@article{kozik_hagan_jadavji_smith_haage_2022, title={The U.S. academic job market survives the SARS-CoV-2 global pandemic}, url={https://doi.org/10.1101/2022.05.27.493714}, DOI={10.1101/2022.05.27.493714}, abstractNote={Abstract}, author={Kozik, Ariangela J and Hagan, Ada and Jadavji, Nafisa M and Smith, Christopher T and Haage, Amanda}, year={2022}, month={May} }
 @article{sarabipour_burgess_niemi_smith_filho_ibrahim_clark_2022, title={The faculty-to-faculty mentorship experience: a survey on challenges and recommendations for improvements}, url={https://doi.org/10.1101/2022.10.17.512624}, DOI={10.1101/2022.10.17.512624}, abstractNote={Abstract}, author={Sarabipour, Sarvenaz and Burgess, Steven J and Niemi, Natalie M and Smith, Christopher T and Filho, Alexandre W Bisson and Ibrahim, Ahmed and Clark, Kelly}, year={2022}, month={Oct} }
 @article{castrellon_young_dang_smith_cowan_zald_samanez-larkin_2021, title={Dopamine biases sensitivity to personal goals and social influence in self-control over everyday desires}, volume={9}, url={https://doi.org/10.1101/2021.09.10.459829}, DOI={10.1101/2021.09.10.459829}, abstractNote={Abstract}, publisher={Cold Spring Harbor Laboratory}, author={Castrellon, Jaime J. and Young, Jacob S. and Dang, Linh C. and Smith, Christopher T. and Cowan, Ronald L. and Zald, David H. and Samanez-Larkin, Gregory R.}, year={2021}, month={Sep} }
 @article{reproducibility of findings in modern pet neuroimaging: insight from the nrm2018 grand challenge_2021, volume={5}, url={http://dx.doi.org/10.1177/0271678x211015101}, DOI={10.1177/0271678x211015101}, abstractNote={ The reproducibility of findings is a compelling methodological problem that the neuroimaging community is facing these days. The lack of standardized pipelines for image processing, quantification and statistics plays a major role in the variability and interpretation of results, even when the same data are analysed. This problem is well-known in MRI studies, where the indisputable value of the method has been complicated by a number of studies that produce discrepant results. However, any research domain with complex data and flexible analytical procedures can experience a similar lack of reproducibility. In this paper we investigate this issue for brain PET imaging. During the 2018 NeuroReceptor Mapping conference, the brain PET community was challenged with a computational contest involving a simulated neurotransmitter release experiment. Fourteen international teams analysed the same imaging dataset, for which the ground-truth was known. Despite a plurality of methods, the solutions were consistent across participants, although not identical. These results should create awareness that the increased sharing of PET data alone will only be one component of enhancing confidence in neuroimaging results and that it will be important to complement this with full details of the analysis pipelines and procedures that have been used to quantify data. }, journal={Journal of Cerebral Blood Flow & Metabolism}, publisher={SAGE Publications}, year={2021}, month={May}, pages={0271678X2110151} }
 @article{fernandes_sarabipour_smith_niemi_jadavji_kozik_holehouse_pejaver_symmons_filho_et al._2020, title={A survey-based analysis of the academic job market}, volume={9}, url={https://doi.org/10.7554/eLife.54097}, DOI={10.7554/eLife.54097}, abstractNote={Many postdoctoral researchers apply for faculty positions knowing relatively little about the hiring process or what is needed to secure a job offer. To address this lack of knowledge about the hiring process we conducted a survey of applicants for faculty positions: the survey ran between May 2018 and May 2019, and received 317 responses. We analyzed the responses to explore the interplay between various scholarly metrics and hiring outcomes. We concluded that, above a certain threshold, the benchmarks traditionally used to measure research success – including funding, number of publications or journals published in – were unable to completely differentiate applicants with and without job offers. Respondents also reported that the hiring process was unnecessarily stressful, time-consuming, and lacking in feedback, irrespective of outcome. Our findings suggest that there is considerable scope to improve the transparency of the hiring process.}, journal={eLife}, publisher={eLife Sciences Publications, Ltd}, author={Fernandes, Jason D and Sarabipour, Sarvenaz and Smith, Christopher T and Niemi, Natalie M and Jadavji, Nafisa M and Kozik, Ariangela J and Holehouse, Alex S and Pejaver, Vikas and Symmons, Orsolya and Filho, Alexandre W Bisson and et al.}, year={2020}, month={Jun} }
 @article{seaman_smith_juarez_dang_castrellon_burgess_juan_kundzicz_cowan_zald_et al._2019, title={Differential regional decline in dopamine receptor availability across adulthood: Linear and nonlinear effects of age}, volume={4}, url={https://doi.org/10.1002/hbm.24585}, DOI={10.1002/hbm.24585}, abstractNote={Abstract}, journal={Human Brain Mapping}, publisher={Wiley}, author={Seaman, Kendra L. and Smith, Christopher T. and Juarez, Eric J. and Dang, Linh C. and Castrellon, Jaime J. and Burgess, Leah L. and Juan, M. Danica San and Kundzicz, Paul M. and Cowan, Ronald L. and Zald, David H. and et al.}, year={2019}, month={Apr} }
 @article{castrellon_seaman_crawford_young_smith_dang_hsu_cowan_zald_samanez-larkin_2019, title={Individual Differences in Dopamine Are Associated with Reward Discounting in Clinical Groups But Not in Healthy Adults}, volume={39}, url={https://doi.org/10.1523/JNEUROSCI.1984-18.2018}, DOI={10.1523/JNEUROSCI.1984-18.2018}, abstractNote={Some people are more willing to make immediate, risky, or costly reward-focused choices than others, which has been hypothesized to be associated with individual differences in dopamine (DA) function. In two studies using PET imaging, one empirical (Study 1:N= 144 males and females across 3 samples) and one meta-analytic (Study 2:N= 307 across 12 samples), we sought to characterize associations between individual differences in DA and time, probability, and physical effort discounting in human adults. Study 1 demonstrated that individual differences in DA D2-like receptors were not associated with time or probability discounting of monetary rewards in healthy humans, and associations with physical effort discounting were inconsistent across adults of different ages. Meta-analytic results for temporal discounting corroborated our empirical finding for minimal effect of DA measures on discounting in healthy individuals but suggested that associations between individual differences in DA and reward discounting depend on clinical features. Addictions were characterized by negative correlations between DA and discounting, but other clinical conditions, such as Parkinson's disease, obesity, and attention-deficit/hyperactivity disorder, were characterized by positive correlations between DA and discounting. Together, the results suggest that trait differences in discounting in healthy adults do not appear to be strongly associated with individual differences in D2-like receptors. The difference in meta-analytic correlation effects between healthy controls and individuals with psychopathology suggests that individual difference findings related to DA and reward discounting in clinical samples may not be reliably generalized to healthy controls, and vice versa.}, number={2}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Castrellon, Jaime J. and Seaman, Kendra L. and Crawford, Jennifer L. and Young, Jacob S. and Smith, Christopher T. and Dang, Linh C. and Hsu, Ming and Cowan, Ronald L. and Zald, David H. and Samanez-Larkin, Gregory R.}, year={2019}, month={Jan}, pages={321–332} }
 @article{fernandes_sarabipour_smith_niemi_jadavji_kozik_holehouse_pejaver_symmons_filho_et al._2019, title={Insights from a survey-based analysis of the academic job market}, volume={10}, url={https://doi.org/10.1101/796466}, DOI={10.1101/796466}, abstractNote={Abstract}, publisher={Cold Spring Harbor Laboratory}, author={Fernandes, Jason D. and Sarabipour, Sarvenaz and Smith, Christopher T. and Niemi, Natalie M. and Jadavji, Nafisa M. and Kozik, Ariangela J. and Holehouse, Alex S. and Pejaver, Vikas and Symmons, Orsolya and Filho, Alexandre W. Bisson and et al.}, year={2019}, month={Oct} }
 @article{smith_dang_burgess_perkins_juan_smith_cowan_le_kessler_samanez-larkin_et al._2019, title={Lack of consistent sex differences in d-amphetamine-induced dopamine release measured with [18F]fallypride PET}, volume={236}, url={https://doi.org/10.1007/s00213-018-5083-5}, DOI={10.1007/s00213-018-5083-5}, abstractNote={Sex differences in the dopaminergic response to psychostimulants could have implications for drug abuse risk and other psychopathology involving the dopamine system, but human data are limited and mixed.Here, we sought to investigate sex differences in dopamine release after oral D-amphetamine administration.We used [18F]fallypride positron emission tomography (PET) to measure the change in dopamine D2/3 receptor availability (%ΔBPND, an index of dopamine release) between placebo and D-amphetamine sessions in two independent datasets containing a total of 39 females (on either hormonal birth control n = 18, postmenopausal n = 10, or studied in the first 10 days of their menstrual cycle n = 11) and 37 males.Using both a priori anatomical regions of interest based on previous findings and voxelwise analyses, we failed to consistently detect broad sex differences in D-amphetamine-induced dopamine release. Nevertheless, there was limited evidence for greater right ventral striatal dopamine release in young adult males relative to similarly aged females, but this was not consistently observed across samples. Plasma estradiol did not correlate with dopamine release and this measure did not differ in females on and off hormonal birth control.While our finding in young adults from one dataset of greater %ΔBPND in males is partially consistent with a previously published study on sex differences in D-amphetamine-induced dopamine release, our data do not support the presence of consistent widespread sex differences in this measure of dopamine release.}, number={2}, journal={Psychopharmacology}, publisher={Springer Science and Business Media LLC}, author={Smith, Christopher T. and Dang, Linh C. and Burgess, Leah L. and Perkins, Scott F. and Juan, M. Danica San and Smith, Darcy K. and Cowan, Ronald L. and Le, Nam T. and Kessler, Robert M. and Samanez-Larkin, Gregory R. and et al.}, year={2019}, month={Feb}, pages={581–590} }
 @article{smith_crawford_dang_seaman_juan_vijay_katz_matuskey_cowan_morris_et al._2019, title={Partial-volume correction increases estimated dopamine D2-like receptor binding potential and reduces adult age differences}, volume={39}, url={https://doi.org/10.1177/0271678X17737693}, DOI={10.1177/0271678X17737693}, abstractNote={ The relatively modest spatial resolution of positron emission tomography (PET) increases the likelihood of partial volume effects such that binding potential (BPND) may be underestimated. Given structural grey matter losses across adulthood, partial volume effects may be even more problematic in older age leading to overestimation of adult age differences. Here we examined the effects of partial volume correction (PVC) in two studies from different sites using different high-affinity D2-like radioligands (18 F-Fallypride, 11C-FLB457) and different PET camera resolutions (∼5 mm, 2.5 mm). Results across both data sets revealed that PVC increased estimated BPND and reduced, though did not eliminate, age effects on BPND. As expected, the effects of PVC were smaller in higher compared to lower resolution data. Analyses using uncorrected data that controlled for grey matter volume in each region of interest approximated PVC corrected data for some but not all regions. Overall, the findings suggest that PVC increases estimated BPND in general and reduces adult age differences especially when using lower resolution cameras. The findings suggest that the past 30 years of research on dopamine receptor availability, for which very few studies use PVC, may overestimate effects of aging on dopamine receptor availability. }, number={5}, journal={Journal of Cerebral Blood Flow & Metabolism}, publisher={SAGE Publications}, author={Smith, Christopher T and Crawford, Jennifer L and Dang, Linh C and Seaman, Kendra L and Juan, M Danica San and Vijay, Aishwarya and Katz, Daniel T and Matuskey, David and Cowan, Ronald L and Morris, Evan D and et al.}, year={2019}, month={May}, pages={822–833} }
 @article{juarez_castrellon_green_crawford_seaman_smith_dang_matuskey_morris_cowan_et al._2019, title={Reproducibility of the correlative triad among aging, dopamine receptor availability, and cognition.}, volume={34}, ISSN={1939-1498 0882-7974}, url={http://dx.doi.org/10.1037/pag0000403}, DOI={10.1037/pag0000403}, abstractNote={The evidence that dopamine function mediates the association between aging and cognition is one of the most cited findings in the cognitive neuroscience of aging. However, few and relatively small studies have directly examined these associations. Here we examined correlations among adult age, dopamine D2-like receptor (D2R) availability, and cognition in two cross-sectional studies of healthy human adults. Participants completed a short cognitive test battery and, on a separate day, a PET scan with either the high-affinity D2R tracer [18F]Fallypride (Study 1) or [11C]FLB457 (Study 2). Digit span, a measure of short-term memory maintenance and working memory, was the only cognitive test for which dopamine D2R availability partially mediated the age effect on cognition. In Study 1, age was negatively correlated with digit span. Striatal D2R availability was positively correlated with digit span controlling for age. The age effect on digit span was smaller when controlling for striatal D2R availability. Although other cognitive measures used here have individually been associated with age and D2R availability in prior studies, we found no consistent evidence for significant associations between low D2R availability and low cognitive performance on these measures. These results at best only partially supported the correlative triad of age, dopamine D2R availability, and cognition. While a wealth of other research in human and nonhuman animals demonstrates that dopamine makes critical contributions to cognition, the present studies suggest caution in interpreting PET findings as evidence that dopamine D2R loss is a primary cause of broad age-related declines in fluid cognition. (PsycINFO Database Record (c) 2019 APA, all rights reserved).}, number={7}, journal={Psychology and Aging}, publisher={American Psychological Association (APA)}, author={Juarez, Eric J. and Castrellon, Jaime J. and Green, Mikella A. and Crawford, Jennifer L. and Seaman, Kendra L. and Smith, Christopher T. and Dang, Linh C. and Matuskey, David and Morris, Evan D. and Cowan, Ronald L. and et al.}, year={2019}, month={Nov}, pages={921–932} }
 @article{seaman_smith_juarez_dang_castrellon_burgess_juan_kundzicz_cowan_zald_et al._2018, title={Differential regional decline in dopamine receptor availability across adulthood: Linear and nonlinear effects of age}, volume={6}, url={https://doi.org/10.1101/358200}, DOI={10.1101/358200}, abstractNote={Abstract}, publisher={Cold Spring Harbor Laboratory}, author={Seaman, Kendra L. and Smith, Christopher T. and Juarez, Eric J. and Dang, Linh C. and Castrellon, Jaime J. and Burgess, Leah L. and Juan, M. Danica San and Kundzicz, Paul M. and Cowan, Ronald L. and Zald, David H. and et al.}, year={2018}, month={Jun} }
 @article{dang_samanez-larkin_smith_castrellon_perkins_cowan_claassen_zald_2018, title={FTO affects food cravings and interacts with age to influence age-related decline in food cravings}, volume={192}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85039461387&partnerID=MN8TOARS}, DOI={10.1016/j.physbeh.2017.12.013}, abstractNote={The fat mass and obesity associated gene (FTO) was the first gene identified by genome-wide association studies to correlate with higher body mass index (BMI) and increased odds of obesity. FTO remains the locus with the largest and most replicated effect on body weight, but the mechanism whereby FTO affects body weight and the development of obesity is not fully understood. Here we tested whether FTO is associated with differences in food cravings and a key aspect of dopamine function that has been hypothesized to influence food reward mechanisms. Moreover, as food cravings and dopamine function are known to decline with age, we explored effects of age on relations between FTO and food cravings and dopamine function. Seven-eight healthy subjects between 22 and 83 years old completed the Food Cravings Questionnaire and underwent genotyping for FTO rs9939609, the first FTO single nucleotide polymorphism associated with obesity. Compared to TT homozygotes, individuals carrying the obesity-susceptible A allele had higher total food cravings, which correlated with higher BMI. Additionally, food cravings declined with age, but this age effect differed across variants of FTO rs9939609: while TT homozygotes showed the typical age-related decline in food cravings, there was no such decline among A carriers. All subjects were scanned with [18F]fallypride PET to assess a recent proposal that at the neurochemical level FTO alters dopamine D2-like receptor (DRD2) function to influence food reward related mechanisms. However, we observed no evidence of FTO effects on DRD2 availability.}, journal={Physiology and Behavior}, author={Dang, L.C. and Samanez-Larkin, G.R. and Smith, C.T. and Castrellon, J.J. and Perkins, S.F. and Cowan, R.L. and Claassen, D.O. and Zald, D.H.}, year={2018}, pages={188–193} }
 @article{castrellon_seaman_crawford_young_smith_dang_hsu_cowan_zald_samanez-larkin_2018, title={Individual differences in dopamine are associated with reward discounting in clinical groups but not in healthy adults}, volume={8}, url={https://doi.org/10.1101/383810}, DOI={10.1101/383810}, abstractNote={abstract}, publisher={Cold Spring Harbor Laboratory}, author={Castrellon, Jaime J. and Seaman, Kendra L. and Crawford, Jennifer L. and Young, Jacob S. and Smith, Christopher T. and Dang, Linh C. and Hsu, Ming and Cowan, Ronald L. and Zald, David H. and Samanez-Larkin, Gregory R.}, year={2018}, month={Aug} }
 @article{stark_smith_lin_petersen_trujillo_van wouwe_kang_donahue_kessler_zald_et al._2018, title={Nigrostriatal and mesolimbic D<inf>2/3</inf>receptor expression in Parkinson’s disease patients with compulsive reward-driven behaviors}, volume={38}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85044789929&partnerID=MN8TOARS}, DOI={10.1523/JNEUROSCI.3082-17.2018}, abstractNote={The nigrostriatal and mesocorticolimbic dopamine networks regulate reward-driven behavior. Regional alterations to mesolimbic dopamine D2/3receptor expression are described in drug-seeking and addiction disorders. Parkinson's disease (PD) patients are frequently prescribed D2-like dopamine agonist (DAgonist) therapy for motor symptoms, yet a proportion develop clinically significant behavioral addictions characterized by impulsive and compulsive behaviors (ICBs). Until now, changes in D2/3receptor binding in both striatal and extrastriatal regions have not been concurrently quantified in this population. We identified 35 human PD patients (both male and female) receiving DAgonist therapy, with (n= 17) and without (n= 18) ICBs, matched for age, disease duration, disease severity, and dose of dopamine therapy. In the off-dopamine state, all completed PET imaging with [18F]fallypride, a high affinity D2-like receptor ligand that can measure striatal and extrastriatal D2/3nondisplaceable binding potential (BPND). Striatal differences between ICB+/ICB− patients localized to the ventral striatum and putamen, where ICB+ subjects had reduced BPND. In this group, self-reported severity of ICB symptoms positively correlated with midbrain D2/3receptor BPND. Group differences in regional D2/3BPNDrelationships were also notable: ICB+ (but not ICB−) patients expressed positive correlations between midbrain and caudate, putamen, globus pallidus, and amygdala BPNDs. These findings support the hypothesis that compulsive behaviors in PD are associated with reduced ventral and dorsal striatal D2/3expression, similar to changes in comparable behavioral disorders. The data also suggest that relatively preserved ventral midbrain dopaminergic projections throughout nigrostriatal and mesolimbic networks are characteristic of ICB+ patients, and may account for differential DAgonist therapeutic response.}, number={13}, journal={Journal of Neuroscience}, author={Stark, A.J. and Smith, C.T. and Lin, Y.-C. and Petersen, K.J. and Trujillo, P. and Van Wouwe, N.C. and Kang, X.H. and Donahue, M.J. and Kessler, R.M. and Zald, D.H. and et al.}, year={2018}, pages={3230–3239} }
 @article{juarez_castrellon_green_crawford_seaman_smith_dang_matuskey_morris_cowan_et al._2018, title={Reproducibility of the correlative triad among aging, dopamine receptor availability, and cognition}, volume={12}, url={https://doi.org/10.1101/494765}, DOI={10.1101/494765}, abstractNote={Abstract}, publisher={Cold Spring Harbor Laboratory}, author={Juarez, Eric J. and Castrellon, Jaime J. and Green, Mikella A. and Crawford, Jennifer L. and Seaman, Kendra L. and Smith, Christopher T. and Dang, Linh C. and Matuskey, David and Morris, Evan D. and Cowan, Ronald L. and et al.}, year={2018}, month={Dec} }
 @article{smith_san juan_dang_katz_perkins_burgess_cowan_manning_nickels_claassen_et al._2018, title={Ventral striatal dopamine transporter availability is associated with lower trait motor impulsivity in healthy adults}, volume={8}, ISSN={2158-3188}, url={http://dx.doi.org/10.1038/s41398-018-0328-y}, DOI={10.1038/s41398-018-0328-y}, abstractNote={Abstract}, number={1}, journal={Translational Psychiatry}, publisher={Springer Science and Business Media LLC}, author={Smith, Christopher T. and San Juan, M. Danica and Dang, Linh C. and Katz, Daniel T. and Perkins, Scott F. and Burgess, Leah L. and Cowan, Ronald L. and Manning, H. Charles and Nickels, Michael L. and Claassen, Daniel O. and et al.}, year={2018}, month={Dec} }
 @article{stark_smith_petersen_trujillo_wouwe_donahue_kessler_deutch_zald_claassen_2018, title={[<sup>18</sup>F]fallypride characterization of striatal and extrastriatal D<inf>2/3</inf>receptors in Parkinson's disease}, volume={18}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85042203364&partnerID=MN8TOARS}, DOI={10.1016/j.nicl.2018.02.010}, abstractNote={Parkinson's disease (PD) is characterized by widespread degeneration of monoaminergic (especially dopaminergic) networks, manifesting with a number of both motor and non-motor symptoms. Regional alterations to dopamine D2/3 receptors in PD patients are documented in striatal and some extrastriatal areas, and medications that target D2/3 receptors can improve motor and non-motor symptoms. However, data regarding the combined pattern of D2/3 receptor binding in both striatal and extrastriatal regions in PD are limited. We studied 35 PD patients off-medication and 31 age- and sex-matched healthy controls (HCs) using PET imaging with [18F]fallypride, a high affinity D2/3 receptor ligand, to measure striatal and extrastriatal D2/3 nondisplaceable binding potential (BPND). PD patients completed PET imaging in the off medication state, and motor severity was concurrently assessed. Voxel-wise evaluation between groups revealed significant BPND reductions in PD patients in striatal and several extrastriatal regions, including the locus coeruleus and mesotemporal cortex. A region-of-interest (ROI) based approach quantified differences in dopamine D2/3 receptors, where reduced BPND was noted in the globus pallidus, caudate, amygdala, hippocampus, ventral midbrain, and thalamus of PD patients relative to HC subjects. Motor severity positively correlated with D2/3 receptor density in the putamen and globus pallidus. These findings support the hypothesis that abnormal D2/3 expression occurs in regions related to both the motor and non-motor symptoms of PD, including areas richly invested with noradrenergic neurons.}, journal={NeuroImage: Clinical}, author={Stark, A.J. and Smith, C.T. and Petersen, K.J. and Trujillo, P. and Wouwe, N.C. and Donahue, M.J. and Kessler, R.M. and Deutch, A.Y. and Zald, D.H. and Claassen, D.O.}, year={2018}, pages={433–442} }
 @article{elton_smith_parrish_boettiger_2017, title={COMT Val158Met Polymorphism Exerts Sex-Dependent Effects on fMRI Measures of Brain Function}, volume={11}, ISSN={1662-5161}, url={http://dx.doi.org/10.3389/fnhum.2017.00578}, DOI={10.3389/fnhum.2017.00578}, abstractNote={Evidence suggests that dopamine levels in the prefrontal cortex (PFC) modulate executive functions. A key regulator of PFC dopamine is catechol-O-methyltransferase (COMT). The activity level of the COMT enzyme are influenced by sex and the Val158Met polymorphism (rs4680) of the COMT gene, with male sex and Val alleles both being associated with higher bulk enzyme activity, and presumably lower PFC dopamine. COMT genotype has not only been associated with individual differences in frontal dopamine-mediated behaviors, but also with variations in neuroimaging measures of brain activity and functional connectivity. In this study, we investigated whether COMT genotype predicts individual differences in neural activity and connectivity, and whether such effects are sex-dependent. We tested 93 healthy adults (48 females), genotyped for the Val158Met polymorphism, in a delay discounting task and at rest during fMRI. Delay discounting behavior was predicted by an interaction of COMT genotype and sex, consistent with a U-shaped relationship with enzyme activity. COMT genotype and sex similarly exhibited U-shaped relationships with individual differences in neural activation, particularly among networks that were most engaged by the task, including the default-mode network. Effects of COMT genotype and sex on functional connectivity during rest were also U-shaped. In contrast, flexible reorganization of network connections across task conditions varied linearly with COMT among both sexes. These data provide insight into the potential influences of COMT-regulated variations in catecholamine levels on brain function, which may represent endophenotypes for disorders of impulsivity.}, journal={Frontiers in Human Neuroscience}, publisher={Frontiers Media SA}, author={Elton, Amanda and Smith, Christopher T. and Parrish, Michael H. and Boettiger, Charlotte A.}, year={2017}, month={Dec} }
 @article{elton_smith_parrish_boettiger_2017, title={Neural systems underlying individual differences in intertemporal decision-making}, volume={29}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85011574004&partnerID=MN8TOARS}, DOI={10.1162/jocn_a_01069}, abstractNote={Abstract}, number={3}, journal={Journal of Cognitive Neuroscience}, author={Elton, A. and Smith, C.T. and Parrish, M.H. and Boettiger, C.A.}, year={2017}, pages={467–479} }
 @article{smith_dang_buckholtz_tetreault_cowan_kessler_zald_2017, title={The impact of common dopamine D2 receptor gene polymorphisms on D2/3 receptor availability: C957T as a key determinant in putamen and ventral striatum}, volume={7}, ISSN={2158-3188}, url={http://dx.doi.org/10.1038/tp.2017.45}, DOI={10.1038/tp.2017.45}, abstractNote={Dopamine function is broadly implicated in multiple neuropsychiatric conditions believed to have a genetic basis. Although a few positron emission tomography (PET) studies have investigated the impact of single-nucleotide polymorphisms (SNPs) in the dopamine D2 receptor gene (DRD2) on D2/3 receptor availability (binding potential, BPND), these studies have often been limited by small sample size. Furthermore, the most commonly studied SNP in D2/3 BPND (Taq1A) is not located in the DRD2 gene itself, suggesting that its linkage with other DRD2 SNPs may explain previous PET findings. Here, in the largest PET genetic study to date (n=84), we tested for effects of the C957T and -141C Ins/Del SNPs (located within DRD2) as well as Taq1A on BPND of the high-affinity D2 receptor tracer 18F-Fallypride. In a whole-brain voxelwise analysis, we found a positive linear effect of C957T T allele status on striatal BPND bilaterally. The multilocus genetic scores containing C957T and one or both of the other SNPs produced qualitatively similar striatal results to C957T alone. The number of C957T T alleles predicted BPND in anatomically defined putamen and ventral striatum (but not caudate) regions of interest, suggesting some regional specificity of effects in the striatum. By contrast, no significant effects arose in cortical regions. Taken together, our data support the critical role of C957T in striatal D2/3 receptor availability. This work has implications for a number of psychiatric conditions in which dopamine signaling and variation in C957T status have been implicated, including schizophrenia and substance use disorders.}, number={4}, journal={Translational Psychiatry}, publisher={Springer Science and Business Media LLC}, author={Smith, C T and Dang, L C and Buckholtz, J W and Tetreault, A M and Cowan, R L and Kessler, R M and Zald, D H}, year={2017}, month={Apr}, pages={e1091–e1091} }
 @article{smith_weafer_cowan_kessler_palmer_de wit_zald_2016, title={Individual differences in timing of peak positive subjective responses to d-amphetamine: Relationship to pharmacokinetics and physiology}, volume={30}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84961250400&partnerID=MN8TOARS}, DOI={10.1177/0269881116631650}, abstractNote={ Rate of delivery of psychostimulants has been associated with their positive euphoric effects and potential addiction liability. However, information on individual differences in onset of d-amphetamine’s effects remains scarce. We examined individual differences in the time to peak subjective and physiological effects and the pharmacokinetics/pharmacodynamics of oral d-amphetamine. We considered two independent studies that used different dosing regimens where subjects completed the drug effects questionnaire at multiple time points post d-amphetamine. Based on the observation of distinct individual differences in time course of drug effects questionnaire “feel”, “high”, and “like” ratings (DEQH+L+F) in Study 1, subjects in both studies were categorized as early peak responders (peak within 60 minutes), late peak responders (peak > 60 minutes) or nonresponders; 20–25% of participants were categorized as early peak responders, 50–55% as late peak responders and 20–30% as nonresponders. Physiological (both studies) and plasma d-amphetamine (Study 1) were compared among these groups. Early peak responders exhibited an earlier rise in plasma d-amphetamine levels and more sustained elevation in heart rate compared to late peak responders. The present data illustrate the presence of significant individual differences in the temporal pattern of responses to oral d-amphetamine, which may contribute to heightened abuse potential. }, number={4}, journal={Journal of Psychopharmacology}, author={Smith, C.T. and Weafer, J. and Cowan, R.L. and Kessler, R.M. and Palmer, A.A. and De Wit, H. and Zald, D.H.}, year={2016}, pages={330–343} }
 @article{smith_dang_cowan_kessler_zald_2016, title={Variability in paralimbic dopamine signaling correlates with subjective responses to d-amphetamine}, volume={108}, url={https://doi.org/10.1016/j.neuropharm.2016.05.004}, DOI={10.1016/j.neuropharm.2016.05.004}, abstractNote={Subjective responses to psychostimulants vary, the basis of which is poorly understood, especially in relation to possible cortical contributions. Here, we tested for relationships between participants' positive subjective responses to oral d-amphetamine (dAMPH) versus placebo and variability in striatal and extrastriatal dopamine (DA) receptor availability and release, measured via positron emission tomography (PET) with the radiotracer (18)F-fallypride. Analyses focused on 35 healthy adult participants showing positive subjective effects to dAMPH measured via the Drug Effects Questionnaire (DEQ) Feel, Like, High, and Want More subscales (Responders), and were repeated after inclusion of 11 subjects who lacked subjective responses. Associations between peak DEQ subscale ratings and both baseline (18)F-fallypride binding potential (BPnd; an index of D2/D3 receptor availability) and the percentage change in BPnd post dAMPH (%ΔBPnd; a measure of DA release) were assessed. Baseline BPnd in ventromedial prefrontal cortex (vmPFC) predicted the peak level of High reported following dAMPH. Furthermore, %ΔBPnd in vmPFC positively correlated with DEQ Want More ratings. DEQ Want More was also positively correlated with %ΔBPnd in right ventral striatum and left insula. This work indicates that characteristics of DA functioning in vmPFC, a cortical area implicated in subjective valuation, are associated with both subjective high and incentive (wanting) responses. The observation that insula %ΔBPnd was associated with drug wanting converges with evidence suggesting its role in drug craving. These findings highlight the importance of variability in DA signaling in specific paralimbic cortical regions in dAMPH's subjective response, which may confer risk for abusing psychostimulants.}, journal={Neuropharmacology}, publisher={Elsevier BV}, author={Smith, Christopher T. and Dang, Linh C. and Cowan, Ronald L. and Kessler, Robert M. and Zald, David H.}, year={2016}, month={Sep}, pages={394–402} }
 @article{smith_steel_parrish_kelm_boettiger_2015, title={Intertemporal Choice Behavior in Emerging Adults and Adults: Effects of Age Interact with Alcohol Use and Family History Status}, volume={9}, DOI={10.3389/fnhum.2015.00627}, abstractNote={Adults with alcohol use disorders (AUDs) show marked immediate reward selection (or “Now”) bias in intertemporal choice tasks. This Now bias persists long into abstinence, suggesting an irreversible consequence of chronic alcohol abuse or a pre-existing AUD intermediate phenotype. However, some data show substantial Now bias among emerging adults (18–25), regardless of drinking behavior, suggesting age-dependent effects on Now bias. The objectives of the present study were to determine (1) whether Now bias is greater among emerging adults relative to adults, (2) whether any such age effect on Now bias is diminished in sub-clinical heavy alcohol users, and (3) whether having a problem drinking first degree relative is independently associated with elevated Now bias. To achieve these objectives, we used an intertemporal choice task to quantify Now bias in n = 237 healthy participants (ages 18–40; 50% female), and a wide range of non-zero alcohol use, based on the Alcohol Use Disorders Identification Test (AUDIT). We found that among non-heavy drinkers, Now bias inversely correlated with age; this relationship was not present among heavy drinkers. We found no significant relationship between AUDIT score and Now bias among emerging adults, but AUDIT scores and Now bias were positively correlated among 26–40 year olds. Additionally, non-heavy drinking adults who reported a problem drinking first degree relative showed greater Now bias compared to those not reporting familial problem drinking. While not definitive, these findings lend support for elevated Now bias in adulthood as an intermediate phenotype for AUDs. Moreover, non-additive effects of age and heavy drinking on Now bias suggest perturbations in largely common neural circuits in both groups.}, journal={Front. Hum. Neurosci.}, publisher={Frontiers Media SA}, author={Smith, Christopher T. and Steel, Eleanor A. and Parrish, Michael H. and Kelm, Mary K. and Boettiger, Charlotte A.}, year={2015}, month={Nov} }
 @article{smith_wallace_dang_aarts_jagust_d'esposito_boettiger_2015, title={Modulation of impulsivity and reward sensitivity in intertemporal choice by striatal and midbrain dopamine synthesis in healthy adults}, volume={115}, DOI={10.1152/jn.00261.2015}, abstractNote={ Converging evidence links individual differences in mesolimbic and mesocortical dopamine (DA) to variation in the tendency to choose immediate rewards (“ Now”) over larger, delayed rewards (“ Later”), or “ Now bias.” However, to date, no study of healthy young adults has evaluated the relationship between Now bias and DA with positron emission tomography (PET). Sixteen healthy adults (ages 24–34 yr; 50% women) completed a delay-discounting task that quantified aspects of intertemporal reward choice, including Now bias and reward magnitude sensitivity. Participants also underwent PET scanning with 6-[18F]fluoro-l- m-tyrosine (FMT), a radiotracer that measures DA synthesis capacity. Lower putamen FMT signal predicted elevated Now bias, a more rapidly declining discount rate with increasing delay time, and reduced willingness to accept low-interest-rate delayed rewards. In contrast, lower FMT signal in the midbrain predicted greater sensitivity to increasing magnitude of the Later reward. These data demonstrate that intertemporal reward choice in healthy humans varies with region-specific measures of DA processing, with regionally distinct associations with sensitivity to delay and to reward magnitude. }, number={3}, journal={J Neurophysiol}, publisher={American Physiological Society}, author={Smith, Christopher T. and Wallace, Deanna L. and Dang, Linh C. and Aarts, Esther and Jagust, William J. and D'Esposito, Mark and Boettiger, Charlotte A.}, year={2015}, pages={1146–1156} }
 @article{swift-scanlan_smith_bardowell_boettiger_2014, title={Comprehensive interrogation of CpG island methylation in the gene encoding COMT, a key estrogen and catecholamine regulator}, volume={7}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84892712317&partnerID=MN8TOARS}, DOI={10.1186/1755-8794-7-5}, abstractNote={The catechol-O-methyltransferase (COMT) enzyme has been widely studied due to its multiple roles in neurological functioning, estrogen biology, and methylation metabolic pathways. Numerous studies have investigated variation in the large COMT gene, with the majority focusing on single nucleotide polymorphisms (SNPs). This body of work has linked COMT genetic variation with a vast array of conditions, including several neurobehavioral disorders, pain sensitivity, and multiple human cancers. Based on COMT’s numerous biological roles and recent studies suggesting that methylation of the COMT gene impacts COMT gene expression, we comprehensively interrogated methylation in over 200 CpG dinucleotide sequences spanning the length of the COMT gene. Using saliva-derived DNA from a non-clinical sample of human subjects, we tested for associations between COMT CpG methylation and factors reported to interact with COMT genetic effects, including demographic factors and alcohol use. Finally, we tested associations between COMT CpG methylation state and COMT gene expression in breast cancer cell lines. We interrogated >200 CpGs in 13 amplicons spanning the 5’ UTR to the last exon of the CpG dinucleotide-rich COMT gene in n = 48 subjects, n = 11 cell lines and 1 endogenous 18S rRNA control. With the exception of the CpG island in the 5’UTR and 1st exon, all other CpG islands were strongly methylated with typical dynamic ranges between 50-90%. In the saliva samples, methylation of multiple COMT loci was associated with socioeconomic status or ethnicity. We found associations between methylation at numerous loci and genotype at the functional Val 158 Met SNP (rs4680), and most of the correlations between methylation and demographic and alcohol use factors were Val 158 Met allele-specific. Methylation at several of these loci also associated with COMT gene expression in breast cancer cell lines. We report the first comprehensive interrogation of COMT methylation. We corroborate previous findings of variation in COMT methylation with gene expression and the Val 158 Met genotype, and also report novel associations with socioeconomic status (SES) and ethnicity at several methylated loci. These results point to novel mechanisms for COMT regulation, which may have broad therapeutic implications.}, number={1}, journal={BMC Medical Genomics}, author={Swift-Scanlan, T. and Smith, C.T. and Bardowell, S.A. and Boettiger, C.A.}, year={2014} }
 @article{smith_boettiger_2014, title={Erratum: Age modulates the effect of COMT genotype on delay discounting behavior (Psychopharmacology (2012) 222 (609617) (DOI 10.1007/s00213-012-2653-9) )}, volume={231}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84892806657&partnerID=MN8TOARS}, DOI={10.1007/s00213-013-3411-3}, number={3}, journal={Psychopharmacology}, author={Smith, C.T. and Boettiger, C.A.}, year={2014}, pages={621} }
 @article{smith_swift-scanlan_boettiger_2014, title={Genetic polymorphisms regulating dopamine signaling in the frontal cortex interact to affect target detection under high working memory load}, volume={26}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84891439676&partnerID=MN8TOARS}, DOI={10.1162/jocn_a_00501}, abstractNote={Abstract}, number={2}, journal={Journal of Cognitive Neuroscience}, author={Smith, C.T. and Swift-Scanlan, T. and Boettiger, C.A.}, year={2014}, pages={395–407} }
 @article{smith_sierra_oppler_boettiger_2014, title={Ovarian cycle effects on immediate reward selection bias in humans: A role for estradiol}, volume={34}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84899482213&partnerID=MN8TOARS}, DOI={10.1523/JNEUROSCI.0014-14.2014}, abstractNote={A variety of evidence suggests that, among humans, the individual tendency to choose immediate rewards (“Now”) over larger, delayed rewards (“Later”), or Now bias, varies with frontal dopamine (DA) levels. As cyclic elevations in estradiol (E+) modulate other frontal DA-dependent behaviors, we tested ovarian cycle effects on Now bias, and whether any such effects are E+ mediated. To do so, we quantified Now/Later choice behavior in naturally cycling adult females (n= 87; ages 18–40 years) during both the menstrual phase (MP; cycle day 1–2; low E+), and the follicular phase (FP; cycle day 11–12; high E+). Now bias decreased an average of 3.6% from MP to FP (p= 0.006). Measures of salivary E+ levels at each visit were available in a subsample of participants (n= 34). Participants with a verified E+ rise from MP to FP showed significantly greater decreases in Now bias at mid-cycle (n= 23) than those without a rise (n= 11;p= 0.03); Now bias decreased an average of 10.2% in the E+ rise group but increased an average of 7.9% in the no E+ rise group. The change in Now bias from MP to FP inversely correlated with the change in E+ (ρ = −0.39;p= 0.023), an effect driven by individuals with putatively lower frontal DA based on genotype at theVal158Metpolymorphism in theCOMTgene. This is the first demonstration that intertemporal choice varies across the ovarian cycle, with Now bias declining at mid-cycle, when fertility peaks. Moreover, our data suggest that the interacting effects of estradiol and frontal DA mediate this cycle effect on decision making.}, number={16}, journal={Journal of Neuroscience}, author={Smith, C.T. and Sierra, Y. and Oppler, S.H. and Boettiger, C.A.}, year={2014}, pages={5468–5476} }
 @article{smith_boettiger_2012, title={Age modulates the effect of COMT genotype on delay discounting behavior}, volume={222}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84864454916&partnerID=MN8TOARS}, DOI={10.1007/s00213-012-2653-9}, abstractNote={A form of impulsivity, the tendency to choose immediate over delayed rewards (delay-discounting) has been associated with a single nucleotide polymorphism (SNP) in the catechol-O-methyltransferase (COMT) gene (COMTval 158 met; rs4680). However, the existing data regarding the nature of this association are in conflict. We have previously reported that adults homozygous for valine (val) at the COMTval 158 met SNP demonstrate greater delay-discounting than do methionine (met) allele carriers (Boettiger et al., J Neurosci 27:14383–14391, 2007). In contrast, a recent study of adolescent males found that those with the met/met genotype demonstrate greater delay-discounting than do val-allele carriers (Paloyelis et al., Neuropsychopharmacology 35:2414–2426, 2010). Based on reported age-related changes in frontal dopamine function and COMT expression, we hypothesized that the association of COMT genotype with delay-discounting behavior is modulated by age from late adolescence to young adulthood. To test this hypothesis, we genotyped late adolescents (18–21 years; n = 72) and adults (22–40 years; n = 70) for the COMTval 158 met polymorphism, measured their delay-discounting behavior, and tested for an interaction between age group and COMT genotype. This cross-sectional study found that age modulates COMTval 158 met genotype effects on delay-discounting behavior. Among met-carriers, delay-discounting was negatively correlated with age from late adolescence to adulthood, while among val/val individuals delay-discounting was positively correlated with age across this range. These results confirm our previous finding of enhanced delay-discounting among val/val adults relative to met-allele carriers, and help reconcile existing literature. We propose a single U-shaped model of the relationship between frontal DA levels and impulsive choice that accounts for both adolescent and adult data.}, number={4}, journal={Psychopharmacology}, author={Smith, C.T. and Boettiger, C.A.}, year={2012}, pages={609–617} }