1.
Michelgård Palmquist, Åsa, 1973-
(författare)
Positron Emission Tomography (PET) Studies in Anxiety Disorders
2010
Doktorsavhandling (övrigt vetenskapligt/konstnärligt) abstract
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.
2.
Fredrikson, Mats, et al.
(författare)
Different genetic factors underlie fear conditioning and episodic memory
2015
Ingår i: Psychiatric Genetics. - 0955-8829 .- 1473-5873. ; 25:4, s. 155-162
Tidskriftsartikel (refereegranskat) abstract
ObjectiveFear conditioning seems to account for the acquisition of post-traumatic stress disorder, whereas conscious recall of events in aftermath of trauma reflects episodic memory. Studies show that both fear conditioning and episodic memory are heritable, but no study has evaluated whether they reflect common or separate genetic factors. To this end, we studied episodic memory and fear conditioning in 173 healthy twin pairs using visual stimuli predicting unconditioned electric shocks.MethodsFear conditioning acquisition and extinction was determined using conditioned visual stimuli predicting unconditioned mild electric shocks, whereas electrodermal activity served as the fear learning index. Episodic memory was evaluated using cued recall of pictorial stimuli unrelated to conditioning. We used multivariate structural equation modeling to jointly analyze memory performance and acquisition as well as extinction of fear conditioning.ResultsBest-fit twin models estimated moderate genetic loadings for conditioning and memory measures, with no genetic covariation between them.ConclusionIndividual differences in fear conditioning and episodic memory reflect distinct genetically influenced processes, suggesting that the genetic risk for learning-induced anxiety disorders includes at least two memory-related genetic factors. These findings are consistent with the facts that the two separate learning forms are distant in their evolutionary development, involve different brain mechanisms, and support that genetically independent memory systems are pivotal in the development and maintenance of syndromes related to fear learning.
3.
Bergman, Olle, 1978, et al.
(författare)
Association between amygdala reactivity and a dopamine transporter gene polymorphism.
2014
Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 4
Tidskriftsartikel (refereegranskat) abstract
Essential for detection of relevant external stimuli and for fear processing, the amygdala is under modulatory influence of dopamine (DA). The DA transporter (DAT) is of fundamental importance for the regulation of DA transmission by mediating reuptake inactivation of extracellular DA. This study examined if a common functional variable number tandem repeat polymorphism in the 3' untranslated region of the DAT gene (SLC6A3) influences amygdala function during the processing of aversive emotional stimuli. Amygdala reactivity was examined by comparing regional cerebral blood flow, measured with positron emission tomography and [(15)O]water, during exposure to angry and neutral faces, respectively, in a Swedish sample comprising 32 patients with social anxiety disorder and 17 healthy volunteers. In a separate US sample, comprising 85 healthy volunteers studied with blood oxygen level-dependent functional magnetic resonance imaging, amygdala reactivity was assessed by comparing the activity during exposure to threatening faces and neutral geometric shapes, respectively. In both the Swedish and the US sample, 9-repeat carriers displayed higher amygdala reactivity than 10-repeat homozygotes. The results suggest that this polymorphism contributes to individual variability in amygdala reactivity.
4.
Ahs, Fredrik, et al.
(författare)
High-frequency heart rate variability and cortico-striatal activity in men and women with social phobia
2009
Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 47:3, s. 815-820
Tidskriftsartikel (refereegranskat) abstract
Identifying brain systems that regulate or modulate autonomic nervous system functions may identify pathways through which psychosocial factors can influence health and disease. Reduced high-frequency heart rate variability (HF-HRV) characterizes anxiety disordered patients and is predictive of adverse myocardial events. Sex differences in the prevalence of anxiety disorders and cardiac diseases implicate the possibility of sex specific neural regulation of HF-HRV. We investigated the correlation between HF-HRV and regional cerebral blood flow (rCBF) in 28 subjects (15 women) with social phobia undergoing a stressful public speaking task. Regional CBF was measured with [(15)O] water positron emission tomography. Stress induced rCBF correlated positively with HF-HRV in the right supra genual anterior cingulate cortex Brodmann's area (BA) 32, the right head of the caudate nucleus and bilaterally in the medial prefrontal cortex (BA10), extending into the dorsolateral prefrontal cortex (BA46) in the left hemisphere. Men showed larger positive co-variation in the caudate than women. These findings underscore the importance of the emotional division of the anterior cingulate cortex, the prefrontal cortex and the striatum in cardiovagal activity. The study replicates and extends results from published functional neuroimaging studies on cardioregulatory or modulatory areas in healthy subjects to men and women with social phobia. Moreover, caudate functions, possibly related to dopaminergic neurotransmission, have sexually dimorphic effects on vagal modulation of the heart.
5.
6.
Bas-Hoogendam, Janna Marie, et al.
(författare)
Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder
2017
Ingår i: NeuroImage. - : Elsevier BV. - 2213-1582. ; 16, s. 678-688
Tidskriftsartikel (refereegranskat) abstract
Social anxiety disorder (SAD) is a prevalent and disabling mental disorder, associated with significant psychiatric co-morbidity. Previous research on structural brain alterations associated with SAD has yielded inconsistent results concerning the direction of the changes in gray matter (GM) in various brain regions, as well as on the relationship between brain structure and SAD-symptomatology. These heterogeneous findings are possibly due to limited sample sizes. Multi-site imaging offers new opportunities to investigate SAD-related alterations in brain structure in larger samples.An international multi-center mega-analysis on the largest database of SAD structural T1-weighted 3T MRI scans to date was performed to compare GM volume of SAD-patients (n = 174) and healthy control (HC)-participants (n = 213) using voxel-based morphometry. A hypothesis-driven region of interest (ROI) approach was used, focusing on the basal ganglia, the amygdala-hippocampal complex, the prefrontal cortex, and the parietal cortex. SAD-patients had larger GM volume in the dorsal striatum when compared to HC-participants. This increase correlated positively with the severity of self-reported social anxiety symptoms. No SAD-related differences in GM volume were present in the other ROIs. Thereby, the results of this mega-analysis suggest a role for the dorsal striatum in SAD, but previously reported SAD-related changes in GM in the amygdala, hippocampus, precuneus, prefrontal cortex and parietal regions were not replicated. Our findings emphasize the importance of large sample imaging studies and the need for meta-analyses like those performed by the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium.
7.
Björkstrand, Johannes, et al.
(författare)
Decrease in amygdala activity during repeated exposure to spider images predicts avoidance behavior in spider fearful individuals.
2020
Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 10:1
Tidskriftsartikel (refereegranskat) abstract
Spider phobia is characterized by exaggerated fear of situations where spiders could be present, resulting in avoidance of such situations and compromised quality of life. An important component in psychological treatment of spider phobia is exposure to phobic situations that reduces avoidance behaviors. At the neural level, amygdala responses to phobic material are elevated, but normalizes following exposure treatment. To what extent amygdala activity decreases during a session of repeated phobic stimulation, and whether activity decrease is related to subsequent avoidance is not well studied. We hypothesized reduced amygdala activity during the course of repeated exposure to spider pictures, and that the degree of reduction would predict subsequent avoidance of spider pictures. To test our hypothesis, functional magnetic resonance imaging was performed in 45 individuals with spider fear during repeated exposure to spider pictures. Results showed that repeated exposure to spider stimuli attenuated amygdala reactivity and individual differences in activity reductions predicted subsequent avoidance behavior to spider pictures in an incentive-conflict task, with larger attenuations predicting less avoidance. At 6-month follow up, initial reductions in amygdala activation still predicted avoidance. This result demonstrates that reduction in amygdala responses is related to clinically meaningful outcomes in human anxiety, and suggests that within-session reductions in amygdala responses could be an important mechanism explaining the clinical effects of exposure therapy.
8.
Björkstrand, Johannes, et al.
(författare)
Disrupting Reconsolidation Attenuates Long-Term Fear Memory in the Human Amygdala and Facilitates Approach Behavior
2016
Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 26:19, s. 2690-95
Tidskriftsartikel (refereegranskat) abstract
Memories become labile and malleable to modification when recalled [1]. Fear-conditioning experiments in both rodents and humans indicate that amygdala-localized short-term fear memories can be attenuated by disruption of their reconsolidation with extinction training soon after memory activation [2-7]. However, this may not be true for natural long-term fears. Studies in rodents indicate that although it is possible to disrupt the reconsolidation of older memories [8-11], they appear to be more resistant [1, 3, 9, 12, 13]. In humans, 1-week-old conditioned fear memories have been attenuated by behaviorally induced disruption of reconsolidation [14], but it remains to be seen whether this is possible for naturally occurring long-term fears and whether the underlying neural mechanisms are similar to those found in experimental fear-conditioning paradigms. Using functional brain imaging in individuals with a lifelong fear of spiders, we show that fear memory activation followed by repeated exposure to feared cues after 10 min, which disrupts reconsolidation, attenuates activity in the basolateral amygdala at re-exposure 24 hr later. In contrast, repeated exposure 6 hr after fear memory activation, which allows for reconsolidation, did not attenuate amygdala activity. Disrupted, but not undisrupted, reconsolidation facilitated approach behavior to feared cues, and approach behavior was inversely related to amygdala activity during re-exposure. We conclude that memory activation immediately preceding exposure attenuates the neural and behavioral expression of decades-old fear memories and that, similar to experimentally induced fear memories, the basolateral amygdala is crucially involved in this process.
9.
10.
Danfors, Torsten, et al.
(författare)
Increased neurokinin-1 receptor availability in temporal lobe epilepsy : A positron emission tomography study using [(11)C]GR205171
2011
Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211 .- 1872-6844. ; 97:1-2, s. 183-189
Tidskriftsartikel (refereegranskat) abstract
PURPOSE: Activation of the neurokinin-1 (NK1) receptor by neuropeptide substance P (SP) induces and maintains epileptic activity in various experimental models of epilepsy. The primary objective of this study was to investigate whether neurobiological changes linked to NK1-SP receptor system are associated with hyperexcitability in patients with temporal lobe epilepsy (TLE). A secondary objective was to investigate the relationship between seizure frequency and NK1 receptor availability. METHODS: A positron emission tomography study was conducted with the selective NK1 receptor antagonist [(11)C]GR205171 in nine patients with TLE and 18 healthy control participants. Parametric PET images were generated using the Patlak graphical method, with cerebellum as reference region. Data analyses including group comparisons were performed using statistical parametric mapping. RESULTS: Patients with TLE showed increased NK1 receptor availability in both hemispheres with the most pronounced increase in anterior cingulate gyrus ipsilateral to seizure onset. A positive correlation between NK1 receptor availability and seizure frequency was observed in the medial temporal lobe and in the lentiform nucleus ipsilateral to the seizure onset. CONCLUSION: Our results suggest that there is an intrinsic network using the NK1-SP receptor system for synaptic transmission and epileptiform activity in TLE.
