| 1 | Neuroreport 2004 Jun 15: 1443-6 |
|---|---|
| PMID | 15194870 |
| Title | Elevated adrenomedullin mRNA in lymphoblastoid cells from schizophrenic patients. |
| Abstract | Adrenomedullin (ADM) is a 52 amino acid peptide with multiple physiological functions and wide tissue distributions including brain. Recently, elevated plasma levels of ADM were found in patients with schizophrenia, bipolar affective disorder and autism, suggesting the involvement of ADM in the pathophysiology of mental diseases. Using real-time quantitative PCR, we compared the ADM mRNA levels in lymphoblastoid cell lines between schizophrenic patients and controls. Male but not female schizophrenia patients had 2- to 3-fold higher ADM mRNA levels than controls (p<0.01). Our data support that ADM may be associated with the pathophysiology of schizophrenia, although the cause of the association needs further study. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Neuroreport 2004 Jun 15: 1443-6 |
| PMID | 15194870 |
| Title | Elevated adrenomedullin mRNA in lymphoblastoid cells from schizophrenic patients. |
| Abstract | Adrenomedullin (ADM) is a 52 amino acid peptide with multiple physiological functions and wide tissue distributions including brain. Recently, elevated plasma levels of ADM were found in patients with schizophrenia, bipolar affective disorder and autism, suggesting the involvement of ADM in the pathophysiology of mental diseases. Using real-time quantitative PCR, we compared the ADM mRNA levels in lymphoblastoid cell lines between schizophrenic patients and controls. Male but not female schizophrenia patients had 2- to 3-fold higher ADM mRNA levels than controls (p<0.01). Our data support that ADM may be associated with the pathophysiology of schizophrenia, although the cause of the association needs further study. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2008 Jul 147B: 557-64 |
| PMID | 18081029 |
| Title | Up-regulation of ADM and SEPX1 in the lymphoblastoid cells of patients in monozygotic twins discordant for schizophrenia. |
| Abstract | 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. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2008 Jul 147B: 557-64 |
| PMID | 18081029 |
| Title | Up-regulation of ADM and SEPX1 in the lymphoblastoid cells of patients in monozygotic twins discordant for schizophrenia. |
| Abstract | 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. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Am J Psychiatry 2010 Oct 167: 1254-63 |
| PMID | 20713499 |
| Title | Cross-disorder genomewide analysis of schizophrenia, bipolar disorder, and depression. |
| Abstract | Family and twin studies indicate substantial overlap of genetic influences on psychotic and mood disorders. Linkage and candidate gene studies have also suggested overlap across schizophrenia, bipolar disorder, and major depressive disorder. The purpose of this study was to apply genomewide association study (GWAS) analysis to address the specificity of genetic effects on these disorders. The authors combined GWAS data from three large effectiveness studies of schizophrenia (CATIE, genotyped: N=741), bipolar disorder (STEP-BD, geno-typed: N=1,575), and major depressive disorder (STAR*D, genotyped: N=1,938) as well as from psychiatrically screened control subjects (NIMH-Genetics Repository: N=1,204). A two-stage analytic procedure involving an omnibus test of allele frequency differences among case and control groups was applied, followed by a model selection step to identify the best-fitting model of allelic effects across disorders. The strongest result was seen for a single nucleotide polymorphism near the adrenomedullin (ADM) gene (rs6484218), with the best-fitting model indicating that the effect was specific to bipolar II disorder. Findings also revealed evidence suggesting that several genes may have effects that transcend clinical diagnostic boundaries, including variants in NPAS3 that showed pleiotropic effects across schizophrenia, bipolar disorder, and major depressive disorder. This study provides the first genomewide significant evidence implicating variants near the ADM gene on chromosome 11p15 in psychopathology, with effects that appear to be specific to bipolar II disorder. Although genomewide significant evidence of cross-disorder effects was not detected, the results provide evidence that there are both pleiotropic and disorder-specific effects on major mental illness and illustrate an approach to dissecting the genetic basis of mood and psychotic disorders that can inform future large-scale cross-disorder GWAS analyses. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2013 Oct 46: 120-5 |
| PMID | 23867466 |
| Title | Possible role of adrenomedullin and nitric oxide in major depression. |
| Abstract | Adrenomedullin (ADM) and nitric oxide (NO) have been implicated in the pathogenesis of certain psychiatric disorders such as schizophrenia and bipolar disorder. ADM induces vasorelaxation by activating adenylate cyclase and stimulating the release of NO. These two molecules are known to influence cerebral activity. In this study, we aimed to examine the serum levels of ADM and NO in patients with major depression (MD). We enrolled 50 patients with MD and 50 healthy control subjects. The diagnosis of MD was established on the basis of a structured clinical interview using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The severity of depressive symptoms was evaluated using Hamilton's 17-item Depression Rating Scale. The mean serum levels of ADM and NO in patients with MD were significantly higher than those in healthy subjects (p=0.001, for both). The severity of psychomotor retardation in patients with MD was significantly correlated with the ADM (r=0.37, p=0.007) and NO levels (r=0.29, p=0.038). The patients with obvious psychomotor retardation had significantly higher levels of ADM and NO than did the patients with no psychomotor retardation (p=0.025, p=0.030). A significantly positive correlation was found between ADM and NO levels in patients with MD (r=0.79, p=0.001). Serum levels of ADM and NO levels were not correlated with the severity or duration of depression or depressive symptoms (except psychomotor retardation). In conclusion, our study indicates that serum levels of ADM and NO are elevated in patients with MD and that increased serum levels of ADM and NO may be associated with psychomotor retardation. The ADM-NO system may serve as a new target in the treatment of patients with MD and psychomotor retardation. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | ISRN Psychiatry 2013 -1 2013: 876171 |
| PMID | 23738224 |
| Title | Disrupted central inhibition after transcranial magnetic stimulation of motor cortex in schizophrenia with long-term antipsychotic treatment. |
| Abstract | Aims. schizophrenia is a neuropsychiatric disorder associated with mental and motor disturbances. We aimed to investigate motor control, especially central silent period (CSP) in subjects with schizophrenia (n = 11) on long-term antipsychotic treatment compared to healthy controls (n = 9). Methods. Latency and duration of motor evoked potentials (MEPs) and CSPs were measured with the help of single pulse transcranial magnetic stimulation (TMS) and intramuscular electrodes. After stimulation of the dominant and nondominant motor cortex of abductor digiti minimi (ADM) and tibialis anterior (TA) muscle areas, respective responses were measured on the contralateral side. Results. MEPs did not differ significantly between the groups. Multiple CSPs were found predominantly in subjects with schizophrenia, which showed a higher number of CSPs in the dominant ADM and the longest summarized duration of CSPs in the nondominant ADM (P < 0.05) compared to controls. Conclusions. There were multiple CSPs predominantly in the upper extremities and in the dominant body side in subjects with schizophrenia. Behind multiple CSPs may lie an impaired regulation of excitatory or inhibitory neurotransmitter systems in central motor pathways. Further research is needed to clarify the role of the intramuscular recording methods and the effect of antipsychotics on the results. |
| SCZ Keywords | schizophrenia, schizophrenic |