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Shinichiro Nanko

Publications and source records attributed to Shinichiro Nanko.

At least 19 recordsLinked to original sources
PubMed2006

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. We conducted the DEX/CRH test in 61 inpatients with major depressive episode (Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV)) and 57 healthy subjects. In all, 35 patients were repeatedly assessed with the DEX/CRH test on admission and before discharge. The possible relationships between clinical variables and the DEX/CRH test were also examined. Significantly enhanced pituitary-adrenocortical responses to the DEX/CRH test were observed in patients on admission compared with controls. Such abnormalities in patients were significantly reduced after treatment, particularly in those who underwent electroconvulsive therapy (ECT) in addition to pharmacotherapy. Age and female gender were associated with enhanced hormonal responses to the DEX/CRH test. Severity of depression correlated with DEX/CRH test results, although this was explained, at least in part, by a positive correlation between age and severity in our patients. Medication per se was unrelated to DEX/CRH test results. These results suggest that the DEX/CRH test is a sensitive state-dependent marker to monitor HPA axis abnormalities in major depressive episode during treatment. Restoration from HPA axis abnormalities occurred with clinical responses to treatment, particularly in depressed patients who underwent ECT.

Adult↗
PubMed2006

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. Among them, 15 patients were diagnosed as bipolar II disorder (BPII), whereas 24 patients were with unipolar depression (UP), using a structured clinical interview to assess the mood spectrum (SCI-MOODS). In addition to ordinary clinical and demographic variables, the authors studied fine symptomatology of depression, premorbid personality, and interpersonal relationship. Continuous variables were analyzed by t-test. Categorical variables were tested by chi2 analysis. In terms of premorbid personality, manic type (Zerssen) was found more frequently in BPII (UP 2/24, BPII 9/15, P < 0.05). Patients with BPII tended to show apparently quick disappearance of depressive symptoms (UP 2/24, BPII 9/15, P = 0.01). The most prominent result was a high prevalence of comorbidity of borderline personality disorder (BPD) among BPII (UP 0/24, BPII 6/15, P = 0.02). As Akiskal indicated that mood lability represents the most powerful predictor of hypomanias, patients with BPII showed quick response in mood to admission. The current subjects with BPII had high frequency of manic type of premorbid personality, indicating the usefulness of this variable for the prediction of hypomanias. Finally, the authors could observe development of BPD during hospitalization exclusively among BPII, to support the possibility of BPD as a state effect of BPII.

Adolescent↗
PubMed2005

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. In Japanese, nominally significant association of one haplotype was observed in extended samples of bipolar disorder but not in schizophrenia. In NIMH trios, no association was found in total samples. However, an exploratory analysis suggested that the other haplotype was significantly over-transmitted to probands only from the paternal side. The associated haplotype in Japanese or NIMH pedigrees shared three common polymorphisms in the promotor, which was found to alter promotor activity. These findings suggested promotor polymorphisms of HSPA5 may affect the interindividual variability of ER stress response and may confer a genetic risk factor for bipolar disorder.

Adult↗
PubMed2005

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. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study--which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent--indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects.

Chromosomes, Human, Pair 1↗
PubMed2005

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. Because patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) sometimes show organic mental disorder, 'atypical psychosis' may be caused by mutations of mitochondrial DNA (mtDNA) in some patients. In the present study whole mtDNA was sequenced for seven patients with various psychotic disorders, who could be categorized as 'atypical psychosis'. None of them had known mtDNA mutations pathogenic for mitochondrial encephalopathy. Two of seven patients belonged to a subhaplogroup F1b1a with low frequency. These results did not support the hypothesis that clinical presentation of some patients with 'atypical psychosis' is a reflection of subclinical mitochondrial encephalopathy. However, the subhaplogroup F1b1a may be a good target for association study of 'atypical psychosis'.

Aged↗
PubMed2004

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. METHODS: We screened the further upstream region of NDUFV2. We performed a case-control study in Japanese patients with bipolar disorder and control subjects and a transmission disequilibrium test in 104 parent and proband trios of the National Institute of Mental Health (NIMH) Genetics Initiative pedigrees. We also performed the promoter assay to examine functional consequence of the -602G> A polymorphism. RESULTS: The -602G> A polymorphism was found to alter the promoter activity. We found that the other haplotype block surrounding -3542G> A was associated with bipolar disorder. The association of the haplotypes consisting of -602G> A and -3542G> A polymorphisms with bipolar disorder was seen both in Japanese case-control samples and NIMH trios. CONCLUSION: Together these findings indicate that the polymorphisms in the promoter region of NDUFV2 are a genetic risk factor for bipolar disorder by affecting promoter activity.

Adult↗
PubMed2004

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 = 0.015). The association was significant in the extended samples [bipolar disorder, 9/630 (1.43%); controls, 1/734 (0.14%); p = 0.007]. On the other hand, only 5 of 25 family members with this mutation developed bipolar disorder, of which 4 patients with 3644C had comorbid physical symptoms. The 3644T-->C mutation converts amino acid 113, valine, to alanine in the NADH-ubiquinone dehydrogenase subunit I, a subunit of complex I, and 113 valine is well conserved from Drosophila to 61 mammalian species. Using transmitochondrial cybrids, 3644T-->C was shown to decrease mitochondrial membrane potential and complex I activity compared with haplogroup-matched controls. According to human mitochondrial genome polymorphism databases, 3644C was not found in centenarians but was found in 3% of patients with Alzheimer disease and 2% with Parkinson disease. The result of modest functional impairment caused by 3644T-->C suggests that this mutation could increase the risk for bipolar disorder.

Adolescent↗
PubMed2004

[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. We have been conducting a systematic survey of the association of reelin-related gene polymorphisms with these disorders. Previously, we examined the association of the triplet repeats of the reelin and VLDLR gene with schizophrenia. We found no significant association of schizophrenia with the trinucleotide repeat polymorphism of the reelin nor VLDLR genes (Akahane et al. 2002). In this study, we performed an allelic association analysis in Alzheimer's disease and schizophrenia with three polymorphisms of the fyn gene reported by Ishiguro et al (2000). Diagnosis was based on DSM-IV and NINCDS-ADRDA. We found no significant differences in genotype distribution or allelic frequency between patient and control groups. Thus, it is unlikely that these polymorphisms play an important role in the pathogenesis of Alzheimer's disease or schizophrenia.

Aged↗
PubMed2004

[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. Brain MRI showed clear swelling of the brain stem area, especially in the pons, in the active phase with low signal in T1-weighted images contrasting with clear high signal in T2-weighted images and FLAIR. At the time of remission, atrophy of the brain stem was shown. These findings were consistent with the view reported in recent years concerning the brain image of Neuro-Behçet's disease, which seemed to be useful for the differential diagnosis. This case manifested two outstanding clinical features. First, it showed bipolar mood swing or mixed state distinguishable from disinhibition or euphoria in deteriorated personality, which is common in this condition. A clear bipolar mood disorder has not been described until now in Neuro-Behçet's disease. Second, subclinical dysthymia or hypomanic phase occurred before clear onset of the disease. In Neuro-Behçet's disease, it is currently considered that psychiatric symptoms may appear in the early stage, but there is controversy as to whether they can precede the other symptoms. Our case indicated very early onset of psychiatric symptoms in this condition.

Behcet Syndrome↗
PubMed2003

Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder.

The pathophysiology of bipolar disorder is still unclear, although family, twin and linkage studies implicate genetic factors. Here we identified XBP1, a pivotal gene in the endoplasmic reticulum (ER) stress response, as contributing to the genetic risk factor for bipolar disorder. Using DNA microarray analysis of lymphoblastoid cells derived from two pairs of twins discordant with respect to the illness, we found downregulated expression of genes related to ER stress response in both affected twins. A polymorphism (-116C-->G) in the promoter region of XBP1, affecting the putative binding site of XBP1, was significantly more common in Japanese patients (odds ratio = 4.6) and overtransmitted to affected offspring in trio samples of the NIMH Bipolar Disorder Genetics Initiative. XBP1-dependent transcription activity of the -116G allele was lower than that of the -116C allele, and in the cells with the G allele, induction of XBP1 expression after ER stress was markedly reduced. Valproate, one of three mood stabilizers, rescued the impaired response by inducing ATF6, the gene upstream of XBP1. These results indicate that the -116C-->G polymorphism in XBP1 causes an impairment of its positive feedback system and increases the risk of bipolar disorder.

Base Sequence↗
PubMed2003

Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with bipolar disorder.

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.

Adult↗
PubMed2003

No association of mutations and mRNA expression of WFS1/wolframin with bipolar disorder in humans.

Association of WFS1 (wolframin) and bipolar disorder has been suggested by psychiatric manifestations in patients or non-symptomatic carriers of Wolfram disease and linkage of bipolar disorder with 4p16, the locus of WFS1. Five studies of WFS1 in bipolar disorder did not support this association, although possible association of several missense mutations has not been excluded yet. In this study, four such mutations were genotyped in 184 patients with bipolar disorder and 207 controls. None had the A559T and A602V mutations, and no association of G576S and H611R with bipolar disorder was found. We also quantified the expression levels of WFS1 mRNA in the postmortem brains of patients with bipolar disorder, depression, schizophrenia, and controls. There was no significant difference of the expression levels. These results did not support the pathophysiological significance of WFS1 in bipolar disorder.

Adult↗
PubMed2003

Prenatal underdevelopment and schizophrenia: a case report of monozygotic twins.

A case is described herein of monozygotic twins discordant for schizophrenia that illustrates possible causal events of prenatal underdevelopment, morphological changes in the brain, poor premorbid functioning, and the development of schizophrenia. The affected twin was born with a birthweight of 1620 g, whereas the unaffected twin weighed 2300 g at birth. Marked differences in sociability and intelligence were observed between the twins from early childhood. Magnetic resonance imaging of the brain revealed high-intensity signals in the white matter and enlarged ventricles in the affected twin, while no such abnormality was detected in the well twin. This twin pair suggests a possibility that hypoxic brain damage associated with prenatal underdevelopment may be a causal factor for abnormalities in psychosocial development and subsequent schizophrenia.

Adult↗
PubMed2002

Association analysis of polymorphic CGG repeat in 5' UTR of the reelin and VLDLR genes with schizophrenia.

Several lines of evidence suggest a possible role for reelin in the pathogenesis of neurodevelopmental diseases, particularly schizophrenia. Genes encoding reelin and proteins involved in the signal pathway of reelin are thus candidate genes for schizophrenia. We examined the polymorphic CGG repeat in the 5'-untranslated region (UTR) of the reelin gene, which was recently found to be associated with autistic disorder, and the CGG repeat in the 5' UTR region of the very low density protein receptor (VLDLR) gene, which was reported to be associated with sporadic Alzheimer's disease, for allelic association with schizophrenia. The subjects consisted of 150 patients and 150 controls matched for sex, age and ethnicity (Japanese). We found no significant association of schizophrenia with the trinucleotide repeat polymorphism of the reelin or VLDLR genes, suggesting that these polymorphisms do not have a major role in the pathogenesis of the disease.

5' Flanking Region↗