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90. Inflammation control augments antidepressant response in bipolar depression
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Abstracts / Brain, Behavior, and Immunity 32 (2013) e1–e47
ute to CIPN. Therefore the second aim was to investigate potential contributions of infiltrating peripheral leukocytes into the dorsal root ganglia (DRG) during CIPN. Chemotherapeutic agents increased mechanical hyperalgesia (von Frey) and increased sensorimotor deficits (ART) in mice when compared to vehicle-treated mice. Increased CD45 + leukocytes in the DRG were also associated with CIPN, suggesting a role for these leukocytes in CIPN. In chemotherapy-treated wild type mice, hyperalgesia subsided approximately 14 days after treatment whereas in immune-deficient mice (Rag1-/-) hyperalgesia persisted for longer (21 days). Rag1-/- mice lack functional adaptive immune cells, suggesting a role for these leukocytes in CIPN. Findings of leukocyte infiltration have been observed in models of nerve injury, but to our knowledge this is the first time that CD45 + leukocyte infiltration has been associated with CIPN. Further investigation into the role of infiltrating leukocyte subpopulations in the DRG will provide insights into mechanisms underlying CIPN. http://dx.doi.org/10.1016/j.bbi.2013.07.100
89. Sleep variability is associated with inflammatory cytokines in pregnant women M. Okun University of Pittsburgh, 3811 O’Hara St. Room E1124, Pittsburgh, PA 15221, United States of America Extreme variability in sleep duration and/or fragmentation impacts physiology and disease risk. Pregnant women have sleep variability given the changes that take place following conception. No investigations have examined the degree to which pregnant women experience sleep variability nor have any examined whether sleep variability results in immunological changes important for a successful pregnancy. Sleep diary and actigraphy-assessed sleep data collected from 168 pregnant women at 10–12 weeks’(T1), 14– 16 weeks’(T2), and 18–20 weeks’(T3) gestation were assessed for intra-individual variability, estimated from each subject’s standard deviation on diary (D) and actigraphy (A) measures. Morning blood samples for assay of cytokines were collected. Greater variability in both D-and A-sleep variables were associated with higher circulating cytokine concentrations. At T1 greater variability in Dassessed sleep efficiency (r = .29, p = .03) was associated with higher IL-6; greater variability in TIB was associated with higher IL-6 (r = .26, p = .05) and TNF-a (r = .23, p = .04). At T3 greater variability in D- and A-assessed sleep latency was associated with higher IL-6 (r = .30, p = .01; r = .32, p = 01); D WASO was associated with lower TNF-a (r = .24, p = .03). Sleep variability appears to be a stressor that could increase in circulating inflammatory markers and adverse pregnancy outcomes. Importantly it is a modifiable stressor that can be intervened upon. http://dx.doi.org/10.1016/j.bbi.2013.07.101
90. Inflammation control augments antidepressant response in bipolar depression A. Halaris, E. Meresh, A. Sharma, N. Alvi, J. Sinacore Loyola University Medical Center, Bldg 54, Rm 204, Maywood, IL 60153, United States There is an association between stress, stress-related mood disorders and inflammation. Control of inflammation in conjunction with antidepressant therapy may augment antidepressant response and convert treatment-resistant patients to responders. Reports with
the use of celecoxib in combination with an antidepressant agent are encouraging based on the hypothesis that inhibition of cyclooxygenase-2 (COX-2) reduces inflammation and enables antidepressant action to occur. We present preliminary data from a study of treatment-resistant bipolar depression. Patients were randomized to receive escitalopram + celecoxib, or escitalopram + placebo. Subjects completed assessments at weeks 0, 1, 2, 4 and 8. Severity of depression and anxiety were quantified using the HAM-D, HAM-A, and MADRS rating scales. Perceived stress was assessed using the PSS-14 scale. There was a statistically significant reduction in HAM-D mean scores in the active group (p = 0.0005) vs. placebo (p = 0.145), MADRS scores in the active group (p < 0.001) vs. placebo (p = 0.172) and HAM-A scores in the active group (p = 0.047) vs. placebo (p = 0.756). The PSS and HAM-D scores were positively correlated (r = 0.684, p = 0.02). There was a statistically significant decrease in post-treatment PSS scores in the active group (p = 0.049) vs. placebo (p = 0.717). The interim analysis of this ongoing study reveals that scores on scales for symptoms of depression, anxiety, and perceived stress significantly improved when subjects were treated with the combination escitalopram + celecoxib. These data suggest that controlling inflammation augments antidepressant response. http://dx.doi.org/10.1016/j.bbi.2013.07.102
91. Acute inflammation modulates substantia nigra responses to stimulus novelty and may underpin effects on exploratory behaviour N.A. Harrison a, E. Cooper a, V. Voon b, H.D. Critchley a a
University of Sussex, Clinical Imaging Sciences Centre, Brighton & amp; Sussex Medical School, Falmer, East Sussex BN1 9RR, UK b University of Cambridge Introduction: Humans are naturally inquisitive. This tendency is adaptive, serving to reduce uncertainty associated with novel stimuli. Dopaminergic substantia nigra (SN) has been shown to mediate effects of novelty and motivation to explore novel and potentially valuable outcomes. Interestingly, inflammation impairs rodent exploration, limiting exposure to uncertain outcomes during times of limited metabolic resource. Though changes in SN activity are observed during inflammation-induced psychomotor slowing whether they also mediate effects on novelty and exploratory behaviour remains unknown. Methods: We scanned 17 healthy human participants twice, 3 h after experimental inflammation (Typhoid vaccination) and placebo (saline injection). Familiarised and novel face and place stimuli were presented during fMRI and magnetisation transfer images acquired to aid visualisation of SN. Results: Typhoid vaccination was associated with an increase in IL-6 and IL-1ra group x time interaction F (1,16) = 6.91, p < 0.02, F (1,16) = 11.77, p < 0.003 demonstrating induction of mild systemic inflammation. Face and place stimuli were associated with anticipated main effects in fusiform face and parahippocampal place area respectively. Neither region showed an interaction with stimulus novelty (p < 0.001). Right SN [10, 17, 16] demonstrated anticipated sensitivity to novelty for places following placebo. However, this was lost following inflammation: group x novelty interaction (p < 0.001). Conclusion: We have previously described SN sensitivity to mild inflammation, these data suggest this may impair processing of stimulus novelty and underpin inflammatory effects on exploratory behaviour. http://dx.doi.org/10.1016/j.bbi.2013.07.103
Abstracts / Brain, Behavior, and Immunity 32 (2013) e1–e47
ute to CIPN. Therefore the second aim was to investigate potential contributions of infiltrating peripheral leukocytes into the dorsal root ganglia (DRG) during CIPN. Chemotherapeutic agents increased mechanical hyperalgesia (von Frey) and increased sensorimotor deficits (ART) in mice when compared to vehicle-treated mice. Increased CD45 + leukocytes in the DRG were also associated with CIPN, suggesting a role for these leukocytes in CIPN. In chemotherapy-treated wild type mice, hyperalgesia subsided approximately 14 days after treatment whereas in immune-deficient mice (Rag1-/-) hyperalgesia persisted for longer (21 days). Rag1-/- mice lack functional adaptive immune cells, suggesting a role for these leukocytes in CIPN. Findings of leukocyte infiltration have been observed in models of nerve injury, but to our knowledge this is the first time that CD45 + leukocyte infiltration has been associated with CIPN. Further investigation into the role of infiltrating leukocyte subpopulations in the DRG will provide insights into mechanisms underlying CIPN. http://dx.doi.org/10.1016/j.bbi.2013.07.100
89. Sleep variability is associated with inflammatory cytokines in pregnant women M. Okun University of Pittsburgh, 3811 O’Hara St. Room E1124, Pittsburgh, PA 15221, United States of America Extreme variability in sleep duration and/or fragmentation impacts physiology and disease risk. Pregnant women have sleep variability given the changes that take place following conception. No investigations have examined the degree to which pregnant women experience sleep variability nor have any examined whether sleep variability results in immunological changes important for a successful pregnancy. Sleep diary and actigraphy-assessed sleep data collected from 168 pregnant women at 10–12 weeks’(T1), 14– 16 weeks’(T2), and 18–20 weeks’(T3) gestation were assessed for intra-individual variability, estimated from each subject’s standard deviation on diary (D) and actigraphy (A) measures. Morning blood samples for assay of cytokines were collected. Greater variability in both D-and A-sleep variables were associated with higher circulating cytokine concentrations. At T1 greater variability in Dassessed sleep efficiency (r = .29, p = .03) was associated with higher IL-6; greater variability in TIB was associated with higher IL-6 (r = .26, p = .05) and TNF-a (r = .23, p = .04). At T3 greater variability in D- and A-assessed sleep latency was associated with higher IL-6 (r = .30, p = .01; r = .32, p = 01); D WASO was associated with lower TNF-a (r = .24, p = .03). Sleep variability appears to be a stressor that could increase in circulating inflammatory markers and adverse pregnancy outcomes. Importantly it is a modifiable stressor that can be intervened upon. http://dx.doi.org/10.1016/j.bbi.2013.07.101
90. Inflammation control augments antidepressant response in bipolar depression A. Halaris, E. Meresh, A. Sharma, N. Alvi, J. Sinacore Loyola University Medical Center, Bldg 54, Rm 204, Maywood, IL 60153, United States There is an association between stress, stress-related mood disorders and inflammation. Control of inflammation in conjunction with antidepressant therapy may augment antidepressant response and convert treatment-resistant patients to responders. Reports with
the use of celecoxib in combination with an antidepressant agent are encouraging based on the hypothesis that inhibition of cyclooxygenase-2 (COX-2) reduces inflammation and enables antidepressant action to occur. We present preliminary data from a study of treatment-resistant bipolar depression. Patients were randomized to receive escitalopram + celecoxib, or escitalopram + placebo. Subjects completed assessments at weeks 0, 1, 2, 4 and 8. Severity of depression and anxiety were quantified using the HAM-D, HAM-A, and MADRS rating scales. Perceived stress was assessed using the PSS-14 scale. There was a statistically significant reduction in HAM-D mean scores in the active group (p = 0.0005) vs. placebo (p = 0.145), MADRS scores in the active group (p < 0.001) vs. placebo (p = 0.172) and HAM-A scores in the active group (p = 0.047) vs. placebo (p = 0.756). The PSS and HAM-D scores were positively correlated (r = 0.684, p = 0.02). There was a statistically significant decrease in post-treatment PSS scores in the active group (p = 0.049) vs. placebo (p = 0.717). The interim analysis of this ongoing study reveals that scores on scales for symptoms of depression, anxiety, and perceived stress significantly improved when subjects were treated with the combination escitalopram + celecoxib. These data suggest that controlling inflammation augments antidepressant response. http://dx.doi.org/10.1016/j.bbi.2013.07.102
91. Acute inflammation modulates substantia nigra responses to stimulus novelty and may underpin effects on exploratory behaviour N.A. Harrison a, E. Cooper a, V. Voon b, H.D. Critchley a a
University of Sussex, Clinical Imaging Sciences Centre, Brighton & amp; Sussex Medical School, Falmer, East Sussex BN1 9RR, UK b University of Cambridge Introduction: Humans are naturally inquisitive. This tendency is adaptive, serving to reduce uncertainty associated with novel stimuli. Dopaminergic substantia nigra (SN) has been shown to mediate effects of novelty and motivation to explore novel and potentially valuable outcomes. Interestingly, inflammation impairs rodent exploration, limiting exposure to uncertain outcomes during times of limited metabolic resource. Though changes in SN activity are observed during inflammation-induced psychomotor slowing whether they also mediate effects on novelty and exploratory behaviour remains unknown. Methods: We scanned 17 healthy human participants twice, 3 h after experimental inflammation (Typhoid vaccination) and placebo (saline injection). Familiarised and novel face and place stimuli were presented during fMRI and magnetisation transfer images acquired to aid visualisation of SN. Results: Typhoid vaccination was associated with an increase in IL-6 and IL-1ra group x time interaction F (1,16) = 6.91, p < 0.02, F (1,16) = 11.77, p < 0.003 demonstrating induction of mild systemic inflammation. Face and place stimuli were associated with anticipated main effects in fusiform face and parahippocampal place area respectively. Neither region showed an interaction with stimulus novelty (p < 0.001). Right SN [10, 17, 16] demonstrated anticipated sensitivity to novelty for places following placebo. However, this was lost following inflammation: group x novelty interaction (p < 0.001). Conclusion: We have previously described SN sensitivity to mild inflammation, these data suggest this may impair processing of stimulus novelty and underpin inflammatory effects on exploratory behaviour. http://dx.doi.org/10.1016/j.bbi.2013.07.103