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. |
- Koenig, Julian, et al.
(author)
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Cortical thickness and resting-state cardiac function across the lifespan : A cross-sectional pooled mega-analysis
- 2021
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In: Psychophysiology. - : Wiley. - 0048-5772 .- 1469-8986 .- 1540-5958. ; 58:7
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Journal article (peer-reviewed)abstract
- Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12–87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS—or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
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3. |
- Cortes, Diana S., et al.
(author)
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Oxytocin may facilitate neural recruitment in medial prefrontal cortex and superior temporal gyrus during emotion recognition in young but not older adults
- 2020
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In: 2020 Cognitive Aging Conference. ; , s. 22-23
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Conference paper (peer-reviewed)abstract
- Normal adult aging is associated with decline in some socioemotional abilities, such as the ability to recognize emotions in others, and age-related neurobiological processes may contribute to these deficits. There is increasing evidence that the neuropeptide oxytocin plays a key role in social cognition, including emotion recognition. The mechanisms through which oxytocin promotes emotion recognition are not well understood yet, and particularly in aging. In a randomized, double-blind, placebo-controlled within-subjects design, we investigated the extent to which a single dose of 40 IU of intranasal oxytocin facilitates emotion recognition in 40 younger (M = 24.90 yrs., SD = 2.97, 48% women) and 40 older (M = 69.70 yrs., SD = 2.99, 55% women) men and women. During two fMRI sessions, participants viewed dynamic positive and negative emotional displays. Preliminary analyses show that younger participants recognized positive and negative emotions more accurately than older participants (p < .001), with this behavioral effect not modulated by oxytocin. In the brain data, however, we found an age x treatment interaction in medial prefrontal cortex (xyz [14, 14, 6], p = .007) and superior temporal gyrus (xyz [53, 9, 2], p = .031). In particular, oxytocin (vs. placebo) reduced activity in these regions for older participants, while it enhanced activity in these regions for younger participants. In line with previous research, these findings support the notion that the effects of oxytocin vary by context and individual factors (e.g., social proficiency, age).
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4. |
- Forsström, David, 1981-, et al.
(author)
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Isolation and worry in relation to gambling and onset of gambling among psychiatry patients during the COVID-19 pandemic : A mediation study
- 2022
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In: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 13
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Journal article (peer-reviewed)abstract
- When the COVID-19 pandemic started spreading globally, there was a fear that addictive behaviors would increase due to changes in everyday life caused by restrictions due to COVID-19. Studies were carried out to explore if this was true for gambling, typically revealing no overall increase in gambling behavior, although individuals who had previous experience with gambling problems were more likely to increase gambling during the pandemic. However, these studies only included individuals with previous gambling problems. It remains unknown whether other vulnerable groups, such as individuals with common mental disorders increased their gambling. This study aimed to explore the level of gambling problems among individuals with a history of mental disorders, namely, (i) pre-pandemic gamblers and (ii) pandemic-onset gamblers. Furthermore, we explored if worry and isolation mediate gambling and problem gambling. The data were analyzed using descriptive statistics and a structural equation model to investigate mediation. The results showed a high prevalence of at-risk and problem gambling in both groups. The pre-pandemic gamblers had a high level of at-risk and problem gambling. Furthermore, the individuals that started to gamble during the pandemic had an even higher degree of at-risk and problem gambling. The mediation showed that the onset of gambling was linked with the worry of COVID-infection and that worry predicted the level of gambling problems. This study highlights that vulnerability factors, isolation, and worry can be triggers for individuals with common mental disorders to engage in gambling as well as the importance of screening this population for gambling problems.
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5. |
- Garke, Maria Å., et al.
(author)
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Improvements in emotion regulation during cognitive behavior therapy predict subsequent social anxiety reductions
- 2024
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In: Cognitive Behaviour Therapy. - : Routledge. - 1650-6073 .- 1651-2316.
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Journal article (peer-reviewed)abstract
- Individuals with social anxiety disorder (SAD) experience overall emotion regulation difficulties, but less is known about the long-term role of such difficulties in cognitive behavior therapy (CBT) for SAD. Forty-six patients with SAD receiving internet-delivered CBT, and matched healthy controls (HCs; n = 39), self-reported the Difficulties in Emotion Regulation Scale (DERS), Liebowitz Social Anxiety Scale (LSAS-SR), and participated in anticipatory speech anxiety behavioral experiments. Patients were measured at seven time points before, during and after CBT over a total period of 28 months, and HCs at two timepoints. Disaggregated growth curve models with a total of 263 observations were used, as well as intra-class correlation coefficients and regression models. Patients' LSAS-SR and DERS ratings were reliable (ICC = .83 and .75 respectively), and patients, relative to controls, showed larger difficulties in emotion regulation at pre-treatment (p < .001). During CBT, within-individual improvements in emotion regulation significantly predicted later LSAS-SR reductions (p = .041, pseudo-R2 = 43%). Changes in emotion regulation may thus be important to monitor on an individual level and may be used to improve outcomes in future developments of internet-delivered CBT.
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6. |
- Hjorth, Olof, et al.
(author)
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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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In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:8, s. 3970-3979
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Journal article (peer-reviewed)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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7. |
- Laukka, Petri, 1971-, et al.
(author)
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Neural correlates of individual differences in multimodal emotion recognition ability
- 2024
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In: Cortex. - : Elsevier. - 0010-9452 .- 1973-8102. ; 175, s. 1-11
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Journal article (peer-reviewed)abstract
- Studies have reported substantial variability in emotion recognition ability (ERA) – an important social skill – but possible neural underpinnings for such individual differences are not well understood. This functional magnetic resonance imaging (fMRI) study investigated neural responses during emotion recognition in young adults (N=49) who were selected for inclusion based on their performance (high or low) during previous testing of ERA. Participants were asked to judge brief video recordings in a forced-choice emotion recognition task, wherein stimuli were presented in visual, auditory and multimodal (audiovisual) blocks. Emotion recognition rates during brain scanning confirmed that individuals with high (vs. low) ERA received higher accuracy for all presentation blocks. fMRI-analyses focused on key regions of interest (ROIs) involved in the processing of multimodal emotion expressions, based on previous meta-analyses. In neural response to emotional stimuli contrasted with neutral stimuli, individuals with high (vs. low) ERA showed higher activation in the following ROIs during the multimodal condition: right middle superior temporal gyrus (mSTG), right posterior superior temporal sulcus (PSTS), and right inferior frontal cortex (IFC). Overall, results suggest that individual variability in ERA may be reflected across several stages of decisional processing, including extraction (mSTG), integration (PSTS) and evaluation (IFC) of emotional information.
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8. |
- Li, Xia, et al.
(author)
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A Quantitative Data-Driven Analysis Framework for Resting-State Functional Magnetic Resonance Imaging : A Study of the Impact of Adult Age
- 2021
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In: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 15
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Journal article (peer-reviewed)abstract
- The objective of this study is to introduce a new quantitative data-driven analysis (QDA) framework for the analysis of resting-state fMRI (R-fMRI) and use it to investigate the effect of adult age on resting-state functional connectivity (RFC). Whole-brain R-fMRI measurements were conducted on a 3T clinical MRI scanner in 227 healthy adult volunteers (N = 227, aged 18–76 years old, male/female = 99/128). With the proposed QDA framework we derived two types of voxel-wise RFC metrics: the connectivity strength index and connectivity density index utilizing the convolutions of the cross-correlation histogram with different kernels. Furthermore, we assessed the negative and positive portions of these metrics separately. With the QDA framework we found age-related declines of RFC metrics in the superior and middle frontal gyri, posterior cingulate cortex (PCC), right insula and inferior parietal lobule of the default mode network (DMN), which resembles previously reported results using other types of RFC data processing methods. Importantly, our new findings complement previously undocumented results in the following aspects: (1) the PCC and right insula are anti-correlated and tend to manifest simultaneously declines of both the negative and positive connectivity strength with subjects’ age; (2) separate assessment of the negative and positive RFC metrics provides enhanced sensitivity to the aging effect; and (3) the sensorimotor network depicts enhanced negative connectivity strength with the adult age. The proposed QDA framework can produce threshold-free and voxel-wise RFC metrics from R-fMRI data. The detected adult age effect is largely consistent with previously reported studies using different R-fMRI analysis approaches. Moreover, the separate assessment of the negative and positive contributions to the RFC metrics can enhance the RFC sensitivity and clarify some of the mixed results in the literature regarding to the DMN and sensorimotor network involvement in adult aging.
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9. |
- Li, Xia, et al.
(author)
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Dataset of whole-brain resting-state fMRI of 227 young and elderly adults acquired at 3T
- 2021
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In: Data in Brief. - : Elsevier BV. - 2352-3409. ; 38
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Journal article (peer-reviewed)abstract
- To investigate the impact of adult age on the brain functional connectivity, whole-brain resting-state functional magnetic resonance imaging (R-fMRI) data were acquired on a 3T clinical MRI scanner in a cohort of 227, right-handed, native Swedish-speaking, healthy adult volunteers (N=227, aged 18-74 years old, male/female=99/128). The dataset is mainly consisted of a younger (18-30 years old n=124, males/females=51/73) and elderly adult (n=76, 60-76 years old, males/females=35/41) subgroups. The dataset was analyzed using a new data-driven analysis (QDA) framework. With QDA two types of threshold-free voxel-wise resting-state functional connectivity (RFC) metrics were derived: the connectivity strength index (CSI) and connectivity density index (CDI), which can be utilized to assess the brain changes in functional connectivity associated with adult age. The dataset can also be useful as a reference to identify abnormal changes in brain functional connectivity resulted from neurodegenerative or neuropsychiatric disorders.
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10. |
- Lindqvist, Daniel, et al.
(author)
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Plasma circulating cell-free mitochondrial DNA in social anxiety disorder
- 2022
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In: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 148
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Journal article (peer-reviewed)abstract
- 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 (9-11 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. Plasma ccf-mtDNA did not significantly correlate with PBMC mtDNA-cn 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.
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11. |
- Månsson, Kristoffer N. T., et al.
(author)
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Anterior insula morphology and vulnerability to psychopathology-related symptoms in response to acute inflammation
- 2022
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In: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 99, s. 9-16
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Journal article (peer-reviewed)abstract
- Introduction: The role of inflammation in common psychiatric diseases is now well acknowledged. However, the factors and mechanisms underlying inter-individual variability in the vulnerability to develop psychopathology related symptoms in response to inflammation are not well characterized. Herein, we aimed at investigating morphological brain regions central for interoception and emotion regulation, and if these are associated with acute inflammation-induced sickness and anxiety responses.Methods: Systemic inflammation was induced using an intravenous injection of lipopolysaccharide (LPS) at a dose of 0.6 ng/kg body weight in 28 healthy individuals, while 21 individuals received an injection of saline (placebo). Individuals' gray matter volume was investigated by automated voxel-based morphometry technique on T1-weighted anatomical images derived from magnetic resonance imaging (MRI). Plasma concentrations of TNF alpha and IL-6, sickness symptoms (SicknessQ), and state anxiety (STAI-S) were measured before and after the injection.Results: A stronger sickness response to LPS was significantly associated with a larger anterior insula gray matter volume, independently from increases in cytokine concentrations, age, sex and body mass index (R-2 = 65.6%). Similarly, a greater LPS-induced state anxiety response was related to a larger anterior insula gray matter volume, and also by a stronger increase in plasma TNF-alpha concentrations (R-2 = 40.4%).Discussion: Anterior insula morphology appears central in the sensitivity to develop symptoms of sickness and anxiety in response to inflammation, and could thus be one risk factor in inflammation-related psychopathologies. Because of the limited sample size, the current results need to be replicated.
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12. |
- Månsson, Kristoffer N. T., et al.
(author)
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Enriching CBT by Neuroscience : Novel Avenues to Achieve Personalized Treatments
- 2021
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In: International Journal of Cognitive Therapy. - : Springer. - 1937-1209 .- 1937-1217. ; 14, s. 182-195
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Journal article (peer-reviewed)abstract
- Although cognitive behavioral therapy (CBT) is an established and efficient treatment for a variety of common mental disorders, a considerable number of patients do not respond to treatment or relapse after successful CBT. Recent findings and approaches from neuroscience could pave the way for clinical developments to enhance the outcome of CBT. Herein, we will present how neuroscience can offer novel perspectives to better understand (a) the biological underpinnings of CBT, (b) how we can enrich CBT with neuroscience-informed techniques (augmentation of CBT), and (c) why some patients may respond better to CBT than others (predictors of therapy outcomes), thus paving the way for more personalized and effective treatments. We will introduce some key topics and describe a selection of findings from CBT-related research using tools from neuroscience, with the hope that this will provide clinicians and clinical researchers with a brief and comprehensible overview of the field.
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13. |
- Månsson, Kristoffer N. T., et al.
(author)
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Moment-to-Moment Brain Signal Variability Reliably Predicts Psychiatric Treatment Outcome
- 2022
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In: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:7, s. 658-666
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Journal article (peer-reviewed)abstract
- Background: Biomarkers of psychiatric treatment response remain elusive. Functional magnetic resonance imaging (fMRI) has shown promise, but low reliability has limited the utility of typical fMRI measures (e.g., average brain signal) as harbingers of treatment success. Notably, although historically considered a source of noise, temporal brain signal variability continues to gain momentum as a sensitive and reliable indicator of individual differences in neural efficacy, yet has not been examined in relation to psychiatric treatment outcomes.Methods: A total of 45 patients with social anxiety disorder were scanned twice (11 weeks apart) using simple task-based and resting-state fMRI to capture moment-to-moment neural variability. After fMRI test-retest, patients underwent a 9-week cognitive behavioral therapy. Multivariate modeling and reliability-based cross-validation were used to perform brain-based prediction of treatment outcomes.Results: Task-based brain signal variability was the strongest contributor in a treatment outcome prediction model (total rACTUAL,PREDICTED = 0.77), outperforming self-reports, resting-state neural variability, and standard mean-based measures of neural activity. Notably, task-based brain signal variability showed excellent test-retest reliability (intraclass correlation coefficient = 0.80), even with a task length less than 3 minutes long.Conclusions: Rather than a source of undesirable noise, moment-to-moment fMRI signal variability may instead serve as a highly reliable and efficient prognostic indicator of clinical outcome.
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14. |
- Olivo, Gaia, et al.
(author)
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Estimated gray matter volume rapidly changes after a short motor task
- 2022
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In: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 32:19, s. 4356-4369
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Journal article (peer-reviewed)abstract
- Skill learning induces changes in estimates of gray matter volume (GMV) in the human brain, commonly detectable with magnetic resonance imaging (MRI). Rapid changes in GMV estimates while executing tasks may however confound between- and within-subject differences. Fluctuations in arterial blood flow are proposed to underlie this apparent task-related tissue plasticity. To test this hypothesis, we acquired multiple repetitions of structural T1-weighted and functional blood-oxygen level-dependent (BOLD) MRI measurements from 51 subjects performing a finger-tapping task (FTT; á 2 min) repeatedly for 30–60 min. Estimated GMV was decreased in motor regions during FTT compared with rest. Motor-related BOLD signal changes did not overlap nor correlate with GMV changes. Nearly simultaneous BOLD signals cannot fully explain task-induced changes in T1-weighted images. These sensitive and behavior-related GMV changes pose serious questions to reproducibility across studies, and morphological investigations during skill learning can also open new avenues on how to study rapid brain plasticity.
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15. |
- Rozental, Alexander, 1985-, et al.
(author)
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Mental health in individuals with self-reported psychiatric symptoms during the COVID-19 pandemic : Baseline data from a swedish longitudinal cohort study
- 2022
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In: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 13
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Journal article (peer-reviewed)abstract
- Objective: Individuals with psychiatric disorders may be both vulnerable and sensitive to rapid societal changes that have occurred during the COVID-19 pandemic. To fully understand these impacts, repeated measurements of these individuals are warranted. The current longitudinal study set out to perform monthly assessment of individuals with common psychiatric disorders using established questionnaires with a possibility for them to self- rate their symptoms, over time.Methods: Recruitment of individuals who identified themselves as struggling with mental health problems, living in Sweden between July 2020 and June 2021 using an online survey. The individuals answered questions on demographics, psychiatric history, current psychiatric symptoms (e.g., Patient Health Questionnaire, PHQ-9; General Anxiety Disorder, GAD-7), somatic health, health-care contacts and any changes therein during the pandemic. Monthly, longitudinal assessments are still ongoing (consenting participants provide data for 1 year), and here we present descriptive statistics from the baseline measurement. All measurements from baseline (>400 items), and follow-ups are presented in detail.Results: A total of 6.095 participants (average age 35 years) submitted complete baseline data. Marital status (43% single) and number of years of education (48% highest degree being high school) were evenly distributed in this population. The most common lifetime psychiatric disorder in the sample was depressive disorder (80.5%) and generalized anxiety disorder (45.9%), with a substantial proportion having severe symptoms of depression. (30.5%) and anxiety (37.1%). Lifetime suicidal ideation (75.0%) and non-suicidal self-harm (57.7%) were prevalent in the group and 14.5% reported drug use during the pandemic. Allergies (36.8%) were the most common somatic condition, followed by irritable bowel syndrome (18.7%). For those having experienced a traumatic event, 39% showed symptoms during the pandemic indicating PTSD. Regarding contact with mental health services during the pandemic, 22% had established a new contact, and 20% reported to have increased their psychiatric medication compared to before the pandemic.Conclusion: Baseline data collected during the pandemic from individuals in Sweden with pre-existing psychiatric disorders demonstrate that this sample represents a population suitable for an investigation on the long-term impact of the pandemic, as intended by the longitudinal investigation that is ongoing. Follow-up questionnaires over a 12-month period are being collected and will indicate how the health and well-being of this population was impacted during the changes and uncertainties that have been characteristic of the past 2 years.
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16. |
- Xiao, Shanshan, et al.
(author)
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Age-dependent effects of oxytocin in brain regions enriched with oxytocin receptors
- 2024
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In: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 160
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Journal article (peer-reviewed)abstract
- Although intranasal oxytocin administration to tap into central functions is the most commonly used non-invasive means for exploring oxytocin’s role in human cognition and behavior, the way by which intranasal oxytocin acts on the brain is not yet fully understood. Recent research suggests that brain regions densely populated with oxytocin receptors may play a central role in intranasal oxytocin’s action mechanisms in the brain. In particular, intranasal oxytocin may act directly on (subcortical) regions rich in oxytocin receptors via binding to these receptors while only indirectly affecting other (cortical) regions via their neural connections to oxytocin receptor-enriched regions. Aligned with this notion, the current study adopted a novel approach to test 1) whether the connections between oxytocin receptor-enriched regions (i.e., the thalamus, pallidum, caudate nucleus, putamen, and olfactory bulbs) and other regions in the brain were responsive to intranasal oxytocin administration, and 2) whether oxytocin-induced effects varied as a function of age. Forty-six young (24.96 ± 3.06 years) and 44 older (69.89 ± 2.99 years) participants were randomized, in a double-blind procedure, to self-administer either intranasal oxytocin or placebo before resting-state fMRI. Results supported age-dependency in the effects of intranasal oxytocin administration on connectivity between oxytocin receptor-enriched regions and other regions in the brain. Specifically, compared to placebo, oxytocin decreased both connectivity density and connectivity strength of the thalamus for young participants while it increased connectivity density and connectivity strength of the caudate for older participants. These findings inform the mechanisms underlying the effects of exogenous oxytocin on brain function and highlight the importance of age in these processes.
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