| 1. |
- Bergman, Olle, 1978, et al.
(author)
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Association between amygdala reactivity and a dopamine transporter gene polymorphism.
- 2014
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In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 4
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Journal article (peer-reviewed)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.
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| 2. |
- Bas-Hoogendam, Janna Marie, et al.
(author)
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Voxel-based morphometry multi-center mega-analysis of brain structure in social anxiety disorder
- 2017
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In: NeuroImage. - : Elsevier BV. - 2213-1582. ; 16, s. 678-688
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Journal article (peer-reviewed)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.
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| 3. |
- Olofsdotter, Susanne, et al.
(author)
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Anxiety disorders among adolescents referred to general psychiatry for multiple causes : clinical presentation, prevalence, and comorbidity
- 2016
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In: Scandinavian Journal of Child and Adolescent Psychiatry and Psychology. - : Walter de Gruyter GmbH. - 2245-8875. ; 4:2, s. 55-64
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Journal article (peer-reviewed)abstract
- Background: Reports of anxiety disorder characteristics among youth in clinical settings typically include descriptions of patients who have been specifically referred for anxiety treatment. At odds with a large body of evidence which demonstrates these disorders to be most common among young people, prevalence studies in samples referred to general psychiatry for multiple causes are scarce and report highly discrepant estimates.Methods: For this study and regardless of their presenting symptoms, 125 adolescents (57.6% girls) between the ages of 12 and 18 years who were consecutively referred to two child and adolescent general psychiatry clinics in Sweden were assessed for anxiety disorders and comorbidity using the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Self-ratings of anxiety symptoms and difficulties with family, school, friends, sleep, and body aches were also obtained.Results: At least one anxiety disorder was found in 46% of participants. Among anxious adolescents, homotypic comorbidity (concurrent anxiety) was observed in 43%, and heterotypic comorbidity (concurrent non-anxiety psychiatric disorders) was observed in 91%. No comorbidity was observed in 5%. Trauma, ache, and difficulties making friends were more common among anxious adolescents as compared with psychiatrically referred adolescents without anxiety.Conclusions: The finding that only 21% of adolescents diagnosed with anxiety disorders were referred for anxiety further supports the routine use of standardized and structured instruments—irrespective of referral cause—to improve both precision and detection rates in the clinical setting. Comprehensive assessments are of utmost importance to fully address the complexity of the symptoms in this patient group.
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| 4. |
- Ahs, Fredrik, et al.
(author)
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High-frequency heart rate variability and cortico-striatal activity in men and women with social phobia
- 2009
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In: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 47:3, s. 815-820
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Journal article (peer-reviewed)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.
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| 5. |
- Åhs, Fredrik, 1972-, et al.
(author)
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Disentangling the web of fear : amygdala reactivity and functional connectivity in spider and snake phobia
- 2009
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In: Psychiatry Research. - : Elsevier BV. - 0925-4927 .- 1872-7506 .- 0165-1781 .- 1872-7123. ; 172:2, s. 103-108
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Journal article (peer-reviewed)abstract
- The objective was to study effects of fear on brain activity, functional connectivity and brain-behavior relationships during symptom provocation in subjects with specific phobia. Positron emission tomography (PET) and (15)O water was used to measure regional cerebral blood flow (rCBF) in 16 women phobic of either snakes or spiders but not both. Subjects watched pictures of snakes and spiders serving either as phobic or fear-relevant, but non-phobic, control stimuli depending on phobia type. Presentation of phobic as compared with non-phobic cues was associated with increased activation of the right amygdala and cerebellum as well as the left visual cortex and circumscribed frontal areas. Activity decreased in the prefrontal, orbitofrontal and ventromedial cortices as well as in the primary somatosensory cortex and auditory cortices. Furthermore, amygdala activation correlated positively with the subjective experience of distress. Connectivity analyses of activity in the phobic state revealed increased functional couplings between voxels in the right amygdala and the periamygdaloid area, fusiform gyrus and motor cortex. During non-phobic stimulation, prefrontal activity correlated negatively with amygdala rCBF, suggesting a phobia-related functional decoupling. These results suggest that visually elicited phobic reactions activate object recognition areas and deactivate prefrontal areas involved in cognitive control over emotion-triggering areas like the amygdala, resulting in motor readiness to support fight or flight.
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| 6. |
- Åhs, Fredrik, et al.
(author)
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Hypothalamic blood flow correlates positively with stress-induced cortisol levels in subjects with social anxiety disorder
- 2006
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In: Psychosomatic Medicine. - : Ovid Technologies (Wolters Kluwer Health). - 0033-3174 .- 1534-7796. ; 68:6, s. 859-862
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Journal article (peer-reviewed)abstract
- Objective: The adrenal excretion of cortisol in animals is dependent on the production of corticotropin-releasing factor in the paraventricular nucleus of the hypothalamus. The a priori hypothesis of this study was that hypothalamic regional cerebral blood flow (rCBF) would correlate positively with salivary cortisol levels in patients with social anxiety disorder (SAD) during anxiety provocation. Another objective was to evaluate whether salivary cortisol levels correlated with rCBF in other brain areas. Method: Regional CBF was measured with oxygen-15-labeled water and positron emission tomography during a public speaking task before and after placebo treatment in 12 subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined SAD. Cortisol concentrations in saliva were measured 15 minutes after the task. The a priori hypothesis of a salivary cortisol-dependent activation of the hypothalamus was studied with region-of-interest analysis. In addition, the covariation between rCBF and salivary cortisol was studied in the whole brain using the general linear model. Results: The region-of-interest analysis revealed a positive correlation between salivary cortisol and hypothalamic rCBF. In the whole brain analysis, a positive covariation between rCBF and salivary cortisol levels was found in a midbrain cluster encompassing the hypothalamus with its statistical maximum in the mamillary bodies. Negative covariations were observed in the medial prefrontal cortex as well as in the motor and premotor cortices. Conclusion: Like in animals, stress-induced cortisol excretion in humans may be inhibited by activity in the medial prefrontal cortex and enhanced by activity in the hypothalamus.
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| 7. |
- Faria, Vanda, et al.
(author)
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Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder : A Randomized Trial
- 2017
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In: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 24, s. 179-188
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Journal article (peer-reviewed)abstract
- Background: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety, but their efficacy relative to placebo has been questioned. We aimed to test how manipulation of verbally induced expectancies, central for placebo, influences SSRI treatment outcome and brain activity in patients with social anxiety disorder (SAD).Methods: We did a randomized clinical trial, within an academic medical center (Uppsala, Sweden), of individuals fulfilling the DSM-IV criteria for SAD, recruited through media advertising. Participants were 18 years or older and randomized in blocks, through a computer-generated sequence by an independent party, to nine weeks of overt or covert treatment with escitalopram(20 mg daily). The overt group received correct treatment information whereas the covert group was treated deceptively with the SSRI described, by the psychiatrist, as active placebo. The treating psychiatrist was necessarily unmasked while the research staff was masked from intervention assignment. Treatment efficacy was assessed primarily with the self-rated Liebowitz Social Anxiety Scale (LSAS-SR), administered at week 0, 1, 3, 6 and 9, also yielding a dichotomous estimate of responder status (clinically significant improvement). Before and at the last week of treatment, brain activity during an emotional face-matching task was assessed with functional magnetic resonance imaging (fMRI) and during fMRI sessions, anticipatory speech anxiety was also assessed with the Spielberger State-Trait Anxiety Inventory - State version (STAI-S). Analyses included all randomized patients with outcome data at posttreatment. This study is registered at ISRCTN, number 98890605.Findings: Between March 17th 2014 and May 22nd 2015, 47 patients were recruited. One patient in the covert group dropped out after a few days of treatment and did not provide fMRI data, leaving 46 patients with complete outcome data. After nine weeks of treatment, overt (n = 24) as compared to covert (n = 22) SSRI administration yielded significantly better outcome on the LSAS-SR (adjusted difference 21.17, 95% CI 10.69–31.65, p < 0.0001) with more than three times higher response rate (50% vs. 14%; χ2(1) = 6.91, p = 0.009) and twice the effect size (d = 2.24 vs. d = 1.13) from pre-to posttreatment. There was no significant between-group difference on anticipatory speech anxiety (STAI-S), both groups improving with treatment. No serious adverse reactions were recorded. On fMRI outcomes, there was suggestive evidence for a differential neural response to treatment between groups in the posterior cingulate, superior temporal and inferior frontal gyri (all z thresholds exceeding 3.68, p ≤ 0.001). Reduced social anxiety with treatment correlated significantly with enhanced posterior cingulate (z threshold 3.24, p = 0.0006) and attenuated amygdala (z threshold 2.70, p = 0.003) activity.Interpretation: The clinical and neural effects of escitalopram were markedly influenced by verbal suggestions. This points to a pronounced placebo component in SSRI-treatment of SAD and favors a biopsychosocial over a biomedical explanatory model for SSRI efficacy.
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| 8. |
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| 9. |
- Olofsdotter, Susanne, et al.
(author)
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The mediating role of parenting behaviors in the relationship between early and late adolescent levels of anxiety : Specificity and informant effects
- 2018
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In: Journal of Adolescence. - : Wiley. - 0140-1971 .- 1095-9254. ; 69, s. 118-129
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Journal article (peer-reviewed)abstract
- INTRODUCTION: The role of parenting behavior is often highlighted in the development of anxiety in youth. However, previous reports are limited in terms of the specificity of relationships between different types of anxiety and parenting behaviors, informant effects on these relationships, and direction of effects.METHODS: This study investigates these questions using longitudinal data from 1350 Swedish adolescents and their parents. Adolescents' self-reports of six dimensions of anxiety and adolescents' and parents' reports of six dimensions of parenting behaviors were used in the analyses. Parallel multiple mediation models were employed to analyze specificity and informant effects within a reciprocal effects model.RESULTS: Overall, and irrespective of informant, this study found little support for a mediating role of parenting behaviors in the relationship between early and late adolescent levels of anxiety. Evidence for specificity within the parenting-anxiety relationship was scarce with specific mediating effects observed only for panic/agoraphobia and total anxiety through the parenting dimension of rejection.CONCLUSIONS: The findings of this study concern the un-conditional mediating role of parenting. Parenting behaviors may be more influential among some adolescents, depending on individual differences in other factors related to the development and course of adolescent anxiety. Thus, further research on moderating factors of the influence of parenting on adolescent anxiety is warranted.
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| 10. |
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