Lack of association of EGR2 variants with bipolar disorder in Japanese population.

The early growth response gene 2 (EGR2) has been recently reported to be associated with bipolar disorder in the Korean population. However replication studies in independent cohorts of same and different ethnicities are essential for establishing the credibility of a genotype-phenotype association. With this notion, in the present study we have performed a replication study of the reported association of SNPs in EGR2 in a case-control study comprising of 867 unrelated Japanese bipolar disorder patients and 895 age-, sex- and ethnicity-matched controls.

A population-specific uncommon variant in GRIN3A associated with schizophrenia.

Background: Genome-wide association studies have successfully identified several common variants showing robust association with schizophrenia. However, individually, these variants only produce a weak effect. To identify genetic variants with larger effect sizes, increasing attention is now being paid to uncommon and rare variants.

Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and age of onset in schizophrenia: a combined analysis of independent samples.

Methylenetetrahydrofolate reductase (MTHFR) is involved in the one-carbon cycle, which is of importance for nucleotide synthesis and methylation of DNA, membranes, proteins and lipids. The MTHFR gene includes two common polymorphisms (rs1801133 or C677T; rs1801131 or A1298C) which both alter enzyme activity. The T-allele of the C677T polymorphism has recently been associated with earlier age at onset of schizophrenia.

Measurement of dopamine D2 receptors in living human brain using [11C]raclopride with ultra-high specific radioactivity.

Introduction: High specific radioactivity is preferable in the measurement of neuroreceptor bindings with positron emission tomography (PET) because receptor occupancy by mixed cold ligand hampers the accurate estimation of receptor binding. Recently, we succeeded in synthesizing [(11)C]raclopride, a dopamine D(2) receptor ligand, with ultra-high specific radioactivity, i.e.

Association study of ubiquitin-specific peptidase 46 (USP46) with bipolar disorder and schizophrenia in a Japanese population.

Recently, ubiquitin-specific peptidase 46 (Usp46) has been identified as a quantitative trait gene responsible for immobility in the tail suspension test and forced swimming test in mice. Mice with 3-bp deletion in Usp46 exhibited loss of 'behavioral despair' under inescapable stresses in addition to abnormalities in circadian behavioral rhythms and the GABAergic system. Considering the face and construct validity as an animal model for bipolar disorder, we explored an association of USP46 and bipolar disorder in a Japanese population.

Association analyses between brain-expressed fatty-acid binding protein (FABP) genes and schizophrenia and bipolar disorder.

Deficits in prepulse inhibition (PPI) are a biological marker for psychiatric illnesses such as schizophrenia and bipolar disorder. To unravel PPI-controlling mechanisms, we previously performed quantitative trait loci (QTL) analysis in mice, and identified Fabp7, that encodes a brain-type fatty acid binding protein (Fabp), as a causative gene. In that study, human FABP7 showed genetic association with schizophrenia.

Preliminary genome-wide association study of bipolar disorder in the Japanese population.

Recent progress in genotyping technology and the development of public databases has enabled large-scale genome-wide association tests with diseases. We performed a two-stage genome-wide association study (GWAS) of bipolar disorder (BD) in Japanese cohorts. First we used Affymetrix 100K GeneChip arrays in the analysis of 107 cases with bipolar I disorder and 107 controls, and selected markers that were nominally significant (P < 0.

Mitochondrial DNA haplogroup analysis in patients with bipolar disorder.

Several lines of evidence support mitochondrial dysfunction in bipolar disorder. Elevated calcium level in platelets is reported in this disease. To verify mitochondrial DNA (mtDNA) haplogroups characteristic to bipolar disorder, we sequenced mtDNA of seven regions and performed haplogroup analysis in 195 patients with bipolar disorder and 255 controls.

Up-regulation of ADM and SEPX1 in the lymphoblastoid cells of patients in monozygotic twins discordant for schizophrenia.

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.

Association analysis of HSP90B1 with bipolar disorder.

Pathophysiological role of endoplasmic reticulum (ER) stress response signaling has been suggested for bipolar disorder. The goal of this study was to test the genetic association between bipolar disorder and an ER chaperone gene, HSP90B1 (GRP94/gp96), which is located on a candidate locus, 12q23.3.

Association analysis of ATF4 and ATF5, genes for interacting-proteins of DISC1, in bipolar disorder.

Disrupted in schizophrenia 1 (DISC1) and its molecular cascade are implicated in the pathophysiology of schizophrenia and bipolar disorder. As interacting-proteins with DISC1, Nudel, ATF4, ATF5, LIS1, alpha-tubulin, PDE4B, eIF3, FEZ1, Kendrin, MAP1A and MIPT3 were identified. We previously showed the down-regulation of ATF5 in the lymphoblastoid cells derived from affected co-twin of monozygotic twins discordant for bipolar disorder.

A promoter haplotype of the inositol monophosphatase 2 gene (IMPA2) at 18p11.2 confers a possible risk for bipolar disorder by enhancing transcription.

Lithium is an effective mood stabilizer for bipolar disorder patients and its therapeutic effect may involve inhibition of inositol monophosphatase activity. In humans, the enzyme is encoded by two genes, IMPA1 and IMPA2. IMPA2 maps to 18p11.

Clinical features of soft bipolarity in major depressive inpatients.

Because of the difficulties of ascertaining episode of hypomania by past history of the patients, it is of clinical value to find variables which predict the development of bipolar II disorder in depressive patients. Taking advantage of relatively long hospitalization, the authors tried to elucidate fine clinical features of the soft bipolarity. The subjects were 39 patients with Major Depressive Episode, diagnosed according to the 4th edition of the Diagnostic and Statistical Manual criteria.

Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p.

The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide-polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese.

Functional polymorphisms of HSPA5: possible association with bipolar disorder.

Altered endoplasmic reticulum stress (ER) response signaling is suggested in bipolar disorder. Previously, we preliminarily reported the genetic association of HSPA5 (GRP78/BiP) with bipolar disorder. Here, we extended our analysis by increasing the number of Japanese case-control samples and NIMH Genetics Initiative bipolar trio samples (NIMH trios), and also analyzed schizophrenia samples.

Assessment of the dexamethasone/CRH test as a state-dependent marker for hypothalamic-pituitary-adrenal (HPA) axis abnormalities in major depressive episode: a Multicenter Study.

There is compelling evidence for the involvement of hypothalamic-pituitary-adrenal (HPA) axis abnormalities in depression. Growing evidence has suggested that the combined dexamethasone (DEX)/corticotropin-releasing hormone (CRH) test is highly sensitive to detect HPA axis abnormalities. We organized a multicenter study to assess the DEX/CRH test as a state-dependent marker for major depressive episode in the Japanese population.

Mitochondrial DNA sequence analysis of patients with 'atypical psychosis'.

Although classical psychopathological studies have shown the presence of an independent diagnostic category, 'atypical psychosis', most psychotic patients are currently classified into two major diagnostic categories, schizophrenia and bipolar disorder, by the Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) criteria. 'Atypical psychosis' is characterized by acute confusion without systematic delusion, emotional instability, and psychomotor excitement or stupor. Such clinical features resemble those seen in organic mental syndrome, and differential diagnosis is often difficult.

Mitochondrial DNA 3644T-->C mutation associated with bipolar disorder.

Mitochondrial dysfunction associated with mutant mitochondrial DNA (mtDNA) has been suggested in bipolar disorder, and comorbidity with neurodegenerative diseases was often noted. We examined the entire sequence of mtDNA in six subjects with bipolar disorder having comorbid somatic symptoms suggestive of mitochondrial disorders and found several uncharacterized homoplasmic nonsynonymous nucleotide substitutions of mtDNA. Of these, 3644C was found in 5 of 199 patients with bipolar disorder but in none of 258 controls (p = 0.

Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with bipolar disorder in Japanese and the National Institute of Mental Health pedigrees.

Background: Linkage with 18p11 is one of the replicated findings in molecular genetics of bipolar disorder. Because mitochondrial dysfunction has been suggested in bipolar disorder, NDUFV2 at 18p11, encoding a subunit of the complex I, reduced nicotinamide adenine dinucleotide (NADH)ubiquinone oxidoreductase, is a candidate gene for this disorder. We previously reported that a polymorphism in the upstream region of NDUFV2, -602G> A, was associated with bipolar disorder in Japanese subjects; however, functional significance of -602G> A was not known.

[A case of Neuro-Behçet's disease with early onset of bipolar mood disorder].

In this report, we describe a case of Neuro-Behçet's disease with early onset of bipolar mood disorder. A 53-year-old man with neuropathy including dysphasia and dyslalia developed bipolar mood disorder with anxiety, agitation, depressive mood, talkativeness, hyperkinesias, and appetite rise, and soon exhibited severe personality deterioration. Oral aphthae, cell proliferation and elevated IL-6 levels in spinal fluid, and the patient's clinical downhill course with remission and relapse in spite of good reaction to steroid preparation indicated the possibility of Neuro-Behçet's disease.

[Analysis of the fyn kinase gene in Alzheimer's disease and schizophrenia].

Reelin is a protein which plays an important role in cell construction and proliferation of neurons during the development of the central nervous system. Several lines of evidence suggest a possible role for reelin-related genes in the etiology of neurodevelopmental as well as neurodegenerative diseases. It is possible that variations in reelin-related genes (Reelin, VLDLR, FYN, CNRs, a3b1INTEGRIN, mDAB1) may be involved in the pathogenesis of schizophrenia and Alzheimer's disease.