Indices of Hemispheric Lateralization: A Methodological Analysis

The authors describe and evaluate several indices of brain hemisphere lateralization. The methods use different data, including response accuracy, reaction times, and EEG asymmetry. They describe an index- free ranking procedure that uses two or more kinds of data and that makes few assumptions and does not impose a numerical scale. EEG asymmetry data entails measurement decisions and scaling assumptions, which the authors discuss in some detail

Speeding up or Reaching out

The Welsh Assembly, a devolved legislature in the UK, and its executive the Welsh Government, have a distinctly intensive commitment to equality -emphasising universality with weighty obligations on public services. This article uses the 'discourse-historical approach' (DHA) to critically review an eleven-year social service reform strategy (produced in 2007), and to weigh up the priorities of fiscal efficiency and universal equality. We refer to these competing priorities as 'speeding up' and 'reaching out', respectively. Our findings show an imbalance towards the former, largely sidelining the possible value of services to those currently underserved. The article discusses this mismatch in respect of the dominant policymaking framework of 'New Public Management' and its emphases on productivity, efficiency, and quantifiable accountability. We also show the value of DHA in analysing 'fights for dominance' -in this case between competing discourses within a flagship policy document

Interaction of opiate peptide and noradrenalin systems: Light microscopic studies

In this light microscopic immunocyto-chemical study [beta]-Endorphin ([beta]-END), leu-enkephalin and dopamine-[beta]hydroxylase (DBH) antisera are used to obtain an overview of the interaction of the noradrenergic and opiate peptide systems in brain. Serial brain areas were analyzed for DBH and then for [beta]-END or leu-enkephalin. Several areas were evaluated for cell and fiber interactions between these systems. The areas of richest possible contact between [beta]-END and DBH positive systems include the rostral locus coeruleus region, the periaqueductal grey, possibly the dorsal thalamus, the paraventricular hypothalamus and the arcuate nucleus. Enkephalin cells and fibers were seen surrounding the locus coeruleus throughout its length with a few fibers in the nucleus itself.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23268/1/0000205.pd

Central epinergic inhibition of corticosterone release in rat

Drugs known to inhibit phenylethanolamine-N-methyltransferase (EC 2.1.1.28), the final enzyme in the epinephrine synthetic pathway were administered to rats and their effects on pituitary-arenal function studied. 2, 3-Dichloro-[alpha]-methylbenzylamine (DCMB) produced dose-related increases in plasma corticosterone in basal and stressed rats. Evidence for the central nature of this tonic inhibitory effect of epinephrine was its continued presence in adrenal demedullated rats. 2-chloro-3-trifluoromethyl-[alpha]-benzylamine (CTFMB) administration elevated plasma corticosterone and this effect was highly correlated to the decrease in hypothalamic epinephrine concentration in both sham operated and adrenal demedullated rats. These findings argue for tonic epinergic inhibition of pituitary-adrenal function.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24373/1/0000642.pd

Genome-wide association study identifies 30 loci associated with bipolar disorder.

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder

PORTAL: Pilot study on the safety and tolerance of preoperative melatonin application in patients undergoing major liver resection: a double-blind randomized placebo-controlled trial

<p>Abstract</p> <p>Background</p> <p>Major surgical procedures facilitate systemic endotoxinemia and formation of free radicals with subsequent inflammatory changes that can influence the postoperative course. Experimental data suggest that preoperative supraphysiological doses of melatonin, a potent immuno-modulator and antioxidant, would decrease postoperative infectious and non-infectious complications induced by major abdominal surgery.</p> <p>Methods/Design</p> <p>A randomized controlled double blind single center clinical trial with two study arms comprising a total of 40 patients has been designed to assess the effects of a single preoperative dose of melatonin before major liver resection. Primary endpoints include the determination of safety and tolerance of the regimen as well as clinical parameters reflecting pathophysiological functions of the liver. Furthermore, data on clinical outcome (infectious and non-infectious complications) will be collected as secondary endpoints to allow a power calculation for a randomized clinical trial aiming at clinical efficacy.</p> <p>Discussion</p> <p>Based on experimental data, this ongoing clinical trial represents an advanced element of the research chain from bench to bedside in order to reach the highest level of evidence-based clinical facts to determine if melatonin can improve the general outcome after liver resection.</p> <p>Trial Registration</p> <p>EudraCT200600530815</p

Mitochondrial Mutations in Subjects with Psychiatric Disorders

A considerable body of evidence supports the role of mitochondrial dysfunction in psychiatric disorders and mitochondrial DNA (mtDNA) mutations are known to alter brain energy metabolism, neurotransmission, and cause neurodegenerative disorders. Genetic studies focusing on common nuclear genome variants associated with these disorders have produced genome wide significant results but those studies have not directly studied mtDNA variants. The purpose of this study is to investigate, using next generation sequencing, the involvement of mtDNA variation in bipolar disorder, schizophrenia, major depressive disorder, and methamphetamine use. MtDNA extracted from multiple brain regions and blood were sequenced (121 mtDNA samples with an average of 8,800x coverage) and compared to an electronic database containing 26,850 mtDNA genomes. We confirmed novel and rare variants, and confirmed next generation sequencing error hotspots by traditional sequencing and genotyping methods. We observed a significant increase of non-synonymous mutations found in individuals with schizophrenia. Novel and rare non-synonymous mutations were found in psychiatric cases in mtDNA genes: ND6, ATP6, CYTB, and ND2. We also observed mtDNA heteroplasmy in brain at a locus previously associated with schizophrenia (T16519C). Large differences in heteroplasmy levels across brain regions within subjects suggest that somatic mutations accumulate differentially in brain regions. Finally, multiplasmy, a heteroplasmic measure of repeat length, was observed in brain from selective cases at a higher frequency than controls. These results offer support for increased rates of mtDNA substitutions in schizophrenia shown in our prior results. The variable levels of heteroplasmic/multiplasmic somatic mutations that occur in brain may be indicators of genetic instability in mtDNA

Exon expression in lymphoblastoid cell lines from subjects with schizophrenia before and after glucose deprivation

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to examine the effects of glucose reduction stress on lymphoblastic cell line (LCL) gene expression in subjects with schizophrenia compared to non-psychotic relatives.</p> <p>Methods</p> <p>LCLs were grown under two glucose conditions to measure the effects of glucose reduction stress on exon expression in subjects with schizophrenia compared to unaffected family member controls. A second aim of this project was to identify cis-regulated transcripts associated with diagnosis.</p> <p>Results</p> <p>There were a total of 122 transcripts with significant diagnosis by probeset interaction effects and 328 transcripts with glucose deprivation by probeset interaction probeset effects after corrections for multiple comparisons. There were 8 transcripts with expression significantly affected by the interaction between diagnosis and glucose deprivation and probeset after correction for multiple comparisons. The overall validation rate by qPCR of 13 diagnosis effect genes identified through microarray was 62%, and all genes tested by qPCR showed concordant up- or down-regulation by qPCR and microarray. We assessed brain gene expression of five genes found to be altered by diagnosis and glucose deprivation in LCLs and found a significant decrease in expression of one gene, glutaminase, in the dorsolateral prefrontal cortex (DLPFC). One SNP with previously identified regulation by a 3' UTR SNP was found to influence IRF5 expression in both brain and lymphocytes. The relationship between the 3' UTR rs10954213 genotype and IRF5 expression was significant in LCLs (p = 0.0001), DLPFC (p = 0.007), and anterior cingulate cortex (p = 0.002).</p> <p>Conclusion</p> <p>Experimental manipulation of cells lines from subjects with schizophrenia may be a useful approach to explore stress related gene expression alterations in schizophrenia and to identify SNP variants associated with gene expression.</p