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Positron Emission Tomography (PET) Studies in Anxiety Disorders
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
2010 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
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.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis , 2010. , s. 83
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 590
Emneord [en]
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
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-129713ISBN: 978-91-554-7875-9 (tryckt)OAI: oai:DiVA.org:uu-129713DiVA, id: diva2:345561
Disputas
2010-10-08, Enghoffsalen, Ing. 50, Uppsala University Hospital, Akademiska Sjukhuset, Uppsala, 13:15 (svensk)
Opponent
Veileder
Tilgjengelig fra: 2010-09-16 Laget: 2010-08-24 Sist oppdatert: 2018-01-12
Delarbeid
1.
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2. Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo.
Åpne denne publikasjonen i ny fane eller vindu >>Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo.
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2005 (engelsk)Inngår i: Biol Psychiatry, ISSN 0006-3223, Vol. 58, nr 2, s. 132-42Artikkel i tidsskrift (Annet vitenskapelig) Published
Abstract [en]

BACKGROUND: Evidence is accumulating that pharmacological blockade of the substance P preferring neurokinin-1 (NK1) receptor reduces anxiety. This study compared the effects of an NK1 receptor antagonist, citalopram, and placebo on brain activity and anxiety symptoms in social phobia. METHODS: Thirty-six patients diagnosed with social phobia were treated for 6 weeks with the NK1 antagonist GR205171 (5 mg), citalopram (40 mg), or matching placebo under randomized double-blind conditions. GR205171 was administered for 4 weeks preceded by 2 weeks of placebo. Before and after treatment, regional cerebral blood flow (rCBF) during a stressful public speaking task was assessed using oxygen-15 positron emission tomography. Response rate was determined by the Clinical Global Impression Improvement Scale. RESULTS: Patients improved to a larger extent with the NK1 antagonist (41.7% responders) and citalopram (50% responders), compared with placebo (8.3% responders). Within- and between-group comparisons showed that symptom improvement was paralleled by a significantly reduced rCBF response to public speaking in the rhinal cortex, amygdala, and parahippocampal-hippocampal regions. The rCBF pattern was corroborated in follow-up analyses of responders and subjects showing large state anxiety reduction. CONCLUSIONS: Short-term administration of GR205171 and citalopram alleviated social anxiety. Neurokinin-1 antagonists may act like serotonin reuptake inhibitors by attenuating neural activity in a medial temporal lobe network.

Emneord
Adult, Anxiety/*drug therapy/physiopathology, Cerebrovascular Circulation/*drug effects, Citalopram/*pharmacology/therapeutic use, Comparative Study, Double-Blind Method, Female, Humans, Male, Phobic Disorders/*drug therapy/physiopathology, Piperidines/*pharmacology/therapeutic use, Positron-Emission Tomography, Receptors; Neurokinin-1/antagonists & inhibitors, Research Support; Non-U.S. Gov't, Serotonin Uptake Inhibitors/*pharmacology/therapeutic use, Temporal Lobe/blood supply/radionuclide imaging, Tetrazoles/*pharmacology/therapeutic use
Identifikatorer
urn:nbn:se:uu:diva-19636 (URN)16038684 (PubMedID)
Tilgjengelig fra: 2006-11-30 Laget: 2006-11-30 Sist oppdatert: 2011-01-12
3.
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4. Enhanced neurokinin 1 receptor availability in the amygdala in posttraumatic stress disorder
Åpne denne publikasjonen i ny fane eller vindu >>Enhanced neurokinin 1 receptor availability in the amygdala in posttraumatic stress disorder
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(engelsk)Manuskript (preprint) (Annet vitenskapelig)
Abstract [en]

Background: Posttraumatic stress disorder (PTSD) may result from experiencing severe distress, and is in part amygdala dependent. Animal studies demonstrate that stress and negative affect enhance the amygdala-release of the neuropeptide substance P (SP) which binds to the neurokinin 1 (NK1) receptor. This positron emission tomography (PET) study investigated if NK1 receptor availability in the amygdala of PTSD patients were different from healthy control subjects. Methods: Eleven male patients with DSM-IV defined PTSD and nine healthy male control subjects were PET scanned during 60 min at rest using the NK1 preferring tracer [11C]GR205171. Parametric Patlak images were generated and analyzed using statistical parametric mapping software. The effect of age was co-varied out because the amount of NK1 receptors decline with age. Results: PTSD patients had elevated uptake of [11C]GR205171 in the amygdala as compared to controls, also when anxiety differences were controlled for. Conclusions: We suggest that enhanced NK1 receptor availability could be a risk factor for developing PTSD rather than reflecting trauma induced alterations.

Emneord
PTSD; NK1 receptor; substance P; PET; amygdala; STAI-S
HSV kategori
Forskningsprogram
Neurovetenskap
Identifikatorer
urn:nbn:se:uu:diva-130093 (URN)
Tilgjengelig fra: 2010-08-31 Laget: 2010-08-31 Sist oppdatert: 2011-02-25bibliografisk kontrollert

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