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Abstract # 1784 Neuronal Pentraxin 2 predicts medial temporal atrophy and memory decline across the Alzheimer’s disease spectrum
Abstracts / Brain, Behavior, and Immunity 57 (2016) e1–e43
Abstract # 1784 Neuronal Pentraxin 2 predicts medial temporal atrophy and memory decline across the Alzheimer’s disease spectrum A. Swanson a, A. Willette a,b,c a
Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, United States b Department of Psychology, Iowa State University, Ames, IA, United States c Aging Mind and Brain Institute, University of Iowa, Iowa City, IA, United States Neuroinflammation is thought to potentiate medial temporal lobe (MTL) atrophy and memory decline in Alzheimer’s disease (AD). It has become increasingly important to find novel immunological biomarkers that can track AD development and progression. Our study examined which pro- and anti-inflammatory cerebrospinal fluid (CSF) biomarkers best predicted AD neuropathology over 24 months. Using Alzheimer’s Disease Neuroimaging Initiative data (N = 285), CSF inflammatory peptides from a mass spectrometry panel were screened with stepwise regression. Linear mixed models regressed selected biomarkers against a memory factor and MTL volume across 24 months. Neuronal Pentraxin 2 (NPTX2) and Chitinase3-like-protein-1 (C3LP1), biomarkers of synaptic plasticity and microglial activation respectively, were the only significantly selected biomarkers. Higher baseline NPTX2 levels corresponded to less MTL atrophy [R2 = .287, p < .001] and substantially less memory decline [R2 = .560, p < .001] by month 24. Conversely, higher C3LP1 modestly predicted more MTL atrophy [R2 = .083, p < .001] and did not significantly track memory decline over time. In conclusion, NPTX2 is a novel proinflammatory cytokine that performs better than any other immunological biomarker to date, substantially accounting for brain atrophy and especially cognitive decline specific to AD. The microglial biomarker, by contrast, performed modestly. This research may advance the current understanding of AD etiopathogenesis, while expanding early diagnostic techniques by using proinflammatory biomarkers such as NPTX2. Future studies should also see if NPTX2 causally affects MTL morphometry and memory performance. http://dx.doi.org/10.1016/j.bbi.2016.07.077
Abstract # 1785 The effects of cannabis use in interferon-alpha treatment for hepatitis C viral infection Z. Zajkowska a,b,c, A. Russell a, N. Hepgul a, A. Cattaneo a, D. Baumeister a, E. Boorman a, D. Forton b, K. Agarwal c, V. Mondelli a, P.A. Zunszain a, C.M. Pariante a a Institute of Psychiatry, Psychology and Neuroscience, King’s College London, The Maurice Wohl Clinical Neuroscience Institute, Cutcombe Road, London, London SE5 9RT, Northern Ireland, UK b Department of Gastroenterology & Hepatology, St George’s University of London, UK c Institute of Liver Studies, King’s College Hospital, UK
Cannabis use in adolescence has been linked with increased risk of developing depression in adulthood and chronic cannabis use has a blunting effect on the endocannabinoid signalling. We investigated the role of cannabis use in the mechanisms underlying depression development and the impact of cannabis use on the endocannabinoid signalling in 74 patients receiving interferon-alpha treatment for hepatitis-C-viral. We measured serum endocannabinoids,
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anandamide (AEA) and 2-arachidonoylglycerol (2-AG) at baseline and treatment week 4 (TW4), using High Performance Liquid Chromatography with Tandem Mass Spectrometry. We used M.I.N. I. International Neuropsychiatric Interview to assess depression development and Cannabis Experience Questionnaire to determine cannabis use during lifetime. Our results show that the proportion of patients who smoke cannabis at baseline is 3.73 greater amongst those who develop depression during treatment compared to those who do not develop depression. When we looked at the effect of interferon-alpha on endocannabinoid levels, we found a significant increase in 2-AG levels, from baseline to TW4, only in patients who never used cannabis and those who used cannabis in the past. Levels of AEA were significantly increased from baseline to TW4 only in patients who never used cannabis. Our findings suggest that current cannabis use may increased the likelihood of developing depression during interferon-alpha treatment in hepatitis-C-viral patients. Cannabis use may have a blunting effect on eCB signaling in response to interferon-alpha treatment. http://dx.doi.org/10.1016/j.bbi.2016.07.078
Abstract # 1786 The PsychoNeuroInflammatory related Inventory (PNISSI) S. Bejerot a, E. Hesselmark b, M.B. Humble a
Signs
and
Severity
a
Örebro university, School of Medical Sciences, Campus USÖ, Örebro SE701 82, Sweden b Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Sweden The symptoms of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) and other putative psychoneuroimmunological disorders are often misinterpreted and misdiagnosed in clinical settings because of the diversity of symptoms and the clinicians’ unfamiliarity with these ‘‘new” disorders. Most of these symptoms are of psychiatric nature. Not only the current psychoneuroimmunological symptoms, but also the course and severity in relation to the premorbid state of the patient should be clarified. There is a need for an instrument that instructs the clinician/psychiatrist to ask relevant questions on the patients’ background, to make observations and to perform simple tests of symptoms and signs supporting the diagnosis. Also such an instrument should provide diagnostic algorithms for different psychoneuroimmunological disorders. A thorough four hours interview was carried out in 2015–2016 with 52 patients (children and adults) that had been assessed for PANDAS or Pediatric AcuteOnset Neuropsychiatric Syndrome (PANS) in Sweden. Our experiences from this process, supplemented with symptoms and signs related to other psychoneuroimmunological disorders described in the literature, were compiled into a self-report form and a structured clinical interview. The PsychoNeuroimmunology Symptom and Severity Inventory (PNISSI) will be presented here. http://dx.doi.org/10.1016/j.bbi.2016.07.079
Abstract # 1787 Unique immune profiles in children with autism who experience gastrointestinal co-morbidity D. Rose, J. Van de Water, P. Ashwood
Abstract # 1784 Neuronal Pentraxin 2 predicts medial temporal atrophy and memory decline across the Alzheimer’s disease spectrum A. Swanson a, A. Willette a,b,c a
Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, United States b Department of Psychology, Iowa State University, Ames, IA, United States c Aging Mind and Brain Institute, University of Iowa, Iowa City, IA, United States Neuroinflammation is thought to potentiate medial temporal lobe (MTL) atrophy and memory decline in Alzheimer’s disease (AD). It has become increasingly important to find novel immunological biomarkers that can track AD development and progression. Our study examined which pro- and anti-inflammatory cerebrospinal fluid (CSF) biomarkers best predicted AD neuropathology over 24 months. Using Alzheimer’s Disease Neuroimaging Initiative data (N = 285), CSF inflammatory peptides from a mass spectrometry panel were screened with stepwise regression. Linear mixed models regressed selected biomarkers against a memory factor and MTL volume across 24 months. Neuronal Pentraxin 2 (NPTX2) and Chitinase3-like-protein-1 (C3LP1), biomarkers of synaptic plasticity and microglial activation respectively, were the only significantly selected biomarkers. Higher baseline NPTX2 levels corresponded to less MTL atrophy [R2 = .287, p < .001] and substantially less memory decline [R2 = .560, p < .001] by month 24. Conversely, higher C3LP1 modestly predicted more MTL atrophy [R2 = .083, p < .001] and did not significantly track memory decline over time. In conclusion, NPTX2 is a novel proinflammatory cytokine that performs better than any other immunological biomarker to date, substantially accounting for brain atrophy and especially cognitive decline specific to AD. The microglial biomarker, by contrast, performed modestly. This research may advance the current understanding of AD etiopathogenesis, while expanding early diagnostic techniques by using proinflammatory biomarkers such as NPTX2. Future studies should also see if NPTX2 causally affects MTL morphometry and memory performance. http://dx.doi.org/10.1016/j.bbi.2016.07.077
Abstract # 1785 The effects of cannabis use in interferon-alpha treatment for hepatitis C viral infection Z. Zajkowska a,b,c, A. Russell a, N. Hepgul a, A. Cattaneo a, D. Baumeister a, E. Boorman a, D. Forton b, K. Agarwal c, V. Mondelli a, P.A. Zunszain a, C.M. Pariante a a Institute of Psychiatry, Psychology and Neuroscience, King’s College London, The Maurice Wohl Clinical Neuroscience Institute, Cutcombe Road, London, London SE5 9RT, Northern Ireland, UK b Department of Gastroenterology & Hepatology, St George’s University of London, UK c Institute of Liver Studies, King’s College Hospital, UK
Cannabis use in adolescence has been linked with increased risk of developing depression in adulthood and chronic cannabis use has a blunting effect on the endocannabinoid signalling. We investigated the role of cannabis use in the mechanisms underlying depression development and the impact of cannabis use on the endocannabinoid signalling in 74 patients receiving interferon-alpha treatment for hepatitis-C-viral. We measured serum endocannabinoids,
e23
anandamide (AEA) and 2-arachidonoylglycerol (2-AG) at baseline and treatment week 4 (TW4), using High Performance Liquid Chromatography with Tandem Mass Spectrometry. We used M.I.N. I. International Neuropsychiatric Interview to assess depression development and Cannabis Experience Questionnaire to determine cannabis use during lifetime. Our results show that the proportion of patients who smoke cannabis at baseline is 3.73 greater amongst those who develop depression during treatment compared to those who do not develop depression. When we looked at the effect of interferon-alpha on endocannabinoid levels, we found a significant increase in 2-AG levels, from baseline to TW4, only in patients who never used cannabis and those who used cannabis in the past. Levels of AEA were significantly increased from baseline to TW4 only in patients who never used cannabis. Our findings suggest that current cannabis use may increased the likelihood of developing depression during interferon-alpha treatment in hepatitis-C-viral patients. Cannabis use may have a blunting effect on eCB signaling in response to interferon-alpha treatment. http://dx.doi.org/10.1016/j.bbi.2016.07.078
Abstract # 1786 The PsychoNeuroInflammatory related Inventory (PNISSI) S. Bejerot a, E. Hesselmark b, M.B. Humble a
Signs
and
Severity
a
Örebro university, School of Medical Sciences, Campus USÖ, Örebro SE701 82, Sweden b Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Sweden The symptoms of Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) and other putative psychoneuroimmunological disorders are often misinterpreted and misdiagnosed in clinical settings because of the diversity of symptoms and the clinicians’ unfamiliarity with these ‘‘new” disorders. Most of these symptoms are of psychiatric nature. Not only the current psychoneuroimmunological symptoms, but also the course and severity in relation to the premorbid state of the patient should be clarified. There is a need for an instrument that instructs the clinician/psychiatrist to ask relevant questions on the patients’ background, to make observations and to perform simple tests of symptoms and signs supporting the diagnosis. Also such an instrument should provide diagnostic algorithms for different psychoneuroimmunological disorders. A thorough four hours interview was carried out in 2015–2016 with 52 patients (children and adults) that had been assessed for PANDAS or Pediatric AcuteOnset Neuropsychiatric Syndrome (PANS) in Sweden. Our experiences from this process, supplemented with symptoms and signs related to other psychoneuroimmunological disorders described in the literature, were compiled into a self-report form and a structured clinical interview. The PsychoNeuroimmunology Symptom and Severity Inventory (PNISSI) will be presented here. http://dx.doi.org/10.1016/j.bbi.2016.07.079
Abstract # 1787 Unique immune profiles in children with autism who experience gastrointestinal co-morbidity D. Rose, J. Van de Water, P. Ashwood