Sarah M. Clinton
- Ph.D. University of Michigan
Dr. Clinton joined VT in the fall 2016 session as one of the first new faculty members hired to join the School of Neuroscience at Virginia Tech.
Throughout her career, Dr. Clinton has been driven by a strong interest in the biological underpinnings of psychiatric disorders. As a Ph.D student at the University of Michigan (1999-2004), Dr. Clinton used human postmortem tissue as well as animal models to examine neuroanatomical and molecular abnormalities involved in the pathophysiology of schizophrenia. During her postdoctoral training at (also at the University of Michigan, 2004-2010), she developed a novel rat model of co-morbid anxiety and depression to study genetic, developmental, and environmental factors that underlie innate differences in emotional behavior and stress susceptibility. In January 2011, Dr. Clinton established her independent research program at the University of Alabama Birmingham and she is excited to join the faculty at VT in mid-2016. Her research uses animal models relevant to psychiatric and neurodevelopmental disorders to study how perturbations of brain development may lead to life-long emotional and/or cognitive dysfunction. The laboratory uses a multidisciplinary approach, combining molecular, neuroanatomical, and behavioral approaches in animal models, to address such questions.
Dr. Clinton is a dedicated and enthusiastic mentor and educator who has trained many undergraduates and graduate students during the course of her career. She has published more than 40 peer-reviewed publications, regularly participates in national and international conferences, and her work has been supported by grants from the National Institute of Health for the last several years.
Clinton laboratory: Studying Brain Development and Risk for Emotional Dysfunction
Individual differences in human temperament and stress coping style can increase risk for psychiatric disorders like depression and anxiety. Dr. Clinton’s laboratory uses rat models to study biological and environmental factors that shape the developing brain and behavior to better understand how emotional disorders may emerge and how we can possibly intervene with early preventative treatments. The laboratory uses a combination of molecular, neuroanatomical, and behavioral approaches to study molecular changes in the brain that influence emotional behavior. Specific projects include the following:
- Epigenetic changes in the developing brain that impact lifelong emotional behavior: Epigenetic mechanisms (such as DNA methylation) are reversible chemical modifications of genetic material that regulate gene expression and function. Because epigenetic mechanisms simultaneously regulate numerous genes, a perturbation of these processes can induce widespread effects on genes, brain function, and behavior. This project examines how DNA methylation processes unfold in the developing brain and how these processes differ in the brains of rats that will grow up to display high (versus low) levels of anxiety and depression-like behavior. Moreover, we are studying how early life experience can change DNA methylation in the developing brain to improve anxiety and depression-like behavior.
- Neurodevelopmental consequences of early life antidepressant exposure: Selective serotonin reuptake inhibitor (SSRI) antidepressant medications are the mainstay treatment for pregnant women suffering with depression, but the effects of SSRIs on brain development and emotional health in their children (exposed to SSRIs in utero) are largely unknown. Our laboratory found widespread developmental gene expression alterations in young rats exposed to SSRIs in utero as well as lifelong behavioral abnormalities. Ongoing studies are testing the hypothesis that these brain and behavioral abnormalities are driven by neonatal SSRI-induced changes in DNA methylation. We want to determine if these changes can be reversed in offspring that have already been exposed to SSRIs in utero and also investigate alternative treatment strategies that may effectively treat depressed mothers without placing children at risk for negative outcomes.
- Role of microRNAs in regulating stress coping style and stress vulnerability: This project focuses on another type of epigenetic mechanism – microRNAs, which are short non-coding RNAs that regulate gene expression. MicroRNAs are sensitive to stress exposure, but there is a limited understanding of their role in shaping behavioral responses to stress and vulnerability to stress-related disorders like depression. This project studies the role of a specific microRNA (miR-101a) in shaping a rat’s stress coping style by testing whether increasing or decreasing miR-101a expression in parts of the brain affects stress coping behavior and stress resilience.
- Rana S, Nam H, Glover ME, Akil H, Watson SJ, Clinton SM, Kerman IA. Protective Effects of Chronic Mild Stress During Adolescence in the Low Novelty Responder Rat. Stress, In Press, 2015. PMID: 26473581 [PubMed – in process].
- Cohen JL*, Glover ME*, Pugh PC, Kerman IA, Fant AD, Simmons RK, Akil H, Clinton SM. Maternal style shapes limbic brain development and emotional behavior in rats genetically-prone to high anxiety. Developmental Neuroscience, In Press 2015, PMID 25791846 [PubMed – in process].
- Glover ME, Pugh PC, Cohen J, Akil H, Clinton SM. Early-life Paroxetine Exposure Exacerbates Depression-like Behavior in Anxiety/Depression-prone rats. Neuroscience, 284: 775-797, 2015. PMC4267992.
- Rana S, Pugh PC, Jackson N, Clinton SM, Kerman IA. Inborn Stress Reactivity Shapes Adult Behavioral Consequences of Early-Life Maternal Separation Stress. Neuroscience Letters, 584: 146-150, 2015. PMC4293031.
- Nam H, Clinton SM, Jackson NL, Kerman IA. Learned helplessness and social avoidance in the Wistar-Kyoto rat. Frontiers in Behavioral Neuroscience, 8:109, 2014. PMC3978372.
- Taylor EW, Wang K, Nelson AR, Bredemann TM, Fraser K, Clinton SM, Marchase RB, Chatham JC, McMahon LL. O-GlcNAcylation of AMPA receptor GluA2 is associated with a novel form of long term depression at hippocampal synapses. Journal of Neuroscience, 34(1): 10-21, 2014. PMC3866478.
- Clinton SM, Miller S, Watson SJ, Akil H. Selectively-bred low novelty-seeking rats are more vulnerable to the negative physiological effects of maternal separation stress compared to high novelty-seekers. Stress, 17(1): 97-107, 2014. PMC4141530.
- Flagel SB, Waselus M, Clinton SM, Watson SJ, Akil H. Antecedents and Consequences of Drug Abuse in Rats Selectively Bred for High and Low Response to Novelty. Neuropharmaocology, 76 Pt B: 425-436, 2014. PMC3766490.
- Cummings JA, Clinton SM, Perry AN, Akil H, Becker JB. Male rats that differ in their response to novelty demonstrate differences in sexual behavior, Behavioral Neuroscience, 127(1): 47-58, 2013. PMC3982402.
- Clinton SM, Glover ME, Maltare A, Mehi SJ, Simmons RK, King GD. Expression of Klotho mRNA and protein in rat brain parenchyma from early postnatal development into adulthood. Brain Research, 1527: 1-14, 2013. PMC3756829.
- Simmons RK, Stringfellow SA, Wagle AA, Glover ME, Clinton SM. Epigenetic markers in the developing rat brain. Brain Research, 1533: 26-36, 2013. PMC3838910.
- Kerman, IA*, Clinton SM*, Simpson DN, Bedrosian TA, Bernard R, Akil H, Watson SJ. Inborn Differences in Environmental Reactivity Predict Divergent Diurnal Behavioral, Endocrine, and Gene Expression Rhythms. Psychoneuroendocrinology, 37(2): 256-69. 2012. PMC3313597.
- Simmons RK, Howard JL, Simpson DN, Akil H, Clinton SM. DNA methylation in the developing hippocampus and amygdala of anxiety-prone versus risk-taking rats. Developmental Neuroscience, 34(1):58-67 2012. PMC3583346.
- García-Fuster MJ, Parks GS; Clinton SM, Watson SJ, Akil H, Civellia O. The Melanin-Concentrating Hormone (MCH) System in an Animal Model of Depression-Like Behavior. European Neuropharmacology,22(8): 607-613, 2012. PMC3319808.
- Clinton SM, Turner CA, Flagel SB, Simpson DN, Watson SJ, Akil H. Neonatal Fibroblast Growth Factor Treatment Enhances Cocaine Sensitization. Pharmacology, Biochemistry & Behavior, 103(1): 6-17, 2012. PMC3496829.
- Flagel SB*, Clark JJ*, Robinson TE, Mayo L, Czuj A, Willuhn I, Akers CA, Clinton SM, Phillips PEM, Akil H. A selective role for dopamine in reward learning. Nature, 469(7328):53-57, 2011. Epub PMC3058375.
- Cummings JA, Gowl BA, Westenbroek C, Clinton SM, Akil H, Becker JBB. Differential Effects of a Selectively-Bred Novelty-Seeking Phenotype and Sex Differences on the Motivation to Take Cocaine in Rats. Biology of Sex Differences, 2:3, 2011. PMC3071306.
- Stedenfeld KA, Clinton SM, Kerman IA, Akil H, Watson SJ, Sved AF. Novelty-Seeking Behavior Predicts Vulnerability in a Rodent Model of Depression. Physiology & Behavior, 103(2):210-16, 2011 Epub PMC3925672.
- Turner CA, Clinton SM, Thompson RC, Watson SJ, Akil H. FGF2 augmentation early in life alters hippocampal development and rescues the anxiety phenotype in vulnerable animals. Proceedings of the National Academy of Sciences of the USA, 108(19): 8021-25, 2011. Epub PMC3093523.
- Clinton SM*, Stead JDH*, Miller S, Watson SJ, Akil H. Developmental underpinnings of individual differences in rodent novelty-seeking and emotional reactivity. European Journal of Neuroscience, 34(6): 994-1005, 2011. PMC3310433.
- Kerman IA*, Clinton SM*, Bedrosian TA, Abraham AD, Rosenthal D, Akil H, Watson SJ. High novelty-seeking predicts aggression and gene expression differences within defined serotonergic cell groups. Brain Research, 1419: 34-45, 2011. PMC3205916.
- Clinton SM*, Kerman IA*, Orr HR, Bedrosian TA, Abraham AD, Simpson DN, Watson SJ, Akil H. Pattern of forebrain activation in high novelty-seeking rats following aggressive encounter. Brain Research, 1422: 20-31, 2011. PMC3200440.
- Flagel SB, Robinson TE, Clark JJ, Clinton SM, Watson SJ, Seeman P, Phillips PEM, Akil H. An Animal Model of Genetic Vulnerability to Behavioral Disinhibition and Responsiveness to Reward-Related Cues: Implications for Addiction. Neuropsychopharmacology, 35(2):388-400, 2010. Epub. PMC2794950.
- García-Fuster MJ, Perez JA, Clinton SM, Watson SJ, Akil H. Impact of cocaine on adult hippocampal neurogenesis in an animal model of differential propensity to drug abuse. European Journal of Neuroscience, 31(1):79-89, 2010. PMC4037740.
- Clinton SM*, Bedrosian TA*, Abraham AD, Watson SJ, Akil H. Neural and Environmental Factors Impacting Maternal Behavior Differences in High- versus Low-Novelty Seeking Rats. Hormones and Behavior, 57(4-5): 463-473, 2010. Epub. PMC2917072.
- García-Fuster MJ, Clinton SM, Watson SJ, and Akil H. Effect of Cocaine on Fas-Associated Protein with Death Domain (FADD) in the Rat Brain: Individual Differences in a Model of Differential Vulnerability to Drug Abuse. Neuropsychopharmacology, 34(5) 1123-34, 2009. PMC2656579.
- Turner CA, Capriles N, Flagel SB, Perez JA, Clinton SM, Watson SJ, Akil H. Neonatal FGF2 alters cocaine self-administration in the adult rat. Pharmacology, Biochemistry, and Behavior, 92(1): 100-104, 2009. PMC3092780.
- Perez JA, Clinton SM, Turner CA, Watson SJ, Akil H. A New Role for FGF2 as an Endogenous Inhibitor of Anxiety. Journal of Neuroscience, 29(19):6379-87, 2009. PMC2748795.
- Clinton SM, Miller S, Watson SJ, Akil H. Prenatal stress does not alter innate novelty-seeking behavioral traits, but differentially affects individual differences in neuroendocrine stress responsivity. Psychoneuroendocrinology, 33(2):162-77, 2008. PMC2430412.
- Davis BA*, Clinton SM*, Huda Akil, Jill B. Becker. The effects of novelty-seeking phenotypes and sex differences on acquisition of cocaine self-administration in selectively-bred High-Responder and Low-Responder rats. Pharmacology, Biochemistry, and Behavior, 90(3):331-8, 2008. PMC2474787.
- Turner CA, Flagel SB, Clinton SM, Akil H, Watson, SJ. Cocaine interacts with the novelty-seeking trait to modulate FGFR1 gene expression in the rat. Neuroscience Letters, 446(2-3): 105-107, 2008. PMC2633028.
- Clinton SM*, Vazquez DM*, Kabbaj M, Kabbaj M-H, Watson SJ and Akil H. Individual differences in novelty-seeking and emotional reactivity correlate with variation in maternal behavior. Hormones and Behavior, 51(5): 655-664, 2007. PMC1945104.
- Stead JDH*, Clinton SM*, Neal CR, Schneider J, Jama A, Miller S, Watson SJ and Akil H. Selective breeding for divergence in novelty-seeking traits: Evidence for enrichment of anxiety-related behaviors. Behavioral Genetics, 36(5):697-712, 2006. PMID 16502134.
- Clinton SM, Ivan Sucharski, Finlay JM. Desipramine attenuates working memory impairments induced by partial loss of dopamine in the rat prefrontal cortex. Psychopharmacology, 183(4):404-12, 2006. PMID 16199832.
- Clinton SM, Haroutunian V, Meador-Woodruff JH. Altered protein expression of select NMDA receptor subunits and associated intracellular proteins in limbic thalamus in schizophrenia. Journal of Neurochemistry, 98(4):1114-25, 2006. PMID 16762023.
- Clinton SM, Ibrahim H, Frey KA, Davis KL, Haroutunian V, and Meador-Woodruff JH. Dopaminergic abnormalities in the thalamus in schizophrenia involve the intracellular signal integrating proteins calcyon and spinophilin. American Journal of Psychiatry, 162: 1859 – 1871, 2005. PMID 16199832.
- Clinton SM, Meador-Woodruff JH. Structural, functional, and neurochemical abnormalities of the thalamus in schizophrenia. Schizophrenia Research, 69(2-3): pp 237-253, 2004. PMID 15469196.
- Clinton SM, Abelson S, Haroutunian V, Davis KL, Meador-Woodruff JH. Neurofilament subunit transcript expression is altered in the thalamus in schizophrenia. Thalamus and Related Systems, 2/4: pp 265-272, 2004.
- Clinton SM and Meador-Woodruff JH. Abnormalities of the NMDA receptor and associated intracellular molecules in the thalamus in schizophrenia and bipolar disorder. Neuropsychopharmacology, 29, pp 1353-1362, 2004. PMID 15054476.
- Clinton SM, Haroutunian V, Davis KL, Meador-Woodruff JH. Altered transcript expression of NMDA receptor-associated postsynaptic density proteins in the thalamus in schizophrenia. American Journal of Psychiatry 160: pp 1100-1109, 2003. PMID 12777268.
- Meador-Woodruff JH, Clinton SM, Beneyto M, and McCullumsmith RE. Molecular abnormalities of the glutamate synapse in the thalamus in schizophrenia. Annals of the New York Academy of Sciences, 1003: pp 7-93, 2003. PMID 140684436.
- Clinton SM, Meador-Woodruff JH. Nucleus-specific expression of NMDA receptor-associated post-synaptic density proteins in primate thalamus. Thalamus and Related Systems 1: pp 303-316, 2002.
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