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Michelgård, Åsa
Alternative names
Publications (10 of 19) Show all publications
Bhatt, D. L., Fox, K., Harrington, R. A., Leiter, L. A., Mehta, S. R., Simon, T., . . . Winder, E. (2019). Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study. Clinical Cardiology, 42(5), 498-505
Open this publication in new window or tab >>Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study
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2019 (English)In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 42, no 5, p. 498-505Article in journal (Refereed) Published
Abstract [en]

In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients >= 50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of >= 50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.

Keywords
antiplatelet therapy, clinical trials, diabetes mellitus, general clinical cardiology, adult, ischemic heart disease
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-387294 (URN)10.1002/clc.23164 (DOI)000468080800001 ()30788847 (PubMedID)
Funder
AstraZeneca
Available from: 2019-06-24 Created: 2019-06-24 Last updated: 2019-06-24Bibliographically approved
Palmquist, Å. M., Frick, A., Fernandez, M., Furmark, T., von Knorring, L., Åhs, F. & Fredrikson, M. (2014). Serotonin Transporter Binding in Posttraumatic Stress Disorder Measured with [11c]-DASB. Paper presented at 69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry, 2014, New York, NY. Biological Psychiatry, 75(9), 357S-357S
Open this publication in new window or tab >>Serotonin Transporter Binding in Posttraumatic Stress Disorder Measured with [11c]-DASB
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2014 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 75, no 9, p. 357S-357SArticle in journal, Meeting abstract (Other academic) Published
Keywords
5-HTT, PTSD, amygdala, anterior cingulate cortex, insula
National Category
Psychiatry Neurosciences
Identifiers
urn:nbn:se:uu:diva-228224 (URN)000334101802254 ()
Conference
69th Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry, 2014, New York, NY
Available from: 2014-07-10 Created: 2014-07-08 Last updated: 2018-01-11Bibliographically approved
Åhs, F., Michelgård Palmquist, Å., Pissiota, A., Appel, L., Frans, Ö., Liberzon, I., . . . Fredrikson, M. (2011). Arousal modulation of memory and amygdala-parahippocampal connectivity: A PET-psychophysiology study in specific phobia. Psychophysiology, 48(11), 1463-1469
Open this publication in new window or tab >>Arousal modulation of memory and amygdala-parahippocampal connectivity: A PET-psychophysiology study in specific phobia
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2011 (English)In: Psychophysiology, ISSN 0048-5772, E-ISSN 1469-8986, Vol. 48, no 11, p. 1463-1469Article in journal (Refereed) Published
Abstract [en]

Phobic fear is accompanied by intense bodily responses modulated by the amygdala. An amygdala moderated psychophysiological measure related to arousal is electrodermal activity. We evaluated the contributions of electrodermal activity to amygdala-parahippocampal regional cerebral blood flow (rCBF) during phobic memory encoding in subjects with spider or snake phobia. Recognition memory was increased for phobia-related slides and covaried with rCBF in the amygdala and the parahippocampal gyrus. The covariation between parahippocampal rCBF and recognition was related to electrodermal activity suggesting that parahippocampal memory processes were associated with sympathetic activity. Electrodermal activity further mediated the amygdala effect on parahippocampal activity. Memory encoding during phobic fear therefore seems contingent on amygdala's influence on arousal and parahippocampal activity.

Keywords
Anxiety, Learning/Memory, fMRI/PET/MRI, Electrodermal, Amygdala, Parahippocampal gyrus
National Category
Psychology Psychiatry
Identifiers
urn:nbn:se:uu:diva-161439 (URN)10.1111/j.1469-8986.2011.01231.x (DOI)000295961700001 ()21729104 (PubMedID)
Available from: 2011-11-16 Created: 2011-11-14 Last updated: 2017-12-08Bibliographically approved
Michelgård Palmquist, Å. (2010). Positron Emission Tomography (PET) Studies in Anxiety Disorders. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Positron Emission Tomography (PET) Studies in Anxiety Disorders
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Anxiety disorders are very common and the primary feature is abnormal or inappropriate anxiety. Fear and anxiety is often mediated by the amygdala, a brain structure rich in substance P (SP) and neurokinin 1 (NK1) receptors.

To learn more about how the human amygdala is modulated by fear and anxiety in event-triggered anxiety disorders and to investigate if the SP/NK1 receptor system is affected, regional cerebral blood flow (rCBF) ([15O]-water; Study I and II) and the SP/NK1 receptor system ([11C]GR205171; Study III and IV) were studied with positron emission tomography (PET).

In Study I we investigated the neural correlates of affective startle modulation in persons with specific phobia by measuring rCBF during exposure to fearful and non-fearful pictures, paired and unpaired with acoustic startle stimuli. Fear-potentiated startle was associated with activation of the affective part of the anterior cingulate cortex and the left amygdaloid–hippocampal area.

In Study II short-term drug treatment effects on rCBF in patients diagnosed with social phobia was evaluated, comparing the NK1 receptor antagonist GR205171 to the selective serotonin reuptake inhibitor citalopram and placebo. Social anxiety and neural activity in the medial temporal lobe including the amygdala was significantly reduced by both drugs but not placebo.

In Study III we investigated if activity in the SP/NK1 receptor system in the amygdala would be affected by fear provocation in individuals with specific snake or spider phobia. Fear provocation was associated with a decreased uptake of the NK1 antagonist [11C]GR205171 in the amygdala, possibly explained by an increase in endogenous SP release occupying the NK1 receptors.

Study IV was conducted to explore the resting state NK1 receptor availability in PTSD patients as compared to healthy controls. Increased resting state binding of the tracer [11C]GR205171 in the amygdala of patients with PTSD suggested an increased amount of available receptors.

In summary, fear and fear-potentiated startle modulates the human amygdala, possibly through the SP/NK1 receptor system.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. p. 83
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 590
Keywords
Positron emission tomography, PET, amygdala, fear, anxiety, anxiety disorders, specific phobia, social phobia, posttraumatic stress disorder, PTSD, regional cerebral blood flow, rCBF, substance P, SP, neurokinin 1 receptor, NK1, GR205171, STAI-S
National Category
Psychiatry Neurosciences Neurosciences Physiology Physiology Radiology, Nuclear Medicine and Medical Imaging Physiology Neurosciences
Identifiers
urn:nbn:se:uu:diva-129713 (URN)978-91-554-7875-9 (ISBN)
Public defence
2010-10-08, Enghoffsalen, Ing. 50, Uppsala University Hospital, Akademiska Sjukhuset, Uppsala, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2010-09-16 Created: 2010-08-24 Last updated: 2018-01-12
Faria, V., Åhs, F., Linnman, C., Pissiota, A., Palmqvist Michelgård, Å., Zancan, S., . . . Furmark, T. (2010). Pretreatment Anterior Cingulate Activity Predicts Amygdala Attenuation in Social Phobic Placebo Responders. In: Biol. Psychiatry 67, 34S-34S: (pp. 34S-34S 109).
Open this publication in new window or tab >>Pretreatment Anterior Cingulate Activity Predicts Amygdala Attenuation in Social Phobic Placebo Responders
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2010 (English)In: Biol. Psychiatry 67, 34S-34S, 2010, p. 34S-34S 109Conference paper, Published paper (Refereed)
Series
Biological Psychiatry, ISSN 0006-3223 ; 67
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-141500 (URN)
Note

Thursday abstracts

Available from: 2011-01-12 Created: 2011-01-12 Last updated: 2014-12-12Bibliographically approved
Appel, L., Michelgård, Å., Linnman, C., Fernandez, M., Furmark, T., Langström, B., . . . Fredrikson, M. (2009). Altered NK1-receptor availability in patients with post traumatic stress disorder. In: [Biological Psychiatry 2009, 65(8), Suppl. 1, 118S, no. 394]. Paper presented at Sixty-Fourth Annual Convention and Scientific Program (pp. 118S).
Open this publication in new window or tab >>Altered NK1-receptor availability in patients with post traumatic stress disorder
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2009 (English)In: [Biological Psychiatry 2009, 65(8), Suppl. 1, 118S, no. 394], 2009, p. 118S-Conference paper, Published paper (Refereed)
Abstract [en]

Background: Posttraumatic stress disorder (PTSD) is an anxiety disorder that can develop after one or more traumatic events causing extreme stress or grave physical harm. The neurokinin-1 (NK1) receptor is the primary receptor for substance P (SP); a neuropeptide suggested being involved in anxiety and depression. The present study investigated differences in NK1-receptor availability between PTSD patients and healthy controls, using positron emission tomography (PET). Methods: Eleven male refugee patients (age: 41±10) with DSM-IV defined PTSD and nine healthy male control subjects (age: 33±10) were investigated using the PET-tracer [11C]GR205171, supplied by Uppsala Imanet. GR205171 is a highly selective NK1-receptor antagonist. Scans were performed during 60 minutes in the resting state. Parametric images were generated using the graphical reference Patlak method assuming irreversible binding of [11C]GR205171 from 20-60 minutes and having cerebellum as reference region. Exploratory whole brain analyses were performed using the statistical parametric mapping (SPM2) software. Results: PTSD patients had lower [11C]GR205171 binding compared to controls, in frontal cortical clusters encompassing bilaterally insula and left Brodmann area 11, reflecting lower NK1-receptor availability. No areas were found in which PTSD patients had higher [11C]GR205171 binding. Conclusions: This is the first study reporting differences in NK1-receptor availability in PTSD patients relative to controls. A tentative conclusion is that PTSD patients have a down regulation of the NK1-receptor system, which could be either a risk factor or due to emotional trauma processing.

National Category
Psychiatry Psychology
Identifiers
urn:nbn:se:uu:diva-125878 (URN)10.1016/j.biopsych.2009.03.002 (DOI)
Conference
Sixty-Fourth Annual Convention and Scientific Program
Available from: 2010-05-28 Created: 2010-05-28 Last updated: 2011-01-11Bibliographically approved
Åhs, F., Michelgård, Å., Pissiota, A., Furmark, T., Appel, L. & Fredrikson, M. (2009). Bodily arousal gates amygdala-hippocampal interaction in phobic memory encoding. Biological Psychiatry, 65(8), 126S-126S
Open this publication in new window or tab >>Bodily arousal gates amygdala-hippocampal interaction in phobic memory encoding
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2009 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 65, no 8, p. 126S-126SArticle in journal, Meeting abstract (Other academic) Published
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-125879 (URN)
Available from: 2010-05-28 Created: 2010-05-28 Last updated: 2017-12-12Bibliographically approved
Furmark, T., Appel, L., Winqvist, I., Michelgård, Å., Åhs, F., Bani, M., . . . Fredrikson, M. (2009). Elevated uptake of [C-11] 5-hydroxy-tryptophan in the amygdala in patients with social anxiety disorder: a PET study. In: Biol. Psychiatry 65, 126S-127S: . Paper presented at 64th Annual Scientific Convention and Meeting of the Society of Biological Psychiatry, May 14-16 2009, Vancouver, Canada (pp. 421).
Open this publication in new window or tab >>Elevated uptake of [C-11] 5-hydroxy-tryptophan in the amygdala in patients with social anxiety disorder: a PET study
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2009 (English)In: Biol. Psychiatry 65, 126S-127S, 2009, p. 421-Conference paper, Published paper (Other academic)
Abstract [en]

Background: Social anxiety disorder (SAD) is associated with amygdala hyperresponsivity and imbalances in serotonergic neurotransmission. We have previously noted altered uptake of carbon-11 labelled 5-hydroxytryptophan (5-HTP) in a small sample of patients with SAD, suggesting deficiencies in presynaptic serotonin synthesis. In the present study, positron emission tomography (PET) was used to assess uptake of [11C]5-HTP in a larger sample of patients with SAD compared with age and sex-matched healthy controls. Methods: PET-data were available for 17 patients (8 females, age 33±8 years) diagnosed with SAD and for 17 healthy controls (9 females, age 35±10 years). Accumulation of the [11C]5-HTP tracer was assessed at Uppsala Imanet during 60 minutes in the resting state. Parametric images were generated using the graphical reference Patlak method assuming irreversible trapping of [11C]5-HTP from 11-60 minutes. Cerebellum was selected as reference region after correction for the decarboxylation rate of [11C]5-HTP. Exploratory and amygdala focused analyses were performed using statistical parametric mapping (SPM2). Results: Patients with SAD had significantly higher [11C]5-HTP uptake than controls in several regions including the superior, medial and inferior frontal gyrus, anterior cingulate cortex, hippocampus and lentiform nucleus, all in the left hemisphere. Region of interest analyses also revealed significantly higher uptake (SAD > controls) in the left (x-28 y-4 z-12; T=3.16) and right (x24 y1 z-15; T=2.82) amygdala (p<0.05 corrected). Conclusions: Higher [11C]5-HTP uptake, suggesting an elevated serotonin synthesis rate, was noted in patients with SAD compared to healthy controls predominantly in frontal and temporal regions including the amygdala.

National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-125882 (URN)
Conference
64th Annual Scientific Convention and Meeting of the Society of Biological Psychiatry, May 14-16 2009, Vancouver, Canada
Note

Meeting abstract

Available from: 2010-05-28 Created: 2010-05-28 Last updated: 2018-06-04Bibliographically approved
Linnman, C., Åhs, F., Faria, V., Michelgård, Å., Appel, L., Bani, M., . . . Furmark, T. (2008). A differential cortisol response to stress after treatment of social phobia with a neurokinin-1 receptor antagonist o SSRIs.. Biological Psychiatry, 553
Open this publication in new window or tab >>A differential cortisol response to stress after treatment of social phobia with a neurokinin-1 receptor antagonist o SSRIs.
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2008 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, p. 553-Article in journal (Other academic) Published
National Category
Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:uu:diva-125874 (URN)
Note

Biol. Psychiatry 63, 177S-177S

Available from: 2010-05-28 Created: 2010-05-28 Last updated: 2017-12-12Bibliographically approved
Åhs, F., Pissiota, A., Michelgård, Å., Appel, L., Furmark, T. & Fredrikson, M. (2008). Functional connectivity of the amygdala in specific phobia. Biological Psychiatry, 63(7), 169S-169S
Open this publication in new window or tab >>Functional connectivity of the amygdala in specific phobia
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2008 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 63, no 7, p. 169S-169SArticle in journal, Meeting abstract (Other academic) Published
National Category
Psychology
Research subject
Psychology
Identifiers
urn:nbn:se:uu:diva-125870 (URN)
Available from: 2010-05-28 Created: 2010-05-28 Last updated: 2017-12-12Bibliographically approved
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