Here's an interesting abstract from a 2005 review paper by Ann Gardner and Richard Boles:
Is a "Mitochondrial Psychiatry" in the Future? A Review
The field of "mitochondrial medicine" has advanced rapidly since the first patient with a mitochondrial disorder, a concept primarily used for defects of the respiratory chain, was described in 1962 and the first mitochondrial DNA (mtDNA) mutations were described in 1988. Because of the ubiquitous requirement for energy and unique aspects of mtDNA genetics, mtDNA mutations are known to cause a bewildering spectrum of clinical manifestations. However, because of its high-energy requirement, brain is the primary tissue affected in mitochondrial disorders. Using a variety of approaches, mitochondrial function has been shown in numerous studies to be abnormal in patients with schizophrenia and depression. Although less studied, an increase of psychiatric symptoms and disorders, in particular depression, are likely present in patients with mitochondrial disorders. The major categories of drugs used to treat schizophrenia and depression have been demonstrated to exert effects on mitochondria. The authors conclude that an association between energy metabolism and the mental disorders of schizophrenia and depression has been well documented, but that no conclusive evidence as yet demonstrates a causal relationship. A "mitochondrial psychiatry" model is proposed in which a moderate reduction in mitochondrial energy metabolism, genetically determined and/or acquired, is one predisposing factor in the multi-factorial development of certain chronic mental disorders. Clinical implications of our hypothesis, present and future, include the presence of co-morbid somatic symptoms/conditions, and specific treatment at least in highly-selected cases.
The association studies linking certain mtDNA polymorphisms to mental disorders like schizophrenia or Alzheimer's are potentially confounded by population history, which has spread some initially rare mtDNA variants far from their points of origin and to relatively high frequencies (see exchange between Kato 2001b and McMahon et al. 2001). Two problems make mtDNA-disease linkage difficult. First, mtDNA is nonspecific in its activity -- expressed in all cell types -- so that it is hard to establish clear biochemical pathways leading to particular neurophysiological disorders. Second, there is no possibility of localizing mtDNA variants by LD, since it is entirely linked.
Another issue is that mtDNA coding polymorphisms in humans often vary among other primate species. There is an argument (employed by McMahon et al. 2001) that coding variation found naturally among different primate lineages is unlikely to be functionally relevant in humans -- in other words, such variations are likely to be functionally neutral. But given the extensive behavioral variability of other primates, this argument by itself seems weak -- there is no reason why a variant allele associated with neurophysiological variation in humans should not also vary amont primate lineages. It seems just as likely that such variants may be especially variable among other primates, because they may provide targets for selection on behavior outside of the human context.
Some of these problems and some other work were reviewed by Tadafumi Kato in a 2001 Molecular Psychiatry review:
The other, forgotten genome: mitochondrial DNA and mental disorders
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.
Later research has employed whole-mtDNA screening to try to resolve such problems. For example, Martorell and colleagues (2006) screened maternal-offspring pairs affected by schizophrenia to find candidate mtDNA polymorphisms that contribute to the disorder:
New variants in the mitochondrial genomes of schizophrenic patients
The impaired mitochondrial function hypothesis in schizophrenia is based on evidence of altered brain metabolism, morphology, biochemistry and gene expression. Mitochondria have their own genome, which is needed to synthesize some of the subunits of the respiratory chain enzymes. Mitochondrial DNA (mtDNA) is maternally inherited and we observed an excess of maternal transmission of schizophrenia in a set of parent-offspring affected pairs. We therefore hypothesized that mutations in the mtDNA may contribute to the complex genetic basis of schizophrenia. The entire mtDNA of six schizophrenic patients with an apparent maternal transmission of the disease was sequenced and compared to the reference sequence. We have identified 50 variants and among these six have not been previously reported. Three of them were missense variants: MTCO2 7750C>A, MTATP6 8857G>A and MTND4 12096T>A. These were maternally inherited because they were also present in the mtDNA of their respective schizophrenic mothers and none of them were found in 95 control individuals. The MTND4 12096T>A (Leu446His) is a heteroplasmic variant present in five of the six mother-offspring patient pairs that triggers a non-conservative substitution in the ND4 subunit of complex I. Sequence alignment of 110 ND4 peptides from all eukaryotic kingdoms shows that only hydrophobic amino acids are found in this position. Moreover, leucine was conserved or substituted by an isoleucine in all mammalian species. This indicates that the presence of histidine could affect complex I activity in patients with schizophrenia.
Well, there's an example of a change not found in other lineages, and putatively under recurrent mutation as a rare disease-associated variant in humans.
Most disease-associated mitochondrial variants presumably do result from recurrent mutations under purifying selection. Different from nuclear genes, the mtDNA has a very high rate of mutations. This means that somatic mosaicism (i.e., different mtDNA mutations accumulating in different parts of the body over time) or heteroplasmy (i.e., different mtDNA sequences within given cells) play a role in some of the disorders of aging and senescence, such as Parkinson's disease.
There is now a substantial literature linking the common mtDNA haplogroups with longevity. For example, De Benedictis et al. (1999) found that Italian centenarians were significantly more likely to carry mtDNA haplogroup J than a set of younger individuals. Interestingly, Rose et al. (2001) found that the haplogroup J mutations were also associated with some complex diseases, concluding:
The general picture that emerges from the study is that the J haplogroup of centenarians is surprisingly similar to that found in complex diseases, as well as in Leber Hereditary Optic Neuropathy. This finding implies that the same mutations could predispose to disease or longevity, probably according to individual-specific genetic backgrounds and stochastic events. This data reveals another paradox of centenarians and confirms the complexity of the longevity trait.
The specificity of genetic background was also suggested by Dato et al. (2004), who found no evidence of an increase of haplogroup J with age cohorts in their southern European sample. Population-specific effects due to allelic background have the potential to confound many kinds of association studies, particularly those related to longevity -- for which frequency changes over time in one or more genes are also a consideration.
All this is a bit of a prologue to a new paper, "An enhanced MITOMAP with a global mtDNA mutational phylogeny", by Eduardo Ruiz-Pesini and colleagues from Doug Wallace's lab:
The MITOMAP (http://www.mitomap.org) data system for the human mitochondrial genome has been greatly enhanced by the addition of a navigable mutational mitochondrial DNA (mtDNA) phylogenetic tree of 3000 mtDNA coding region sequences plus expanded pathogenic mutation tables and a nuclear-mtDNA pseudogene (NUMT) data base. The phylogeny reconstructs the entire mutational history of the human mtDNA, thus defining the mtDNA haplogroups and differentiating ancient from recent mtDNA mutations. Pathogenic mutations are classified by both genotype and phenotype, and the NUMT sequences permits detection of spurious inclusion of pseudogene variants during mutation analysis. These additions position MITOMAP for the implementation of our automated mtDNA sequence analysis system, Mitomaster.
The map characterizes apparent disease-linked mutations, which anyone can cruise to her heart's content. The paper also provides a brief account of the way that different haplogroups got their names, and their geographical distributions.
That paper is part of a <a href-"http://nar.oxfordjournals.org/content/vol35/suppl_1/index.dtl">special database issue</a> of Nucleic Acids Research, which has short articles on the latest and greatest versions of many publicly accessible databases in molecular biology and genetics. All the papers are free, and it is a tremendous opportunity to learn about the fundamental data of genomics.
Dato S, Passarino G, Rose G, Altomare K, Bellizi D, Mari V, Feraco E, Franceschi C, De Benedictis G. 2004. Association of the mitochondrial DNA haplogroup J with longevity is population specific. Eur J Hum Genet 12:1080-1282. doi:10.1038/sj.ejhg.5201278
De Benedictis G, Rose G, Carrieri G, De Luca M, Falcone E, Passarino G, Bonafé M, Monti D, Baggio G, Bertolini S, Mari D, Mattace R, Franceschi C. 1999. Mitochondrial DNA inherited variants are associated with successful aging and longevity in humans. FASEB Journal 13:1532-1536.
Gardner A, Boles RG. 2005. Is a "Mitochondrial Psychiatry" in the future? A review. Curr Psychiatry Rev 1:255-251. doi:10.2174/157340005774575064
Kato T. 2001a. The other, forgotten genome. mitochondrial DNA and mental disorders. Mol Psychiatry 6:625-633. Abstract
Kato T. 2001b. DNA Polymorphisms and bipolar disorder (letter). Am J Psychiatry 158:1169-1170.
Martorell L, Segués T, Folch G, Valero J, Joven J, Labad A, Vilella E. 2006. New variants in the mitochondrial genomes of schizophrenic patients. Eur J Hum Genet 14:520-528. doi:10.1038/sj.ejhg.5201606
McMahon FJ, Chen Y, Torroni A. 2001. Dr. McMahon and colleagues reply to "DNA Polymorphisms and bipolar disorder." Am J Psychiatry 158:1170.
Rose G, Passarino G, Carrieri G, Altomare K, Greco V, Bertolini S, Bonafè M, Franceschi C, De Benedictis G. 2001. Paradoxes in longevity: sequence analysis of mtDNA haplogroup J in centenarians. Eur J Hum Genet 9:701-707. Abstract
Ruiz-Pesini E, Lott MT, Procaccio V, Poole JC, Brandon MC, Mishmar D, Yi C, Kreuzinger J, Baldi P, Wallace DC. 2007. An enhanced MITOMAP with a global mtDNA mutational phylogeny. Nucleic Acids Res 35:D823-D828. doi:10.1093/nar/gkl927