Accepted Article
Received Date : 13-Feb-2015 Accepted Date : 15-Feb-2015 Article type
: Research Letter
Brain inflammation and psoriasis: a [11C]-(R)-PK11195 positron emission tomography study.
Running head: Brain inflammation and psoriasis
Authors: H.J.A. Hunter1, R. Hinz2, A. Gerhard2, P.S. Talbot2, Z. Su2, G. Holland2, S.J. Hopkins3, C.E.M. Griffiths1 and C.E. Kleyn1
Name of institution: 1The Dermatology Centre and 3The Stroke & Vascular Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. 2Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK.
Name of corresponding author: Dr C Elise Kleyn, Dermatological Sciences, The University of Manchester, Salford Royal NHS Foundation Trust, Manchester, M6 8HD, United Kingdom Tel: + 44 (0)161 206 4392 Fax: + 44 (0) 161 206 1095 Email: [email protected]
Funding sources: This investigator led study was sponsored by the University of Manchester and funded by Janssen. HJAH was in part funded by an unrestricted grant
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bjd.13788 This article is protected by copyright. All rights reserved.
Accepted Article
from Pfizer. We acknowledge the support of the National Institute for Health Research (NIHR), through the Comprehensive Clinical Research Network and CEMG is an NIHR Senior Investigator.
Conflicts of interest: CEMG and CEK have received honoraria, lecture fees and research grants from Janssen.
Psoriasis is a chronic, immune-mediated inflammatory skin disease affecting approximately 2% of the population.1 It is associated with multiple comorbidities including arthritis, cardiovascular disease and the metabolic syndrome and as such is widely regarded as a systemic inflammatory condition.2 Depression is also overrepresented in psoriasis3 and may itself have a systemic inflammatory component to its aetiology.4 The imiquimod mouse model of psoriasis provides further evidence of a brain-skin connection; with investigators noting not only psoriasiform skin inflammation but also the upregulation of interferon-stimulated genes in the brain.5 Neuroinflammation of the brain lacks the lymphocytic infiltrates of classical brain pathologies such as multiple sclerosis6 and has been reported in brain diseases including Parkinson’s disease,7 stroke8 and neoplasm.9 Furthermore, neuroinflammation has been noted in response to peripheral inflammatory insults in: susceptible mice fed an atherogenic diet;10 baboons injected intravenously with E. coli lipopolysaccharide11 and humans with risk factors for stroke, including a raised Creactive protein (CRP) but no actual infarct.10
Microglia, the principal cells of the brain’s innate immune system, normally reside in a quiescent, dendritic form but following challenge by stimuli including interferon-γ transform into an activated amoeboid state (hallmark of neuroinflammation) en route to becoming phagocytes.12 When activated microglia overexpress translocator protein (TSPO), a cholesterol transporter localized to their outer mitochondrial membrane; they can be visualised using positron emission tomography (PET) and [11C]-(R)-
This article is protected by copyright. All rights reserved.
Accepted Article
PK11195, a radioligand specific to TSPO.6 We therefore used [11C]-(R)-PK11195 PET co-registered with magnetic resonance imaging (MRI) to test the hypothesis that the brains of patients with psoriasis exhibit higher levels of neuroinflammation than those of healthy controls. In a case-controlled study approved by Greater Manchester East Local Research Ethics Committee, UK, the Administration of Radioactive Substances Advisory Committee (ARSAC) and local NHS R&D departments and after written, informed consent, 12 patients with moderate to severe psoriasis and 6 healthy controls were recruited (April 2012 to May 2013). An additional 6 healthy controls were drawn from a historical PK11195 cohort in accordance with our ARSAC approval; to reduce radiation exposure to healthy subjects. All subjects satisfied the inclusion/exclusion criteria which were, in brief: either gender, between 18-50 years of age; moderate to severe, early-onset, chronic plaque psoriasis or no history of skin disease; did not suffer from affective disorders, active infection, peripheral or central nervous system complaints or severe systemic illness; were not pregnant or taking medication which might interfere with [11C]-(R)-PK11195 binding and psoriasis subjects had not received recent photo, systemic (past month) or biological therapy (preceding 3 months).
Subjects completed psychometric questionnaires (Table 1), were venepunctured and undertook our standard scanning protocol.9 In brief, a T1 weighted structural MR scan to aid in definition of regions of interest (ROI) was followed by a dynamic [11C]-(R)-PK11195 PET scan. Bilateral cerebellar grey matter and a six class supervised cluster analysis were used as input functions to the simplified reference tissue model to generate parametric binding potential (BPND) maps as previously described.9 BPND quantifies specific tracer binding and represented neuroinflammation in our study. A brain atlas was used to extract BPND for anatomical ROI.13 Serum levels of CRP, interleukin (IL)-6 and IL-8 were measured14 in 18 subjects; data were not available for the 6 controls from our historical control cohort. Baseline
This article is protected by copyright. All rights reserved.
Accepted Article
characteristics, psychometric questionnaire scores and inflammatory cytokine levels are summarised in Table 1. All psoriasis patients had moderate to severe disease (mean psoriasis area and severity index (PASI) scores: 17.7±3.9, range: 12.2-25.3). The mean waist circumference was significantly larger (p=0.02) in the psoriasis group and may reflect an increased prevalence of the metabolic syndrome.2 All peripheral inflammatory markers were higher in the psoriasis group compared with controls but only reached significance (p=0.04, Mann-Whitney U test) for IL-8; a cytokine also known as neutrophil chemotactic factor and of pivotal importance in the pathogenesis of psoriasis.15 Across ROI for both input functions there were no significant (p=0.221.00) differences (Mann-Whitney U test) in mean [11C]-(R)-PK11195 BPND in the brains of psoriasis patients compared with those of controls (Fig 1a). However, there was marked intragroup heterogeneity in [11C]-(R)-PK11195 BPND (Figs 1b, 1c) but this did not correlate with age, body habitus, disease severity (PASI, dermatology life quality index; DLQI) or duration.
Our findings may seem at odds with former studies.10,11 However, the clinical arm of the Drake study10 was small (n=4) and investigated an older population (mean age of subjects 63yrs., controls 64yrs. v 39.3yrs. and 33.6yrs. respectively in our study). It required patients to have at least three risk factors for stroke and/or established arterial disease and a CRP greater than 3 on two occasions. By contrast, only one of our patients had evidence of arterial disease (controlled hypertension) and the mean level of inflammatory markers in our patient group was much lower than those of Drake’s at-risk patients (CRP: 3.86 v 11.93, IL-6: 2.70 v. 10.55). Furthermore, in their study the peripheral insults were related to vascular/atherogenic inflammation and the study was unable to identify whether the origin of raised [11C](R)-PK11195 binding was in brain parenchyma or endothelial cells of the vasculature. Comparing the Hannestad study11 to ours, they used a different study population
This article is protected by copyright. All rights reserved.
Accepted Article
(non-human primates), a different radioligand ([11C]-PBR28) and an infective rather than an inflammatory peripheral insult. Our study suggests, in this population, that peripheral inflammation associated with chronic plaque psoriasis is not associated with neuroinflammation as evidenced by activated microglia in the brain. It may be, that in contrast to the infective or atherogenic insults reported above which are capable of inducing neuroinflammation, the relatively lower inflammatory burden associated with psoriasis is not sufficient to induce significant neuroinflammation or [11C]-(R)-PK11195 is not sensitive enough to detect the level of neuroinflammation associated with psoriasis. Alternatively, the brains of patients with psoriasis may be protected against the detrimental effects of systemic inflammation. Whether the blood-brain barrier confers this protection remains speculative. To our knowledge, this is the first in vivo study in man to look at the association between systemic and neuroinflammation in any peripheral autoimmune inflammatory condition and highlights a fascinating area for future research.
1 2
3
4 5 6 7 8
Griffiths CEM, Barker JNWN. Psoriasis: pathogenesis and clinical features of psoriasis. Lancet 2007; 370: 263-71. Dauden E, Castaneda S, Suarez C et al. Clinical practice guideline for an integrated approach to comorbidity in patients with psoriasis. Journal of the European Academy of Dermatology and Venereology : JEADV 2013; 27: 1387404. Dowlatshahi EA, Wakkee M, Arends LR et al. The prevalence and odds of depressive symptoms and clinical depression in psoriasis patients: a systematic review and meta-analysis. The Journal of investigative dermatology 2014; 134: 1542-51. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 2006; 27: 24-31. Thomson CA, McColl A, Cavanagh J et al. Peripheral inflammation is associated with remote global gene expression changes in the brain. J Neuroinflammation 2014; 11: 73. Cagnin A, Gerhard A, Banati RB. In vivo imaging of neuroinflammation. Eur Neuropsychopharmacol 2002; 12: 581-6. Gerhard A, Pavese N, Hotton G et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease. Neurobiol Dis 2006; 21: 404-12. Gerhard A, Schwarz J, Myers R et al. Evolution of microglial activation in patients after ischemic stroke: a [11C](R)-PK11195 PET study. Neuroimage 2005; 24: 591-5.
This article is protected by copyright. All rights reserved.
Accepted Article
9 10 11 12 13 14
15
Su Z, Herholz K, Gerhard A et al. [(1)(1)C]-(R)PK11195 tracer kinetics in the brain of glioma patients and a comparison of two referencing approaches. Eur J Nucl Med Mol Imaging 2013; 40: 1406-19. Drake C, Boutin H, Jones MS et al. Brain inflammation is induced by comorbidities and risk factors for stroke. Brain Behav Immun 2011; 25: 111322. Hannestad J, Gallezot JD, Schafbauer T et al. Endotoxin-induced systemic inflammation activates microglia: [(1)(1)C]PBR28 positron emission tomography in nonhuman primates. Neuroimage 2012; 63: 232-9. Garden GA, Moller T. Microglia biology in health and disease. J Neuroimmune Pharmacol 2006; 1: 127-37. Hammers A, Allom R, Koepp MJ et al. Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe. Hum Brain Mapp 2003; 19: 224-47. Singh N, Hopkins SJ, Hulme S et al. The effect of intravenous interleukin-1 receptor antagonist on inflammatory mediators in cerebrospinal fluid after subarachnoid haemorrhage: a phase II randomised controlled trial. J Neuroinflammation 2014; 11: 1. Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature 2007; 445: 866-73.
Figure Legend: Figure 1. Mean [11C]-(R)-PK11195 BPND across regions of interest. (a) There were no significant differences in mean [11C]-(R)-PK11195 binding potential (BPND) across regions of interest between groups. Cortical ROIs (bilateral, temporal, frontal, occipital and parietal lobes) were defined using individualised grey matter object maps and subcortical ROIs (bilateral thalamus and brainstem) and whole brain were defined using individualised unsegmented object maps. Data shown was derived using the cerebellar input function. For each region of interest, the median and interquartile ranges are shown. P values derived from Mann-Whitney U test. *whole brain excluding cerebellum, corpus callosum and brainstem.(b) [11C]-(R)-PK11195 BPND parametric maps superimposed on T1 weighted MRI scans for a psoriasis patient with low [11C]-(R)-PK11195 uptake (transverse, coronal and sagittal planes); represented by green circles on the dot plot. (c) Similar scans for a psoriasis patient with high [11C]-(R)-PK11195 uptake; represented by pink circles on the dot plot. Colour bars = [11C]-(R)-PK11195 binding potential (BPND).
This article is protected by copyright. All rights reserved.
Accepted Article
Table 1. Summary of subject characteristics and baseline psychometric and peripheral inflammatory marker data. Psoriasis group
Control group
(Mean ± S.D.)
(Mean ± S.D.)
Age (yrs.)
39.3 ± 9
33.6 ± 10
0.18
Gender (M : F)
11 : 1
7:5
-
BMI (Kg/M2)
27.8 ± 4.4
24.3 ± 3.5
0.06
Waist circumference (CM)
100.6 ± 11.3
84.5 ± 16.5
0.02*
HADS (anxiety)
2.00 ± 2.00
1.67 ± 1.37
1.00
HADS (depression)
0.92 ± 1.08
0
0.10
BDI
2.58 ± 5.68
0.67 ± 1.21
0.55
SRRS
127.25 ± 98.11
54.67 ± 24.52
0.12
PLSI
14.00 ± 10.99
-
-
DLQI
9.00 ± 8.36
-
-
PASI
17.7 ± 3.9
-
-
WCC (x 109/L)
6.87 ± 2.60
6.43 ± 1.44
0.89
TNC (x 109/L)
4.71 ± 2.40
4.10 ± 1.47
0.89
CRP (mg/L)
3.86 ± 5.53
2.75 ± 2.20
0.96
IL-6 (ng/L)
2.70 ± 2.21
1.86 ± 1.54
0.38
IL-8 (ng/L)
9.16 ± 3.34
4.13 ± 4.12
0.04*
Variable
P value
S.D., Standard deviation; ; M,male; F,Female; BMI, Body mass index; HADS, Hospital anxiety and depression scale; BDI, Beck depression inventory; SRRS, Social readjustment rating scale; PLSI, Psoriasis living stress index; DLQI, Dermatology life quality index; PASI, psoriasis area and severity index; WCC, total white cell count; TNC, total neutrophil count; CRP, C-reactive protein; IL-6, interleukin-6; IL-8, interleukin-8. P value derived using Mann-Whitney U test. *Significant result (P
Received Date : 13-Feb-2015 Accepted Date : 15-Feb-2015 Article type
: Research Letter
Brain inflammation and psoriasis: a [11C]-(R)-PK11195 positron emission tomography study.
Running head: Brain inflammation and psoriasis
Authors: H.J.A. Hunter1, R. Hinz2, A. Gerhard2, P.S. Talbot2, Z. Su2, G. Holland2, S.J. Hopkins3, C.E.M. Griffiths1 and C.E. Kleyn1
Name of institution: 1The Dermatology Centre and 3The Stroke & Vascular Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. 2Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK.
Name of corresponding author: Dr C Elise Kleyn, Dermatological Sciences, The University of Manchester, Salford Royal NHS Foundation Trust, Manchester, M6 8HD, United Kingdom Tel: + 44 (0)161 206 4392 Fax: + 44 (0) 161 206 1095 Email: [email protected]
Funding sources: This investigator led study was sponsored by the University of Manchester and funded by Janssen. HJAH was in part funded by an unrestricted grant
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bjd.13788 This article is protected by copyright. All rights reserved.
Accepted Article
from Pfizer. We acknowledge the support of the National Institute for Health Research (NIHR), through the Comprehensive Clinical Research Network and CEMG is an NIHR Senior Investigator.
Conflicts of interest: CEMG and CEK have received honoraria, lecture fees and research grants from Janssen.
Psoriasis is a chronic, immune-mediated inflammatory skin disease affecting approximately 2% of the population.1 It is associated with multiple comorbidities including arthritis, cardiovascular disease and the metabolic syndrome and as such is widely regarded as a systemic inflammatory condition.2 Depression is also overrepresented in psoriasis3 and may itself have a systemic inflammatory component to its aetiology.4 The imiquimod mouse model of psoriasis provides further evidence of a brain-skin connection; with investigators noting not only psoriasiform skin inflammation but also the upregulation of interferon-stimulated genes in the brain.5 Neuroinflammation of the brain lacks the lymphocytic infiltrates of classical brain pathologies such as multiple sclerosis6 and has been reported in brain diseases including Parkinson’s disease,7 stroke8 and neoplasm.9 Furthermore, neuroinflammation has been noted in response to peripheral inflammatory insults in: susceptible mice fed an atherogenic diet;10 baboons injected intravenously with E. coli lipopolysaccharide11 and humans with risk factors for stroke, including a raised Creactive protein (CRP) but no actual infarct.10
Microglia, the principal cells of the brain’s innate immune system, normally reside in a quiescent, dendritic form but following challenge by stimuli including interferon-γ transform into an activated amoeboid state (hallmark of neuroinflammation) en route to becoming phagocytes.12 When activated microglia overexpress translocator protein (TSPO), a cholesterol transporter localized to their outer mitochondrial membrane; they can be visualised using positron emission tomography (PET) and [11C]-(R)-
This article is protected by copyright. All rights reserved.
Accepted Article
PK11195, a radioligand specific to TSPO.6 We therefore used [11C]-(R)-PK11195 PET co-registered with magnetic resonance imaging (MRI) to test the hypothesis that the brains of patients with psoriasis exhibit higher levels of neuroinflammation than those of healthy controls. In a case-controlled study approved by Greater Manchester East Local Research Ethics Committee, UK, the Administration of Radioactive Substances Advisory Committee (ARSAC) and local NHS R&D departments and after written, informed consent, 12 patients with moderate to severe psoriasis and 6 healthy controls were recruited (April 2012 to May 2013). An additional 6 healthy controls were drawn from a historical PK11195 cohort in accordance with our ARSAC approval; to reduce radiation exposure to healthy subjects. All subjects satisfied the inclusion/exclusion criteria which were, in brief: either gender, between 18-50 years of age; moderate to severe, early-onset, chronic plaque psoriasis or no history of skin disease; did not suffer from affective disorders, active infection, peripheral or central nervous system complaints or severe systemic illness; were not pregnant or taking medication which might interfere with [11C]-(R)-PK11195 binding and psoriasis subjects had not received recent photo, systemic (past month) or biological therapy (preceding 3 months).
Subjects completed psychometric questionnaires (Table 1), were venepunctured and undertook our standard scanning protocol.9 In brief, a T1 weighted structural MR scan to aid in definition of regions of interest (ROI) was followed by a dynamic [11C]-(R)-PK11195 PET scan. Bilateral cerebellar grey matter and a six class supervised cluster analysis were used as input functions to the simplified reference tissue model to generate parametric binding potential (BPND) maps as previously described.9 BPND quantifies specific tracer binding and represented neuroinflammation in our study. A brain atlas was used to extract BPND for anatomical ROI.13 Serum levels of CRP, interleukin (IL)-6 and IL-8 were measured14 in 18 subjects; data were not available for the 6 controls from our historical control cohort. Baseline
This article is protected by copyright. All rights reserved.
Accepted Article
characteristics, psychometric questionnaire scores and inflammatory cytokine levels are summarised in Table 1. All psoriasis patients had moderate to severe disease (mean psoriasis area and severity index (PASI) scores: 17.7±3.9, range: 12.2-25.3). The mean waist circumference was significantly larger (p=0.02) in the psoriasis group and may reflect an increased prevalence of the metabolic syndrome.2 All peripheral inflammatory markers were higher in the psoriasis group compared with controls but only reached significance (p=0.04, Mann-Whitney U test) for IL-8; a cytokine also known as neutrophil chemotactic factor and of pivotal importance in the pathogenesis of psoriasis.15 Across ROI for both input functions there were no significant (p=0.221.00) differences (Mann-Whitney U test) in mean [11C]-(R)-PK11195 BPND in the brains of psoriasis patients compared with those of controls (Fig 1a). However, there was marked intragroup heterogeneity in [11C]-(R)-PK11195 BPND (Figs 1b, 1c) but this did not correlate with age, body habitus, disease severity (PASI, dermatology life quality index; DLQI) or duration.
Our findings may seem at odds with former studies.10,11 However, the clinical arm of the Drake study10 was small (n=4) and investigated an older population (mean age of subjects 63yrs., controls 64yrs. v 39.3yrs. and 33.6yrs. respectively in our study). It required patients to have at least three risk factors for stroke and/or established arterial disease and a CRP greater than 3 on two occasions. By contrast, only one of our patients had evidence of arterial disease (controlled hypertension) and the mean level of inflammatory markers in our patient group was much lower than those of Drake’s at-risk patients (CRP: 3.86 v 11.93, IL-6: 2.70 v. 10.55). Furthermore, in their study the peripheral insults were related to vascular/atherogenic inflammation and the study was unable to identify whether the origin of raised [11C](R)-PK11195 binding was in brain parenchyma or endothelial cells of the vasculature. Comparing the Hannestad study11 to ours, they used a different study population
This article is protected by copyright. All rights reserved.
Accepted Article
(non-human primates), a different radioligand ([11C]-PBR28) and an infective rather than an inflammatory peripheral insult. Our study suggests, in this population, that peripheral inflammation associated with chronic plaque psoriasis is not associated with neuroinflammation as evidenced by activated microglia in the brain. It may be, that in contrast to the infective or atherogenic insults reported above which are capable of inducing neuroinflammation, the relatively lower inflammatory burden associated with psoriasis is not sufficient to induce significant neuroinflammation or [11C]-(R)-PK11195 is not sensitive enough to detect the level of neuroinflammation associated with psoriasis. Alternatively, the brains of patients with psoriasis may be protected against the detrimental effects of systemic inflammation. Whether the blood-brain barrier confers this protection remains speculative. To our knowledge, this is the first in vivo study in man to look at the association between systemic and neuroinflammation in any peripheral autoimmune inflammatory condition and highlights a fascinating area for future research.
1 2
3
4 5 6 7 8
Griffiths CEM, Barker JNWN. Psoriasis: pathogenesis and clinical features of psoriasis. Lancet 2007; 370: 263-71. Dauden E, Castaneda S, Suarez C et al. Clinical practice guideline for an integrated approach to comorbidity in patients with psoriasis. Journal of the European Academy of Dermatology and Venereology : JEADV 2013; 27: 1387404. Dowlatshahi EA, Wakkee M, Arends LR et al. The prevalence and odds of depressive symptoms and clinical depression in psoriasis patients: a systematic review and meta-analysis. The Journal of investigative dermatology 2014; 134: 1542-51. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 2006; 27: 24-31. Thomson CA, McColl A, Cavanagh J et al. Peripheral inflammation is associated with remote global gene expression changes in the brain. J Neuroinflammation 2014; 11: 73. Cagnin A, Gerhard A, Banati RB. In vivo imaging of neuroinflammation. Eur Neuropsychopharmacol 2002; 12: 581-6. Gerhard A, Pavese N, Hotton G et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease. Neurobiol Dis 2006; 21: 404-12. Gerhard A, Schwarz J, Myers R et al. Evolution of microglial activation in patients after ischemic stroke: a [11C](R)-PK11195 PET study. Neuroimage 2005; 24: 591-5.
This article is protected by copyright. All rights reserved.
Accepted Article
9 10 11 12 13 14
15
Su Z, Herholz K, Gerhard A et al. [(1)(1)C]-(R)PK11195 tracer kinetics in the brain of glioma patients and a comparison of two referencing approaches. Eur J Nucl Med Mol Imaging 2013; 40: 1406-19. Drake C, Boutin H, Jones MS et al. Brain inflammation is induced by comorbidities and risk factors for stroke. Brain Behav Immun 2011; 25: 111322. Hannestad J, Gallezot JD, Schafbauer T et al. Endotoxin-induced systemic inflammation activates microglia: [(1)(1)C]PBR28 positron emission tomography in nonhuman primates. Neuroimage 2012; 63: 232-9. Garden GA, Moller T. Microglia biology in health and disease. J Neuroimmune Pharmacol 2006; 1: 127-37. Hammers A, Allom R, Koepp MJ et al. Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe. Hum Brain Mapp 2003; 19: 224-47. Singh N, Hopkins SJ, Hulme S et al. The effect of intravenous interleukin-1 receptor antagonist on inflammatory mediators in cerebrospinal fluid after subarachnoid haemorrhage: a phase II randomised controlled trial. J Neuroinflammation 2014; 11: 1. Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature 2007; 445: 866-73.
Figure Legend: Figure 1. Mean [11C]-(R)-PK11195 BPND across regions of interest. (a) There were no significant differences in mean [11C]-(R)-PK11195 binding potential (BPND) across regions of interest between groups. Cortical ROIs (bilateral, temporal, frontal, occipital and parietal lobes) were defined using individualised grey matter object maps and subcortical ROIs (bilateral thalamus and brainstem) and whole brain were defined using individualised unsegmented object maps. Data shown was derived using the cerebellar input function. For each region of interest, the median and interquartile ranges are shown. P values derived from Mann-Whitney U test. *whole brain excluding cerebellum, corpus callosum and brainstem.(b) [11C]-(R)-PK11195 BPND parametric maps superimposed on T1 weighted MRI scans for a psoriasis patient with low [11C]-(R)-PK11195 uptake (transverse, coronal and sagittal planes); represented by green circles on the dot plot. (c) Similar scans for a psoriasis patient with high [11C]-(R)-PK11195 uptake; represented by pink circles on the dot plot. Colour bars = [11C]-(R)-PK11195 binding potential (BPND).
This article is protected by copyright. All rights reserved.
Accepted Article
Table 1. Summary of subject characteristics and baseline psychometric and peripheral inflammatory marker data. Psoriasis group
Control group
(Mean ± S.D.)
(Mean ± S.D.)
Age (yrs.)
39.3 ± 9
33.6 ± 10
0.18
Gender (M : F)
11 : 1
7:5
-
BMI (Kg/M2)
27.8 ± 4.4
24.3 ± 3.5
0.06
Waist circumference (CM)
100.6 ± 11.3
84.5 ± 16.5
0.02*
HADS (anxiety)
2.00 ± 2.00
1.67 ± 1.37
1.00
HADS (depression)
0.92 ± 1.08
0
0.10
BDI
2.58 ± 5.68
0.67 ± 1.21
0.55
SRRS
127.25 ± 98.11
54.67 ± 24.52
0.12
PLSI
14.00 ± 10.99
-
-
DLQI
9.00 ± 8.36
-
-
PASI
17.7 ± 3.9
-
-
WCC (x 109/L)
6.87 ± 2.60
6.43 ± 1.44
0.89
TNC (x 109/L)
4.71 ± 2.40
4.10 ± 1.47
0.89
CRP (mg/L)
3.86 ± 5.53
2.75 ± 2.20
0.96
IL-6 (ng/L)
2.70 ± 2.21
1.86 ± 1.54
0.38
IL-8 (ng/L)
9.16 ± 3.34
4.13 ± 4.12
0.04*
Variable
P value
S.D., Standard deviation; ; M,male; F,Female; BMI, Body mass index; HADS, Hospital anxiety and depression scale; BDI, Beck depression inventory; SRRS, Social readjustment rating scale; PLSI, Psoriasis living stress index; DLQI, Dermatology life quality index; PASI, psoriasis area and severity index; WCC, total white cell count; TNC, total neutrophil count; CRP, C-reactive protein; IL-6, interleukin-6; IL-8, interleukin-8. P value derived using Mann-Whitney U test. *Significant result (P
