I Conejero1, I Jaussent2, A Cazals3, E Thouvenot4, T Mura5, E Le Bars6, S Guillaume7, S Squalli8, P Courtet7, E Olié7. 1. Department of Psychiatry, CHU Nimes, University of Montpellier, Montpellier, France; Inserm, Unit 1061 "Neuropsychiatry: Epidemiological and Clinical Research", Montpellier, France. Electronic address: ismael.conejero@gmail.com. 2. Inserm, Unit 1061 "Neuropsychiatry: Epidemiological and Clinical Research", Montpellier, France. 3. Department of Emergency Psychiatry & Acute Care, CHU Montpellier, University of Montpellier, Montpellier, France. 4. Department of Neurology, CHU Nîmes, University of Montpellier, Montpellier, France. 5. Department of Clinical Investigation, CHU Montpellier, University of Montpellier, Montpellier, France. 6. Department of Neuroradiology, CHU Montpellier, University of Montpellier, Montpellier, France; Inserm Unit 1051, Montpellier, France; Institut of Neurosciences of Montpellier, Montpellier, France; CNRS, UMR 5221, Montpellier, France. 7. Department of Emergency Psychiatry & Acute Care, CHU Montpellier, University of Montpellier, Montpellier, France; Inserm, Unit 1061 "Neuropsychiatry: Epidemiological and Clinical Research", Montpellier, France. 8. Department of Immunology, CHU Nimes, University of Montpellier, Montpellier, France.
Abstract
BACKGROUND: Neuroimaging studies suggest that social distress and suicidal vulnerability share common cerebral bases. Moreover, increased peripheral inflammatory activity is involved in both social distress and suicidal behavior. OBJECTIVE: To evaluate, in suicidal and non-suicidal individuals, the association between the activation of specific cerebral regions (anterior cingulate, insula and orbitofrontal cortex) during experimental social exclusion and the baseline blood levels of the pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) and of the anti-inflammatory cytokine interleukin-2 (IL-2). METHODS: In total, 101 euthymic women were recruited: 42 suicide attempters (SA), 40 affective controls (AC), and 19 healthy controls (HC). During functional MRI (fMRI), they performed the Cyberball game, a validated social exclusion task. Blood levels of IL-1β, IL-6, TNF-α and IL-2 were measured prior to fMRI. The activation of insula, orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC) during the explicit social exclusion (ESE) vs social inclusion (INC) conditions of the Cyberball game was analyzed in function of the baseline cytokine levels. RESULTS: IL-1β was negatively associated with right OFC activation (p = 0.01) in ESE vs. INC, whereas IL-2 was positively associated with activation of the right ACC (p = 0.02), insula (p = 0.002) and OFC (p = 0.004) in ESE vs. INC. These associations remained significant after controlling for group, indicating that they were independent of the suicidal status. CONCLUSION: Baseline IL-1β and IL-2 blood levels are differentially associated with cerebral activation involved in the perception of social exclusion, independently of suicidal behavior. Our results may help to better understand the role of basal inflammation in social distress and its link with mood disorder pathophysiology.
BACKGROUND: Neuroimaging studies suggest that social distress and suicidal vulnerability share common cerebral bases. Moreover, increased peripheral inflammatory activity is involved in both social distress and suicidal behavior. OBJECTIVE: To evaluate, in suicidal and non-suicidal individuals, the association between the activation of specific cerebral regions (anterior cingulate, insula and orbitofrontal cortex) during experimental social exclusion and the baseline blood levels of the pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) and of the anti-inflammatory cytokine interleukin-2 (IL-2). METHODS: In total, 101 euthymic women were recruited: 42 suicide attempters (SA), 40 affective controls (AC), and 19 healthy controls (HC). During functional MRI (fMRI), they performed the Cyberball game, a validated social exclusion task. Blood levels of IL-1β, IL-6, TNF-α and IL-2 were measured prior to fMRI. The activation of insula, orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC) during the explicit social exclusion (ESE) vs social inclusion (INC) conditions of the Cyberball game was analyzed in function of the baseline cytokine levels. RESULTS: IL-1β was negatively associated with right OFC activation (p = 0.01) in ESE vs. INC, whereas IL-2 was positively associated with activation of the right ACC (p = 0.02), insula (p = 0.002) and OFC (p = 0.004) in ESE vs. INC. These associations remained significant after controlling for group, indicating that they were independent of the suicidal status. CONCLUSION: Baseline IL-1β and IL-2 blood levels are differentially associated with cerebral activation involved in the perception of social exclusion, independently of suicidal behavior. Our results may help to better understand the role of basal inflammation in social distress and its link with mood disorder pathophysiology.
Authors: Gianluca Serafini; Valentina Maria Parisi; Andrea Aguglia; Andrea Amerio; Gaia Sampogna; Andrea Fiorillo; Maurizio Pompili; Mario Amore Journal: Int J Environ Res Public Health Date: 2020-04-01 Impact factor: 3.390