The Functional DRD3 Ser9Gly Polymorphism (rs6280) Is Pleiotropic, Affecting Reward as Well as Movement

Abnormalities of motivation and behavior in the context of reward are a fundamental component of addiction and mood disorders. Here we test the effect of a functional missense mutation in the dopamine 3 receptor (DRD3) gene (ser9gly, rs6280) on reward-associated dopamine (DA) release in the striatum. Twenty-six healthy controls (HCs) and 10 unmedicated subjects with major depressive disorder (MDD) completed two positron emission tomography (PET) scans with [11C]raclopride using the bolus plus constant infusion method. On one occasion subjects completed a sensorimotor task (control condition) and on another occasion subjects completed a gambling task (reward condition). A linear regression analysis controlling for age, sex, diagnosis, and self-reported anhedonia indicated that during receipt of unpredictable monetary reward the glycine allele was associated with a greater reduction in D2/3 receptor binding (i.e., increased reward-related DA release) in the middle (anterior) caudate (p<0.01) and the ventral striatum (p<0.05). The possible functional effect of the ser9gly polymorphism on DA release is consistent with previous work demonstrating that the glycine allele yields D3 autoreceptors that have a higher affinity for DA and display more robust intracellular signaling. Preclinical evidence indicates that chronic stress and aversive stimulation induce activation of the DA system, raising the possibility that the glycine allele, by virtue of its facilitatory effect on striatal DA release, increases susceptibility to hyperdopaminergic responses that have previously been associated with stress, addiction, and psychosis

Coronavirus and State Actions: Questions by and for policy planners and analysts

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Incidence of Insomnia in OSA patients and its correlations with parameters of polysomnography

Background/Aims: Prevalence of insomnia in obstructive sleep apnoea (OSA) patients has been estimated in many studies and has been found to be a frequent symptom (38% in a recent review 1).Our study aims to estimate the incidence of insomnia in Greek patients presenting to a public hospital sleep clinic, and correlate it with the severity of OSA and parameters of polysomnography (PSG). Methods: 100 patients who visited the sleep unit of the General Hospital ‘Evangelismos’ completed the Athens Insomnia Scale (AIS) and underwent a polysomnographic study. 56% were men, with mean age 54,7±12,5 years and BMI 31,5±6,2. Results: 70% of patients had insomnia. Insomnia (AIS≥6) and OSA (AHI≥5) were coexistent in 71,4 %. There was no correlation between insomnia and severity of OSA. A strong positive correlation was found/evident between difficulty in initiating sleep and number of hypopneas (r: 0,20 p:0,049), diminished functioning during the day and leg movements (r:0,21 p:0,050) and between daytime sleepiness and wake after sleep onset (WASO) (r:0,2 p:0,038). A negative correlation was found between overnight awakenings and sleep efficiency (r: -0,23 p: 0,021). Also, negative correlation was found between early morning awakening and minimum SpO2 (r=0.27, p=0,021), and between insufficient duration of sleep (r:-0,22 p: 0,021) and minimum SpO2. Conclusions: We found a high incidence of insomnia in patients with OSA, which does not correlate with severity of OSA. Contrary to many other studies, insomnia was not more common in women. More studies are required to clarify the significance of the positive correlation between insomnia and number of hypopneas and minimum SpO2

Community Violence Exposure and Conduct Problems in Children and Adolescents with Conduct Disorder and Healthy Controls

Exposure to community violence through witnessing or being directly victimized has been associated with conduct problems in a range of studies. However, the relationship between community violence exposure (CVE) and conduct problems has never been studied separately in healthy individuals and individuals with conduct disorder (CD). Therefore, it is not clear whether the association between CVE and conduct problems is due to confounding factors, because those with high conduct problems also tend to live in more violent neighborhoods, i.e., an ecological fallacy. Hence, the aim of the present study was: (1) to investigate whether the association between recent CVE and current conduct problems holds true for healthy controls as well as adolescents with a diagnosis of CD; (2) to examine whether the association is stable in both groups when including effects of aggression subtypes (proactive/reactive aggression), age, gender, site and socioeconomic status (SES); and (3) to test whether proactive or reactive aggression mediate the link between CVE and conduct problems. Data from 1178 children and adolescents (62% female; 44% CD) aged between 9 years and 18 years from seven European countries were analyzed. Conduct problems were assessed using the Kiddie-Schedule of Affective Disorders and Schizophrenia diagnostic interview. Information about CVE and aggression subtypes was obtained using self-report questionnaires (Social and Health Assessment and Reactive-Proactive aggression Questionnaire (RPQ), respectively). The association between witnessing community violence and conduct problems was significant in both groups (adolescents with CD and healthy controls). The association was also stable after examining the mediating effects of aggression subtypes while including moderating effects of age, gender and SES and controlling for effects of site in both groups. There were no clear differences between the groups in the strength of the association between witnessing violence and conduct problems. However, we found evidence for a ceiling effect, i.e., individuals with very high levels of conduct problems could not show a further increase if exposed to CVE and vice versa. Results indicate that there was no evidence for an ecological fallacy being the primary cause of the association, i.e., CVE must be considered a valid risk factor in the etiology of CD

A genome-wide association study of anorexia nervosa.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field

Potential-of-Mean-Force Description of Ionic Interactions and Structural Hydration in Biomolecular Systems

To understand the functioning of living organisms on a molecular level, it is crucial to dissect the intricate interplay of the immense number of biological molecules. Most of the biochemical processes in cells occur in a liquid environment formed mainly by water and ions. This solvent environment plays an important role in biological systems. The potential-of-mean-force (PMF) formalism attempts to describe quantitatively the interactions of the solvent with biological macromolecules on the basis of an approximate statistical-mechanical representation. At its current status of development, it deals with ionic effects on the biomolecular structure and with the structural hydration of biomolecules. The underlying idea of the PMF formalism is to identify the dominant sources of interactions and incorporate these interactions into the theoretical formalism using PMF`s (or particle correlation functions) extracted from bulk-liquid systems. In the following, the authors shall briefly outline the statistical-mechanical foundation of the PMF formalism and introduce the PMF expansion formalism, which is intimately linked to superposition approximations for higher-order particle correlation functions. The authors shall then sketch applications, which describe the effects of the ionic environment on nucleic-acid structure. Finally, the authors shall present the more recent extension of the PMF idea to describe quantitatively the structural hydration of biomolecules. Results for the interface of ice and water and for the hydration of deoxyribonucleic acid (DNA) will be discussed

Resting autonomic nervous system activity is unrelated to antisocial behaviour dimensions in adolescents: Cross-sectional findings from a European multi-centre study

Purpose: Autonomic nervous system (ANS) functioning has long been studied in relation to antisocial behaviour, but relevant measures (heart rate, heart rate variability, pre-ejection period, respiration rate) have rarely been considered together. This study investigated the relationship between these measures and antisocial behaviour. Methods: Using a sample of 1010 youths with (47.8%) and without conduct disorder (52.2%) aged between 9 and 18. years (659 females, 351 males, mean age = 14.2. years, SD = 2.4), principal component analysis (PCA) was applied to various measures of psychopathology and antisocial behavior. Structural equation modelling was performed in order to test whether the ANS measures predicted PCA-dimensions. Cluster analysis was used in order to classify patterns of ANS activity. Analyses were performed separately for males/females and controlled for body-mass-index, age, caffeine use, cigarette smoking, sports, socioeconomic status, medication, cardiac problems. Results: The PCA yielded three components: antisocial behaviour/comorbid psychopathology, narcissistic traits, and callous-unemotional traits. ANS measures were only weakly correlated with these components. Cluster analysis yielded high and low arousal clusters in both sexes. When controlling for covariates, all associations disappeared. Conclusion: Our findings suggest that resting ANS measures are only weakly related to antisocial behaviour and indicate that smoking should be considered as an important covariate in future psychophysiological studies

The Neuropsychological and Emotional Profile of Adults with Parasomnia: A Case Series

Although parasomnias are nocturnal phenomena occurring during sleep or during arousals from sleep, there is increasing evidence that they are associated with daytime dysfunction as well. However, systematic studies in this field are scarce. The aim of the current case series was to investigate the sleep–wake, neuropsychological and emotional profiles of patients with parasomnias. Thirty patients with parasomnia (13 NREM, 17 REM) and 30 healthy subjects matched for age, sex and educational status were included. All participants underwent comprehensive neuropsychological, cognitive and behavioral evaluation. We found that parasomnia patients scored higher in all neuropsychological, emotional, sleep–wake and quality of life scales compared to healthy subjects. The presence of a parasomnia was associated with major impact on daytime functioning across several domains with increased levels of fatigue (FSS > 4) in 56%, sleepiness (ESS > 10) in 47%, depressive symptoms (BDI > 20) in 17%, anxiety (PSWQ > 52) in 17%, anger expression out (STAXI A > 16) in 27% and anger expression in (STAXI B > 16) in 23%, as well as a reduced average quality of life score (RAND derived from SF-36). Sleep–wake disturbances were significantly correlated with QoL scores. In the intergroup analysis between REM/NREM, we found that the REM group had worse cognitive performance and lower levels of fatigue/energy compared to NREM patients. These findings suggest that parasomnia is associated with difficulties in several aspects of daytime functioning (cognitive, affective/emotional and physical) and, therefore, parasomnia diagnostic workup should not be limited only to nocturnal phenomena