Kailyn A Bradley1, Emily R Stern2, Carmen M Alonso3, Hui Xie4, Seunghee Kim-Schulze5, Vilma Gabbay6. 1. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1230, New York, NY 10029, USA. Electronic address: kailyn.bradley@mssm.edu. 2. Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Orangeburg, NY 10962, USA; Department of Psychiatry, New York University School of Medicine, One Park Ave, 8th Floor, New York, NY 10016, USA. Electronic address: Emily.stern@nyumc.org. 3. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1230, New York, NY 10029, USA. Electronic address: Carmen.alonso@mssm.edu. 4. Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, Hess 6th Floor, New York, NY 10029, USA; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, Box 1630, New York, NY 10029, USA. Electronic address: hui.xie@mssm.edu. 5. Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, 1470 Madison Ave, Hess 6th Floor, New York, NY 10029, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1130, New York, NY 10029, USA. Electronic address: seunghee.kim-schulze@mssm.edu. 6. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, Box 1230, New York, NY 10029, USA; Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Rd., Orangeburg, NY 10962, USA. Electronic address: vilma.gabbay@mssm.edu.
Abstract
BACKGROUND: Inflammation has been hypothesized to contribute to reward dysfunction across psychiatric conditions, but little is known about this relationship in youth. Therefore, the present study investigated the associations between general and specific markers of inflammation and neural activation during reward processing, including anticipation and attainment, in youth with diverse psychiatric symptoms. METHODS: Forty-six psychotropic medication-free youth with diverse psychiatric symptoms underwent a blood draw to measure 41 cytokines, as well as structural and functional magnetic resonance imaging. The Reward Flanker Task examined neural activation during reward anticipation and attainment. Relationships between inflammation and neural activation were assessed using data reduction techniques across the whole-brain, as well as in specific reward regions of interest (basal ganglia, anterior and mid-cingulate cortex [ACC/MCC]). RESULTS: Whole-brain principal component analyses showed that factor 3 (12 cytokines: FGF-2, Flt3-L, fractalkine, GM-CSF, IFN-α2, IFN-γ, IL-3, IL-4, IL-7, IL-17A, MDC, and VEGF) was negatively correlated with precuneus/posterior cingulate cortex activity during anticipation. Factor 2 (11 cytokines: eotaxin, IL-1α, IL-1Rα, IL-2, IL-5, IL-9, IL-12p40, IL-13, IL-15, MCP-3, and TNF-β) was negatively correlated with angular gyrus activity during attainment. ROI analyses additionally showed that multiple cytokines were related to activity in the basal ganglia (EGF, FGF-2, Flt-3L, IL-2, IL-13, IL-15, IL-1Rα, MCP-3) and ACC/MCC (Flt-3L) during attainment. C-reactive protein (CRP) was not associated with neural activation. CONCLUSIONS: Investigation of specific markers of immune function showed associations between inflammatory processes and activation of posterior default mode network, prefrontal cortex, and basal ganglia regions during multiple phases of reward processing.
BACKGROUND:Inflammation has been hypothesized to contribute to reward dysfunction across psychiatric conditions, but little is known about this relationship in youth. Therefore, the present study investigated the associations between general and specific markers of inflammation and neural activation during reward processing, including anticipation and attainment, in youth with diverse psychiatric symptoms. METHODS: Forty-six psychotropic medication-free youth with diverse psychiatric symptoms underwent a blood draw to measure 41 cytokines, as well as structural and functional magnetic resonance imaging. The Reward Flanker Task examined neural activation during reward anticipation and attainment. Relationships between inflammation and neural activation were assessed using data reduction techniques across the whole-brain, as well as in specific reward regions of interest (basal ganglia, anterior and mid-cingulate cortex [ACC/MCC]). RESULTS: Whole-brain principal component analyses showed that factor 3 (12 cytokines: FGF-2, Flt3-L, fractalkine, GM-CSF, IFN-α2, IFN-γ, IL-3, IL-4, IL-7, IL-17A, MDC, and VEGF) was negatively correlated with precuneus/posterior cingulate cortex activity during anticipation. Factor 2 (11 cytokines: eotaxin, IL-1α, IL-1Rα, IL-2, IL-5, IL-9, IL-12p40, IL-13, IL-15, MCP-3, and TNF-β) was negatively correlated with angular gyrus activity during attainment. ROI analyses additionally showed that multiple cytokines were related to activity in the basal ganglia (EGF, FGF-2, Flt-3L, IL-2, IL-13, IL-15, IL-1Rα, MCP-3) and ACC/MCC (Flt-3L) during attainment. C-reactive protein (CRP) was not associated with neural activation. CONCLUSIONS: Investigation of specific markers of immune function showed associations between inflammatory processes and activation of posterior default mode network, prefrontal cortex, and basal ganglia regions during multiple phases of reward processing.
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