Recent studies suggest that mutations/polymorphisms of mitochondrial DNA (mtDNA) are associated with neuropsychiatric diseases. We identified a patient with major depression and epilepsy. Some family members in the pedigree of the proband had bipolar disorder, depression, suicide, or psychotic disorder not otherwise specified. The mode of inheritance was compatible with maternal inheritance with low penetration. We assumed that the mental disorder in this family might be associated with maternally inherited mitochondrial DNA (mtDNA) mutation. We sequenced the entire mtDNA of the proband. Among the 34 base substitutions detected in the proband, two homoplasmic, nonsynonymous single substitutions of mtDNA, T3394C in MT-ND1 and A9115G in MT-ATP6, were suspected to cause functional impairment, because the former was reported to be disease-related and the latter is vary rare. To study the functional outcome of these substitutions, we examined mitochondrial membrane potential and the activity of mitochondrial ATP synthesis in the transmitochondrial cybrids, but no significant impairment was detected. The data did not support our hypothesis that these disorders in this family are caused by mtDNA mutation(s).