 289–295

    CAS  PubMed  Google Scholar 

  79. Moore CM, Christensen JD, Lafer B, Fava M, Renshaw PF . Lower levels of nucleoside triphosphate in the basal ganglia of depressed subjects: a phosphorous-31 magnetic resonance spectroscopy study Am J Psychiatry 1997 154: 116–118

    CAS  PubMed  Google Scholar 

  80. Murashita J, Kato T, Shioiri T, Inubushi T, Kato N . Altered brain energy metabolism in lithium-resistant bipolar disorder detected by photic stimulated 31P-MR spectroscopy Psychol Med 2000 30: 107–115

    CAS  PubMed  Google Scholar 

  81. Kato T, Murashita J, Shioiri T, Terada M, Inubushi T, Kato N . Photic stimulation-induced alteration of brain energy metabolism measured by 31P-MR spectroscopy in patients with MELAS J Neurol Sci 1998 155: 182–185

    CAS  PubMed  Google Scholar 

  82. Rango M, Bozzali M, Prelle A, Scarlato G, Bresolin N . Brain activation in normal subjects and in patients affected by mitochondrial disease without clinical central nervous system involvement: a phosphorus magnetic resonance spectroscopy study J Cereb Blood Flow Metab 2001 21: 85–91

    CAS  PubMed  Google Scholar 

  83. Winokur G, Reich T . Two genetic factors in manic-depressive disease Compr Psychiatry 1970 11: 93–99

    CAS  PubMed  Google Scholar 

  84. McMahon FJ, Stine OC, Meyers DA, Simpson SG, DePaulo JR . Patterns of maternal transmission in bipolar affective disorder Am J Hum Genet 1995 56: 1277–1286

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Gershon ES, Badner JA, Detera-Wadleigh SD, Ferraro TN, Berrettini WH . Maternal inheritance and chromosome 18 allele sharing in unilineal bipolar pedigrees Am J Med Genet 1996 67: 202–207

    CAS  PubMed  Google Scholar 

  86. Grigoroiu-Serbanescu M, Nothen M, Propping P, Poustka F, Magureanu S, Vasilescu R et al. Clinical evidence for genomic imprinting in bipolar I disorder Acta Psychiat Scand 1995 92: 365–370

    CAS  PubMed  Google Scholar 

  87. Kato T, Winokur G, Coryell W, Keller MB, Endicott J, Rice J . Parent-of-origin effect in the transmission of bipolar disorder Am J Med Genet 1996 67: 546–550

    CAS  PubMed  Google Scholar 

  88. Kornberg JR, Brown JL, Sadovnick AD, Remick RA, Keck PE, McElroy SL et al. Evaluating the parent-of-origin effect in bipolar affective disorder Is a more penetrant subtype transmitted paternally? J Affect Disord 2000 59: 183–192

    CAS  PubMed  Google Scholar 

  89. Stine OC, Xu J, Koskela R, McMahon FJ, Gschwend M, Friddle C et al. Evidence for linkage of bipolar disorder to chromosome 18 with a parent-of-origin effect Am J Hum Genet 1995 57: 1384–1394

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Grigoroiu-Serbanescu M, Martinez M, Nothern MM, Propping P . Patterns of parental transmission and familial aggregation models in bipolar affective disorder Am J Med Genet 1998 81: 397–404

    CAS  PubMed  Google Scholar 

  91. Wallace DC . A new manifestation of Leber's disease and a new explanation for the agency responsible for its unusual pattern of inheritance Brain 1970 93: 121–132

    CAS  PubMed  Google Scholar 

  92. Nakamura K, Yasaki S, Tani H, Tadokoro M, Ogata A, Moriya N . A case of mitochondrial encephalopathy misdiagnosed as Alzheimer's disease, with various kinds of neurological and psychiatric symptoms Seishin Igaku (Clin Psychiatry) 1989 31: 651–659

    Google Scholar 

  93. Stewart JB, Naylor GJ . Manic-depressive psychosis in a patient with mitochondrial myopathy—a case report Med Sci Res 1990 18: 265–266

    Google Scholar 

  94. Ciafaloni E, Shanske S, Apostolski S, Griggs RL, Bird TD, Sumi M et al. Multiple deletions of mitochondrial DNA (Abst) Neurol 1991 41: 207

    Google Scholar 

  95. Suomalainen A, Majander A, Haltia M, Somer H, Lonnqvist J, Savontaus M et al. Multiple deletions of mitochondrial DNA in several tissues of a patient with severe retarded depression and familial progressive external ophthalmoplegia J Clin Invest 1992 90: 61–66

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Sweeney MG, Bundey S, Brockington M, Poulton KR, Winer JB, Harding AE . Mitochondrial myopathy associated with sudden death in young adults and a novel mutation in the mitochondrial DNA leucine transfer RNA(UUR) gene Quarterly J Med 1993 86: 709–713

    CAS  Google Scholar 

  97. Shanske AL, Shanske S, Silvestri G, Tanji K, Wertheim D, Lipper S . MELAS point mutation with unusual clinical presentation Neuromuscular Disord 1993 3: 191–193

    CAS  Google Scholar 

  98. Kato T, Takahashi Y . Deletion of leukocyte mitochondrial DNA in bipolar disorder J Affect Disord 1996 37: 67–73

    CAS  PubMed  Google Scholar 

  99. Suzuki Y, Miyaoka H, Taniyama M, Atsumi Y, Hosokawa K, Tanaka Y et al. Psychiatric disturbance in mitochondrial diabetes due to 3243 mitochondrial tRNA mutation J Japanese Diabetes Soc 1995 38: 905–908

    Google Scholar 

  100. Onishi H, Kawanishi C, Iwasawa T, Osaka H, Hanihara T, Inoue K et al. Depressive disorder due to mitochondrial tRNALeu(UUR) mutation Biol Psychiatry 1997 41: 1137–1139

    CAS  PubMed  Google Scholar 

  101. Miyaoka H, Suzuki Y, Taniyama M, Miyaoka Y, Shishikura K, Kamijima K et al. Mental disorders in diabetic patients with mitochondrial transfer RNALeu(UUR) mutation at position 3243 Biol Psychiatry 1997 42: 524–526

    CAS  PubMed  Google Scholar 

  102. Kato T, Winokur G, McMahon FJ, Depaulo JR, Crowe RR . Quantitative analysis of leukocyte mitochondrial DNA deletion in affective disorders Biol Psychiatry 1997 42: 311–316

    CAS  PubMed  Google Scholar 

  103. Barrientos A, Volpini V, Casademont J, Genis D, Manzanares JM, Ferrer I et al. A nuclear defect in the 4p16 region predisposes to multiple mitochondrial DNA deletions in families with Wolfram syndrome J Clin Invest 1996 97: 1570–1576

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Swift RG, Polymeropoulos MH, Torres R, Swift M . Predisposition of Wolfram syndrome heterozygotes to psychiatric illness Mol Psychiatry 1998 3: 86–91

    CAS  PubMed  Google Scholar 

  105. Inoue H, Tanizawa Y, Wasson J, Behn P, Kalidas K, Bernal-Mizrachi E, et al . A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome) Nat Genet 1998 20: 143–148

    CAS  PubMed  Google Scholar 

  106. Strom TM, Hortnagel K, Hofmann S, Gekeler F, Scharfe C, Rabl W et al. Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein Hum Mol Genet 1998 7: 2021–2028

    CAS  PubMed  Google Scholar 

  107. Blackwood DH, He L, Morris SW, McLean A, Whitton C, Thomson M et al. A locus for bipolar affective disorder on chromosome 4p Nature Genet 1996 12: 427–430

    CAS  PubMed  Google Scholar 

  108. Furlong RA, Ho LW, Rubinsztein JS, Michael A, Walsh C, Paykel ES et al. A rare coding variant within the wolframin gene in bipolar and unipolar affective disorder cases Neurosci Lett 1999 277: 123–126

    CAS  PubMed  Google Scholar 

  109. Evans KL, Lawson D, Meitinger T, Blackwood DH, Porteous DJ . Mutational analysis of the wolfram syndrome gene in two families with chromosome 4p-linked bipolar affective disorder Am J Med Genet 2000 96: 158–160

    CAS  PubMed  Google Scholar 

  110. Middle F, Jones I, McCandless F, Barrett T, Khanim F, Owen MJ et al. Bipolar disorder and variation at a common polymorphism (A1832G) within exon 8 of the wolfram gene Am J Med Genet 2000 96: 154–157

    CAS  PubMed  Google Scholar 

  111. Ohtsuki T, Ishiguro H, Yoshikawa T, Arinami T . WFS1 gene mutation search in depressive patients: detection of five missense polymorphisms but no association with depression or bipolar affective disorder J Affect Disord 2000 58: 11–17

    CAS  PubMed  Google Scholar 

  112. Takeda T, Inoue H, Tanizawa Y, Matsuzaki Y, Oba J, Watanabe Y et al. WFS1 (Wolfram syndrome 1) gene product: predominant subcellular localization to endoplasmic reticulum in cultured cells and neuronal expression in rat brain Hum Mol Genet 2001 10: 477–484

    CAS  PubMed  Google Scholar 

  113. El-Shanti H, Lidral AC, Jarrah N, Druhan L, Ajlouni K . Homozygosity mapping identifies an additional locus for Wolfram syndrome on chromosome 4q Am J Hum Genet 2000 66: 1229–1236

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Stine OC, Luu SU, Zito M . The possible association between affective disorder and partially deleted mitochondrial DNA Biol Psychiatry 1993 33: 141–142

    CAS  PubMed  Google Scholar 

  115. Kato T, Stine OC, McMahon FJ, Crowe RR . Increased levels of a mitochondrial DNA deletion in the brain of patients with bipolar disorder Biol Psychiatry 1997 42: 871–875

    CAS  PubMed  Google Scholar 

  116. Kirk R, Furlong RA, Amos W, Cooper G, Rubinsztein JS, Walsh C et al. Mitochondrial genetic analyses suggest selection against maternal lineages in bipolar affective disorder Am J Hum Genet 1999 65: 508–518

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Kato T, Kunugi H, Nanko S, Kato N . Mitochondrial DNA polymorphisms in bipolar disorder J Affect Disord 2001 52: 151–164

    Google Scholar 

  118. Kato T, Kunugi H, Nanko S, Kato N . Association of bipolar disorder with the 5178 polymorphism in mitochondrial DNA Am J Med Genet 2000 96: 182–186

    CAS  PubMed  Google Scholar 

  119. McMahon FJ, Chen YS, Patel S, Kokoszka J, Brown MD, Torroni AJ et al. Mitochondrial DNA sequence diversity in bipolar affective disorder Am J Psychiatry 2000 157: 1058–1064

    CAS  PubMed  Google Scholar 

  120. Kato T, Kato N . Mitochondrial dysfunction in bipolar disorder Bipolar Disorder 2000 2: 180–190

    CAS  Google Scholar 

  121. Niculescu III AB, Segal DS, Kuczenski R, Barrett T, Hauger RL, Kelsoe JR . Identifying a series of candidate genes for mania and psychosis: a convergent functional genomics approach Physiol Genomics 2000 4: 83–91

    Google Scholar 

  122. Appleby RD, Porteous WK, Hughes G, James AM, Shannon D, Wei YH et al. Quantitation and origin of the mitochondrial membrane potential in human cells lacking mitochondrial DNA Eur J Biochem 1999 262: 108–116

    CAS  PubMed  Google Scholar 

  123. Berger AK, Fratiglioni L, Forsell Y, Winblad B, Backman L . The occurrence of depressive symptoms in the preclinical phase of AD: a population-based study Neurology 1999 53: 1998–2002

    CAS  PubMed  Google Scholar 

  124. Kessing LV, Olsen EW, Mortensen PB, Andersen PK . Dementia in affective disorder: a case-register study Acta Psychiat Scand 1999 100: 176–185

    CAS  PubMed  Google Scholar 

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Acknowledgements

The author is grateful to Dr Michael Miller for help in preparing the manuscript.

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  1. Laboratory for Molecular Dynamics of Mental Disorders, Brain Science Institute, RIKEN, Wako, Saitama, Japan

    T Kato

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Kato, T. The other, forgotten genome: mitochondrial DNA and mental disorders. Mol Psychiatry 6, 625–633 (2001). https://doi.org/10.1038/sj.mp.4000926

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  • DOI: https://doi.org/10.1038/sj.mp.4000926

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