Altered development of white matter in youth at high familial risk for bipolar disorder: a diffusion tensor imaging study

Objective: To study white matter (WM) development in youth at high familial risk for bipolar disorder (BD). WM alterations are reported in youth and adults with BD. WM undergoes important maturational changes in adolescence. Age-related changes in WM microstructure using diffusion tensor imaging with tract-based spatial statistics in healthy offspring having a parent with BD were compared with those in healthy controls. Method: A total of 45 offspring participated, including 20 healthy offspring with a parent diagnosed with BD (HBO) and 25 healthy control offspring of healthy parents (CONT). All were free of medical and psychiatric disorders. Mean fractional anisotropy (FA), radial diffusivity (RD), and longitudinal diffusivity were examined using whole-brain analyses, co-varying for age. Results: Group-by-age interactions showed a linear increase in FA and a linear decrease in RD in CONT in the left corpus callosum and right inferior longitudinal fasciculus. In HBO, there was a linear decrease in FA and an increase in RD with age in the left corpus callosum and no relation between FA or RD and age in the right inferior longitudinal fasciculus. Curve fitting confirmed linear and showed nonlinear relations between FA and RD and age in these regions in CONT and HBO. Conclusions: This is the first study to examine WM in healthy offspring at high familial risk for BD. Results from this cross-sectional study suggest altered development of WM in HBO compared with CONT in the corpus callosum and temporal associative tracts, which may represent vulnerability markers for future BD and other psychiatric disorders in HBO. J. Am. Acad. Child Adolesc. Psychiatry, J. Am. Acad. Child Adolesc. Psychiatry, 2010; 49(12):1249 -1259. Key words: bipolar disorder, familial risk, white matter, diffusion tensor imaging, neurodevelopment B ipolar disorder (BD) is a serious psychiatric illness affecting 1% to 3% of the adult population and remains a leading cause of morbidity, functional impairment, and completed suicide. 1 BD is characterized by difficulties in the regulation of emotions and behavior, as indicated by episodes of mania and depression. BD is highly heritable: the risk of BD is much greater in first-degree relatives of individuals diagnosed with BD. 2,3 Recent evidence has indicated that offspring of parents with BD are at increased risk for BD and other psychiatric disorders, including BD spectrum disorder, anxiety, and depression disorders. 2 Although genetic and environmental factors and their interactions are important in the development of BD, abnormalities of brain structure and function that most likely mediate these effects have yet to be elucidated. Converging evidence from epidemiologic, genetic, and neuroimaging studies has suggested that abnormalities in the development of white matter (WM) may play an important role in the neuropathophysiology of BD

Identification of Resource Use and Associated Costs for Viral Meningitis

ABSTRACT Purpose: This study involved identifying resource use and assigning monetary value to the diagnostic work-up and management of viral meningitis. Methodology: Using a previously established decision analytic framework, various resources were identified as part of routine management of viral meningitis. Secondary database analyses were used to quantify resources and assign a monetary value as a part of routine management of viral meningitis requiring use of the resource units identified in the decision analytic framework. Discharge data sources from the states of California, Florida, and Illinois, and Medicaid data sources from the state of Pennsylvania, were used for the purpose of analysis. Principal Findings: Physician visits, emergency room visits, hospital admissions, procedures, and medications were identified as the major resources used. Lumbar punctures, CT scans, and antibiotics were identified as the major procedures and medications utilized. No significant difference was found in the major resources used between the states' discharge data and the Medicaid data sources. The mean total charges for patient admissions with CT scans were significantly higher than for patient admissions without CT scans ($11,531.80 vs.$7,841.30, P<0.05). The mean lengths of stay for patients with CT scan were significantly higher than for patient admissions without CT scans (4.71 days vs. 3.88 days, P<0.05). The patient readmission rate was 10.7 percent, while the readmission rate for episodes with more than one hospitalization was 11.1 percent. The mean charge associated with readmission was $12,200

Absenteeism in a Represented Environment

Abstrac

PNPLA3 rs738409 causes steatosis according to viral & IL28B genotypes in hepatitis C

Background. Hepatitis C virus (HCV) is associated with a higher prevalence of steatosis compared to the general population. Aim. Our aim was to assess the impact of PNPLA3 rs738409 G-allele on steatosis in HCV patients.Material and methods. We included 474 HCV patients treated with peginterferon plus ribavirin. PNPLA3 rs738409 was genotyped and patients were classified according to alleles and genotypes. Steatosis was detected in 46.4% (220/474). Fibrosis was assessed by Scheuer score. Gene expression was analyzed in Huh7.5 and Huh7 cells using Real Time-PCR.Results. PNPLA3 allele-G was associated with steatosis [54.1% (126/233) vs. 39% (94/241)] (p = 0.0001). In HCV-1, allele-G was related to steatosis [50.6% (82/162) vs. 32.3% (53/164)] (p = 0.001), but did not in HCV-3 [61.9% (26/42) vs. 62% (31/50)] (p = 0.993). PNPLA3 allele-G was associated with steatosis in patients with IL28B-CT/TT [57.7% (82/142) vs. 37.1% (56/151)] (p = 0.0001), but did not in IL28B-CC [47.8% (43/90) vs. 42% (37/88)] (p = 0.442). Independent variables associated with steatosis were: PNPLA3 G-allele [O.R. 1.84 (CI95%: 1.06-3.21); p = 0.007], age [O.R. 1.04 (CI95%: 1.01-1.07); p = 0.017], HCV-genotype 3 [O.R. 2.46 (CI95%: 1.30-4.65); p = 0.006], HOMA > 4 [O.R. 2.72 (CI95%: 1.27-5.82); p = 0.010]. Since PNPLA3 RNA could not be detected on PBMC from HCV patients, an in vitro analysis was performed. Huh7.5 cells infected with JFH1 had a decreased PNPLA3 gene expression (fold inhibition = 3.2 ± 0.2), while Huh7 cells presented increased PNPLA3 gene expression (fold induction = 1.5 ± 0.2).Conclusion. PNPLA3 allele-G modulated the development of steatosis, particularly in patients with HCV-1 and IL28B-CT/TT genotype, but was not associated with SVR. Metabolic but not viral steatosis seems to be PNPLA3 regulated. Gene interaction may result in differential PNPLA3 gene expression levels in HCV infection