Gene by Disease Interaction on Orbitofrontal Gray Matter in Cocaine Addiction

Chronic cocaine use has been associated with structural deficits in brain regions having dopamine receptive neurons. However, the concomitant use of other drugs and common genetic variability in monoamine regulation present additional structural variability. We therefore examined variations in gray matter volume (GMV) as a function of lifetime drug use and the monoamine oxidase A (MAOA) genotype in cocaine use disorders (CUD) and healthy controls

Valuing Health Gain from Composite Response Endpoints for Multisystem Diseases

Objectives: This study aimed to demonstrate how to estimate the value of health gain after patients with a multisystem disease achieve a condition-specific composite response endpoint. Methods: Data from patients treated in routine practice with an exemplar multisystem disease (systemic lupus erythematosus) were extracted from a national register (British Isles Lupus Assessment Group Biologics Register). Two bespoke composite response endpoints (Major Clinical Response and Improvement) were developed in advance of this study. Difference-in-differences regression compared health utility values (3-level version of EQ-5D; UK tariff) over 6 months for responders and nonresponders. Bootstrapped regression estimated the incremental quality-adjusted life-years (QALYs), probability of QALY gain after achieving the response criteria, and population monetary benefit of response. Results: Within the sample (n = 171), 18.2% achieved Major Clinical Response and 49.1% achieved Improvement at 6 months. Incremental health utility values were 0.0923 for Major Clinical Response and 0.0454 for Improvement. Expected incremental QALY gain at 6 months was 0.020 for Major Clinical Response and 0.012 for Improvement. Probability of QALY gain after achieving the response criteria was 77.6% for Major Clinical Response and 72.7% for Improvement. Population monetary benefit of response was £1 106 458 for Major Clinical Response and £649 134 for Improvement. Conclusions: Bespoke composite response endpoints are becoming more common to measure treatment response for multisystem diseases in trials and observational studies. Health technology assessment agencies face a growing challenge to establish whether these endpoints correspond with improved health gain. Health utility values can generate this evidence to enhance the usefulness of composite response endpoints for health technology assessment, decision making, and economic evaluation

Long-term impacts of prenatal synthetic glucocorticoids exposure on functional brain correlates of cognitive monitoring in adolescence

The fetus is highly responsive to the level of glucocorticoids in the gestational environment. Perturbing glucocorticoids during fetal development could yield long-term consequences. Extending prior research about effects of prenatally exposed synthetic glucocorticoids (sGC) on brain structural development during childhood, we investigated functional brain correlates of cognitive conflict monitoring in term-born adolescents, who were prenatally exposed to sGC. Relative to the comparison group, behavioral response consistency (indexed by lower reaction time variability) and a brain correlate of conflict monitoring (the N2 event-related potential) were reduced in the sGC exposed group. Relatedly, source localization analyses showed that activations in the fronto-parietal network, most notably in the cingulate cortex and precuneus, were also attenuated in these adolescents. These regions are known to subserve conflict detection and response inhibition as well as top-down regulation of stress responses. Moreover, source activation in the anterior cingulate cortex correlated negatively with reaction time variability, whereas activation in the precuneus correlated positively with salivary cortisol reactivity to social stress in the sGC exposed group. Taken together, findings of this study indicate that prenatal exposure to sGC yields lasting impacts on the development of fronto-parietal brain functions during adolescence, affecting multiple facets of adaptive cognitive and behavioral control

Role of nucleus accumbens core but not shell in incubation of methamphetamine craving after voluntary abstinence

We recently introduced an animal model to study incubation of drug craving after prolonged voluntary abstinence, mimicking the human condition of relapse after successful contingency management treatment. Here we studied the role of the nucleus accumbens (NAc) in this model. We trained rats to self-administer a palatable solution (sucrose+maltodextrin 1%, 6 h/day, 6 days) and methamphetamine (6 h/day, 12 days). We then evaluated relapse to methamphetamine seeking after 1 and 15 days of voluntary abstinence, achieved via a discrete choice procedure between the palatable solution and methamphetamine (14 days). We used RNAscope in-situ hybridization to quantify the co-labeling of the neuronal activity marker Fos, and dopamine Drd1- and Drd2-expressing medium spiny neurons (MSNs) in NAc core and shell during the incubation tests. Next, we determined the effect of pharmacological inactivation of NAc core and shell by either GABAA and GABAB agonists (muscimol+baclofen, 50+50 ng/side), Drd1-Drd2 antagonist (flupenthixol, 10 µg/side) or the selective Drd1 or Drd2 antagonists (SCH39166 1.0 µg/side or raclopride 1.0 µg/side) during the relapse tests. Incubated methamphetamine seeking after voluntary abstinence was associated with a selective increase of Fos expression in the NAc core, but not shell, and Fos was co-labeled with both Drd1- and Drd2-MSNs. NAc core, but not shell, injections of muscimol+baclofen, flupenthixol, SCH39166, and raclopride reduced methamphetamine seeking after 15 days of abstinence. Together, our results suggest that dopamine transmission through Drd1 and Drd2 in NAc core is critical to the incubation of methamphetamine craving after voluntary abstinence

Comparative investigation of personality traits in migraine patients and sound people by personality MMPI questionaire.

Aim of this study was to investigate the relationship between migraine attacks and mental disorders.mental disorders is that disorders which assessed by Minnesota multiphasic personality inventory (MMPI), and migrain predicated to transient ischemic attacks. The investigation hypothesis was: tendency to mental disorders assessed by MMPI in migraine patients is mor than normal population.fortesting hypothesis 66 persons diagnosed as migraine patient selected on medicine dosiers and compared with 66 sound person.in this study MMPI and a qustionaire related to history of migraine administered and Multivariate Analysis Of Variance (MANOVA) is used for analysis of data.results confirmed our hypothesis.migraine patients had mor tendency to mental disorders in comparative with sound persons.thisdisorders were depression,hysteria,psychopath,paranoia,psychasthenia,chizophrenia,hypomania and hypochondria.totally results similar to former studies supported our hypothesis and this differences are significant in statistical viewpoint

The mRNA Expression and Circulating Levels of Visfatin and Their Correlation with Coronary Artery Disease Severity and 25-Hydroxyvitamin D

It is evident that coronary artery disease (CAD) is closely associated with abnormal glucose and lipid metabolism. Notably, dysregulation of inflammatory pathways and immune system also contribute to CAD development. Recently, it has been suggested that visfatin, a proinflammatory adipocytokine, may be involved in several inflammatory and metabolic diseases. In this study, we evaluated the serum visfatin levels and its mRNA expression in peripheral blood mononuclear cells (PBMCs) from CAD patients compared with control subjects. We also studied the correlation between visfatin gene expression and serum levels with clinical and metabolic parameters. This study was conducted on 56 male patients with CAD confirmed by angiography and 30 healthy men as controls. CAD severity was determined based on the number of vessels. Study of gene expression in PBMCs was performed using real time-PCR, and serum levels of visfatin and 25-hydroxyvitamin D were measured by ELISA. We found that serum visfatin levels and its gene expression in PBMCs were increased in patients with CAD compared with the control group (p=0.027 and p=0.016, respectively). Also, visfatin gene expression was positively correlated with visfatin levels and both these variables had a strong positive correlation with the severity of CAD. It appears that elevated mRNA expression and circulating level of visfatin might be of relevance to the pathogenesis and severity of CAD. However, further studies are necessary to better clarify the associations between visfatin and CAD. © Georg Thieme Verlag KG Stuttgart · New York