Browsing by Subject "5-HTTLPR"
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Item Characterizing the age-related decline of memory monitoring : neuroimaging and genetic approaches(2011-05) Pacheco, Jennifer Lynn; Schnyer, David M.; Maddox, W T.; Beevers, Christopher G.; Haley, Andreana; Holahan, CaroleMemory monitoring, or the ability to accurately assess one’s memory retrieval success, is known to be declined for older adults. The behavioral decline has been well explored, and is specific to tasks of source monitoring; tasks involving item memory monitoring do not show age-related deficits. This study attempts to further characterize the decline by exploring neuroanatomical contributions to the decline, and genetic influences that may explain performance variability in older adults. Older adults were genotyped for the serotonin transporter (5-HTTLPR) gene, and those that are carriers of the low-expressing allele demonstrate the expected age-related decline of source monitoring performance when compared to younger adults. Interestingly, older adults who lack this allele did not display any decline in performance when compared to younger adults. Neuroanatomical correlates of task performance indicate that prefrontal regions in the inferior and lateral cortices support accurate source memory monitoring, likely through their role in the proper selection of memory cues and inhibition of irrelevant information. This relationship suggests that age-related atrophy occurring in these structures could be responsible for the performance deficits on source memory monitoring tasks. There was no direct relationship seen between genotype for the 5-HTTLPR gene and cortical volumes, however diffusion tensor imaging shows that older adults who carry this allele have altered connections between the medial temporal lobe, responsible for memory retrieval, and prefrontal cortex, which monitors the retrieval process. Through stronger connections of critical networks, older adults who lack the 5-HTTLPR short allele may be able to compensate for the age-related atrophy seen in the prefrontal cortex. Functional results further indicate that the older adult non-carriers recruit inferior and lateral frontal regions to a greater extent than the older adult carriers during accurate memory monitoring. These results begin to suggest a neuroprotective mechanism for the 5-HTTLPR genotype, wherein some older adults may be able to postpone the expected decline of memory monitoring by retaining the ability to recruit essential inferior frontal structures through more organized white matter pathways.Item Differential susceptibility to social status(2012-05) Cason, Margaret Julia; Josephs, Robert A.; Beevers, Christopher; Buss, David M.; Martorana, Paul; McGeary, John E.The diathesis-stress model focuses on the interaction between gene polymorphisms and negative environmental conditions (i.e., stressors); however, Belsky and Pluess (2009) recently proposed an alternative to diathesis-stress: the differential susceptibility hypothesis, which states that some individuals may be predisposed to be more adversely affected by negative environments but, also, to benefit more from positive environments. Nevertheless, the differential susceptibly hypothesis has not been rigorous tested. Thus, the purpose of this study was to test the differential susceptibility hypothesis by examining individual differences in men’s testosterone, behavioral, and psychological responses to social status as a function of the serotonin transporter promoter region polymorphism (5-HTTLPR), which was cited by Belsky and Pluess as a potential “plasticity gene” because one variant – the long (l) allele – appears to be associated with lower susceptibility/plasticity and another – the short allele (s) – appears to be associated with higher susceptibility/plasticity. In this study, groups of 3-4 male participants were allowed to socialize before being told that they were part of a larger initiative to create a student-run Honor Committee. They were asked to nominate one person to be the leader and one person to not be on the committee. Then, participants were told privately that everyone voted them to either (1) be the leader or (2) not be on the committee. Salivary hormone samples were collected at baseline and 20 minutes after vote feedback. In addition, after receiving the vote feedback, participants completed a series of dating anxiety and mate preference tasks and were given the option to examine an “actual honor violation” case either alone or as part of the committee. The results support the differential susceptibility hypothesis. In terms of testosterone response, ss individuals showed both greater reactivity and differential responses to vote feedback. Furthermore, the testosterone responses of ss individuals were moderated by basal cortisol, which is associated with approach/avoidance behavior (Kagan et al., 2003; Shoal, Giancola, & Kirillova, 2003). In addition, ss individuals’ decisions to work on the committee or work alone and responses to the mating tasks were dependent upon the vote feedback, whereas l-carriers’ decisions and responses were not.Item Elaborative processing biases associated with vulnerability and maintenance of depression : evidence across levels of analysis(2014-08) Clasen, Peter Cunningham; Beevers, Christopher G.Major depressive disorder (MDD) will soon represent the most costly and debilitating disorder in the world. Yet, a clear model of the mechanisms underlying MDD remains elusive. This lack of clarity obscures efforts to prevent and treat MDD more effectively. This dissertation seeks to advance an integrated model of the mechanisms underlying MDD across cognitive, neural, and genetic levels of analysis. Building on the empirical foundation of cognitive theories of MDD, the dissertation includes three studies that help address questions about the cognitive mechanisms underlying depression vulnerability and maintenance. Specifically, the three studies focus on identifying 1) how elaborative processing biases, including attentional biases and rumination, give rise to specific symptoms of MDD and 2) elucidating biological mechanisms that may give rise to these biases. Together, these studies help advance an integrated model of MDD that, ultimately, may help facilitate the prevention and treatment of this costly and debilitating disorder.Item Individual differences in the impact of stress on alcohol use, binge drinking, and alcohol use onset: The role of developmental and biological variation(2017-04-19) Wells, Jessica; Boisvert, Danielle; Bouffard, Leana; Franklin, CortneyPrevious research suggests that both distal and proximal environmental stressors impact later alcohol use behaviors. Introduction of the stress sensitization hypothesis has highlighted that the effects of these environmental stressors may not be limited to direct effects but, rather, are interactive wherein the impact of proximal life stress are greater for individuals who have experienced distal stress such as childhood abuse (ExE). At the same time, gene-environment (GxE) interaction studies have examined how the effects of both distal and environmental stress is moderated by genetic polymorphisms in two-way interactions. The current study seeks to add to a small body of literature seeking to merge these two processes by examining a genetically moderated stress sensitization hypothesis (GxExE) on alcohol use, binge drinking, and alcohol use onset. The current dissertation further contributes to this body of literature by assessing gender-specific GxExE effects and presenting preliminary models gender-specific alcohol dependence and the role of sex-role identification in alcohol use, binge drinking, and alcohol use onset. Mixed results concerning the serotonergic polymorphisms, MAOA and 5-HTTLPR, two-way and three-way interactions with distal and proximal environmental stress were found. These findings and implications for programming designed to reduce alcohol use are discussed.Item Serotonin transporter gene variation and its association with cognitive vulnerability to depression(2011-08) Wells, Tony Terry; Beevers, Christopher G.; Tucker, David; Schallert, Timothy J.; Rude, Stephanie S.; Telch, Michael J.Depression is a serious condition that affects a significant proportion of the population and causes substantial life impairment (Kessler et al., 2003). Cognitive models of depression vulnerability (e.g., Teasdale, 1988) posit that information processing biases for negative and positive stimuli play a critical role in the disorder. Change in negative thinking in response to dysphoric moods is referred to as cognitive reactivity and has been shown to be a risk factor for future increases in depression (e.g., Beevers & Carver, 2003; Segal et al., 2006). Interestingly, recent behavioral genetics research indicates that certain genes may influence cognitive factors associated with depression. The short allele of a polymorphism of the serotonin transporter gene (5-HTTLPR) has been associated with increased risk for depression in the context of life stress (Caspi et al., 2003); however, the psychological mechanisms that increase depression risk for short 5-HTTLPR allele-carriers have not been definitively identified. Recent work has begun to reveal an association between the 5-HTTLPR and cognitive factors associated with depression such as attention bias for emotional information (Beevers et al., 2007) and negative thinking style (Hayden et al., 2007). A pilot study (n = 156) revealed an association between 5-HTTLPR and cognitive reactivity for attention bias for happy faces. The current study (n = 180) extended and improved upon the pilot study’s methodology and examined the relationship between the 5-HTTLPR and cognitive reactivity for attention to sad and happy faces as well as cognitive reactivity for dysfunctional attitudes. Cognitive variables were assessed after a neutral mood induction and after a sad mood induction at two laboratory sessions separated by at least 24 hours. There was a significant association between the 5-HTTLPR and cognitive reactivity for attention bias for emotional faces among Caucasian participants. Specifically, the short allele was associated with increased bias for emotional faces after the sad mood induction compared to the neutral mood induction. There was a linear relationship between number of short alleles possessed by participants and increase in bias for emotional information. The 5-HTTLPR was not significantly associated with cognitive reactivity for dysfunctional attitudes, but the effect was in the expected direction. Results are discussed in the context of recent neuroimaging research and plasticity models of behavior genetics. Implications for a model of depression vulnerability integrating genetic, neural, and cognitive factors and future directions for similar behavioral genetics studies are discussed.