Assistant Professor, Department of Human Physiology
Ph.D. Oregon Health and Science University
Elinor Sullivan’s teaching focus is in the areas of nutrition, endocrinology, and neurobiology.
Dr. Sullivan’s research focuses on examining the influence of maternal metabolic state and dietary environment on offspring behavioral regulation, with an emphasis on behaviors that relate to mental health and behavioral disorders including autism spectrum disorders, attention deficit hyperactivity disorder, anxiety, and depression.
Her areas of expertise include behavioral neuroscience, with training and expertise in human and nonhuman primate behavior, brain development, developmental programming, maternal nutrition, and neurodevelopmental disorders.
Dr. Sullivan received her Ph.D. in Physiology from Oregon Health and Science University. She received her postdoctoral training at the University of California San Francisco and Oregon Health and Science University. Prior to coming to the University of Oregon, Dr. Sullivan was an Assistant Professor in the Biology Department at the University of Portland. Dr. Sullivan is currently an Assistant Professor in the Divisions of Neuroscience and Cardiometabolic health at the Oregon National Primate Research Center. She joined the UO Department of Human Physiology in 2017.
Dr. Sullivan has received research grants from the National Institute of Health, the Bill and Melinda Gates Foundation, the Murdock Charitable Trust, and the Obesity Society.
Perinatal Nutrition and Programmed Risk for Neuropsychiatric Disorders: A Focus on Animal Models.
Biol Psychiatry. 2019 Jan 15;85(2):122-134
Authors: DeCapo M, Thompson JR, Dunn G, Sullivan EL
Maternal nutrition is critically important for fetal development. Recent human studies demonstrate a strong connection between diet during pregnancy and offspring risk for neuropsychiatric disorders including depression, anxiety, and attention-deficit/hyperactivity disorder. Animal models have emerged as a crucial tool for understanding maternal nutrition's contribution to prenatal programming and the later development of neuropsychiatric disorders. This review highlights preclinical studies examining how maternal consumption of the three macronutrients (protein, fats, and carbohydrates) influence offspring negative-valence behaviors relevant to neuropsychiatric disorders. We highlight the translational aspects of animal models and so examine exposure periods that mirror the neurodevelopmental stages of human gestation. Because of our emphasis on programmed changes in neurobehavioral development, studies that continue diet exposure until assessment in adulthood are not discussed. The presented research provides a strong foundation of preclinical evidence of nutritional programming of neurobehavioral impairments. Alterations in risk assessment and response were observed alongside neurodevelopmental impairments related to neurogenesis, synaptogenesis, and synaptic plasticity. To date, the large majority of studies utilized rodent models, and the field could benefit from additional study of large-animal models. Additional future directions are discussed, including the need for further studies examining how sex as a biological variable affects the contribution of maternal nutrition to prenatal programming.
PMID: 30293647 [PubMed - in process]
An Open Resource for Non-human Primate Imaging.
Neuron. 2018 Oct 10;100(1):61-74.e2
Authors: Milham MP, Ai L, Koo B, Xu T, Amiez C, Balezeau F, Baxter MG, Blezer ELA, Brochier T, Chen A, Croxson PL, Damatac CG, Dehaene S, Everling S, Fair DA, Fleysher L, Freiwald W, Froudist-Walsh S, Griffiths TD, Guedj C, Hadj-Bouziane F, Ben Hamed S, Harel N, Hiba B, Jarraya B, Jung B, Kastner S, Klink PC, Kwok SC, Laland KN, Leopold DA, Lindenfors P, Mars RB, Menon RS, Messinger A, Meunier M, Mok K, Morrison JH, Nacef J, Nagy J, Rios MO, Petkov CI, Pinsk M, Poirier C, Procyk E, Rajimehr R, Reader SM, Roelfsema PR, Rudko DA, Rushworth MFS, Russ BE, Sallet J, Schmid MC, Schwiedrzik CM, Seidlitz J, Sein J, Shmuel A, Sullivan EL, Ungerleider L, Thiele A, Todorov OS, Tsao D, Wang Z, Wilson CRE, Yacoub E, Ye FQ, Zarco W, Zhou YD, Margulies DS, Schroeder CE
Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets.
PMID: 30269990 [PubMed - in process]
Early High-Fat Diet Exposure Causes Dysregulation of the Orexin and Dopamine Neuronal Populations in Nonhuman Primates.
Front Endocrinol (Lausanne). 2018;9:508
Authors: True C, Arik A, Lindsley S, Kirigiti M, Sullivan E, Kievit P
Maternal obesity and consumption of a high-fat diet (HFD) during pregnancy has a negative impact on offspring, including an increased risk for the development of obesity in adolescence. The mechanism for this transferred metabolic risk is unclear, but many studies have focused on the brain due to its important role in appetite and body-weight regulation. Two main pathways regulate appetite in the brain; homeostatic regulation that occurs predominantly in hypothalamic circuits and hedonic regulation of feeding that occurs via dopaminergic pathways. The current proposal examined the impact of early HFD exposure on the dopaminergic control of hedonic feeding pathways in a translational nonhuman primate model. Japanese macaque offspring from mothers consuming a control (CTR) or HFD were weaned onto control or HFD at an average 8 months of age yielding four groups: maternal and post-weaning control diet (mCTRpCTR), maternal control diet and post-weaning HFD (mCTRpHFD), maternal HFD and post-weaning control diet (mHFDpCTR) and maternal and post-weaning HFD (mHFDpHFD). Brains from 13-month-old offspring were evaluated for expression of neuropeptides that regulate dopaminergic pathways including orexin, melanin-concentrating hormone (MCH) in the lateral hypothalamus (LH), and tyrosine hydroxylase expression in the ventral tegmental area (VTA). Orexin cell numbers in the LH were significantly increased in animals exposed to a post-weaning HFD, while no difference was observed for orexin mRNA content or MCH cell numbers. Orexin fiber projections to the rostral VTA were significantly reduced in mCTRpHFD, mHFDpCTR, and mHFDpHFD groups, but these differences were not significant in the caudal VTA. There was no difference in the percentage of dopamine neurons receiving close appositions from orexin fibers in either the rostral or caudal VTA, nor was there any difference between groups in the number of orexin contacts per TH cell. In conclusion, the current study finds that prolonged early exposure to HFD during the in utero and postnatal period causes alterations at several levels in the dopaminergic circuits regulating reward.
PMID: 30258403 [PubMed]
Maternal High-Fat Diet Effects on Adaptations to Metabolic Challenges in Male and Female Juvenile Nonhuman Primates.
Obesity (Silver Spring). 2018 Sep;26(9):1430-1438
Authors: True C, Dean T, Takahashi D, Sullivan E, Kievit P
OBJECTIVE: This study aimed to determine whether maternal high-fat diet (HFD) consumption in nonhuman primates alters the ability of offspring to adapt metabolically to nutrient and caloric challenges.
METHODS: Offspring from Japanese macaque dams fed either a control (CTR) diet or HFD were weaned onto a CTR diet creating two groups: maternal HFD (mHFD, n = 18) and maternal CTR (mCTR) diet (n = 12). Male and female offspring were exposed to a 5-day 30% calorie restriction and to a 35-day HFD challenge (HFDC), at 16 and 24 months of age, respectively. Caloric intake, body weight, and energy expenditure were measured.
RESULTS: Offspring from both groups showed similar body weight, food intake, and metabolic adaptations to a 5-day calorie restriction. mHFD offspring demonstrated increased food intake and early weight gain in response to a 35-day HFDC; however, group differences in weight dissipated during the challenge. Unlike mCTR animals, the mHFD group had a significant increase in fasting insulin after acute HFD exposure.
CONCLUSIONS: The current findings indicate that offspring exposed to an mHFD show metabolic adaptations to calorie restriction that are largely similar to those of offspring exposed to a mCTR diet but show delayed adaptation upon exposure to an acute HFDC.
PMID: 30226008 [PubMed - in process]
Maternal prenatal depression predicts infant negative affect via maternal inflammatory cytokine levels.
Brain Behav Immun. 2018 10;73:470-481
Authors: Gustafsson HC, Sullivan EL, Nousen EK, Sullivan CA, Huang E, Rincon M, Nigg JT, Loftis JM
Maternal depressive symptoms during pregnancy are associated with risk for offspring emotional and behavioral problems, but the mechanisms by which this association occurs are not known. Infant elevated negative affect (increased crying, irritability, fearfulness, etc.) is a key risk factor for future psychopathology, so understanding its determinants has prevention and early intervention potential. An understudied yet promising hypothesis is that maternal mood affects infant mood via maternal prenatal inflammatory mechanisms, but this has not been prospectively examined in humans. Using data from a pilot study of women followed from the second trimester of pregnancy through six months postpartum (N = 68) our goal was to initiate a prospective study as to whether maternal inflammatory cytokines mediate the association between maternal depressive symptoms and infant offspring negative affect. The study sample was designed to examine a broad range of likely self-regulation and mood-regulation problems in offspring; to that end we over-selected women with a family history or their own history of elevated symptoms of attention-deficit/hyperactivity disorder. Results supported the hypothesis: maternal pro-inflammatory cytokines during the third trimester (indexed using a latent variable that included plasma interleukin-6, tumor necrosis factor-alpha and monocyte chemoattractant protein-1 concentrations as indicators) mediated the effect, such that higher maternal depressive symptoms were associated with higher maternal inflammation, and this mediated the effect on maternal report of infant negative affect (controlling for maternal affect during the infant period). This is the first human study to demonstrate that maternal inflammatory cytokines mediate the association between prenatal depression and infant outcomes, and the first to demonstrate a biological mechanism through which depressive symptoms impact infant temperament.
PMID: 29920327 [PubMed - in process]
Maternal Diet, Metabolic State, and Inflammatory Response Exert Unique and Long-Lasting Influences on Offspring Behavior in Non-Human Primates.
Front Endocrinol (Lausanne). 2018;9:161
Authors: Thompson JR, Gustafsson HC, DeCapo M, Takahashi DL, Bagley JL, Dean TA, Kievit P, Fair DA, Sullivan EL
Nutritional status influences brain health and gestational exposure to metabolic disorders (e.g. obesity and diabetes) increases the risk of neuropsychiatric disorders. The aim of the present study was to further investigate the role of maternal Western-style diet (WSD), metabolic state, and inflammatory factors in the programming of Japanese macaque offspring behavior. Utilizing structural equation modeling, we investigated the relationships between maternal diet, prepregnancy adiposity, third trimester insulin response, and plasma cytokine levels on 11-month-old offspring behavior. Maternal WSD was associated with greater reactive and ritualized anxiety in offspring. Maternal adiposity and third trimester macrophage-derived chemokine (MDC) exerted opposing effects on offspring high-energy outbursts. Elevated levels of this behavior were associated with low maternal MDC and increased prepregnancy adiposity. This is the first study to show that maternal MDC levels influence offspring behavior. We found no evidence suggesting maternal peripheral inflammatory response mediated the effect of maternal diet and metabolic state on aberrant offspring behavior. Additionally, the extent of maternal metabolic impairment differentially influenced chemokine response. Elevated prepregnancy adiposity suppressed third trimester chemokines, while obesity-induced insulin resistance augmented peripheral chemokine levels. WSD also directly increased maternal interleukin-12. This is the first non-human primate study to delineate the effects of maternal diet and metabolic state on gestational inflammatory environment and subsequent offspring behavior. Our findings give insight to the complex mechanisms by which diet, metabolic state, and inflammation during pregnancy exert unique influences on offspring behavioral regulation.
PMID: 29740395 [PubMed]
Delineating the Macroscale Areal Organization of the Macaque Cortex In Vivo.
Cell Rep. 2018 Apr 10;23(2):429-441
Authors: Xu T, Falchier A, Sullivan EL, Linn G, Ramirez JSB, Ross D, Feczko E, Opitz A, Bagley J, Sturgeon D, Earl E, Miranda-Domínguez O, Perrone A, Craddock RC, Schroeder CE, Colcombe S, Fair DA, Milham MP
Complementing long-standing traditions centered on histology, fMRI approaches are rapidly maturing in delineating brain areal organization at the macroscale. The non-human primate (NHP) provides the opportunity to overcome critical barriers in translational research. Here, we establish the data requirements for achieving reproducible and internally valid parcellations in individuals. We demonstrate that functional boundaries serve as a functional fingerprint of the individual animals and can be achieved under anesthesia or awake conditions (rest, naturalistic viewing), though differences between awake and anesthetized states precluded the detection of individual differences across states. Comparison of awake and anesthetized states suggested a more nuanced picture of changes in connectivity for higher-order association areas, as well as visual and motor cortex. These results establish feasibility and data requirements for the generation of reproducible individual-specific parcellations in NHPs, provide insights into the impact of scan state, and motivate efforts toward harmonizing protocols.
PMID: 29642002 [PubMed - in process]
Gadolinium Chelate Safety in Pregnancy: Barely Detectable Gadolinium Levels in the Juvenile Nonhuman Primate after in Utero Exposure.
Radiology. 2018 01;286(1):122-128
Authors: Prola-Netto J, Woods M, Roberts VHJ, Sullivan EL, Miller CA, Frias AE, Oh KY
Purpose To determine whether gadolinium remains in juvenile nonhuman primate tissue after maternal exposure to intravenous gadoteridol during pregnancy. Materials and Methods Gravid rhesus macaques and their offspring (n = 10) were maintained, as approved by the institutional animal care and utilization committee. They were prospectively studied as part of a pre-existing ongoing research protocol to evaluate the effects of maternal malnutrition on placental and fetal development. On gestational days 85 and 135, they underwent placental magnetic resonance imaging after intravenous gadoteridol administration. Amniocentesis was performed on day 135 prior to administration of the second dose of gadoteridol. After delivery, the offspring were followed for 7 months. Tissue samples from eight different organs and from blood were harvested from each juvenile macaque. Gadolinium levels were measured by using inductively coupled plasma mass spectrometry. Results Gadolinium concentration in the amniotic fluid was 0.028 × 10-5 %ID/g (percentage injected dose per gram of tissue) 50 days after administration of one gadoteridol dose. Gadolinium was most consistently detected in the femur (mean, 2.5 × 10-5 %ID/g; range, [0.81-4.1] × 10-5 %ID/g) and liver (mean, 0.15 × 10-5 %ID/g; range, [0-0.26] × 10-5 %ID/g). Levels were undetectable in the remaining sampled tissues, with the exception of one juvenile skin sample (0.07 × 10-5 %ID/g), one juvenile spleen sample (0.039 × 10-5 %ID/g), and one juvenile brain (0.095 × 10-5 %ID/g) and kidney (0.13 × 10-5 %ID/g) sample. Conclusion The presence of gadoteridol in the amniotic fluid after maternal injection enables confirmation that it crosses the placenta. Extremely low levels of gadolinium are found in juvenile macaque tissues after in utero exposure to two doses of gadoteridol, indicating that a very small amount of gadolinium persists after delivery. © RSNA, 2017.
PMID: 28873045 [PubMed - indexed for MEDLINE]