Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin
Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enrich...
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| Autor*in: |
Mansur, Rodrigo B. [verfasserIn] Delgado-Peraza, Francheska [verfasserIn] Subramaniapillai, Mehala [verfasserIn] Lee, Yena [verfasserIn] Iacobucci, Michelle [verfasserIn] Nasri, Flora [verfasserIn] Rodrigues, Nelson [verfasserIn] Rosenblat, Joshua D. [verfasserIn] Brietzke, Elisa [verfasserIn] Cosgrove, Victoria E. [verfasserIn] Kramer, Nicole E. [verfasserIn] Suppes, Trisha [verfasserIn] Raison, Charles L. [verfasserIn] Fagiolini, Andrea [verfasserIn] Rasgon, Natalie [verfasserIn] Chawla, Sahil [verfasserIn] Nogueras-Ortiz, Carlos [verfasserIn] Kapogiannis, Dimitrios [verfasserIn] McIntyre, Roger S. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2020 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Journal of psychiatric research - Amsterdam [u.a.] : Elsevier Science, 1961, 133, Seite 82-92 |
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| Übergeordnetes Werk: |
volume:133 ; pages:82-92 |
| DOI / URN: |
10.1016/j.jpsychires.2020.12.007 |
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| Katalog-ID: |
ELV005324157 |
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| 100 | 1 | |a Mansur, Rodrigo B. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin |
| 264 | 1 | |c 2020 | |
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| 520 | |a Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma samples from a randomized, double-blind, placebo-controlled, 12-week clinical trial evaluating infliximab as a treatment of bipolar depression. We isolated NEVs using immunoprecipitation against neuronal marker L1CAM from samples collected at baseline and weeks 2, 6 and 12 (endpoint) and measured NEV biomarkers using immunoassays. We assessed neuronal insulin signaling at its first node (IRS-1) and along the canonical (Akt, GSK-3β, p70S6K) and alternative (ERK1/2, JNK and p38-MAPK) pathways. A subset of participants (n = 27) also underwent whole-brain magnetic resonance imaging (MRI) at baseline and endpoint. Pre-treatment, NEV biomarkers of insulin signaling were independently associated with cognitive function and MRI measures (i.e. hippocampal and ventromedial prefrontal cortex [vmPFC] volumes). In fact, the association between IRS-1 phosphorylation at serine site 312 (pS312-IRS-1), an indicator of insulin resistance, and cognitive dysfunction was mediated by vmPFC volume. In the longitudinal analysis, patients treated with infliximab, a tumor necrosis factor-alpha antagonist with known insulin sensitizing properties, compared to those treated with placebo, had augmented phosphorylation of proteins from the alternative pathway. Infliximab responders had significant increases in phosphorylated JNK levels, relative to infliximab non-responders and placebo responders. In addition, treatment with infliximab resulted in increase in MRI measures of brain volume; treatment-related changes in the dorsolateral prefrontal cortex volume were mediated by changes in biomarkers from the insulin alternative pathway. In conclusion, our findings support the idea that brain insulin signaling is a target for further mechanistic and therapeutic investigations. | ||
| 650 | 4 | |a Bipolar disorders | |
| 650 | 4 | |a Insulin | |
| 650 | 4 | |a Extracellular vesicles | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a TNF-α | |
| 650 | 4 | |a Cognition | |
| 700 | 1 | |a Delgado-Peraza, Francheska |e verfasserin |0 (orcid)0000-0003-0201-0248 |4 aut | |
| 700 | 1 | |a Subramaniapillai, Mehala |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Yena |e verfasserin |4 aut | |
| 700 | 1 | |a Iacobucci, Michelle |e verfasserin |4 aut | |
| 700 | 1 | |a Nasri, Flora |e verfasserin |4 aut | |
| 700 | 1 | |a Rodrigues, Nelson |e verfasserin |4 aut | |
| 700 | 1 | |a Rosenblat, Joshua D. |e verfasserin |4 aut | |
| 700 | 1 | |a Brietzke, Elisa |e verfasserin |4 aut | |
| 700 | 1 | |a Cosgrove, Victoria E. |e verfasserin |4 aut | |
| 700 | 1 | |a Kramer, Nicole E. |e verfasserin |4 aut | |
| 700 | 1 | |a Suppes, Trisha |e verfasserin |4 aut | |
| 700 | 1 | |a Raison, Charles L. |e verfasserin |4 aut | |
| 700 | 1 | |a Fagiolini, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Rasgon, Natalie |e verfasserin |4 aut | |
| 700 | 1 | |a Chawla, Sahil |e verfasserin |4 aut | |
| 700 | 1 | |a Nogueras-Ortiz, Carlos |e verfasserin |4 aut | |
| 700 | 1 | |a Kapogiannis, Dimitrios |e verfasserin |0 (orcid)0000-0003-2181-3118 |4 aut | |
| 700 | 1 | |a McIntyre, Roger S. |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of psychiatric research |d Amsterdam [u.a.] : Elsevier Science, 1961 |g 133, Seite 82-92 |h Online-Ressource |w (DE-627)30666111X |w (DE-600)1500641-4 |w (DE-576)081986718 |x 1879-1379 |7 nnns |
| 773 | 1 | 8 | |g volume:133 |g pages:82-92 |
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10.1016/j.jpsychires.2020.12.007 doi (DE-627)ELV005324157 (ELSEVIER)S0022-3956(20)31115-8 DE-627 ger DE-627 rda eng 610 DE-600 44.91 bkl Mansur, Rodrigo B. verfasserin aut Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma samples from a randomized, double-blind, placebo-controlled, 12-week clinical trial evaluating infliximab as a treatment of bipolar depression. We isolated NEVs using immunoprecipitation against neuronal marker L1CAM from samples collected at baseline and weeks 2, 6 and 12 (endpoint) and measured NEV biomarkers using immunoassays. We assessed neuronal insulin signaling at its first node (IRS-1) and along the canonical (Akt, GSK-3β, p70S6K) and alternative (ERK1/2, JNK and p38-MAPK) pathways. A subset of participants (n = 27) also underwent whole-brain magnetic resonance imaging (MRI) at baseline and endpoint. Pre-treatment, NEV biomarkers of insulin signaling were independently associated with cognitive function and MRI measures (i.e. hippocampal and ventromedial prefrontal cortex [vmPFC] volumes). In fact, the association between IRS-1 phosphorylation at serine site 312 (pS312-IRS-1), an indicator of insulin resistance, and cognitive dysfunction was mediated by vmPFC volume. In the longitudinal analysis, patients treated with infliximab, a tumor necrosis factor-alpha antagonist with known insulin sensitizing properties, compared to those treated with placebo, had augmented phosphorylation of proteins from the alternative pathway. Infliximab responders had significant increases in phosphorylated JNK levels, relative to infliximab non-responders and placebo responders. In addition, treatment with infliximab resulted in increase in MRI measures of brain volume; treatment-related changes in the dorsolateral prefrontal cortex volume were mediated by changes in biomarkers from the insulin alternative pathway. In conclusion, our findings support the idea that brain insulin signaling is a target for further mechanistic and therapeutic investigations. Bipolar disorders Insulin Extracellular vesicles Inflammation TNF-α Cognition Delgado-Peraza, Francheska verfasserin (orcid)0000-0003-0201-0248 aut Subramaniapillai, Mehala verfasserin aut Lee, Yena verfasserin aut Iacobucci, Michelle verfasserin aut Nasri, Flora verfasserin aut Rodrigues, Nelson verfasserin aut Rosenblat, Joshua D. verfasserin aut Brietzke, Elisa verfasserin aut Cosgrove, Victoria E. verfasserin aut Kramer, Nicole E. verfasserin aut Suppes, Trisha verfasserin aut Raison, Charles L. verfasserin aut Fagiolini, Andrea verfasserin aut Rasgon, Natalie verfasserin aut Chawla, Sahil verfasserin aut Nogueras-Ortiz, Carlos verfasserin aut Kapogiannis, Dimitrios verfasserin (orcid)0000-0003-2181-3118 aut McIntyre, Roger S. verfasserin aut Enthalten in Journal of psychiatric research Amsterdam [u.a.] : Elsevier Science, 1961 133, Seite 82-92 Online-Ressource (DE-627)30666111X (DE-600)1500641-4 (DE-576)081986718 1879-1379 nnns volume:133 pages:82-92 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.91 Psychiatrie Psychopathologie AR 133 82-92 |
| spelling |
10.1016/j.jpsychires.2020.12.007 doi (DE-627)ELV005324157 (ELSEVIER)S0022-3956(20)31115-8 DE-627 ger DE-627 rda eng 610 DE-600 44.91 bkl Mansur, Rodrigo B. verfasserin aut Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma samples from a randomized, double-blind, placebo-controlled, 12-week clinical trial evaluating infliximab as a treatment of bipolar depression. We isolated NEVs using immunoprecipitation against neuronal marker L1CAM from samples collected at baseline and weeks 2, 6 and 12 (endpoint) and measured NEV biomarkers using immunoassays. We assessed neuronal insulin signaling at its first node (IRS-1) and along the canonical (Akt, GSK-3β, p70S6K) and alternative (ERK1/2, JNK and p38-MAPK) pathways. A subset of participants (n = 27) also underwent whole-brain magnetic resonance imaging (MRI) at baseline and endpoint. Pre-treatment, NEV biomarkers of insulin signaling were independently associated with cognitive function and MRI measures (i.e. hippocampal and ventromedial prefrontal cortex [vmPFC] volumes). In fact, the association between IRS-1 phosphorylation at serine site 312 (pS312-IRS-1), an indicator of insulin resistance, and cognitive dysfunction was mediated by vmPFC volume. In the longitudinal analysis, patients treated with infliximab, a tumor necrosis factor-alpha antagonist with known insulin sensitizing properties, compared to those treated with placebo, had augmented phosphorylation of proteins from the alternative pathway. Infliximab responders had significant increases in phosphorylated JNK levels, relative to infliximab non-responders and placebo responders. In addition, treatment with infliximab resulted in increase in MRI measures of brain volume; treatment-related changes in the dorsolateral prefrontal cortex volume were mediated by changes in biomarkers from the insulin alternative pathway. In conclusion, our findings support the idea that brain insulin signaling is a target for further mechanistic and therapeutic investigations. Bipolar disorders Insulin Extracellular vesicles Inflammation TNF-α Cognition Delgado-Peraza, Francheska verfasserin (orcid)0000-0003-0201-0248 aut Subramaniapillai, Mehala verfasserin aut Lee, Yena verfasserin aut Iacobucci, Michelle verfasserin aut Nasri, Flora verfasserin aut Rodrigues, Nelson verfasserin aut Rosenblat, Joshua D. verfasserin aut Brietzke, Elisa verfasserin aut Cosgrove, Victoria E. verfasserin aut Kramer, Nicole E. verfasserin aut Suppes, Trisha verfasserin aut Raison, Charles L. verfasserin aut Fagiolini, Andrea verfasserin aut Rasgon, Natalie verfasserin aut Chawla, Sahil verfasserin aut Nogueras-Ortiz, Carlos verfasserin aut Kapogiannis, Dimitrios verfasserin (orcid)0000-0003-2181-3118 aut McIntyre, Roger S. verfasserin aut Enthalten in Journal of psychiatric research Amsterdam [u.a.] : Elsevier Science, 1961 133, Seite 82-92 Online-Ressource (DE-627)30666111X (DE-600)1500641-4 (DE-576)081986718 1879-1379 nnns volume:133 pages:82-92 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.91 Psychiatrie Psychopathologie AR 133 82-92 |
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10.1016/j.jpsychires.2020.12.007 doi (DE-627)ELV005324157 (ELSEVIER)S0022-3956(20)31115-8 DE-627 ger DE-627 rda eng 610 DE-600 44.91 bkl Mansur, Rodrigo B. verfasserin aut Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma samples from a randomized, double-blind, placebo-controlled, 12-week clinical trial evaluating infliximab as a treatment of bipolar depression. We isolated NEVs using immunoprecipitation against neuronal marker L1CAM from samples collected at baseline and weeks 2, 6 and 12 (endpoint) and measured NEV biomarkers using immunoassays. We assessed neuronal insulin signaling at its first node (IRS-1) and along the canonical (Akt, GSK-3β, p70S6K) and alternative (ERK1/2, JNK and p38-MAPK) pathways. A subset of participants (n = 27) also underwent whole-brain magnetic resonance imaging (MRI) at baseline and endpoint. Pre-treatment, NEV biomarkers of insulin signaling were independently associated with cognitive function and MRI measures (i.e. hippocampal and ventromedial prefrontal cortex [vmPFC] volumes). In fact, the association between IRS-1 phosphorylation at serine site 312 (pS312-IRS-1), an indicator of insulin resistance, and cognitive dysfunction was mediated by vmPFC volume. In the longitudinal analysis, patients treated with infliximab, a tumor necrosis factor-alpha antagonist with known insulin sensitizing properties, compared to those treated with placebo, had augmented phosphorylation of proteins from the alternative pathway. Infliximab responders had significant increases in phosphorylated JNK levels, relative to infliximab non-responders and placebo responders. In addition, treatment with infliximab resulted in increase in MRI measures of brain volume; treatment-related changes in the dorsolateral prefrontal cortex volume were mediated by changes in biomarkers from the insulin alternative pathway. In conclusion, our findings support the idea that brain insulin signaling is a target for further mechanistic and therapeutic investigations. Bipolar disorders Insulin Extracellular vesicles Inflammation TNF-α Cognition Delgado-Peraza, Francheska verfasserin (orcid)0000-0003-0201-0248 aut Subramaniapillai, Mehala verfasserin aut Lee, Yena verfasserin aut Iacobucci, Michelle verfasserin aut Nasri, Flora verfasserin aut Rodrigues, Nelson verfasserin aut Rosenblat, Joshua D. verfasserin aut Brietzke, Elisa verfasserin aut Cosgrove, Victoria E. verfasserin aut Kramer, Nicole E. verfasserin aut Suppes, Trisha verfasserin aut Raison, Charles L. verfasserin aut Fagiolini, Andrea verfasserin aut Rasgon, Natalie verfasserin aut Chawla, Sahil verfasserin aut Nogueras-Ortiz, Carlos verfasserin aut Kapogiannis, Dimitrios verfasserin (orcid)0000-0003-2181-3118 aut McIntyre, Roger S. verfasserin aut Enthalten in Journal of psychiatric research Amsterdam [u.a.] : Elsevier Science, 1961 133, Seite 82-92 Online-Ressource (DE-627)30666111X (DE-600)1500641-4 (DE-576)081986718 1879-1379 nnns volume:133 pages:82-92 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.91 Psychiatrie Psychopathologie AR 133 82-92 |
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10.1016/j.jpsychires.2020.12.007 doi (DE-627)ELV005324157 (ELSEVIER)S0022-3956(20)31115-8 DE-627 ger DE-627 rda eng 610 DE-600 44.91 bkl Mansur, Rodrigo B. verfasserin aut Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma samples from a randomized, double-blind, placebo-controlled, 12-week clinical trial evaluating infliximab as a treatment of bipolar depression. We isolated NEVs using immunoprecipitation against neuronal marker L1CAM from samples collected at baseline and weeks 2, 6 and 12 (endpoint) and measured NEV biomarkers using immunoassays. We assessed neuronal insulin signaling at its first node (IRS-1) and along the canonical (Akt, GSK-3β, p70S6K) and alternative (ERK1/2, JNK and p38-MAPK) pathways. A subset of participants (n = 27) also underwent whole-brain magnetic resonance imaging (MRI) at baseline and endpoint. Pre-treatment, NEV biomarkers of insulin signaling were independently associated with cognitive function and MRI measures (i.e. hippocampal and ventromedial prefrontal cortex [vmPFC] volumes). In fact, the association between IRS-1 phosphorylation at serine site 312 (pS312-IRS-1), an indicator of insulin resistance, and cognitive dysfunction was mediated by vmPFC volume. In the longitudinal analysis, patients treated with infliximab, a tumor necrosis factor-alpha antagonist with known insulin sensitizing properties, compared to those treated with placebo, had augmented phosphorylation of proteins from the alternative pathway. Infliximab responders had significant increases in phosphorylated JNK levels, relative to infliximab non-responders and placebo responders. In addition, treatment with infliximab resulted in increase in MRI measures of brain volume; treatment-related changes in the dorsolateral prefrontal cortex volume were mediated by changes in biomarkers from the insulin alternative pathway. In conclusion, our findings support the idea that brain insulin signaling is a target for further mechanistic and therapeutic investigations. Bipolar disorders Insulin Extracellular vesicles Inflammation TNF-α Cognition Delgado-Peraza, Francheska verfasserin (orcid)0000-0003-0201-0248 aut Subramaniapillai, Mehala verfasserin aut Lee, Yena verfasserin aut Iacobucci, Michelle verfasserin aut Nasri, Flora verfasserin aut Rodrigues, Nelson verfasserin aut Rosenblat, Joshua D. verfasserin aut Brietzke, Elisa verfasserin aut Cosgrove, Victoria E. verfasserin aut Kramer, Nicole E. verfasserin aut Suppes, Trisha verfasserin aut Raison, Charles L. verfasserin aut Fagiolini, Andrea verfasserin aut Rasgon, Natalie verfasserin aut Chawla, Sahil verfasserin aut Nogueras-Ortiz, Carlos verfasserin aut Kapogiannis, Dimitrios verfasserin (orcid)0000-0003-2181-3118 aut McIntyre, Roger S. verfasserin aut Enthalten in Journal of psychiatric research Amsterdam [u.a.] : Elsevier Science, 1961 133, Seite 82-92 Online-Ressource (DE-627)30666111X (DE-600)1500641-4 (DE-576)081986718 1879-1379 nnns volume:133 pages:82-92 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.91 Psychiatrie Psychopathologie AR 133 82-92 |
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10.1016/j.jpsychires.2020.12.007 doi (DE-627)ELV005324157 (ELSEVIER)S0022-3956(20)31115-8 DE-627 ger DE-627 rda eng 610 DE-600 44.91 bkl Mansur, Rodrigo B. verfasserin aut Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma samples from a randomized, double-blind, placebo-controlled, 12-week clinical trial evaluating infliximab as a treatment of bipolar depression. We isolated NEVs using immunoprecipitation against neuronal marker L1CAM from samples collected at baseline and weeks 2, 6 and 12 (endpoint) and measured NEV biomarkers using immunoassays. We assessed neuronal insulin signaling at its first node (IRS-1) and along the canonical (Akt, GSK-3β, p70S6K) and alternative (ERK1/2, JNK and p38-MAPK) pathways. A subset of participants (n = 27) also underwent whole-brain magnetic resonance imaging (MRI) at baseline and endpoint. Pre-treatment, NEV biomarkers of insulin signaling were independently associated with cognitive function and MRI measures (i.e. hippocampal and ventromedial prefrontal cortex [vmPFC] volumes). In fact, the association between IRS-1 phosphorylation at serine site 312 (pS312-IRS-1), an indicator of insulin resistance, and cognitive dysfunction was mediated by vmPFC volume. In the longitudinal analysis, patients treated with infliximab, a tumor necrosis factor-alpha antagonist with known insulin sensitizing properties, compared to those treated with placebo, had augmented phosphorylation of proteins from the alternative pathway. Infliximab responders had significant increases in phosphorylated JNK levels, relative to infliximab non-responders and placebo responders. In addition, treatment with infliximab resulted in increase in MRI measures of brain volume; treatment-related changes in the dorsolateral prefrontal cortex volume were mediated by changes in biomarkers from the insulin alternative pathway. In conclusion, our findings support the idea that brain insulin signaling is a target for further mechanistic and therapeutic investigations. Bipolar disorders Insulin Extracellular vesicles Inflammation TNF-α Cognition Delgado-Peraza, Francheska verfasserin (orcid)0000-0003-0201-0248 aut Subramaniapillai, Mehala verfasserin aut Lee, Yena verfasserin aut Iacobucci, Michelle verfasserin aut Nasri, Flora verfasserin aut Rodrigues, Nelson verfasserin aut Rosenblat, Joshua D. verfasserin aut Brietzke, Elisa verfasserin aut Cosgrove, Victoria E. verfasserin aut Kramer, Nicole E. verfasserin aut Suppes, Trisha verfasserin aut Raison, Charles L. verfasserin aut Fagiolini, Andrea verfasserin aut Rasgon, Natalie verfasserin aut Chawla, Sahil verfasserin aut Nogueras-Ortiz, Carlos verfasserin aut Kapogiannis, Dimitrios verfasserin (orcid)0000-0003-2181-3118 aut McIntyre, Roger S. verfasserin aut Enthalten in Journal of psychiatric research Amsterdam [u.a.] : Elsevier Science, 1961 133, Seite 82-92 Online-Ressource (DE-627)30666111X (DE-600)1500641-4 (DE-576)081986718 1879-1379 nnns volume:133 pages:82-92 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.91 Psychiatrie Psychopathologie AR 133 82-92 |
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Enthalten in Journal of psychiatric research 133, Seite 82-92 volume:133 pages:82-92 |
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Bipolar disorders Insulin Extracellular vesicles Inflammation TNF-α Cognition |
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Mansur, Rodrigo B. @@aut@@ Delgado-Peraza, Francheska @@aut@@ Subramaniapillai, Mehala @@aut@@ Lee, Yena @@aut@@ Iacobucci, Michelle @@aut@@ Nasri, Flora @@aut@@ Rodrigues, Nelson @@aut@@ Rosenblat, Joshua D. @@aut@@ Brietzke, Elisa @@aut@@ Cosgrove, Victoria E. @@aut@@ Kramer, Nicole E. @@aut@@ Suppes, Trisha @@aut@@ Raison, Charles L. @@aut@@ Fagiolini, Andrea @@aut@@ Rasgon, Natalie @@aut@@ Chawla, Sahil @@aut@@ Nogueras-Ortiz, Carlos @@aut@@ Kapogiannis, Dimitrios @@aut@@ McIntyre, Roger S. @@aut@@ |
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2020-01-01T00:00:00Z |
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Mansur, Rodrigo B. |
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Mansur, Rodrigo B. ddc 610 bkl 44.91 misc Bipolar disorders misc Insulin misc Extracellular vesicles misc Inflammation misc TNF-α misc Cognition Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin |
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610 DE-600 44.91 bkl Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin Bipolar disorders Insulin Extracellular vesicles Inflammation TNF-α Cognition |
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ddc 610 bkl 44.91 misc Bipolar disorders misc Insulin misc Extracellular vesicles misc Inflammation misc TNF-α misc Cognition |
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ddc 610 bkl 44.91 misc Bipolar disorders misc Insulin misc Extracellular vesicles misc Inflammation misc TNF-α misc Cognition |
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ddc 610 bkl 44.91 misc Bipolar disorders misc Insulin misc Extracellular vesicles misc Inflammation misc TNF-α misc Cognition |
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Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin |
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Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin |
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Mansur, Rodrigo B. |
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Mansur, Rodrigo B. Delgado-Peraza, Francheska Subramaniapillai, Mehala Lee, Yena Iacobucci, Michelle Nasri, Flora Rodrigues, Nelson Rosenblat, Joshua D. Brietzke, Elisa Cosgrove, Victoria E. Kramer, Nicole E. Suppes, Trisha Raison, Charles L. Fagiolini, Andrea Rasgon, Natalie Chawla, Sahil Nogueras-Ortiz, Carlos Kapogiannis, Dimitrios McIntyre, Roger S. |
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10.1016/j.jpsychires.2020.12.007 |
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exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin |
| title_auth |
Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin |
| abstract |
Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma samples from a randomized, double-blind, placebo-controlled, 12-week clinical trial evaluating infliximab as a treatment of bipolar depression. We isolated NEVs using immunoprecipitation against neuronal marker L1CAM from samples collected at baseline and weeks 2, 6 and 12 (endpoint) and measured NEV biomarkers using immunoassays. We assessed neuronal insulin signaling at its first node (IRS-1) and along the canonical (Akt, GSK-3β, p70S6K) and alternative (ERK1/2, JNK and p38-MAPK) pathways. A subset of participants (n = 27) also underwent whole-brain magnetic resonance imaging (MRI) at baseline and endpoint. Pre-treatment, NEV biomarkers of insulin signaling were independently associated with cognitive function and MRI measures (i.e. hippocampal and ventromedial prefrontal cortex [vmPFC] volumes). In fact, the association between IRS-1 phosphorylation at serine site 312 (pS312-IRS-1), an indicator of insulin resistance, and cognitive dysfunction was mediated by vmPFC volume. In the longitudinal analysis, patients treated with infliximab, a tumor necrosis factor-alpha antagonist with known insulin sensitizing properties, compared to those treated with placebo, had augmented phosphorylation of proteins from the alternative pathway. Infliximab responders had significant increases in phosphorylated JNK levels, relative to infliximab non-responders and placebo responders. In addition, treatment with infliximab resulted in increase in MRI measures of brain volume; treatment-related changes in the dorsolateral prefrontal cortex volume were mediated by changes in biomarkers from the insulin alternative pathway. In conclusion, our findings support the idea that brain insulin signaling is a target for further mechanistic and therapeutic investigations. |
| abstractGer |
Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma samples from a randomized, double-blind, placebo-controlled, 12-week clinical trial evaluating infliximab as a treatment of bipolar depression. We isolated NEVs using immunoprecipitation against neuronal marker L1CAM from samples collected at baseline and weeks 2, 6 and 12 (endpoint) and measured NEV biomarkers using immunoassays. We assessed neuronal insulin signaling at its first node (IRS-1) and along the canonical (Akt, GSK-3β, p70S6K) and alternative (ERK1/2, JNK and p38-MAPK) pathways. A subset of participants (n = 27) also underwent whole-brain magnetic resonance imaging (MRI) at baseline and endpoint. Pre-treatment, NEV biomarkers of insulin signaling were independently associated with cognitive function and MRI measures (i.e. hippocampal and ventromedial prefrontal cortex [vmPFC] volumes). In fact, the association between IRS-1 phosphorylation at serine site 312 (pS312-IRS-1), an indicator of insulin resistance, and cognitive dysfunction was mediated by vmPFC volume. In the longitudinal analysis, patients treated with infliximab, a tumor necrosis factor-alpha antagonist with known insulin sensitizing properties, compared to those treated with placebo, had augmented phosphorylation of proteins from the alternative pathway. Infliximab responders had significant increases in phosphorylated JNK levels, relative to infliximab non-responders and placebo responders. In addition, treatment with infliximab resulted in increase in MRI measures of brain volume; treatment-related changes in the dorsolateral prefrontal cortex volume were mediated by changes in biomarkers from the insulin alternative pathway. In conclusion, our findings support the idea that brain insulin signaling is a target for further mechanistic and therapeutic investigations. |
| abstract_unstemmed |
Accumulating evidence suggests that disrupted insulin signaling is involved in bipolar disorder (BD) pathogenesis. Herein, we aimed to directly explore the potential role of neuronal insulin signaling using an innovative technique based on biomarkers derived from plasma extracellular vesicles enriched for neuronal origin (NEVs). We leveraged plasma samples from a randomized, double-blind, placebo-controlled, 12-week clinical trial evaluating infliximab as a treatment of bipolar depression. We isolated NEVs using immunoprecipitation against neuronal marker L1CAM from samples collected at baseline and weeks 2, 6 and 12 (endpoint) and measured NEV biomarkers using immunoassays. We assessed neuronal insulin signaling at its first node (IRS-1) and along the canonical (Akt, GSK-3β, p70S6K) and alternative (ERK1/2, JNK and p38-MAPK) pathways. A subset of participants (n = 27) also underwent whole-brain magnetic resonance imaging (MRI) at baseline and endpoint. Pre-treatment, NEV biomarkers of insulin signaling were independently associated with cognitive function and MRI measures (i.e. hippocampal and ventromedial prefrontal cortex [vmPFC] volumes). In fact, the association between IRS-1 phosphorylation at serine site 312 (pS312-IRS-1), an indicator of insulin resistance, and cognitive dysfunction was mediated by vmPFC volume. In the longitudinal analysis, patients treated with infliximab, a tumor necrosis factor-alpha antagonist with known insulin sensitizing properties, compared to those treated with placebo, had augmented phosphorylation of proteins from the alternative pathway. Infliximab responders had significant increases in phosphorylated JNK levels, relative to infliximab non-responders and placebo responders. In addition, treatment with infliximab resulted in increase in MRI measures of brain volume; treatment-related changes in the dorsolateral prefrontal cortex volume were mediated by changes in biomarkers from the insulin alternative pathway. In conclusion, our findings support the idea that brain insulin signaling is a target for further mechanistic and therapeutic investigations. |
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Exploring brain insulin resistance in adults with bipolar depression using extracellular vesicles of neuronal origin |
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Delgado-Peraza, Francheska Subramaniapillai, Mehala Lee, Yena Iacobucci, Michelle Nasri, Flora Rodrigues, Nelson Rosenblat, Joshua D. Brietzke, Elisa Cosgrove, Victoria E. Kramer, Nicole E. Suppes, Trisha Raison, Charles L. Fagiolini, Andrea Rasgon, Natalie Chawla, Sahil Nogueras-Ortiz, Carlos Kapogiannis, Dimitrios McIntyre, Roger S. |
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