| 1. |
- Appel, Lieuwe, et al.
(författare)
-
Altered NK1-receptor availability in patients with post traumatic stress disorder
- 2009
-
Ingår i: [Biological Psychiatry 2009, 65(8), Suppl. 1, 118S, no. 394]. - : Elsevier BV. ; , s. 118S-
-
Konferensbidrag (refereegranskat)abstract
- 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.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Frick, Andreas, et al.
(författare)
-
Overlapping expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder : a multi-tracer PET study
- 2016
-
Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 21:10, s. 1400-7
-
Tidskriftsartikel (refereegranskat)abstract
- The brain serotonergic system is colocalized and interacts with the neuropeptidergic substance P/neurokinin-1 (SP/NK1) system. Both these neurochemical systems have independently been implicated in stress and anxiety, but interactions between them might be crucial for human anxiety conditions. Here, we examined the serotonin and substance P/neurokinin-1 (SP/NK1) systems individually as well as their overlapping expression in 16 patients with posttraumatic stress disorder (PTSD) and 16 healthy controls. Participants were imaged with the highly selective radiotracers [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB) and [(11)C]GR205171 assessing serotonin transporter (SERT) and NK1 receptor availability, respectively. Voxel-wise analyses in the amygdala, our a priori-defined region of interest, revealed increased number of NK1 receptors, but not SERT in the PTSD group. Symptom severity, as indexed by the Clinician-administered PTSD Scale, was negatively related to SERT availability in the amygdala, and NK1 receptor levels moderated this relationship. Exploratory, voxel-wise whole-brain analyses revealed increased SERT availability in the precentral gyrus and posterior cingulate cortex of PTSD patients. Patients, relative to controls, displayed lower degree of overlapping expression between SERT and NK1 receptors in the putamen, thalamus, insula and lateral orbitofrontal gyrus, lower overlap being associated with higher PTSD symptom severity. Expression overlap also explained more of the symptomatology than did either system individually, underscoring the importance of taking interactions between the neurochemical systems into account. Thus, our results suggest that aberrant serotonergic-SP/NK1 couplings contribute to the pathophysiology of PTSD and, consequently, that normalization of these couplings may be therapeutically important.
|
|
| 5. |
- Michelgård Palmquist, Åsa, 1973-, et al.
(författare)
-
Enhanced neurokinin 1 receptor availability in the amygdala in posttraumatic stress disorder
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- 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.
|
|
| 6. |
|
|
| 7. |
- Motilla Hoppe, Johanna, et al.
(författare)
-
Association between amygdala neurokinin-1 receptor availability and anxiety-related personality traits
- 2018
-
Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Animal studies indicate that substance P (SP) and its preferred neurokinin-1 (NK1) receptor modulate stress and anxiety-related behavior. Alterations in the SP-NK1 system have also been observed in human anxiety disorders, yet little is known about the relation between this system and individual differences in personality traits associated with anxiety propensity and approach-avoidance behavior, including trait anxiety, neuroticism, and extraversion. Exploring this relation could provide important insights into the neurobiological underpinnings of human anxiety and the etiology of anxiety disorders, as anxious traits are associated with increased susceptibility to develop psychopathological conditions. Here we examined the relationship between central NK1 receptor availability and selfrated measures of trait anxiety, neuroticism, and extraversion. The amygdala was chosen as the primary region of interest since this structure has been suggested to mediate the effect of the SP-NK1 system on anxiety. Anxious traits and NK1 receptor availability, determined with positron emission tomography and the radiotracer [C-11]GR205171, were measured in 17 healthy individuals. Voxel-wise analyses showed a significant positive correlation between bilateral amygdala NK1 receptor availability and trait anxiety, and a trend in similar direction was observed for neuroticism. Conversely, extraversion was found to be negatively associated with amygdala NK1 receptor availability. Extraversion also correlated negatively with the NK1 measure in the cuneus/precuneus and fusiform gyrus according to exploratory whole-brain analyses. In conclusion, our findings indicate that amygdala NK1 receptor availability is associated with anxiety-related personality traits in healthy subjects, consistent with a modulatory role for the SP-NK1 system in human anxiety.
|
|
| 8. |
|
|
