CNVs in Three Psychiatric Disorders

BACKGROUND: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). METHODS: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. RESULTS: In genic CNVs, we found an increased burden of smaller (500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25–0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. CONCLUSIONS: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD

HYPOXIC-ISCHEMIC BRAIN INJURY IN NEWBORN RAT : NEUROPROTECTIVE EFFECTS OF ACETAMINOPHEN AND THE INVOLVEMENT OF ACID SPHINGOMYELINASE ACTIVATION

Acetaminophen is widely used as an analgesic and antipyretic medication. Recently, acetaminophen has been shown as effective against neuronal cell death through its antioxidant and anti-inflammatory properties. In this study, we used the Rice-Vannucci model to examine whether the administration of acetaminophen was protective against hypoxic-ischemic brain injury in immature rat brain. Seven-day-old rat pups that had ligation of the right carotid artery received 20 mg/kg of acetaminophen intraperitoneally immediately before hypoxic exposure of 8% oxygen for 90 min. Compared to controls, acetaminophen treatment group showed decreased macroscopic brain injury scores at 48 h and 168 h after hypoxia-ischemia. Acetaminophen significantly decreased the number of apoptotic and necrotic cells in the cortex, caudate putamen, thalamus, and hippocampus. In addition, the percent brain damage of hypoxia-ischemia, which is another index for brain injury, was improved by the administration of acetaminophen. Our results suggested that acetaminophen inhibited apoptotic and necrotic cell death and played a role in neuroprotection after hypoxia-ischemia in immature rat brain. In addition, we showed that acid sphingomyelinase (ASM), which is as an important enzyme for cellular responses to reactive oxygen species (ROS), might be involved in brain injuries after hypoxie-ischemia.　The activation of ASM after hypoxia-ischemia was attenuated by the administration of acetaminophen in our rat model. This attenuation might be caused by the antioxidant property of acetaminophen, supporting the suggestion of its neuroprotective effect on the hypoxic-ischemic brain injury

ACOUSTIC RADIATION FORCE IMPULSE ELASTOGRAPHY FOR THE DIFFERENTIAL DIAGNOSIS OF LIVER TUMORS IN PATIENTS WITH LIVER DYSFUNCTION

Objective : Acoustic radiation force impulse (ARFI) technology can measure the elasticity of tissueand tumor. The aim of this study was to evaluate whether the ARFI technology can differentiatecavernous hemangioma, hepatocellular carcinoma (HCC) and metastatic liver tumors inpatients with liver dysfunction.Materials and Methods : Forty patients with liver dysfunction and liver tumors were enrolledin the study. The shear wave velocities (SWVs) in the tumors and background liver were examinedby ARFI elastography under ultrasonography (US).Results : The SWVs in livers bearing HCCs were significantly higher than those of livers bearingcavernous hemangiomas. The SWVs in HCCs and metastatic liver tumors were significantlyhigher than those in cavernous hemangiomas. The SWVs in metastatic liver tumors were significantlyhigher than those in HCCs. The SWV ratio of metastatic liver tumor/parenchyma wassignificantly higher than that of cavernous hemangioma/parenchyma and HCC/parenchyma.There was a significant correlation between the tumor sizes and the SWVs in metastaticliver tumors.Conclusions : We herein demonstrated that ARFI elastography could noninvasively provide helpfulinformation, without the need for biopsy, that could be used for the differential diagnosis amongcavernous hemangiomas, HCCs and metastatic liver tumors in patients with liver dysfunction