The interplay between a dietary preference for fat and sugar, gene expression in the dopaminergic system and executive cognition in humans

Obesity is a health issue of both individual and global importance. Evidence from rodent literature suggests that dietary preferences for fat and sugar might influence dopaminergic signaling in the brain and thus executive cognition. These diet-related changes could provide a mechanistic basis potentially explaining obesity-promoting behaviour. However, valid evidence for this link in humans is still scarce. This thesis aimed to add to this gap by studying dopamine-related gene expression profiles in peripheral cells and executive cognition in a human sample (n = 75). The results provide indications for an association between dietary preference and alterations in dopamingeric sigaling on a peripheral gene expression level even though the group differences were not statistically significant. A link to cognition could not be established with the methods applied. Yet, several targets for future research are suggested to further explore this interplay

Socioeconomic Stress by Dopamine Receptor 2 Gene Interactions in the Development of Obesity

<p>Background: Previous research suggests that early life socioeconomic stress and certain genetic polymorphisms may be partly associated with increased adiposity; however, research on both genetic and environmental predictors fail to account for the dramatic increase in obesity over that last several decades. Hypothesis: It was hypothesized that a GxE interaction between DRD2-related SNPs and parental education would predict trunk and total fat mass. This same interaction would also predict total calories from a 24-hour diet recall, which would mediate its effect on trunk and total fat mass. Sample: The current study analyzed genetic and psychosocial data from 697 participants collected for the Family Heart Study, an investigation examining the relationship between psychosocial behaviors and cardiovascular risk factors. Methods: Interactions were assessed between four single nucleotide polymorphisms (SNPs) in the D2 receptor and ANKK1 genes and tertiles of parental education predicting DXA-scan-measured trunk and total body fat mass. A measure of total calories, as assessed by a 24-hour diet recall, was tested as a mediator of this effect. Results: An interaction between mother's education and RS1116313 SNP predicted trunk fat (F(4,191)=2.94, p=0.022) and total body fat (F(4, 191)=3.94, p=0.004). The effects were driven by a reduction in trunk and total fat mass among C/C or T/T homozygotes with a high mother's education, which was not observed among C/T heterozygotes. Father's education was neither an interactive nor a main effect predictor in any models. Interactions predicting total calories were also non-significant, and no support for mediation was found. Post-hoc analyses revealed that leisure activity was also not a mediator. Alternatively, certain dietary components were predicted by the interactions between mother's education and RS1124492 and between mother's education and RS1800498. Conclusions: Trunk and total body fat composition are predicted by an interaction between mother's education and the RS1116313 SNP. This effect does not appear to be mediated by total calories or leisure activity. Other SNPs associated with the D2 receptor interact with mother's education to predict dietary components.</p>Dissertatio

Smoking cessation : a report of the Surgeon General

Tobacco smoking is the leading cause of preventable disease, disability, and death in the United States (U.S. Department of Health and Human Services [USDHHS] 2014). Smoking harms nearly every organ in the body and costs the United States billions of dollars in direct medical costs each year (USDHHS 2014). Although considerable progress has been made in reducing cigarette smoking since the first U.S. Surgeon General\u2019s report was released in 1964 (USDHHS 2014), in 2018, 13.7% of U.S. adults (34.2 million people) were still current cigarette smokers (Creamer et al. 2019). One of the main reasons smokers keep smoking is nicotine (USDHHS 1988). Nicotine, a drug found naturally in the tobacco plant, is highly addictive, as with such drugs as cocaine and heroin; acti- vates the brain\u2019s reward circuits; and reinforces repeated nicotine exposure (USDHHS 1988, 2010, 2014; National Institute on Drug Abuse [NIDA] 2018).The majority of cigarette smokers (68%) want to quit smoking completely (Babb et al. 2017). The 1990 Surgeon General\u2019s report, The Health Benefits of Smoking Cessation, was the last Surgeon General\u2019s report to focus on cur- rent research on smoking cessation and to predominantly review the health benefits of quitting smoking (USDHHS 1990). Because of limited data at that time, the 1990 report did not review the determinants, processes, or outcomes of attempts at smoking cessation. Pharmacotherapy for smoking cessation was not introduced until the 1980s. Additionally, behavioral and other counseling approaches were slow to develop and not widely available at the time of the 1990 report because few were covered under health insurance, and programs such as group counseling ses- sions were hard for smokers to access, even by those who were motivated to quit (Fiore et al. 1990).The purpose of this report is to update and expand the 1990 Surgeon General\u2019s report based on new scien- tific evidence about smoking cessation. Since 1990, the scientific literature has expanded greatly on the deter- minants and processes of smoking cessation, informing the development of interventions that promote cessa- tion and help smokers quit (Fiore et al. 2008; Schlam and Baker 2013). This knowledge and other major develop- ments have transformed the landscape of smoking ces- sation in the United States. This report summarizes this enhanced knowledge and specifically reviews patterns and trends of smoking cessation; biologic mechanisms; various health benefits; overall morbidity, mortality, and economic benefits; interventions; and strategies that pro- mote smoking cessation.Suggested citation: U.S. Department of Health and Human Services. Smoking Cessation. A Report of the Surgeon General. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2020.2020-cessation-sgr-full-report.pdf2020713

Modelling the Neuropsychopharmacology of Obsessive-Compulsive Disorder in the Common Marmoset (Callithrix jacchus)

This thesis extends the understanding of the neural and neurochemical contributions to two forms of behavioural adaptation, reversal learning and contingency degradation, in which stimulus/action–reward contingencies are altered. The results are interpreted within the psychological framework of the compulsivity construct, and their implications for the pathological behaviour of obsessive-compulsive-disorder (OCD) are considered. The orbitofrontal cortex (OFC) and striatum are key brain structures involved in reversal learning, as are the neurotransmitters serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA) within those respective regions. However, there has been little empirical evidence of how these two structures and neurochemical systems interact, especially in the functional context of reversal learning. In Chapter Three, the impact of experimentally-induced reductions of 5-HT in the anterior OFC on monoamine levels in subcortical structures such as the striatum and amygdala was determined, DA being found to be significantly up-regulated in the amygdala. Functionally, 5-HT depletion of the OFC has previously been shown to induce deficits in reversal learning. To determine the possible causal significance of amygdala dopamine up-regulation for said reversal learning deficit, the effects of blocking the upregulation with the infusion of intra amygdala DA receptor antagonists following bilateral OFC 5-HT depletion were investigated in a reversal learning paradigm. In Chapter Four, the differential roles of regions of striatum were examined in visual reversal learning. Two recent investigations in non-human primates highlighted the role of the striatum in reversal learning,but pinpointed the critical region to be either the ventromedial caudate or the putamen. Marmosets were trained on a serial reversal task that allowed multiple acute neural manipulations, and the ventromedial caudate and putamen were then reversibly inactivated using the GABAA agonist muscimol. Results indicated dose-related impairments specifically in reversal learning within the putamen, with sparing of discrimination retention. By contrast, similar reversible inactivation of the caudate nucleus produced marked deficits in visual discrimination performance (retention). In Chapter Five, the neural basis of action–outcome contingency knowledge was investigated by inactivating distinct regions of the PFC, the perigenual ACC (pgACC; area 32) and the anterior OFC, and determining response sensitivity to the degradation of action–outcome contingencies. In previous work, excitotoxic lesions of either the pgACC or the OFC had been found to induce insensitivity to contingency degradation in marmosets. However, the design of that experiment did not allow specification of whether stimulus– or action–outcome associations were disrupted, and a precise neural locus could not be determined for the behavioural effects as the OFC lesions included parts of the lateral and medial OFC. I therefore developed a novel contingency degradation paradigm that distinguished between stimulus– and action–outcome associations to enable the study of acute pharmacological manipulations in both brain regions. The pgACC and OFC were reversibly inactivated using GABAA–GABAB agonists (muscimol–baclofen). Whereas the pgACC inactivation produced selective deficits in sensitivity to action–outcome contingency degradation, OFC inactivation reduced the suppressive effect of noncontingent reward on responding more generally but left intact sensitivity to degradation of the contingencies. These results are discussed in terms of different theories of the functions of the pgACC and OFC. In the final discussion the findings on the neural substrates of reversal learning and contingency degradation are drawn together in terms of their significance for theories of PFC involvement in cognitive control, and for the understanding of OCD and other neuropsychiatric disorders.Research that formed the thesis was supported by a Programme Grant (G0901884) from the Medical Research Council UK (MRC) to Professor Angela Roberts and a Wellcome Trust Senior Investigator Award (104631/Z/14/Z) to Professor Trevor Robbins. I was personally supported by a BCNI-MRC studentship. The research was conducted at the Behavioural and Clinical Neuroscience Institute, which was supported by a joint award from the MRC and Wellcome Trust (G00001354)

Saliva continine levels of babies and mothers living with smoking fathers under different housing types in Hong Kong: a cross-sectional study

Paper Session 15 - The Challenge of Second-Hand Smoke: PA15-3BACKGROUND: After the Smoking Ordinance enacted in HK since 1/2007, shifting of smoking from outdoor to home was found, home becomes a major source of secondhand smoke (SHS) exposure of nonsmokers. OBJECTIVES: It aimed to assess the SHS exposure of babies and mothers living with smoking fathers of two housing types by using a biomarker. METHODS: Trios of smoking father, non-smoking mother and a baby under 18-months were recruited from Maternal and Child Health Centres (MCHCs) from 6/2008 to 10/2009. Consented couples completed the baseline survey including demographic data, fathers’ household smoking behaviors and mothers’ actions in protecting babies from household SHS exposure. Saliva samples from baby and mother were collected and then sent to the National University of Singapore for cotinine analyses. Log-transformations were used for the saliva cotinine due to skewed data. There were 2 housing types (public/private) and father was asked if they smoked at home (yes/no). MANOVA was used to compare the babies’ and mothers’ cotinine levels when fathers smoked at home under the 2 housing types. RESULTS: 1,158 trios were consented. 1,142 mothers’ and 1,058 babies’ samples were assayed. The mean age of the fathers and mothers was 35.5(±7.0) and 31.2(±4.9). The mean mothers’ cotinine level was 12.15ng/ml (±61.20) while babies’ was 2.38ng/ml (±6.01). 606 and 501 trios were living in public and private housing. Fathers’ smoked at home led to higher mothers’ and babies’ saliva cotininary (mean log of mothers’ cotininary: 0.14±0.62 vs. 0.05±0.55, p=0.06; babies: 0.16±0.38 vs. 0.07±0.34, p=0.003). Housing types influenced babies’ cotinine level (public: 0.17±0.37; private: 0.10±0.36, p=0.01). MANOVA showed that fathers smoked at home (Λ=0.99, p=0.01) and housing types (Λ=0.99, p=0.01) were positively related to the saliva cotinine levels. CONCLUSIONS: Father smoked at home and the housing types have greater impact on babies’ saliva cotininary, showing that they were highly exposed at home and in public housing environment. HK government should promote smoke-free homes and to provide more smoking cessation services to minimize the household SHS exposure to babiespublished_or_final_versio