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Abstract # 3090 Prospective effects of latent infection on self-regulation and executive function in older adults
Abstracts / Brain, Behavior, and Immunity 76 (2019) e1–e43 a Laureate Institute for Brain Research, 6655 S Yale Ave, Tulsa, OK 74136, United States b Department of Biological Science, The University of Tulsa, Tulsa, OK, United States c Sheppard Pratt Health System, United States d University of Oklahoma School of Community Medicine, United States e Stanley Division of Developmental Neurovirology, Johns Hopkins University, United States f Oxley College of Health Sciences, University of Tulsa, United States
Early life stress (ELS) has negative sequelae, increasing the risk for mood disorders, medical illness, and inflammation in adulthood. However, its impact on vulnerability to infectious disease is largely unknown. Current stress and depression increase vulnerability to infection, begging the question of whether this association is driven by ELS. We addressed this question in a sample of volunteers with a DSM-IV diagnosis of a mood disorder (n = 262), and a replication sample of volunteers who met DSM-V criteria for a mood or anxiety disorder (n = 431). IgG antibodies to cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) were quantified by enzymelinked immunosorbent assay. ELS was measured with the Childhood Trauma Questionnaire (CTQ). Logistic regression models controlling for age and sex revealed that for every point increase on the CTQ (total CTQ score with a possible range of 25–125) the odds of testing seropositive for CMV was increased by a factor of 1.01 (p = 0.062) in the discovery sample and a factor of 1.02 (p < 0.001) in the replication sample. Similarly, for every point increase on the CTQ the odds of testing seropositive for HSV-1 was increased by a factor of 1.01 (p = 0.031) in the discovery sample and a factor of 1.01 (p = 0.008) in the replication sample. This study contributes to our understanding of how childhood adversity leads to medical problems and conceivably, reduced life expectancy in mood disorders. http://dx.doi.org/10.1016/j.bbi.2018.11.217
Abstract # 3090 Prospective effects of latent infection on self-regulation and executive function in older adults S.C. Segerstrom, R. Reed University of Kentucky, Psychology, 125 Kastle Hall, Lexington, KY 40506-0044, United States Recent attention to the effects of latent infection on human brain and behavior has focused on the parasite Toxoplasma, which directly infects the brain, and herpesviruses, which infect diverse cells and also promote proinflammatory immunosenescence, which in turn could affect the brain. The present investigation tested prospective effects of baseline Toxoplasmaand cytomegalovirus (CMV) latent infection among 147 older adults (age 60–93 at baseline). Participants were administered a measure of self-regulation (BRIEF) and a battery of executive function tests semiannually up to 9 times. Multi-level models with administrations at Level 1 and people at Level 2 included baseline age, education, and administrations as covariates. CMV + status (79%) and CMV titers were associated with poorer self-regulation over the 4-year follow-up (status: t(637)=2.58, p=.01; titers: t(284)=2.75, p=.006). Log CMV titers also weakly predicted executive function (t(210)=1.80, p=.07). Toxoplasma + status (23%) and log titers associated with poorer self-regulation, but only among women (status: t(137)=2.07, p=.04; titers: t(139)=2.00, p=.05). The proinflammatory immunosenescence associated with CMV may have implications for control over behavior and cognition with aging. Sex differences in the effects of direct infection of the brain by Toxoplasmasupport theories that posit
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non–hormonal mechanisms of latent infection such as interference with folate uptake. http://dx.doi.org/10.1016/j.bbi.2018.11.218
Abstract # 3091 Inflammation is Associated with Decreased Amygdala to Ventromedial Prefrontal Functional Connectivity in Association with Symptoms of Anxiety in Patients with Depression N.D. Mehta a,d, Z. Li a,b,c, B.J. Woolwine a, E. Haroon a,e, J.C. Felger a,e a
Emory University, Department of Psychiatry and Behavioral Sciences, Atlanta, Georgia 30322, United States b School of Psychology and Sociology, Shenzhen University, Shenzhen, Guangdong Sheng 518060, China c Shenzhen Key Laboratory of Affective and Social Cognitive Science, Shenzhen University, Shenzhen, Guangdong Sheng 518060, China d Neuroscience Graduate Program, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA 30322, United States e Winship Cancer Institute, Emory University, Atlanta, GA 30322, United States Inflammation, as evidenced by inflammatory cytokines and the acute-phase reactant C-reactive protein (CRP), is reliably elevated in patients with depression and fear and anxiety-related disorders and is thought to contribute to symptom severity. Previous work shows that administration of inflammatory stimuli affects brain regions such as amygdala that are involved in fear, anxiety, and emotional processing. However, whether increased inflammation affects the amygdala or its functional connectivity in patients with depression and/or fear and anxiety-related disorders is only beginning to be explored. We conducted resting-state functional MRI in medicallystable, unmedicated outpatients with depression (n = 48) to investigate whether increased inflammation was associated with altered functional connectivity of the amygdala to whole brain in relation to symptoms of anxiety. Results indicated that increased inflammation (plasma CRP and cytokines) was associated with decreased functional connectivity between the right amygdala and ventromedial prefrontal cortex (vmPFC; corrected p < 0.05), which in turn correlated with increased symptoms of anxiety (r= 0.33, df = 46, p = 0.022). Of note, the relationship between inflammation-related decreases in amygdala-vmPFC connectivity and increased anxiety was significant only in patients with a secondary diagnosis of PTSD (r= 0.45, df = 17, p = 0.005) compared to those without PTSD (p= 0.10, df = 27, p = 0.646), and these findings were driven by females with PTSD (r= 0.60, df = 15, p = 0.011). These results suggest that increased inflammation compromises amygdalaprefrontal circuitry in association with increased anxiety in patients with depression, particularly those with comorbid PTSD. http://dx.doi.org/10.1016/j.bbi.2018.11.219
Abstract # 3094 Microbiota-neuroimmune interactions in a humanized mouse model of IBS: The role of diet and mast cells C. Shimbori a, G. De Palma a, D. Reed b, M. Pigrau a, J. Lu a, Y. Zhang b, Y. Yu b, N. Jimenez-Vargas b, J. Sessenwein b, C. Lopez-Lopez b, J. Jaramillo-Polanco b, E. Verdu a, A. Lomax b, M. Beyak b, S. Collins a, S. Vanner b, P. Bercik a a Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario L8N 4A6, United States b GI Diseases Research Unit, Queens University, Canada
Early life stress (ELS) has negative sequelae, increasing the risk for mood disorders, medical illness, and inflammation in adulthood. However, its impact on vulnerability to infectious disease is largely unknown. Current stress and depression increase vulnerability to infection, begging the question of whether this association is driven by ELS. We addressed this question in a sample of volunteers with a DSM-IV diagnosis of a mood disorder (n = 262), and a replication sample of volunteers who met DSM-V criteria for a mood or anxiety disorder (n = 431). IgG antibodies to cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1) were quantified by enzymelinked immunosorbent assay. ELS was measured with the Childhood Trauma Questionnaire (CTQ). Logistic regression models controlling for age and sex revealed that for every point increase on the CTQ (total CTQ score with a possible range of 25–125) the odds of testing seropositive for CMV was increased by a factor of 1.01 (p = 0.062) in the discovery sample and a factor of 1.02 (p < 0.001) in the replication sample. Similarly, for every point increase on the CTQ the odds of testing seropositive for HSV-1 was increased by a factor of 1.01 (p = 0.031) in the discovery sample and a factor of 1.01 (p = 0.008) in the replication sample. This study contributes to our understanding of how childhood adversity leads to medical problems and conceivably, reduced life expectancy in mood disorders. http://dx.doi.org/10.1016/j.bbi.2018.11.217
Abstract # 3090 Prospective effects of latent infection on self-regulation and executive function in older adults S.C. Segerstrom, R. Reed University of Kentucky, Psychology, 125 Kastle Hall, Lexington, KY 40506-0044, United States Recent attention to the effects of latent infection on human brain and behavior has focused on the parasite Toxoplasma, which directly infects the brain, and herpesviruses, which infect diverse cells and also promote proinflammatory immunosenescence, which in turn could affect the brain. The present investigation tested prospective effects of baseline Toxoplasmaand cytomegalovirus (CMV) latent infection among 147 older adults (age 60–93 at baseline). Participants were administered a measure of self-regulation (BRIEF) and a battery of executive function tests semiannually up to 9 times. Multi-level models with administrations at Level 1 and people at Level 2 included baseline age, education, and administrations as covariates. CMV + status (79%) and CMV titers were associated with poorer self-regulation over the 4-year follow-up (status: t(637)=2.58, p=.01; titers: t(284)=2.75, p=.006). Log CMV titers also weakly predicted executive function (t(210)=1.80, p=.07). Toxoplasma + status (23%) and log titers associated with poorer self-regulation, but only among women (status: t(137)=2.07, p=.04; titers: t(139)=2.00, p=.05). The proinflammatory immunosenescence associated with CMV may have implications for control over behavior and cognition with aging. Sex differences in the effects of direct infection of the brain by Toxoplasmasupport theories that posit
e15
non–hormonal mechanisms of latent infection such as interference with folate uptake. http://dx.doi.org/10.1016/j.bbi.2018.11.218
Abstract # 3091 Inflammation is Associated with Decreased Amygdala to Ventromedial Prefrontal Functional Connectivity in Association with Symptoms of Anxiety in Patients with Depression N.D. Mehta a,d, Z. Li a,b,c, B.J. Woolwine a, E. Haroon a,e, J.C. Felger a,e a
Emory University, Department of Psychiatry and Behavioral Sciences, Atlanta, Georgia 30322, United States b School of Psychology and Sociology, Shenzhen University, Shenzhen, Guangdong Sheng 518060, China c Shenzhen Key Laboratory of Affective and Social Cognitive Science, Shenzhen University, Shenzhen, Guangdong Sheng 518060, China d Neuroscience Graduate Program, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA 30322, United States e Winship Cancer Institute, Emory University, Atlanta, GA 30322, United States Inflammation, as evidenced by inflammatory cytokines and the acute-phase reactant C-reactive protein (CRP), is reliably elevated in patients with depression and fear and anxiety-related disorders and is thought to contribute to symptom severity. Previous work shows that administration of inflammatory stimuli affects brain regions such as amygdala that are involved in fear, anxiety, and emotional processing. However, whether increased inflammation affects the amygdala or its functional connectivity in patients with depression and/or fear and anxiety-related disorders is only beginning to be explored. We conducted resting-state functional MRI in medicallystable, unmedicated outpatients with depression (n = 48) to investigate whether increased inflammation was associated with altered functional connectivity of the amygdala to whole brain in relation to symptoms of anxiety. Results indicated that increased inflammation (plasma CRP and cytokines) was associated with decreased functional connectivity between the right amygdala and ventromedial prefrontal cortex (vmPFC; corrected p < 0.05), which in turn correlated with increased symptoms of anxiety (r= 0.33, df = 46, p = 0.022). Of note, the relationship between inflammation-related decreases in amygdala-vmPFC connectivity and increased anxiety was significant only in patients with a secondary diagnosis of PTSD (r= 0.45, df = 17, p = 0.005) compared to those without PTSD (p= 0.10, df = 27, p = 0.646), and these findings were driven by females with PTSD (r= 0.60, df = 15, p = 0.011). These results suggest that increased inflammation compromises amygdalaprefrontal circuitry in association with increased anxiety in patients with depression, particularly those with comorbid PTSD. http://dx.doi.org/10.1016/j.bbi.2018.11.219
Abstract # 3094 Microbiota-neuroimmune interactions in a humanized mouse model of IBS: The role of diet and mast cells C. Shimbori a, G. De Palma a, D. Reed b, M. Pigrau a, J. Lu a, Y. Zhang b, Y. Yu b, N. Jimenez-Vargas b, J. Sessenwein b, C. Lopez-Lopez b, J. Jaramillo-Polanco b, E. Verdu a, A. Lomax b, M. Beyak b, S. Collins a, S. Vanner b, P. Bercik a a Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario L8N 4A6, United States b GI Diseases Research Unit, Queens University, Canada