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1.
Behav Brain Res ; : 112994, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33160010

RESUMO

Cognitive-behavioral therapy (CBT), a first-line treatment for pediatric anxiety disorders, is based on principles of threat learning and extinction. However, CBT does not work sufficiently for up to 40% of clinically anxious youth. The neural and behavioral correlates of conditioned inhibition might provide promising targets for attempts to improve CBT response. During conditioned inhibition, threat and safety cues appear together, forming a safety compound. Here, we test whether this safety compound elicits a reduced fear response compared to pairing the threat cue with a novel cue (novel compound). The current pilot study compares behavioral, physiological, and neural correlates of conditioned inhibition between children with (n = 17, Mage = 13.09, SDage = 3.05) and without (n = 18, Mage = 14.49, SDage = 2.38) anxiety disorders. Behavioral and physiological measures did not differ between children with and without anxiety disorders during fear acquisition. During testing, children with anxiety disorders showed overall higher skin conductance response and expected to hear the aversive sound following the novel compound more often than children without anxiety disorders. Children with anxiety disorders showed more activity in the right ventromedial prefrontal cortex (vmPFC) to the safety versus novel compound. Children without anxiety disorders showed the opposite pattern - more right vmPFC activity to the novel versus safety compound (F(1,31) = 5.40, p = 0.03). No group differences manifested within the amygdala, dorsal anterior cingulate cortex, or hippocampus. These pilot findings suggest a feasible approach for examining conditioned inhibition in pediatric anxiety disorders. If replicated in larger samples, findings may implicate perturbed conditioned inhibition in pediatric anxiety disorders and provide targets for CBT.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33095373

RESUMO

This report examines the relationship between pediatric anxiety disorders and implicit bias evoked by threats. To do so, the report uses two tasks that assess implicit bias to negative-valence faces, the first by eye-gaze and the second by measuring body-movement parameters. The report contrasts task performance in 51 treatment-seeking, medication-free pediatric patients with anxiety disorders and 36 healthy peers. Among these youth, 53 completed an eye-gaze task, 74 completed a body-movement task, and 40 completed both tasks. On the eye-gaze task, patients displayed longer gaze duration on negative relative to non-negative valence faces than healthy peers, F(1, 174) = 8.27, p = .005. In contrast, on the body-movement task, patients displayed a greater tendency to behaviorally avoid negative-valence faces than healthy peers, F(1, 72) = 4.68, p = .033. Finally, implicit bias measures on the two tasks were correlated, r(38) = .31, p = .049. In sum, we found an association between pediatric anxiety disorders and implicit threat bias on two tasks, one measuring eye-gaze and the other measuring whole-body movements. Converging evidence for implicit threat bias encourages future research using multiple tasks in anxiety.

3.
Hum Brain Mapp ; 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32618421

RESUMO

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.

4.
Hum Brain Mapp ; 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32596977

RESUMO

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.

5.
Psychoneuroendocrinology ; 120: 104775, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32592873

RESUMO

To arrive at a coherent understanding of the relation between glucocorticoids and the human brain, we systematically reviewed the literature for studies examining the associations between endogenous or exogenous cortisol and human brain function. Higher levels of endogenous cortisol during psychological stress were related to increased activity in the middle temporal gyrus and perigenual anterior cingulate cortex (ACC), decreased activity in the ventromedial prefrontal cortex, and altered function (i.e., mixed findings, increased or decreased) in the amygdala, hippocampus and inferior frontal gyrus. Moreover, endogenous cortisol response to psychological stress was related to increased activity in the inferior temporal gyrus and altered function in the amygdala during emotional tasks that followed psychological stress. Exogenous cortisol administration was related to increased activity in the postcentral gyrus, superior frontal gyrus and ACC, and altered function in the amygdala and hippocampus during conditioning, emotional and reward-processing tasks after cortisol administration. These findings were in line with those from animal studies on amygdala activity during and after stress.

6.
Neuroimage ; 205: 116301, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31639510

RESUMO

Neuroimaging studies typically focus on either resting state or task-based fMRI data. Prior research has shown that similarity in functional connectivity between rest and cognitive tasks, interpreted as reconfiguration efficiency, is related to task performance and IQ. Here, we extend this approach from adults to children, and from cognitive tasks to a threat-based attention task. The goal of the current study was to examine whether similarity in functional connectivity during rest and an attention bias task relates to threat bias, IQ, anxiety symptoms, and social reticence. fMRI was measured during resting state and during the dot-probe task in 41 children (M = 13.44, SD = 0.70). Functional connectivity during rest and dot-probe was positively correlated, suggesting that functional hierarchies in the brain are stable. Similarity in functional connectivity between rest and the dot-probe task only related to threat bias (puncorr < .03). This effect did not survive correction for multiple testing. Overall, children who allocate more attention towards threat also may possess greater reconfiguration efficiency in switching from intrinsic to threat-related attention states. Finally, functional connectivity correlated negatively across the two conditions of the dot-probe task. Opposing patterns of modulation of functional connectivity by threat-congruent and threat-incongruent trials may reflect task-specific network changes during two different attentional processes.

7.
Depress Anxiety ; 36(8): 701-711, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31373756

RESUMO

BACKGROUND: Clinical researchers face challenges when trying to quantify diverse processes engaged during social interactions. We report results from two studies, each demonstrating the potential utility of tools for examining processes engaged during social interactions. METHOD: In the first study, youth (n = 57) used a smartphone-based tool to rate mood and responses to social events. A subset (n = 20) completed the second, functional magnetic resonance imaging study. This second study related anxiety to error-evoked brain responses in two social conditions-while being observed and when alone. We also combined these tools to bridge clinical, social-contextual, and neural levels of measurement. RESULTS: Results from the first study showed an association between negatively-perceived social experiences and a range of negative emotions. In the second study there was a positive correlation during error monitoring between social-anxiety severity and context-specific activation of the pregenual anterior cingulate cortex. Finally, during imaging, the perceived quality of peer interactions as assessed using the smartphone-based tool, interacted with social context to predict levels of activation in the hippocampus and superior frontal gyrus. CONCLUSIONS: By improving measurement, enhanced tools may provide new means for studying relationships among anxiety, brain function, and social interactions.


Assuntos
Encéfalo/fisiopatologia , Relações Interpessoais , Imagem por Ressonância Magnética/métodos , Fobia Social/diagnóstico , Fobia Social/psicologia , Adolescente , Mapeamento Encefálico , Criança , Medo/fisiologia , Medo/psicologia , Feminino , Humanos , Masculino , Fobia Social/fisiopatologia , Smartphone
8.
Artigo em Inglês | MEDLINE | ID: mdl-31324591

RESUMO

BACKGROUND: Aberrations in both neural reward processing and stress reactivity are associated with increased risk for mental illness; yet, how these two factors relate to each other remains unclear. Several studies suggest that stress exposure impacts reward function, thus increasing risk for psychopathology. However, the alternative hypothesis, in which reward dysfunction impacts stress reactivity, has been rarely examined. The current study aimed to test both hypotheses using a longitudinal design. METHODS: Participants were 38 children (23 girls; 61%) from a prospective cohort study. A standard stress-exposure measure was collected at 7 years of age. Children performed a well-validated imaging reward paradigm at age 10, and a standardized acute psychological stress laboratory protocol was administered both at age 10 and at age 13. Structural equation modeling was used to examine bidirectional associations between stress and neural response to reward anticipation. RESULTS: Higher exposure to stressful life events at age 7 predicted lower neural response to reward anticipation in regions of the basal ganglia at age 10, which included ventral caudate, nucleus accumbens, putamen, and globus pallidus. Lower response to reward anticipation in medial prefrontal and anterior cingulate cortex predicted higher stress reactivity at age 13. CONCLUSIONS: Our findings provide support for bidirectional associations between stress and reward processing, in that stress may impact reward anticipation, but also in that reduced reward anticipation may increase susceptibility to stress.


Assuntos
Encéfalo/fisiopatologia , Depressão/fisiopatologia , Neuroimagem , Recompensa , Estresse Psicológico/fisiopatologia , Adolescente , Antecipação Psicológica/fisiologia , Criança , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Neuroimagem/métodos , Estudos Prospectivos
9.
Cogn Affect Behav Neurosci ; 18(4): 764-777, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29777479

RESUMO

Cross-frequency coupling (CFC) between frontal delta (1-4 Hz) and beta (14-30 Hz) oscillations has been suggested as a candidate neural correlate of social anxiety disorder, a disorder characterized by fear and avoidance of social and performance situations. Prior studies have used amplitude-amplitude correlation (AAC) as a CFC measure and hypothesized it as a candidate neural mechanism of affective control. However, using this metric has yielded inconsistent results regarding the direction of CFC, and the functional significance of coupling strength is uncertain. To offer a better understanding of CFC in social anxiety, we compared frontal delta-beta AAC with phase-amplitude coupling (PAC) - a mechanism for information transfer through neural circuits. Twenty high socially anxious (HSA) and 32 low socially anxious (LSA) female undergraduates participated in a social performance task (SPT). Delta-beta PAC and AAC were estimated during the resting state, as well as the anticipation and recovery conditions. Results showed significantly more AAC in LSA than HSA participants during early anticipation, as well as significant values during all conditions in LSA participants only. PAC did not distinguish between LSA and HSA participants, and instead was found to correlate with state nervousness during early anticipation, but in LSA participants only. Together, these findings are interpreted to suggest that delta-beta AAC is a plausible neurobiological index of adaptive stress regulation and can distinguish between trait high and low social anxiety during stress, while delta-beta PAC might be sensitive enough to reflect mild state anxiety in LSA participants.


Assuntos
Ansiedade/fisiopatologia , Ritmo beta , Encéfalo/fisiopatologia , Ritmo Delta , Personalidade/fisiologia , Comportamento Social , Adaptação Psicológica/fisiologia , Adolescente , Adulto , Antecipação Psicológica/fisiologia , Ritmo beta/fisiologia , Ritmo Delta/fisiologia , Feminino , Humanos , Estresse Psicológico/fisiopatologia , Adulto Jovem
10.
Int J Methods Psychiatr Res ; 27(2): e1616, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29700902

RESUMO

OBJECTIVES: Social anxiety disorder (SAD) is a serious and prevalent psychiatric condition, with a heritable component. However, little is known about the characteristics that are associated with the genetic component of SAD, the so-called "endophenotypes". These endophenotypes could advance our insight in the genetic susceptibility to SAD, as they are on the pathway from genotype to phenotype. The Leiden Family Lab study on Social Anxiety Disorder (LFLSAD) is the first multiplex, multigenerational study aimed to identify neurocognitive endophenotypes of social anxiety. METHODS: The LFLSAD is characterized by a multidisciplinary approach and encompasses a variety of measurements, including a clinical interview, functional and structural magnetic resonance imaging and an electroencephalography experiment. Participants are family members from 2 generations, from families genetically enriched for SAD. RESULTS: The sample (n = 132 participants, from 9 families) was characterized by a high prevalence of SAD, in both generations (prevalence (sub)clinical SAD: 38.3%). Furthermore, (sub)clinical SAD was positively related to self-reported social anxiety, fear of negative evaluation, trait anxiety, behavioral inhibition, negative affect, and the level of depressive symptoms. CONCLUSIONS: By the multidimensional character of the measurements and thorough characterization of the sample, the LFLSAD offers unique opportunities to investigate candidate neurocognitive endophenotypes of SAD.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Conectoma/métodos , Endofenótipos , Fobia Social/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Adolescente , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Criança , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/genética , Estudos Transversais , Eletroencefalografia , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Linhagem , Fobia Social/complicações , Fobia Social/diagnóstico por imagem , Fobia Social/genética , Córtex Pré-Frontal/diagnóstico por imagem , Adulto Jovem
11.
Neuroimage Clin ; 17: 549-562, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29527481

RESUMO

Social anxiety disorder is an invalidating psychiatric disorder characterized by extreme fear and avoidance of one or more social situations in which patients might experience scrutiny by others. The goal of this two-generation family study was to delineate behavioral and electrocortical endophenotypes of social anxiety disorder related to social evaluation. Nine families of patients with social anxiety disorder (their spouse and children, and siblings of these patients with spouse and children) performed a social judgment paradigm in which they believed to be evaluated by peers. For each peer, participants indicated their expectation about the evaluative outcome, after which they received social acceptance or rejection feedback. Task behavior, as well as the feedback-related EEG brain potentials (N1, FRN, P3) and theta power were tested as candidate endophenotypes based on two criteria: co-segregation with social anxiety disorder within families and heritability. Results indicated that reaction time for indicating acceptance-expectations might be a candidate behavioral endophenotype of social anxiety disorder, possibly reflecting increased uncertainty or self-focused attention and vigilance during the social judgment paradigm. N1 in response to expected rejection feedback and P3 in response to acceptance feedback might be candidate electrocortical endophenotypes of social anxiety disorder, although the heritability analyses did not remain significant after correcting for multiple tests. Increased N1 possibly reflects hypervigilance to socially threatening stimuli, and increased P3 might reflect that positive feedback is more important for, and/or less expected by, participants with social anxiety disorder. Finally, increased feedback-related negativity and theta power in response to unexpected rejection feedback compared to the other conditions co-segregated with social anxiety disorder, but these EEG measures were not heritable. The candidate endophenotypes might play a new and promising role in future research on genetic mechanisms, early detection and/or prevention of social anxiety disorder.


Assuntos
Potenciais Evocados/fisiologia , Saúde da Família , Fobia Social/fisiopatologia , Fobia Social/psicologia , Adolescente , Adulto , Criança , Eletroencefalografia , Retroalimentação Sensorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Escalas de Graduação Psiquiátrica , Fatores de Tempo , Adulto Jovem
12.
Biol Psychol ; 135: 18-28, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29524466

RESUMO

The current study examined neural and behavioral responses to social-evaluative feedback processing in social anxiety. Twenty-two non-socially and 17 socially anxious females (mean age = 19.57 years) participated in a Social Judgment Paradigm in which they received peer acceptance/rejection feedback that was either congruent or incongruent with their prior predictions. Results indicated that socially anxious participants believed they would receive less social acceptance feedback than non-socially anxious participants. EEG results demonstrated that unexpected social rejection feedback elicited a significant increase in theta (4-8 Hz) power relative to other feedback conditions. This theta response was only observed in non-socially anxious individuals. Together, results corroborate cognitive-behavioral studies demonstrating a negative expectancy bias in socially anxiety with respect to social evaluation. Furthermore, the present findings highlight a functional role for theta oscillatory dynamics in processing cues that convey social-evaluative threat, and this social threat-monitoring mechanism seems less sensitive in socially anxious females.


Assuntos
Ansiedade/fisiopatologia , Retroalimentação Psicológica/fisiologia , Julgamento/fisiologia , Grupo Associado , Ritmo Teta , Ansiedade/psicologia , Eletroencefalografia , Feminino , Humanos , Adulto Jovem
13.
J Affect Disord ; 227: 398-405, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29154156

RESUMO

BACKGROUND: Social anxiety disorder (SAD) is characterized by an extreme and intense fear and avoidance of social situations. In this two-generation family study we examined delta-beta correlation during a social performance task as candidate endophenotype of SAD. METHODS: Nine families with a target participant (diagnosed with SAD), their spouse and children, as well as target's siblings with spouse and children performed a social performance task in which they gave a speech in front of a camera. EEG was measured during resting state, anticipation, and recovery. Our analyses focused on two criteria for endophenotypes: co-segregation within families and heritability. RESULTS: Co-segregation analyses revealed increased negative delta-low beta correlation during anticipation in participants with (sub)clinical SAD compared to participants without (sub)clinical SAD. Heritability analyses revealed that delta-low beta and delta-high beta correlation during anticipation were heritable. Delta-beta correlation did not differ between participants with and without (sub)clinical SAD during resting state or recovery, nor between participants with and without SAD during all phases of the task. LIMITATIONS: It should be noted that participants were seen only once, they all performed the EEG tasks in the same order, and some participants were too anxious to give a speech. CONCLUSIONS: Delta-low beta correlation during anticipation of giving a speech might be a candidate endophenotype of SAD, possibly reflecting increased crosstalk between cortical and subcortical regions. If validated as endophenotype, delta-beta correlation during anticipation could be useful in studying the genetic basis, as well as improving treatment and early detection of persons at risk for developing SAD.


Assuntos
Ritmo beta/genética , Ritmo Delta/genética , Eletroencefalografia , Endofenótipos , Estudos de Associação Genética , Fobia Social/genética , Adolescente , Adulto , Nível de Alerta/genética , Nível de Alerta/fisiologia , Ritmo beta/fisiologia , Criança , Ritmo Delta/fisiologia , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Fobia Social/diagnóstico , Fobia Social/fisiopatologia , Fobia Social/psicologia , Estatística como Assunto
14.
Biol Psychol ; 129: 324-348, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28964790

RESUMO

Social anxiety disorder (SAD) is characterized by information processing biases, however, their underlying neural mechanisms remain poorly understood. The goal of this review was to give a comprehensive overview of the most frequently studied EEG spectral and event-related potential (ERP) measures in social anxiety during rest, anticipation, stimulus processing, and recovery. A Web of Science search yielded 35 studies reporting on electrocortical measures in individuals with social anxiety or related constructs. Social anxiety was related to increased delta-beta cross-frequency correlation during anticipation and recovery, and information processing biases during early processing of faces (P1) and errors (error-related negativity). These electrocortical measures are discussed in relation to the persistent cycle of information processing biases maintaining SAD. Future research should further investigate the mechanisms of this persistent cycle and study the utility of electrocortical measures in early detection, prevention, treatment and endophenotype research.


Assuntos
Ansiedade/fisiopatologia , Encéfalo/fisiopatologia , Potenciais Evocados/fisiologia , Fobia Social/fisiopatologia , Cognição/fisiologia , Humanos
15.
Psychoneuroendocrinology ; 63: 26-33, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26402923

RESUMO

Gaze avoidance is one of the most characteristic and persistent social features in people with Social Anxiety Disorder (SAD). It signals social submissiveness and hampers adequate social interactions. Patients with SAD typically show reduced testosterone levels, a hormone that facilitates socially dominant gaze behavior. Therefore we tested as a proof of principle whether single dose testosterone administration can reduce gaze avoidance in SAD. In a double-blind, within-subject design, 18 medication-free female participants with SAD and 19 female healthy control participants received a single dose of 0.5mg testosterone and a matched placebo, at two separate days. On each day, their spontaneous gaze behavior was recorded using eye-tracking, while they looked at angry, happy, and neutral facial expressions. Testosterone enhanced the percentage of first fixations to the eye-region in participants with SAD compared to healthy controls. In addition, SAD patients' initial gaze avoidance in the placebo condition was associated with more severe social anxiety symptoms and this relation was no longer present after testosterone administration. These findings indicate that single dose testosterone administration can alleviate gaze avoidance in SAD. They support theories on the dominance enhancing effects of testosterone and extend those by showing that effects are particularly strong in individuals featured by socially submissive behavior. The finding that this core characteristic of SAD can be directly influenced by single dose testosterone administration calls for future inquiry into the clinical utility of testosterone in the treatment of SAD.


Assuntos
Androgênios/farmacologia , Fixação Ocular/efeitos dos fármacos , Transtornos Fóbicos/tratamento farmacológico , Comportamento Social , Testosterona/farmacologia , Mulheres/psicologia , Adolescente , Adulto , Androgênios/uso terapêutico , Estudos de Casos e Controles , Método Duplo-Cego , Medições dos Movimentos Oculares , Movimentos Oculares , Expressão Facial , Feminino , Humanos , Transtornos Fóbicos/psicologia , Testosterona/uso terapêutico , Adulto Jovem
16.
Front Hum Neurosci ; 7: 936, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24478667

RESUMO

Cognitive models posit that the fear of negative evaluation (FNE) is a hallmark feature of social anxiety. As such, individuals with high FNE may show biased information processing when faced with social evaluation. The aim of the current study was to examine the neural underpinnings of anticipating and processing social-evaluative feedback, and its correlates with FNE. We used a social judgment paradigm in which female participants (N = 31) were asked to indicate whether they believed to be socially accepted or rejected by their peers. Anticipatory attention was indexed by the stimulus preceding negativity (SPN), while the feedback-related negativity and P3 were used to index the processing of social-evaluative feedback. Results provided evidence of an optimism bias in social peer evaluation, as participants more often predicted to be socially accepted than rejected. Participants with high levels of FNE needed more time to provide their judgments about the social-evaluative outcome. While anticipating social-evaluative feedback, SPN amplitudes were larger for anticipated social acceptance than for social rejection feedback. Interestingly, the SPN during anticipated social acceptance was larger in participants with high levels of FNE. None of the feedback-related brain potentials correlated with the FNE. Together, the results provided evidence of biased information processing in individuals with high levels of FNE when anticipating (rather than processing) social-evaluative feedback. The delayed response times in high FNE individuals were interpreted to reflect augmented vigilance imposed by the upcoming social-evaluative threat. Possibly, the SPN constitutes a neural marker of this vigilance in females with higher FNE levels, particularly when anticipating social acceptance feedback.

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