| 1. |
- Björkstrand, Johannes, et al.
(författare)
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Decrease in amygdala activity during repeated exposure to spider images predicts avoidance behavior in spider fearful individuals.
- 2020
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 10:1
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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.
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| 2. |
- Costache, Madalina Elena, et al.
(författare)
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Higher- and lower-order personality traits and cluster subtypes in social anxiety disorder
- 2020
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Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- Social anxiety disorder (SAD) can come in different forms, presenting problems for diagnostic classification. Here, we examined personality traits in a large sample of patients (N = 265) diagnosed with SAD in comparison to healthy controls (N = 164) by use of the Revised NEO Personality Inventory (NEO-PI-R) and Karolinska Scales of Personality (KSP). In addition, we identified subtypes of SAD based on cluster analysis of the NEO-PI-R Big Five personality dimensions. Significant group differences in personality traits between patients and controls were noted on all Big Five dimensions except agreeableness. Group differences were further noted on most lower-order facets of NEO-PI-R, and nearly all KSP variables. A logistic regression analysis showed, however, that only neuroticism and extraversion remained significant independent predictors of patient/control group when controlling for the effects of the other Big Five dimensions. Also, only neuroticism and extraversion yielded large effect sizes when SAD patients were compared to Swedish normative data for the NEO-PI-R. A two-step cluster analysis resulted in three separate clusters labelled Prototypical (33%), Introvert-Conscientious (29%), and Instable-Open (38%) SAD. Individuals in the Prototypical cluster deviated most on the Big Five dimensions and they were at the most severe end in profile analyses of social anxiety, self-rated fear during public speaking, trait anxiety, and anxiety-related KSP variables. While additional studies are needed to determine if personality subtypes in SAD differ in etiological and treatment-related factors, the present results demonstrate considerable personality heterogeneity in socially anxious individuals, further underscoring that SAD is a multidimensional disorder.
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| 3. |
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| 4. |
- Frick, Andreas, Docent, et al.
(författare)
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Neuroimaging, genetic, clinical, and demographic predictors of treatment response in patients with social anxiety disorder
- 2020
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 261, s. 230-237
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Tidskriftsartikel (refereegranskat)abstract
- Background: Correct prediction of treatment response is a central goal of precision psychiatry. Here, we tested the predictive accuracy of a variety of pre-treatment patient characteristics, including clinical, demographic, molecular genetic, and neuroimaging markers, for treatment response in patients with social anxiety disorder (SAD). Methods: Forty-seven SAD patients (mean±SD age 33.9 ± 9.4 years, 24 women) were randomized and commenced 9 weeks’ Internet-delivered cognitive behavior therapy (CBT) combined either with the selective serotonin reuptake inhibitor (SSRI) escitalopram (20 mg daily [10 mg first week], SSRI+CBT, n = 24) or placebo (placebo+CBT, n = 23). Treatment responders were defined from the Clinical Global Impression-Improvement scale (CGI-I ≤ 2). Before treatment, patients underwent functional magnetic resonance imaging and the Multi-Source Interference Task taxing cognitive interference. Support vector machines (SVMs) were trained to separate responders from nonresponders based on pre-treatment neural reactivity in the dorsal anterior cingulate cortex (dACC), amygdala, and occipital cortex, as well as molecular genetic, demographic, and clinical data. SVM models were tested using leave-one-subject-out cross-validation. Results: The best model separated treatment responders (n = 24) from nonresponders based on pre-treatment dACC reactivity (83% accuracy, P = 0.001). Responders had greater pre-treatment dACC reactivity than nonresponders especially in the SSRI+CBT group. No other variable was associated with clinical response or added predictive accuracy to the dACC SVM model. Limitations: Small sample size, especially for genetic analyses. No replication or validation samples were available. Conclusions: The findings demonstrate that treatment outcome predictions based on neural cingulate activity, at the individual level, outperform genetic, demographic, and clinical variables for medication-assisted Internet-delivered CBT, supporting the use of neuroimaging in precision psychiatry.
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| 5. |
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| 6. |
- Gil-Paterna, Patricia, et al.
(författare)
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Imaging the cerebellum in post-traumatic stress and anxiety disorders : a mini-review
- 2023
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Ingår i: Frontiers in Systems Neuroscience. - : Frontiers Media S.A.. - 1662-5137. ; 17
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Forskningsöversikt (refereegranskat)abstract
- Post-traumatic stress disorder (PTSD) and anxiety disorders are among the most prevalent psychiatric conditions worldwide sharing many clinical manifestations and, most likely, neural mechanisms as suggested by neuroimaging research. While the so-called fear circuitry and traditional limbic structures of the brain, particularly the amygdala, have been extensively studied in sufferers of these disorders, the cerebellum has been relatively underexplored. The aim of this paper was to present a mini-review of functional (task-activity or resting-state connectivity) and structural (gray matter volume) results on the cerebellum as reported in magnetic resonance imaging studies of patients with PTSD or anxiety disorders (49 selected studies in 1,494 patients). While mixed results were noted overall, e.g., regarding the direction of effects and anatomical localization, cerebellar structures like the vermis seem to be highly involved. Still, the neurofunctional and structural alterations reported for the cerebellum in excessive anxiety and trauma are complex, and in need of further evaluation.
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| 7. |
- Groenewold, Nynke A., et al.
(författare)
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Volume of subcortical brain regions in social anxiety disorder : mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group
- 2023
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 28:3, s. 1079-1089
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Tidskriftsartikel (refereegranskat)abstract
- There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE < 0.001; right: d = −0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.
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| 8. |
- Hjorth, Olof, et al.
(författare)
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Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder : a randomized clinical trial
- 2021
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- It has been extensively debated whether selective serotonin reuptake inhibitors (SSRIs) are more efficacious than placebo in affective disorders, and it is not fully understood how SSRIs exert their beneficial effects. Along with serotonin transporter blockade, altered dopamine signaling and psychological factors may contribute. In this randomized clinical trial of participants with social anxiety disorder (SAD) we investigated how manipulation of verbally-induced expectancies, vital for placebo response, affect brain monoamine transporters and symptom improvement during SSRI treatment. Twenty-seven participants with SAD (17 men, 10 women), were randomized, to 9 weeks of overt or covert treatment with escitalopram 20 mg. The overt group received correct treatment information whereas the covert group was treated deceptively with escitalopram, described as an active placebo in a cover story. Before and after treatment, patients underwent positron emission tomography (PET) assessments with the [C-11]DASB and [C-11]PE2I radiotracers, probing brain serotonin (SERT) and dopamine (DAT) transporters. SAD symptoms were measured by the Liebowitz Social Anxiety Scale. Overt was superior to covert SSRI treatment, resulting in almost a fourfold higher rate of responders. PET results showed that SERT occupancy after treatment was unrelated to anxiety reduction and equally high in both groups. In contrast, DAT binding decreased in the right putamen, pallidum, and the left thalamus with overt SSRI treatment, and increased with covert treatment, resulting in significant group differences. DAT binding potential changes in these regions correlated negatively with symptom improvement. Findings support that the anxiolytic effects of SSRIs involve psychological factors contingent on dopaminergic neurotransmission while serotonin transporter blockade alone is insufficient for clinical response.
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| 9. |
- Hjorth, Olof, et al.
(författare)
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Expression and co-expression of serotonin and dopamine transporters in social anxiety disorder : a multitracer positron emission tomography study
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:8, s. 3970-3979
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Tidskriftsartikel (refereegranskat)abstract
- Serotonin and dopamine are putatively involved in the etiology and treatment of anxiety disorders, but positron emission tomography (PET) studies probing the two neurotransmitters in the same individuals are lacking. The aim of this multitracer PET study was to evaluate the regional expression and co-expression of the transporter proteins for serotonin (SERT) and dopamine (DAT) in patients with social anxiety disorder (SAD). Voxel-wise binding potentials (BPND) for SERT and DAT were determined in 27 patients with SAD and 43 age- and sex-matched healthy controls, using the radioligands [11C]DASB (3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile) and [11C]PE2I (N-(3-iodopro-2E-enyl)-2beta-carbomethoxy-3beta-(4'-methylphenyl)nortropane). Results showed that, within transmitter systems, SAD patients exhibited higher SERT binding in the nucleus accumbens while DAT availability in the amygdala, hippocampus, and putamen correlated positively with symptom severity. At a more lenient statistical threshold, SERT and DAT BPND were also higher in other striatal and limbic regions in patients, and correlated with symptom severity, whereas no brain region showed higher binding in healthy controls. Moreover, SERT/DAT co-expression was significantly higher in SAD patients in the amygdala, nucleus accumbens, caudate, putamen, and posterior ventral thalamus, while lower co-expression was noted in the dorsomedial thalamus. Follow-up logistic regression analysis confirmed that SAD diagnosis was significantly predicted by the statistical interaction between SERT and DAT availability, in the amygdala, putamen, and dorsomedial thalamus. Thus, SAD was associated with mainly increased expression and co-expression of the transporters for serotonin and dopamine in fear and reward-related brain regions. Resultant monoamine dysregulation may underlie SAD symptomatology and constitute a target for treatment.
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| 10. |
- Hjorth, Olof
(författare)
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Imaging serotonin and dopamine transporters in social anxiety disorder : Characterization, treatment and expectancy effects
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The monoamines serotonin and dopamine are likely to be involved in the pathophysiology of social anxiety and other affective disorders, but their respective contributions and putative interactions in the causes and cures of these disorders are still not well understood. It is also largely unknown if and how expectations of treatment success affect brain neurochemistry and neural activations, and if expectations interact with antidepressants like selective serotonin reuptake inhibitors (SSRIs). In this thesis some of these issues were addressed by use of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Using the highly selective radiotracers [11C]DASB and [11C]PE2I to characterize the availability of serotonin (SERT) and dopamine (DAT) transporter proteins, study I compared non-displaceable binding potentials (BPND), probing the transporters, between patients with social anxiety disorder and healthy controls. Increased SERT binding was observed in the reward related region nucleus accumbens (NAcc), in the social anxiety group. Moreover, increased DAT binding was associated with severity of the disorder and social anxiety was also associated with higher SERT-DAT co-expression in fear- and reward-related areas, including the amygdala and NAcc. Study II showed that verbal instructions regarding expected treatment efficacy strongly affected the clinical outcome of SSRI-treatment. Overt treatment, when patients with social anxiety disorder were correctly informed, was vastly superior to covert SSRI treatment, when patients expected an ineffective placebo. Groups were also differentiated on objective brain activity measures. Study III further demonstrated different SERT and DAT binding changes in limbic and striatal areas with overt as compared to covert SSRI-treatment. Decreased DAT BPND in the striatum, as assessed with PET, correlated with improvement in the overt group, suggesting increased dopaminergic signalling. Study IV compared treatment-induced changes in SERT and DAT binding after cognitive-behavior therapy (CBT) combined with an SSRI or placebo in patients with social anxiety disorder. Both groups showed initial co-expression similar to study I. The SSRI+CBT and placebo+CBT combinations yielded dissimilar transporter change patterns. Higher SERT occupancy in the NAcc correlated with reduced symptoms and this relationship was moderated by the change in DAT BPND. The results of this thesis support that functional interactions between serotonin and dopamine modulate social anxiety symptomatology and are important brain targets for successful treatment. Further it demonstrates that the treatment success of SSRIs in social anxiety disorder depends on how the treatment is presented. These results can be informative for the practice of clinicians, but also highlights an ethical dilemma because a large portion of the total treatment effects is elicited by processes within the patient itself.
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