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Scholten, W., Seldenrijk, A., Hoogendoorn, A., Bosman, R., Muntingh, A., Karyotaki, E., . . . Batelaan, N. (2023). Baseline Severity as a Moderator of the Waiting List–Controlled Association of Cognitive Behavioral Therapy With Symptom Change in Social Anxiety Disorder. JAMA Psychiatry, 80(8), 822-831
Åpne denne publikasjonen i ny fane eller vindu >>Baseline Severity as a Moderator of the Waiting List–Controlled Association of Cognitive Behavioral Therapy With Symptom Change in Social Anxiety Disorder
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2023 (engelsk)Inngår i: JAMA Psychiatry, ISSN 2168-622X, Vol. 80, nr 8, s. 822-831Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Importance  Social anxiety disorder (SAD) can be adequately treated with cognitive behavioral therapy (CBT). However, there is a large gap in knowledge on factors associated with prognosis, and it is unclear whether symptom severity predicts response to CBT for SAD.

Objective  To examine baseline SAD symptom severity as a moderator of the association between CBT and symptom change in patients with SAD.

Data Sources  For this systematic review and individual patient data meta-analysis (IPDMA), PubMed, PsycInfo, Embase, and the Cochrane Library were searched from January 1, 1990, to January 13, 2023. Primary search topics were social anxiety disorder, cognitive behavior therapy, and randomized controlled trial.

Study Selection  Inclusion criteria were randomized clinical trials comparing CBT with being on a waiting list and using the Liebowitz Social Anxiety Scale (LSAS) in adults with a primary clinical diagnosis of SAD.

Data Extraction and Synthesis  Authors of included studies were approached to provide individual-level data. Data were extracted by pairs of authors following the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline, and risk of bias was assessed using the Cochrane tool. An IPDMA was conducted using a 2-stage approach for the association of CBT with change in LSAS scores from baseline to posttreatment and for the interaction effect of baseline LSAS score by condition using random-effects models.

Main Outcomes and Measures  The main outcome was the baseline to posttreatment change in symptom severity measured by the LSAS.

Results  A total of 12 studies including 1246 patients with SAD (mean [SD] age, 35.3 [10.9] years; 738 [59.2%] female) were included in the meta-analysis. A waiting list–controlled association between CBT and pretreatment to posttreatment LSAS change was found (b = –20.3; 95% CI, −24.9 to −15.6; P < .001; Cohen d = –0.95; 95% CI, −1.16 to −0.73). Baseline LSAS scores moderated the differences between CBT and waiting list with respect to pretreatment to posttreatment symptom reductions (b = –0.22; 95% CI, −0.39 to −0.06; P = .009), indicating that individuals with severe symptoms had larger waiting list–controlled symptom reductions after CBT (Cohen d = –1.13 [95% CI, −1.39 to −0.88] for patients with very severe SAD; Cohen d = –0.54 [95% CI, −0.80 to −0.29] for patients with mild SAD).

Conclusions and Relevance  In this systematic review and IPDMA, higher baseline SAD symptom severity was associated with greater (absolute but not relative) symptom reductions after CBT in patients with SAD. The findings contribute to personalized care by suggesting that clinicians can confidently offer CBT to individuals with severe SAD symptoms.

sted, utgiver, år, opplag, sider
American Medical Association (AMA), 2023
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-503128 (URN)10.1001/jamapsychiatry.2023.1291 (DOI)001000481100003 ()37256597 (PubMedID)
Tilgjengelig fra: 2023-06-01 Laget: 2023-06-01 Sist oppdatert: 2024-01-26bibliografisk kontrollert
Wlad, M., Frick, A., Engman, J., Hjorth, O., Motilla Hoppe, J., Faria, V., . . . Gingnell, M. (2023). Dorsal anterior cingulate cortex activity during cognitive challenge in social anxiety disorder. Behavioural Brain Research, 442, Article ID 114304.
Åpne denne publikasjonen i ny fane eller vindu >>Dorsal anterior cingulate cortex activity during cognitive challenge in social anxiety disorder
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2023 (engelsk)Inngår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 442, artikkel-id 114304Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background: Social anxiety disorder (SAD) is associated with aberrant emotional information processing while little is known about non-emotional cognitive processing biases. The dorsal anterior cingulate cortex (dACC) has been implicated in SAD neuropathology and is activated both by emotional and non-affective cognitive challenges like the Multisource Interference Task (MSIT).

Methods: Here, we used fMRI to compare dACC activity and test performance during MSIT in 69 SAD patients and 38 healthy controls. In addition to patient-control comparisons, we examined whether neural activity in the dACC correlated with social anxiety, trait anxiety or depression levels.

Results: The MSIT activated the dACC as expected but with no differences in task performance or neural reactivity between SAD patients and controls. There were no significant correlations between dACC activity and social or trait anxiety symptom severity. In patients, there was a significant negative correlation between dACC activity and depressive symptoms.

Conclusions: In absence of affective challenge, we found no disorder-related cognitive profile in SAD patients since neither MSIT task performance nor dACC neural activity deviated in patients relative to controls.

sted, utgiver, år, opplag, sider
Elsevier, 2023
Emneord
Social Anxiety Disorder, Functional magnetic resonance imaging, Anterior Cingulate Cortex
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-494834 (URN)10.1016/j.bbr.2023.114304 (DOI)000923264600001 ()36681164 (PubMedID)
Merknad

De två sista författarna delar sistaförfattarskapet.

Tilgjengelig fra: 2023-01-20 Laget: 2023-01-20 Sist oppdatert: 2023-03-07bibliografisk kontrollert
Gil-Paterna, P. & Furmark, T. (2023). Imaging the cerebellum in post-traumatic stress and anxiety disorders: a mini-review. Frontiers in Systems Neuroscience, 17, Article ID 1197350.
Åpne denne publikasjonen i ny fane eller vindu >>Imaging the cerebellum in post-traumatic stress and anxiety disorders: a mini-review
2023 (engelsk)Inngår i: Frontiers in Systems Neuroscience, E-ISSN 1662-5137, Vol. 17, artikkel-id 1197350Artikkel, forskningsoversikt (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
Frontiers Media S.A., 2023
Emneord
cerebellum, vermis, anxiety, stress, PTSD, human neuroimaging, MRI
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-511596 (URN)10.3389/fnsys.2023.1197350 (DOI)001054997900001 ()37645454 (PubMedID)
Forskningsfinansiär
EU, Horizon 2020, 956414
Tilgjengelig fra: 2023-09-18 Laget: 2023-09-18 Sist oppdatert: 2023-10-16bibliografisk kontrollert
Lindqvist, D., Furmark, T., Lavebratt, C., Ohlsson, L. & Månsson, K. N. (2023). Plasma circulating cell-free mitochondrial DNA in social anxiety disorder. Psychoneuroendocrinology, 148, Article ID 106001.
Åpne denne publikasjonen i ny fane eller vindu >>Plasma circulating cell-free mitochondrial DNA in social anxiety disorder
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2023 (engelsk)Inngår i: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 148, artikkel-id 106001Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Objective To investigate plasma levels of circulating cell-free mitochondrial DNA (ccf-mtDNA) in patients with social anxiety disorder (SAD) and healthy controls (HC). Methods In this study, 88 participants (46 patients with SAD and 42 HCs) were enrolled and both ccf-mtDNA and peripheral blood mononuclear cells (PBMC) mtDNA copy number (mtDNA-cn) were measured at up to three times per individual (9 to 11 weeks apart). SAD patients also received cognitive behavioral therapy (CBT) between the second and third time-point. Results SAD patients had significantly lower ccf-mtDNA compared to HCs at all time points, but ccf-mtDNA did not change significantly after CBT, and was not associated with severity of anxiety symptoms. PBMC mtDNA-cn did not significantly correlate with plasma ccf-mtDNA in patients. Conclusion This is the first report of lower ccf-mtDNA in patients with an anxiety disorder. Our findings could reflect a more chronic illness course in SAD patients with prolonged periods of psychological stress leading to decreased levels of ccf-mtDNA, but future longitudinal studies are needed to confirm or refute this hypothesis.

sted, utgiver, år, opplag, sider
Elsevier, 2023
Emneord
circulating cell-free mitochondrial DNA, social anxiety disorder, cognitive behavioural therapy
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-490367 (URN)10.1016/j.psyneuen.2022.106001 (DOI)000918010400006 ()
Tilgjengelig fra: 2022-12-09 Laget: 2022-12-09 Sist oppdatert: 2023-02-23bibliografisk kontrollert
Jonasson, M., Frick, A., Fazio, P., Hjorth, O., Danfors, T., Axelsson, J., . . . Lubberink, M. (2023). Striatal dopamine transporter and receptor availability correlate with relative cerebral blood flow measured with [11C]PE2I, [18F]FE-PE2I and [11C]raclopride PET in healthy individuals. Journal of Cerebral Blood Flow and Metabolism, 43(7), 1206-1215
Åpne denne publikasjonen i ny fane eller vindu >>Striatal dopamine transporter and receptor availability correlate with relative cerebral blood flow measured with [11C]PE2I, [18F]FE-PE2I and [11C]raclopride PET in healthy individuals
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2023 (engelsk)Inngår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 43, nr 7, s. 1206-1215Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The aim of this retrospective study was to investigate relationships between relative cerebral blood flow and striatal dopamine transporter and dopamine D2/3 availability in healthy subjects. The data comprised dynamic PET scans with two dopamine transporter tracers [11C]PE2I (n = 20) and [18F]FE-PE2I (n = 20) and the D2/3 tracer [11C]raclopride (n = 18). Subjects with a [11C]PE2I scan also underwent a dynamic scan with the serotonin transporter tracer [11C]DASB. Binding potential (BPND) and relative tracer delivery (R1) values were calculated on regional and voxel-level. Striatal R1 and BPND values were correlated, using either an MRI-based volume of interest (VOI) or an isocontour VOI based on the parametric BPND image. An inter-tracer comparison between [11C]PE2I BPND and [11C]DASB R1 was done on a VOI-level and simulations were performed to investigate whether the constraints of the modeling could cause correlation of the parameters. A positive association was found between BPND and R1 for all three dopamine tracers. A similar correlation was found for the inter-tracer correlation between [11C]PE2I BPND and [11C]DASB R1. Simulations showed that this relationship was not caused by cross-correlation between parameters in the kinetic model. In conclusion, these results suggest an association between resting-state striatal dopamine function and relative blood flow in healthy subjects.

sted, utgiver, år, opplag, sider
Sage Publications, 2023
Emneord
Binding potential, dopamine system, kinetic modelling, PET, relative cerebral blood flow
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-499545 (URN)10.1177/0271678X231160881 (DOI)000948378700001 ()36912083 (PubMedID)
Forskningsfinansiär
Swedish Foundation for Strategic Research
Tilgjengelig fra: 2023-03-31 Laget: 2023-03-31 Sist oppdatert: 2023-10-05bibliografisk kontrollert
Groenewold, N. A., Bas-Hoogendam, J. M., Amod, A. R., Laansma, M. A., Van Velzen, L. S., Aghajani, M., . . . Van der Wee, N. J. A. (2023). Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group. Molecular Psychiatry, 28(3), 1079-1089
Åpne denne publikasjonen i ny fane eller vindu >>Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group
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2023 (engelsk)Inngår i: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 28, nr 3, s. 1079-1089Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
Springer Nature, 2023
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-498484 (URN)10.1038/s41380-022-01933-9 (DOI)000928330100001 ()36653677 (PubMedID)
Forskningsfinansiär
EU, European Research Council, ERC_CoG-2017_772337Swedish Research Council, 2018-06729The Swedish Brain FoundationRiksbankens Jubileumsfond
Tilgjengelig fra: 2023-03-16 Laget: 2023-03-16 Sist oppdatert: 2024-01-26bibliografisk kontrollert
Kumar, P., Stiernborg, M., Fogdell-Hahn, A., Mansson, K., Furmark, T., Berglind, D., . . . Lavebratt, C. (2022). Physical exercise is associated with a reduction in plasma levels of fractalkine, TGF-beta 1, eotaxin-1 and IL-6 in younger adults with mobility disability. PLOS ONE, 17(2), Article ID e0263173.
Åpne denne publikasjonen i ny fane eller vindu >>Physical exercise is associated with a reduction in plasma levels of fractalkine, TGF-beta 1, eotaxin-1 and IL-6 in younger adults with mobility disability
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2022 (engelsk)Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 17, nr 2, artikkel-id e0263173Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Mobility disability (MD) refers to substantial limitations in life activities that arise because of movement impairments. Although MD is most prevalent in older individuals, it can also affect younger adults. Increasing evidence suggests that inflammation can drive the development of MD and may need to be targeted for MD prevention. Physical exercise has anti-inflammatory properties and has been associated with MD prevention. However, no studies to date have examined whether exercise interventions affect the peripheral inflammatory status in younger adults with MD. To this end, we used blood samples from young and middle-aged adults with MD (N = 38; median age = 34 years) who participated in a 12-week intervention that included aerobic and resistance exercise training. A pre-post assessment of inflammatory biomarkers was conducted in plasma from two timepoints, i.e., before the exercise trial and at follow-up (3-7 days after the last exercise session). We successfully measured 15 inflammatory biomarkers and found that exercise was associated with a significant reduction in levels of soluble fractalkine, transforming growth factor beta 1 (TGF-beta 1), eotaxin-1 and interleukin (IL) 6 (corrected alpha = 0.004). We also found significant male-specific effects of exercise on (i) increasing IL-16 and (ii) decreasing vascular endothelial growth factor-A (VEGF-A). In line with our results, previous studies have also found that exercise can reduce levels of TGF-beta 1, eotaxin-1 and IL-6. However, our finding that exercise reduces plasma levels of fractalkine in younger adults with MD, as well as the sex-dependent findings, have not been previously reported and warrant replication in larger cohorts. Given the suggested role of inflammation in promoting MD development, our study provides additional support for the use of physical exercise as a treatment modality for MD.

sted, utgiver, år, opplag, sider
Public Library of Science (PLoS), 2022
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-481809 (URN)10.1371/journal.pone.0263173 (DOI)000823694700059 ()35113938 (PubMedID)
Forskningsfinansiär
Forte, Swedish Research Council for Health, Working Life and WelfareSwedish Research Council, 2014-10171
Tilgjengelig fra: 2022-08-17 Laget: 2022-08-17 Sist oppdatert: 2023-03-23bibliografisk kontrollert
Hjorth, O., Frick, A., Gingnell, M., Engman, J., Björkstrand, J., Faria, V., . . . Furmark, T. (2022). Serotonin and dopamine transporter availability in social anxiety disorder after combined treatment with escitalopram and cognitive-behavioral therapy. Translational Psychiatry, 12, Article ID 436.
Åpne denne publikasjonen i ny fane eller vindu >>Serotonin and dopamine transporter availability in social anxiety disorder after combined treatment with escitalopram and cognitive-behavioral therapy
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2022 (engelsk)Inngår i: Translational Psychiatry, E-ISSN 2158-3188, Vol. 12, artikkel-id 436Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Selective serotonin reuptake inhibitors (SSRIs) and internet-based cognitive behavioral therapy (ICBT) are recommended treatments of social anxiety disorder (SAD), and often combined, but their effects on monoaminergic signaling are not well understood. In this multi-tracer positron emission tomography (PET) study, 24 patients with SAD were randomized to treatment with escitalopram+ICBT or placebo+ICBT under double-blind conditions. Before and after 9 weeks of treatment, patients were examined with positron emission tomography and the radioligands [11C]DASB and [11C]PE2I, probing the serotonin (SERT) and dopamine (DAT) transporter proteins respectively. Both treatment combinations resulted in significant improvement as measured by the Liebowitz Social Anxiety Scale (LSAS). At baseline, SERT-DAT co-expression was high and, in the putamen and thalamus, co-expression showed positive associations with symptom severity. SERT-DAT co-expression was also predictive of treatment success, but predictor-outcome associations differed in direction between the treatments. After treatment, average SERT occupancy in the SSRI + ICBT group was >80%, with positive associations between symptom improvement and occupancy in the nucleus accumbens, putamen and anterior cingulate cortex. Following placebo+ICBT, SERT binding increased in the raphe nuclei. DAT binding increased in both groups in limbic and striatal areas, but relations with symptom improvement differed, being negative for SSRI + ICBT and positive for placebo + ICBT. Thus, serotonin-dopamine transporter co-expression exerts influence on symptom severity and remission rate in the treatment of social anxiety disorder. However, the monoamine transporters are modulated in dissimilar ways when cognitive-behavioral treatment is given concomitantly with either SSRI-medication or pill placebo.

sted, utgiver, år, opplag, sider
Springer Nature, 2022
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-486623 (URN)10.1038/s41398-022-02187-3 (DOI)000864640500001 ()36202797 (PubMedID)
Forskningsfinansiär
Swedish Research CouncilThe Swedish Brain FoundationRiksbankens Jubileumsfond
Merknad

De två första författarna delar förstaförfattarskapet.

Tilgjengelig fra: 2022-10-13 Laget: 2022-10-13 Sist oppdatert: 2024-01-17bibliografisk kontrollert
Hjorth, O., Frick, A., Gingnell, M., Hoppe, J. M., Faria, V., Hultberg, S., . . . Furmark, T. (2021). Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder: a randomized clinical trial. Translational Psychiatry, 11(1), Article ID 559.
Åpne denne publikasjonen i ny fane eller vindu >>Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder: a randomized clinical trial
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2021 (engelsk)Inngår i: Translational Psychiatry, E-ISSN 2158-3188, Vol. 11, nr 1, artikkel-id 559Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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 [11C]DASB and [11C]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.

sted, utgiver, år, opplag, sider
Springer Nature, 2021
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-458181 (URN)10.1038/s41398-021-01682-3 (DOI)000714361700002 ()34732695 (PubMedID)
Tilgjengelig fra: 2021-11-07 Laget: 2021-11-07 Sist oppdatert: 2024-01-17bibliografisk kontrollert
Hjorth, O., Frick, A., Gingnell, M., Hoppe, J. M., Faria, V., Hultberg, S., . . . Furmark, T. (2021). Expression and co-expression of serotonin and dopamine transporters in social anxiety disorder: a multitracer positron emission tomography study. Molecular Psychiatry, 26(8), 3970-3979
Åpne denne publikasjonen i ny fane eller vindu >>Expression and co-expression of serotonin and dopamine transporters in social anxiety disorder: a multitracer positron emission tomography study
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2021 (engelsk)Inngår i: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 26, nr 8, s. 3970-3979Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
Springer Nature, 2021
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-400349 (URN)10.1038/s41380-019-0618-7 (DOI)000731712800027 ()31822819 (PubMedID)
Forskningsfinansiär
Swedish Research CouncilRiksbankens Jubileumsfond
Tilgjengelig fra: 2019-12-19 Laget: 2019-12-19 Sist oppdatert: 2024-01-15bibliografisk kontrollert
Prosjekter
Ångest och ångestbehandling ur ett neurovetenskapligt perspektiv: Könsskillnader, serotonerga processer och genetiska faktorer [2009-07021_VR]; Uppsala universitet Ångest och ångestbehandling ur ett neurovetenskapligt perspektiv: Könsskillnader, serotonerga processer och genetiska faktorer [2009-08251_VR]; Uppsala universitetNeurobiologi i psykologins tjänst: Nya möjligheter att kunna förstå och behandla social fobi [2010-02082_VR]; Uppsala universitetSocial ångest undersökt med magnetkamera: Nya möjligheter att förstå och behandla ett folkhälsoproblem [2011-01368_Forte]; Uppsala universitetFunktionell och strukturell neuroanatomi hos patienter med social fobi efter kognitiv-beteendeterapi eller SSRI-preparat givet som enskild eller kombinerad behandling [2013-01366_VR]; Uppsala universitetDet tysta fängelset - nya möjligheter att förklara blyghet [P13-1270:1_RJ]; Uppsala universitetUppsala möte om hjärnan och ångestsyndrom [2016-00602_VR]; Uppsala universitetDopaminsyntes och hjärnans belöningssystem vid behandling av social ångest [2016-02228_VR]; Uppsala universitetBlyghetens personkemi: Serotonin-dopamin interaktioner vid social ångest [P17-0639:1_RJ]; Uppsala universitetSocial ångest i fokus: Multimodal hjärnavbildning av monoaminerga neurotransmittorer och neurala aktiveringar före och efter behandling [2020-02426_VR]; Uppsala universitet
Organisasjoner
Identifikatorer
ORCID-id: ORCID iD iconorcid.org/0000-0001-6821-9058