| 1. |
- Groenewold, Nynke A., et al.
(author)
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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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In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 28:3, s. 1079-1089
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Journal article (peer-reviewed)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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| 2. |
- Bas-Hoogendam, Janna Marie, et al.
(author)
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ENIGMA-anxiety working group : Rationale for and organization of large-scale neuroimaging studies of anxiety disorders
- 2022
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In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 83-112
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Research review (peer-reviewed)abstract
- Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.
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| 3. |
- Björkstrand, Johannes, et al.
(author)
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Evaluating an internet-delivered fear conditioning and extinction protocol using response times and affective ratings
- 2022
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12
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Journal article (peer-reviewed)abstract
- Pavlovian fear conditioning is widely used to study mechanisms of fear learning, but high-throughput studies are hampered by the labor-intensive nature of examining participants in the lab. To circumvent this bottle-neck, fear conditioning tasks have been developed for remote delivery. Previous studies have examined remotely delivered fear conditioning protocols using expectancy and affective ratings. Here we replicate and extend these findings using an internet-delivered version of the Screaming Lady paradigm, evaluating the effects on negative affective ratings and response time to an auditory probe during stimulus presentation. In a sample of 80 adults, we observed clear evidence of both fear acquisition and extinction using affective ratings. Response times were faster when probed early, but not later, during presentation of stimuli paired with an aversive scream. The response time findings are at odds with previous lab-based studies showing slower as opposed to faster responses to threat-predicting cues. The findings underscore the feasibility of employing remotely delivered fear conditioning paradigms with affective ratings as outcome. Findings further highlight the need for research examining optimal parameters for concurrent response time measures or alternate non-verbal indicators of conditioned responses in Pavlovian conditioning protocols.
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| 4. |
- Filippi, Courtney A., et al.
(author)
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Developmental Changes in the Association Between Cognitive Control and Anxiety
- 2022
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In: Child Psychiatry and Human Development. - : Springer Nature. - 0009-398X .- 1573-3327. ; 53:3, s. 599-609
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Journal article (peer-reviewed)abstract
- Anxiety has been associated with reliance on reactive (stimulus-driven/reflexive) control strategies in response to conflict. However, this conclusion rests primarily on indirect evidence. Few studies utilize tasks that dissociate the use of reactive ('just in time') vs. proactive (anticipatory/preparatory) cognitive control strategies in response to conflict, and none examine children diagnosed with anxiety. The current study utilizes the AX-CPT, which dissociates these two types of cognitive control, to examine cognitive control in youth (ages 8-18) with and without an anxiety diagnosis (n = 56). Results illustrate that planful behavior, consistent with using a proactive strategy, varies by both age and anxiety symptoms. Young children (ages 8-12 years) with high anxiety exhibit significantly less planful behavior than similarly-aged children with low anxiety. These findings highlight the importance of considering how maturation influences relations between anxiety and performance on cognitive-control tasks and have implications for understanding the pathophysiology of anxiety in children.
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| 5. |
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| 6. |
- Guath, Mona, et al.
(author)
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Pupil dilation during negative prediction errors is related to brain choline concentration and depressive symptoms in adolescents
- 2023
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In: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 436
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Journal article (peer-reviewed)abstract
- Depressive symptoms are associated with altered pupillary responses during learning and reward prediction as well as with changes in neurometabolite levels, including brain concentrations of choline, glutamate and gamma-aminobutyric acid (GABA). However, the full link between depressive symptoms, reward-learning-related pupillary responses and neurometabolites is yet to be established as these constructs have not been assessed in the same individuals. The present pilot study, investigated these relations in a sample of 24 adolescents aged 13 years. Participants completed the Revised Child Anxiety and Depression Scale (RCADS) and underwent a reward learning task while measuring pupil dilation and a single voxel dorsal anterior cingulate cortex (dACC) MEGA-PRESS magnetic resonance spectroscopy scan assessing choline, glutamate and GABA concentrations. Pupil dilation was related to prediction errors (PE) during learning, which was captured by a prediction error-weighted pupil dilation response index (PE-PDR) for each individual. Higher PE-PDR scores, indicating larger pupil dilations to negative prediction errors, were related to lower depressive symptoms and lower dACC choline concentrations. Dorsal ACC choline was positively associated with depressive symptoms, whereas glutamate and GABA were not related to PE-PDR or depressive symptoms. The findings support notions of cholinergic involvement in depressive symptoms and cholinergic influence on reward-related pupillary response, suggesting that pupillary responses to negative prediction errors may hold promise as a biomarker of depressive states.
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| 7. |
- Hilbert, Kevin, et al.
(author)
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Cortical and Subcortical Brain Alterations in Specific Phobia and Its Animal and Blood-Injection-Injury Subtypes: A Mega-Analysis From the ENIGMA Anxiety Working Group.
- 2024
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In: The American Journal of Psychiatry. - 1535-7228.
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Journal article (peer-reviewed)abstract
- Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors investigated associations of brain structure with symptom severity and age (youths vs. adults).Data sets from 31 original studies were combined to create a final sample with 1,452 participants with phobia and 2,991 healthy participants (62.7% female; ages 5-90). Imaging processing and quality control were performed using established ENIGMA protocols. Subcortical volumes as well as cortical surface area and thickness were examined in a preregistered analysis.Compared with the healthy control group, the phobia group showed mostly smaller subcortical volumes, mixed surface differences, and larger cortical thickness across a substantial number of regions. The phobia subgroups also showed differences, including, as hypothesized, larger medial orbitofrontal cortex thickness in BII phobia (N=182) compared with animal phobia (N=739). All findings were driven by adult participants; no significant results were observed in children and adolescents.Brain alterations associated with specific phobia exceeded those of other anxiety disorders in comparable analyses in extent and effect size and were not limited to reductions in brain structure. Moreover, phenomenological differences between phobia subgroups were reflected in diverging neural underpinnings, including brain areas related to fear processing and higher cognitive processes. The findings implicate brain structure alterations in specific phobia, although subcortical alterations in particular may also relate to broader internalizing psychopathology.
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| 8. |
- Lau, Jennifer Y. F., et al.
(author)
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Greater Response Interference to Pain Faces Under Low Perceptual Load Conditions in Adolescents With Impairing Pain : A Role for Poor Attention Control Mechanisms in Pain Disability?
- 2019
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In: Journal of Pain. - : CHURCHILL LIVINGSTONE. - 1526-5900 .- 1528-8447. ; 20:4, s. 453-461
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Journal article (peer-reviewed)abstract
- Persistent pain in young people in the community is common, but individuals vary in how much pain impacts daily life. Information-processing accounts of chronic pain partly attribute the fear and avoidance of pain, as well as associated interference, to a set of involuntary biases, including the preferential allocation of attention resources toward potential threats. Far less research has focused on the role of voluntary goal-directed attention control processes, the ability to flexibly direct attention toward and away from threats, in explaining pain-associated interference. Using a visual search task, we explored a poor attention control account of pain interference in young people with persistent pain from the community. One hundred and forty five young people aged 16 to 19 years were categorized into three groups: non-chronic pain (n = 68), low-interfering persistent pain (n = 40), and moderate- to high-interfering persistent pain (n = 22). We found that only adolescents with moderate-to high-interfering persistent pain but not the other two groups of adolescents were affected by a search task preceded by a pain face (compared to a neutral face), but this within-group difference emerged only under low perceptual load conditions. Because low perceptual load conditions are thought to require more strategic attention resources to suppress the interfering effects of pain face primes, our findings are consistent with a poor attention control account of pain interference in young people. Analyses further showed that these differences in task performance were not explained by confounding effects of anxiety. If replicated, these findings may have implications for understanding and managing the pain-associated disability in adolescents with chronic pain. Perspective: Young people with moderately and highly interfering pain responded slower on an easy search task after seeing a pain face than after seeing a neutral face. If replicated, these findings could mean that boosting the ability to control attention toward and away from threatening cues is an effective strategy for managing interference from pain.
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| 9. |
- Penninx, Brenda W. J. H., et al.
(author)
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Anxiety disorders
- 2021
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 397:10277, s. 914-927
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Journal article (peer-reviewed)abstract
- Anxiety disorders form the most common group of mental disorders and generally start before or in early adulthood. Core features include excessive fear and anxiety or avoidance of perceived threats that are persistent and impairing. Anxiety disorders involve dysfunction in brain circuits that respond to danger. Risk for anxiety disorders is influenced by genetic factors, environmental factors, and their epigenetic relations. Anxiety disorders are often comorbid with one another and with other mental disorders, especially depression, as well as with somatic disorders. Such comorbidity generally signifies more severe symptoms, greater clinical burden, and greater treatment difficulty. Reducing the large burden of disease from anxiety disorders in individuals and worldwide can be best achieved by timely, accurate disease detection and adequate treatment administration, scaling up of treatments when needed. Evidence-based psychotherapy (particularly cognitive behavioural therapy) and psychoactive medications (particularly serotonergic compounds) are both effective, facilitating patients' choices in therapeutic decisions. Although promising, no enduring preventive measures are available, and, along with frequent therapy resistance, clinical needs remain unaddressed. Ongoing research efforts tackle these problems, and future efforts should seek individualised, more effective approaches for treatment with precision medicine.
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| 10. |
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