| 1. |
- Hilbert, Kevin, et al.
(författare)
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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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Ingår i: The American Journal of Psychiatry. - 1535-7228.
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Rayner, C, et al.
(författare)
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A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 150-
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Tidskriftsartikel (refereegranskat)abstract
- Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.
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| 3. |
- Pircher, J, et al.
(författare)
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Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 1523-
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Tidskriftsartikel (refereegranskat)abstract
- Leukocyte-released antimicrobial peptides contribute to pathogen elimination and activation of the immune system. Their role in thrombosis is incompletely understood. Here we show that the cathelicidin LL-37 is abundant in thrombi from patients with acute myocardial infarction. Its mouse homologue, CRAMP, is present in mouse arterial thrombi following vascular injury, and derives mainly from circulating neutrophils. Absence of hematopoietic CRAMP in bone marrow chimeric mice reduces platelet recruitment and thrombus formation. Both LL-37 and CRAMP induce platelet activation in vitro by involving glycoprotein VI receptor with downstream signaling through protein tyrosine kinases Src/Syk and phospholipase C. In addition to acute thrombosis, LL-37/CRAMP-dependent platelet activation fosters platelet–neutrophil interactions in other inflammatory conditions by modulating the recruitment and extravasation of neutrophils into tissues. Absence of CRAMP abrogates acid-induced lung injury, a mouse pneumonia model that is dependent on platelet–neutrophil interactions. We suggest that LL-37/CRAMP represents an important mediator of platelet activation and thrombo-inflammation.
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| 4. |
- Rossaint, J, et al.
(författare)
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Platelets orchestrate the resolution of pulmonary inflammation in mice by T reg cell repositioning and macrophage education
- 2021
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 218:7
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Tidskriftsartikel (refereegranskat)abstract
- Beyond hemostasis, platelets actively participate in immune cell recruitment and host defense, yet their potential in the resolution of inflammatory processes remains unknown. Here, we demonstrate that platelets are recruited into the lung together with neutrophils during the onset of inflammation and alongside regulatory T (T reg) cells during the resolution phase. This partnering dichotomy is regulated by differential adhesion molecule expression during resolution. Mechanistically, intravascular platelets form aggregates with T reg cells, a prerequisite for their recruitment into the lung. This interaction relies on platelet activation by sCD40L and platelet P-selectin binding to PSGL-1 on T reg cells. Physical platelet–T reg cell interactions are necessary to modulate the transcriptome and instruct T reg cells to release the anti-inflammatory mediators IL-10 and TGFβ. Notably, the presence of platelet–T reg cell aggregates in the lung was also required for macrophage transcriptional reprogramming, polarization toward an anti-inflammatory phenotype, and effective resolution of pulmonary inflammation. Thus, platelets partner with successive immune cell subsets to orchestrate both the initiation and resolution of inflammation.
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| 5. |
- Pfaltz, Monique C., et al.
(författare)
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Metabolic decoupling in daily life in patients with panic disorder andagoraphobia
- 2015
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Ingår i: Journal of Psychiatric Research. - : Elsevier Ltd. - 0022-3956 .- 1879-1379. ; 68, s. 377-383
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Tidskriftsartikel (refereegranskat)abstract
- Various studies have assessed autonomic and respiratory underpinnings of panic attacks, yet the psychophysiological functioning of panic disorder (PD) patients has rarely been examined under naturalistic conditions at times when acute attacks were not reported. We hypothesized that emotional activation in daily life causes physiologically demonstrable deviations from efficient metabolic regulation in PD patients. Metabolic coupling was estimated as within-individual correlations between heart rate (HR) and indices of metabolic activity, i.e., physical activity (measured by 3-axial accelerometry, Acc), and minute ventilation (Vm, measured by calibrated inductive plethysmography, as proxy for oxygen consumption). A total of 565 daytime hours were recorded in 19 PD patients and 20 healthy controls (HC). Pairwise cross-correlations of minute-by-minute averages of these metabolic indices were calculated for each participant and then correlated with several indices of self-reported anxiety. Ambulatory HR was elevated in PD (p=.05, d=0.67). Patients showed reduced HR-Acc (p<.006, d=0.97) and HR-Vm coupling (p<.009, d=0.91). Combining Vm and Acc to predict HR showed the strongest group separation (p<.002, d=1.07). Discriminant analyses, based on the combination of Vm and Acc to predict HR, classified 77% of all participants correctly. In PD, HR-Acc coupling was inversely related to trait anxiety sensitivity, as well as tonic and phasic daytime anxiety. The novel method that was used demonstrates that anxiety in PD may reduce efficient long-term metabolic coupling. Metabolic decoupling may serve as physiological characteristic of PD and might aid diagnostics for PD and other anxiety disorders. This measure deserves further study in research on health consequences of anxiety and psychosocial stress. © 2015 Elsevier Ltd.
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| 6. |
- Pfaltz, Monique C., et al.
(författare)
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Instability of physical anxiety symptoms in daily life of patients with panic disorder and patients with posttraumatic stress disorder
- 2010
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Ingår i: Journal of Anxiety Disorders. - : Elsevier BV. - 0887-6185 .- 1873-7897. ; 24:7, s. 792-798
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Tidskriftsartikel (refereegranskat)abstract
- The present study examined severity as well as degree and temporal pattern of instability of DSM-IV-based bodily symptoms of anxiety (BSA) in daily life of 26 panic disorder (PD) patients, 17 posttraumatic stress disorder (PTSD) patients, and 28 healthy controls (HC) during 1 week, using electronic diaries. The ecological momentary assessment around every 3. h during wake times was accepted well by patients. Compared to HC, patient groups exhibited elevated instability of BSA. BSA instability was more pronounced in PTSD than PD (p<0.005), even after controlling for mean symptom level. Numbers of symptomatic episodes were comparable in PTSD and PD, but the duration of symptom-free episodes was shorter in PTSD than PD. Results indicate that PTSD patients are particularly burdened by fluctuations in somatic symptoms of anxiety, implying perceived unpredictability and uncontrollability. Electronic diaries can be applied in innovative ways to provide novel insights into the phenomenology of anxiety disorders that may not be captured well by retrospective interviews and questionnaires. © 2010 Elsevier Ltd.
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| 7. |
- Pfaltz, Monique C., et al.
(författare)
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Physical activity and respiratory behavior in daily life of patients with panic disorder and healthy controls
- 2010
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Ingår i: International Journal of Psychophysiology. - : Elsevier BV. - 0167-8760 .- 1872-7697. ; 78:1, s. 42-49
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Tidskriftsartikel (refereegranskat)abstract
- Panic disorder (PD) has been linked in laboratory investigations to respiratory alterations, particularly persistent respiratory variability. However, studies of PD respiratory pattern outside the laboratory are rare, have not controlled for the confounding influence of varying levels of physical activity, and have not addressed whether abnormalities in respiratory pattern vary depending on the intensity of physical activity. Cognitive and biological theories of PD, in fact, predict that respiratory alterations may be particularly pronounced when patients are physically active. This study assessed physical activity and respiratory pattern of 26 PD patients and 26 healthy controls (HC) during two waking periods of daily life (9:00-21:00) one week apart. Respiratory data were stratified for predefined levels of physical activity (inactivity, minimal movement, slow/moderate/fast walking, and running) and analyzed using linear mixed models. Groups did not generally differ in respiratory measures, although PD patients did show elevated variability of absolute levels of tidal volume during minimal movement and slow walking (root mean squared successive differences). Other ways of analyzing tidal volume variability based on relative levels, percentage of sighing, or pooled activity levels did not substantiate this finding. Amount of time spent at different activity levels did not differ between groups, which is at variance with studies linking anticipatory anxiety with motoric agitation, and PD with self-reported avoidance of exercise. In conclusion, results provided little evidence for respiratory abnormalities or central respiratory dysregulation in PD at varying levels of activity, although instability of tidal volume regulation during low activity remains a possibility. Our research approach indicates the usefulness of stratification of real life data on the basis of levels of activity, as well as how ambulatory assessment strategies, complementarily to laboratory studies, may improve understanding of biological and psychological factors contributing to development and maintenance of PD and other anxiety disorders. © 2010 Elsevier B.V.
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| 8. |
- Woud, Marcella L., et al.
(författare)
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Investigating d-cycloserine as a potential pharmacological enhancer of an emotional bias learning procedure
- 2018
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Ingår i: Journal of Psychopharmacology. - : SAGE PUBLICATIONS LTD. - 0269-8811 .- 1461-7285. ; 32:5, s. 569-577
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Tidskriftsartikel (refereegranskat)abstract
- The partial N-methyl-D-aspartate receptor agonist d-cycloserine may enhance psychological therapies. However, its exact mechanism of action is still being investigated. Cognitive bias modification techniques allow isolation of cognitive processes and thus investigation of how they may be affected by d-cycloserine. We used a cognitive bias modification paradigm targeting appraisals of a stressful event, Cognitive Bias Modification-Appraisal, to investigate whether d-cycloserine enhanced the modification of appraisal, and whether it caused greater reduction in indices of psychopathology. Participants received either 250 mg of d-cycloserine (n=19) or placebo (n=19). As a stressor task, participants recalled a negative life event, followed by positive Cognitive Bias Modification-Appraisal training. Before and after Cognitive Bias Modification-Appraisal, appraisals and indices of psychopathology related to the stressor were assessed. Cognitive Bias Modification-Appraisal successfully modified appraisals, but d-cycloserine did not affect appraisals post-training. There were no post-training group differences in frequency of intrusions. Interestingly, d-cycloserine led to a greater reduction in distress and impact on state mood from recalling the event, and lower distress post-training was associated with fewer intrusions. Therefore, d-cycloserine may affect emotional reactivity to recalling a negative event when combined with induction of a positive appraisal style, but via a mechanism other than enhanced learning of the appraisal style.
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