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Mitochondrial calcium regulation plays a number of important roles in neurons. Mitochondrial DNA (mtDNA) is highly polymorphic, and its interindividual variation is associated with various neuropsychiatric diseases and mental functions. An mtDNA polymorphism, 10398A>G, was reported to affect mitochondrial calcium regulation. Volume of hippocampus and amygdala is reportedly associated with various mental disorders and mental functions and is regarded as an endophenotype of mental disorders. The present study investigated the relationship between the mtDNA 10398A>G polymorphism and the volume of hippocampus and amygdala in 118 right-handed healthy subjects. The brain morphometry using magnetic resonance images employed both manual tracing volumetry in the native space and voxel-based morphometry (VBM) in the spatially normalized space. Amygdala volume was found to be significantly larger in healthy subjects with 10398A than in those with 10398G by manual tracing, which was confirmed by the VBM. Brain volumes in the other gray matter regions and all white matter regions showed no significant differences associated with the polymorphism. These provocative findings might provide a clue to the complex relationship between mtDNA, brain structure and mental disorders. [ABSTRACT FROM AUTHOR]

Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by chronic motor and vocal tics. Although there is a large genetic contribution, the genetic architecture of TS remains unclear. Exome sequencing has successfully revealed the contribution of de novo mutations in sporadic cases with neuropsychiatric disorders such as autism and schizophrenia. Here, using exome sequencing, we investigated de novo mutations in individuals with sporadic TS to identify novel risk loci and elucidate the genetic background of TS. Exome analysis was conducted for sporadic TS cases: nine trio families and one quartet family with concordant twins were investigated. Missense mutations were evaluated using functional prediction algorithms, and their population frequencies were calculated based on three public databases. Gene expression patterns in the brain were analyzed using the BrainSpan Developmental Transcriptome. Thirty de novo mutations, including four synonymous and four missense mutations, were identified. Among the missense mutations, one in the rapamycin-insensitive companion of mammalian target of rapamycin (RICTOR)-coding gene (rs140964083: G > A, found in one proband) was predicted to be hazardous. In the three public databases analyzed, variants in the same SNP locus were absent, and variants in the same gene were either absent or present at an extremely low frequency (3/5,008), indicating the rarity of hazardous RICTOR mutations in the general population. The de novo variant of RICTOR may be implicated in the development of sporadic TS, and RICTOR is a novel candidate factor for TS etiology., (© 2017 Wiley Periodicals, Inc.)

The contribution of genetic factors to schizophrenia is well established and recent studies have indicated several strong candidate genes. However, the pathophysiology of schizophrenia has not been totally elucidated yet. To date, studies of monozygotic twins discordant for schizophrenia have provided insight into the pathophysiology of this illness; this type of study can exclude inter-individual variability and confounding factors such as effects of drugs. In this study we used DNA microarray analysis to examine the mRNA expression patterns in the lymphoblastoid (LB) cells derived from two pairs of monozygotic twins discordant for schizophrenia. From five independent replicates for each pair of twins, we selected five genes, which included adrenomedullin (ADM) and selenoprotein X1 (SEPX1), as significantly changed in both twins with schizophrenia. Interestingly, ADM was previously reported to be up-regulated in both the LB cells and plasma of schizophrenic patients, and SEPX1 was included in the list of genes up-regulated in the peripheral blood cells of schizophrenia patients by microarray analysis. Then, we performed a genetic association study of schizophrenia in the Japanese population and examined the copy number variations, but observed no association. These findings suggest the possible role of ADM and SEPX1 as biomarkers of schizophrenia. The results also support the usefulness of gene expression analysis in LB cells of monozygotic twins discordant for an illness., (Copyright 2007 Wiley-Liss, Inc.)

Recently, a polymorphism of the XBP1 gene (-116 C/G) was observed to play a significant role in the development of bipolar mood disorder from the Japanese population. The present study investigated a role of the polymorphism in the development of personality in healthy Japanese volunteers (n = 195). Personality traits were evaluated using NEO Personality Inventory-Revised (NEO PI-R). As a result, a statistical trend for association between the polymorphism (genotype) and the NEO PI-R scores of agreeableness and neuroticism was observed (ANOVA, P = 0.01 and 0.006, respectively). Subjects with the G allele, especially those with G-G genotype, tended to show lower neuroticism and higher agreeableness in the present study. The result is provisional and should be interpreted with caution, partly because the previous study suggested the allele as a risk allele for bipolar disorder. Further studies are required to confirm the results., (Copyright 2005 Wiley-Liss, Inc.)

Linkage of bipolar disorder with 18p11 has been replicated by several investigators. A nuclear-encoded mitochondrial complex I subunit gene, NDUFV2, is one of the candidate genes in this locus, since the possible pathophysiological significance of mitochondrial dysfunction in bipolar disorder has been suggested. The objective of our study was to clarify the association between the NDUFV2 gene and bipolar disorder. We performed the real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) for NDUFV2 mRNA expression in lymphoblastoid cell lines derived from patients with bipolar disorder and healthy controls. We also screened novel polymorphisms using denaturing high performance liquid chromatography (D-HPLC) and PCR-direct sequencing method. Detected five single nucleotide polymorphisms (SNPs) were genotyped. A decrease of the expression level of NDUFV2 gene was found in patients with bipolar I disorder compared with controls (P = 0.006). We also found that the haplotype frequencies of the four polymorphisms in the upstream region of NDUFV2 were significantly different between bipolar disorders and controls (P = 0.0001). Our findings suggest that polymorphisms of the NDUFV2 gene may be one of the genetic risk factors for bipolar disorder., (Copyright 2003 Wiley-Liss, Inc.)