Neural correlates of context-dependent extinction recall in social anxiety disorder: relevance of intrusions in response to aversive social experiences.

BACKGROUND: There are phenomenological similarities between social anxiety disorder (SAD) and posttraumatic stress disorder, such as a provoking aversive event, posttraumatic stress symptoms (e.g. intrusions) in response to these events and deficient (context-dependent) fear conditioning processes. This study investigated the neural correlates of context-dependent extinction recall and fear renewal in SAD, specifically in patients with intrusions in response to an etiologically relevant aversive social event. METHODS: During functional magnetic resonance imaging a two-day context-dependent fear conditioning paradigm was conducted in 54 patients with SAD and 54 healthy controls (HC). This included fear acquisition (context A) and extinction learning (context B) on one day, and extinction recall (context B) as well as fear renewal (contexts C and A) one day later. The main outcome measures were blood oxygen level-dependent responses in regions of interest and skin conductance responses. RESULTS: Patients with SAD showed reduced differential conditioned amygdala activation during extinction recall in the safe extinction context and during fear renewal in the acquisition context compared to HC. Patients with clinically relevant intrusions moreover exhibited hypoactivation of the ventromedial prefrontal cortex (vmPFC) during extinction learning, extinction recall, and fear renewal in a novel context, while amygdala activation more strongly decreased during extinction learning and increased during fear renewal in the acquisition context compared with patients without intrusions. CONCLUSIONS: Our study provides first evidence that intrusions in SAD are associated with similar deficits in context-dependent regulation of conditioned fear via the vmPFC as previously demonstrated in posttraumatic stress disorder.

Correspondence to Antici et al. Salivary CRP predicts treatment response to virtual reality exposure therapy for social anxiety disorder.

The study by Antici et al. (2024) investigates the effects of virtual reality exposure therapy on social anxiety disorder (SAD), focusing on the relationship between C-reactive protein (CRP) levels in saliva and therapy outcomes. Findings indicate that this therapy not only reduces SAD symptoms and discomfort but also correlates with decreased systemic inflammation, as evidenced by lowered CRP levels. Remarkably, higher baseline CRP levels predicted a greater reduction in anxiety symptoms, suggesting a unique response pattern in SAD compared to other psychological disorders. This study highlights systemic inflammation's significance in SAD and the promise of non-invasive biomarkers like salivary CRP for managing psychological disorders. It calls for more research to understand the underlying mechanisms and validate these initial findings.

Social fear extinction susceptibility is associated with Microbiota-Gut-Brain axis alterations.

Social anxiety disorder is a common psychiatric condition that severely affects quality of life of individuals and is a significant societal burden. Although many risk factors for social anxiety exist, it is currently unknown how social fear sensitivity manifests biologically. Furthermore, since some individuals are resilient and others are susceptible to social fear, it is important to interrogate the mechanisms underpinning individual response to social fear situations. The microbiota-gut-brain axis has been associated with social behaviour, has recently been linked with social anxiety disorder, and may serve as a therapeutic target for modulation. Here, we assess the potential of this axis to be linked with social fear extinction processes in a murine model of social anxiety disorder. To this end, we correlated differential social fear responses with microbiota composition, central gene expression, and immune responses. Our data provide evidence that microbiota variability is strongly correlated with alterations in social fear behaviour. Moreover, we identified altered gene candidates by amygdalar transcriptomics that are linked with social fear sensitivity. These include genes associated with social behaviour (Armcx1, Fam69b, Kcnj9, Maoa, Serinc5, Slc6a17, Spata2, and Syngr1), inflammation and immunity (Cars, Ckmt1, Klf5, Maoa, Map3k12, Pex5, Serinc5, Sidt1, Spata2), and microbe-host interaction (Klf5, Map3k12, Serinc5, Sidt1). Together, these data provide further evidence for a role of the microbiota-gut-brain axis in social fear responses.

Salivary CRP predicts treatment response to virtual reality exposure therapy for social anxiety disorder.

BACKGROUND: Social anxiety disorder (SAD) places a profound burden on public health and individual wellbeing. Systemic inflammation may be important to the onset and maintenance of SAD, and anti-inflammatory treatments have shown promise in relieving symptoms of SAD. In the present study, we conducted secondary analyses on data from a randomized clinical trial to determine whether C-reactive protein (CRP) concentrations and social anxiety symptoms decreased over the course of virtual reality exposure therapy, and whether changes in social anxiety symptoms as a function of treatment varied as a function of CRP. METHOD: Adult participants (N = 78) with a diagnosis of SAD (59 % female) were randomized to receive exposure therapy alone, or exposure therapy supplemented with scopolamine. Social anxiety symptoms, salivary CRP, and subjective units of distress were measured across three exposure therapy sessions, at a post-treatment extinction retest, and at a 1-month follow-up. RESULTS: CRP decreased over the course of treatment, b = -0.03 (SE = 0.01), p =.02 95 %CI [-0.06, -0.004], as did all social anxiety symptom domains and subjective distress. Higher CRP was associated with greater decreases from pre-treatment to 1-month follow-up in fear, b = -0.45 (SE = 0.15), p =.004 95 %CI [-0.74, -0.15], and avoidance, b = -0.62 (SE = 0.19), p =.002 95 %CI [-1.01, -0.23], and in-session subjective distress from pre-treatment to post-treatment, b = -0.42 (SE = 0.21), p =.05 95 %CI [-0.83, -0.001]. However, declines in CRP were not correlated with declines in fear, r = -0.07, p =.61, or avoidance, r = -0.10, p =.49, within-persons. CONCLUSIONS: Virtual reality exposure therapy may be associated with an improvement in systemic inflammation in patients with severe SAD. Pre-treatment CRP may also be of value in predicting which patients stand to benefit the most from this treatment.

Emotional Changes during Imagery Rescripting of Aversive Social Memories in Social Anxiety Disorder: A Randomized Controlled Trial.

INTRODUCTION: Imagery rescripting (ImRs) is a psychotherapeutic intervention targeting aversive memories. During the three-phase intervention, patients reexperience their aversive memory (phase 1), observe the scene from their adult perspective, and intervene to help their former selves (phase 2), and reexperience it again with the positive changes (phase 3). Previous studies have rarely investigated emotional and regulatory processes taking place during the intervention. OBJECTIVE: This randomized controlled trial investigated self-reported affective and physiological responses during ImRs. METHODS: Seventy-seven patients with social anxiety disorder (SAD) were randomly assigned to a single session of ImRs or a control intervention (recall and discussion of the memory) targeting an aversive social memory. Heart rate (HR) and heart rate variability (HRV) were assessed during and post hoc ratings of positive and negative feelings after baseline and the intervention phases. RESULTS: Relative to the control intervention, ImRs resulted in an initial increase in negative feelings from baseline to phase 1 and a following larger (phase 1 to phase 2) and more stable (phase 2 to phase 3) decrease in negative feelings/increase in positive feelings. On the physiological level, during ImRs compared to the control intervention, mean HR was significantly higher during phase 1 and HRV during phase 3, each compared to baseline. CONCLUSIONS: These results provide further information about the specific sequence of emotional responses on different response levels during ImRs, being consistent with known theories of emotional processing and supposed mechanisms of ImRs.

Antipsychotic agents in anxiety disorders: An umbrella review.

BACKGROUND: Although not approved for the treatment of anxiety disorders (except trifluoperazine) there is ongoing off-label, unapproved use of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) for anxiety disorders. There have been systematic reviews and meta-analyses on the use of antipsychotics in anxiety disorders, most of which focused on SGAs. OBJECTIVE: The specific aims of this umbrella review are to: (1) Evaluate the evidence of efficacy of FGAs and SGAs in anxiety disorders as an adjunctive treatment to traditional antidepressant treatments and other nonantipsychotic medications; (2) Compare monotherapy with antipsychotics to first-line treatments for anxiety disorders in terms of effectiveness, risks, and side effects. The review protocol is registered on PROSPERO (CRD42021237436). METHODS: An initial search was undertaken to identify systematic reviews and meta-analyses from inception until 2020, with an updated search completed August 2021 and January 2023. The searches were conducted in PubMed, MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), CINAHL Complete (EBSCOhost), and the Cochrane Library through hand searches of references of included articles. Review quality was measured using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) scale. RESULTS: The original and updated searches yielded 1796 and 3744 articles respectively, of which 45 were eligible. After final review, 25 systematic reviews and meta-analyses were included in the analysis. Most of the systematic reviews and meta-analyses were deemed low-quality through AMSTAR-2 with only one review being deemed high-quality. In evaluating the monotherapies with antipsychotics compared with first-line treatments for anxiety disorder there was insufficient evidence due to flawed study designs (such as problems with randomization) and small sample sizes within studies. There was limited evidence suggesting efficacy of antipsychotic agents in anxiety disorders other than quetiapine in generalized anxiety disorder (GAD). CONCLUSIONS: This umbrella review indicates a lack of high-quality studies of antipsychotics in anxiety disorders outside of the use of quetiapine in GAD. Although potentially effective for anxiety disorders, FGAs and SGAs may have risks and side effects that outweigh their efficacy, although there were limited data. Further long-term and larger-scale studies of antipsychotics in anxiety disorders are needed.

Altered single-subject gray matter structural networks in social anxiety disorder.

Previous fMRI studies have reported more random brain functional graph configurations in social anxiety disorder (SAD). However, it is still unclear whether the same configurations would occur in gray matter (GM) graphs. Structural MRI was performed on 49 patients with SAD and on 51 age- and gender-matched healthy controls (HC). Single-subject GM networks were obtained based on the areal similarities of GM, and network topological properties were analyzed using graph theory. Group differences in each topological metric were compared, and the structure-function coupling was examined. These network measures were further correlated with the clinical characteristics in the SAD group. Compared with controls, the SAD patients demonstrated globally decreased clustering coefficient and characteristic path length. Altered topological properties were found in the fronto-limbic and sensory processing systems. Altered metrics were associated with the illness duration of SAD. Compared with the HC group, the SAD group exhibited significantly decreased structural-functional decoupling. Furthermore, structural-functional decoupling was negatively correlated with the symptom severity in SAD. These findings highlight less-optimized topological configuration of the brain structural networks in SAD, which may provide insights into the neural mechanisms underlying the excessive fear and avoidance of social interactions in SAD.

Disrupted brain gray matter connectome in social anxiety disorder: a novel individualized structural covariance network analysis.

Phenotyping approaches grounded in structural network science can offer insights into the neurobiological substrates of psychiatric diseases, but this remains to be clarified at the individual level in social anxiety disorder (SAD). Using a recently developed approach combining probability density estimation and Kullback-Leibler divergence, we constructed single-subject structural covariance networks (SCNs) based on multivariate morphometry (cortical thickness, surface area, curvature, and volume) and quantified their global/nodal network properties using graph-theoretical analysis. We compared network metrics between SAD patients and healthy controls (HC) and analyzed the relationship to clinical characteristics. We also used support vector machine analysis to explore the ability of graph-theoretical metrics to discriminate SAD patients from HC. Globally, SAD patients showed higher global efficiency, shorter characteristic path length, and stronger small-worldness. Locally, SAD patients showed abnormal nodal centrality mainly involving left superior frontal gyrus, right superior parietal lobe, left amygdala, right paracentral gyrus, right lingual, and right pericalcarine cortex. Altered topological metrics were associated with the symptom severity and duration. Graph-based metrics allowed single-subject classification of SAD versus HC with total accuracy of 78.7%. This finding, that the topological organization of SCNs in SAD patients is altered toward more randomized configurations, adds to our understanding of network-level neuropathology in SAD.

The Bergen 4-day treatment for social anxiety disorder: a pilot study.

BACKGROUND: Few studies have examined the use of concentrated and intensified cognitive behaviour therapy for treating social anxiety disorder (SAD). The aim of this study was to examine the feasibility of the Bergen 4-Day Treatment (B4DT) for treating SAD. METHODS: This study adopted an open trial design without a control group. Thirty consecutively referred patients who were diagnosed with SAD were treated and assessed at pre-treatment, at post-treatment, and at the 3-month follow-up. The Liebowitz Social Anxiety Scale was used to assess symptoms of SAD; the Generalized Anxiety Disorder-7 scale was used to assess anxiety symptoms; and the Patient Health Questionnaire-9 was used to assess symptoms of anxiety and depression. The Client Satisfaction Questionnaire-8 was administered posttreatment. RESULTS: Overall, patients reported a high level of satisfaction with the B4DT. Large effect sizes were observed for symptoms of SAD (d = 1.94-2.66) and for the secondary outcomes, i.e., generalized anxiety (d = 0.86-0.99) and depression (d = 0.62-0.83). The remission rate was 55.2% at follow-up, while the treatment response rate was 89.7%. CONCLUSIONS: The B4DT is a promising treatment approach for patients with SAD. In the future, controlled trials should be performed to compare the efficacy of this treatment approach with standard outpatient treatment. Practical consequences, policy implications, and suggestions for future research are discussed herein.

Effect of fasedienol (PH94B) pherine nasal spray and steroidal hormones on electrogram responses and autonomic nervous system activity in healthy adult volunteers.

OBJECTIVE: Fasedienol (PH94B) is a pherine compound formulated as a nasal spray that is hypothesized to regulate olfactory-amygdala circuits of fear and anxiety. Fasedienol's effect on the local electrogram of nasal chemosensory neurons (EGNR) and autonomic nervous system (ANS) responses versus steroidal hormones and controls in healthy adults is reported. METHODS: Eight males and 8 females randomly received aerosolized control (propylene glycol) and study drugs (fasedienol, 17ß-estradiol, progesterone, cortisol, and testosterone, 0.4 µg each in propylene glycol) onto the nasal septum mucosal lining at 30-min intervals over 2 sessions. EGNR was continuously monitored; autonomic parameters were recorded before and after administration. RESULTS: Fasedienol significantly increased EGNR amplitude (males: 5.0 vs. 0.6 mV, p < 0.001; females:5.7 vs. 0.6 mV, p < 0.001), and rapidly reduced respiratory rate (p < 0.05), heart rate (p < 0.01), and electrodermal activity (p < 0.05) versus control. EGNR and ANS responses after steroidal hormone administration were similar to control. 81% reported feeling less tense/more relaxed after receiving fasedienol, but not after receiving either control or steroidal hormones. CONCLUSIONS: Intranasal fasedienol, but not control or steroidal hormones, activated EGNR and rapidly reduced ANS responses, consistent with sympatholytic effects. Combined with subjective reports, results suggest fasedienol may provide acute relief in anxiety conditions.

Risk factor patterns define social anxiety subtypes in adolescents with brain and clinical feature differences.

Social anxiety disorder (SAD) is one of the most common psychiatric disorders in adolescents. The heterogeneity of both symptoms and etiology is an essential source of difficulties in the treatment and prevention of SAD. The study aimed to identify subtypes of adolescent SAD based on etiology-related phenotype dimensions and examine symptom and brain associations of the subtypes. We used a deeply phenotyped sample (47 phenotype subscales from 13 measures) of adolescents with SAD (n = 196) and healthy controls (n = 109) to extract etiology-relevant risk factors, based on which we identified subtypes of SAD. We compared the subtypes on clinical characteristics and brain morphometrics and functional connectivity, and examined subtype-specific links between risk factors, brain aberrance, and clinical characteristics. We identified six etiology-relevant risk factors and two subtypes of adolescent SAD. One subtype showed mainly elevated negative emotionality trait and coping style and diminished positive emotionality trait and coping style, while the other additionally had significantly high environmental risk factors, more severe impairments in social functioning, and significant abnormalities in brain structure and function. There were subtype-specific links between the risk factor profiles, brain aberrance, and clinical characteristics. The finding suggests two etiology-based subtypes of adolescent SAD, providing novel insights to the diversity of pathological pathways and precise intervention strategies.

The psychometric properties of the Mini Social Phobia Inventory in a treatment seeking sample of children and their caregivers.

The Mini Social Phobia Inventory (Mini-SPIN) is a short 3-item measure of social anxiety disorder (SAD). Using existing data, the current study examined the psychometric properties of the Mini-SPIN using a large, treatment seeking sample of children aged 6-16 years with data available for youth (n = 695, 170) and their caregivers (n = 703, 177) at pre-treatment and follow-up, respectively. The ability of the Mini-SPIN to discriminate between those with and without SAD was examined at pre-treatment and 6-month follow-up, across caregiver and child report. The criterion group validity, internal consistency and construct validity of the measure was also examined. Results revealed that at pre-treatment the Mini-SPIN demonstrated good discriminant validity in detecting cases of SAD from non-SAD (with cut-off of 4 on child report, and 6 on caregiver report). At 6-month follow-up, the discriminant ability of the Mini-SPIN was found to be less than acceptable for child reported scores, but acceptable for caregiver reported scores. The Mini-SPIN further demonstrated good criterion group validity, internal consistency and construct validity across caregiver and child report. Overall, the findings from the current study lend further support for the use of the Mini-SPIN as a screening tool for SAD.

Anger in social anxiety disorder.

The present study focused on the emotional experience of anger among individuals with and without social anxiety disorder (SAD). Eighty-eight participants took part in the study, half (n = 44) met diagnostic criteria for SAD and half (n = 44) did not meet criteria for SAD. Participants completed a 21-day experience sampling measurement (ESM) in which they reported on daily social interactions and emotions. Using multilevel linear modeling we found that individuals with SAD experienced more anger compared to individuals without SAD. We also found a Diagnosis × Social Context interaction such that interactions with distant others were associated with elevated anger compared to interactions with close others for individuals with SAD but not for individuals without SAD. Finally, we found that for individuals with SAD (but not those without SAD) anger on a given day (day t) was associated with elevated anxiety on the following day (day t + 1), above and beyond previous anxiety, sadness and guilt (i.e. anxiety, sadness and guilt reported on day t). This suggests that anger may play a unique role in maintaining or exacerbating anxiety among individuals with SAD. Additional implications of our findings for models of psychopathology and for treatment of SAD are discussed.

Improvements in emotion regulation during cognitive behavior therapy predict subsequent social anxiety reductions.

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.

Mediation of social anxiety and depression during internet-delivered treatment for social anxiety disorder.

Many individuals with social anxiety disorder (SAD) have depressive symptoms that meet criteria for major depressive disorder (MDD). In our study, we examined the temporal relationship between symptoms of social anxiety and symptoms of depression during the course of an 11-week internet-delivered cognitive behavioral treatment (ICBT) for SAD (n = 170). Specifically, we investigated whether weekly changes in social anxiety mediated changes in depression, changes in depression mediated changes in anxiety, both or neither. In addition, we compared individuals with SAD and MDD (n = 50) and individuals with SAD and no MDD (n = 120) to examine the role of MDD as a moderator of the social anxiety-depression relationship. Lower-level mediational modeling revealed that changes in social anxiety symptoms mediated changes in depression symptoms to a greater extent than vice versa. In addition, mediation among individuals with SAD and MDD was significantly greater compared to individuals with SAD and no MDD. Our findings suggest that ICBT is effective in treating individuals with SAD regardless of comorbid depression, and that focusing ICBT interventions on social anxiety can lead to significant reductions in depression among individuals with SAD.

Negative Flashforward Imagery in Adolescent Social Anxiety Disorder: A Pilot Study of Imagery Reports and a Short EMDR Intervention.

Psychological treatments for social anxiety disorder (SAD) in adolescents have shown poorer outcomes than for other anxiety disorders. A relevant factor to consider for improving outcomes may be negative imagery. In this pilot study, we examined negative 'flashforward' imagery of feared catastrophic outcomes in adolescents with SAD and evaluated the feasibility and preliminary outcomes of a short eye movement desensitization and reprocessing (EMDR) intervention targeting this imagery. We used a case series design with a 1-week baseline period. Outcomes included symptoms of social anxiety and avoidance related to selected social situations and features of associated flashforward imagery as the proposed mechanism of change during the intervention. We found that six out of seven assessed adolescents reported to experience flashforwards and rated image distress, vividness and threat appraisal as high. In these six participants (aged 14-17 years old), the short EMDR flashforward intervention appeared feasible and was followed by a decrease in social anxiety and avoidance in five participants, while no notable changes were observed during the baseline period. Furthermore, we observed a decrease in flashforward imagery features in at least five participants. Nonparametric tests of the overall (group-based) changes during the intervention period partially supported these findings. Limitations include the small sample size and the lack of a control group. Results suggest that vivid and distressing flashforward imagery is a common experience and that targeting flashforwards with EMDR may be beneficial in treating social anxiety in youth. Further experimental research on effects and added value to current treatments is necessary. Trial Registration: Dutch Clinical Trial Register (National Trial Register [NTR]): NL8974.

Avoidance and fear day by day in social anxiety disorder.

OBJECTIVE: Theories assert that avoidance maintains maladaptive anxiety over time, yet a clear prospective test of this effect in the day-by-day lives of people with social anxiety disorder (SAD) is lacking. METHOD: We used intensive longitudinal data to test prospective relationships between social fear and social avoidance in 32 participants with SAD who reported on a total of 4256 time points. RESULTS: Results suggested that avoidance strongly predicted future anxiety, but only in a minority of people with SAD. Relationships between anxiety and avoidance varied considerably across individuals. Pre-registered tests found that the strength of autocorrelation for social fear is a good target for future testing of prediction of exposure response. Participants with lower autocorrelations were less likely to show between-session habituation. CONCLUSIONS: Overall, results suggest avoidance maintains fear in SAD for at least some individuals, but also indicates considerable variability. Further intensive longitudinal data is needed to examine individuals with SAD across varying time courses.

Resting state connectivity predictors of symptom change during gaze-contingent music reward therapy of social anxiety disorder.

BACKGROUND: Social anxiety disorder (SAD) is common, first-line treatments are often only partially effective, and reliable predictors of treatment response are lacking. Here, we assessed resting state functional connectivity (rsFC) at pre-treatment and during early treatment as a potential predictor of response to a novel attention bias modification procedure, gaze-contingent music reward therapy (GC-MRT). METHODS: Thirty-two adults with SAD were treated with GC-MRT. rsFC was assessed with multi-voxel pattern analysis of fMRI at pre-treatment and after 2-3 weeks. For comparison, 20 healthy control (HC) participants without treatment were assessed twice for rsFC over the same time period. All SAD participants underwent clinical evaluation at pre-treatment, early-treatment (week 2-3), and post-treatment. RESULTS: SAD and depressive symptoms improved significantly from pre-treatment to post-treatment. After 2-3 weeks of treatment, decreased connectivity between the executive control network (ECN) and salience network (SN), and increased connectivity within the ECN predicted improvement in SAD and depressive symptoms at week 8. Increased connectivity between the ECN and default mode network (DMN) predicted greater improvement in SAD but not depressive symptoms at week 8. Connectivity within the DMN decreased significantly after 2-3 weeks of treatment in the SAD group, while no changes were found in HC over the same time interval. CONCLUSION: We identified early changes in rsFC during a course of GC-MRT for SAD that predicted symptom change. Connectivity changes within the ECN, ECN-DMN, and ECN-SN may be related to mechanisms underlying the clinical effects of GC-MRT and warrant further study in controlled trials.

Large-scale brain functional network abnormalities in social anxiety disorder.

BACKGROUND: Although aberrant brain regional responses are reported in social anxiety disorder (SAD), little is known about resting-state functional connectivity at the macroscale network level. This study aims to identify functional network abnormalities using a multivariate data-driven method in a relatively large and homogenous sample of SAD patients, and assess their potential diagnostic value. METHODS: Forty-six SAD patients and 52 demographically-matched healthy controls (HC) were recruited to undergo clinical evaluation and resting-state functional MRI scanning. We used group independent component analysis to characterize the functional architecture of brain resting-state networks (RSNs) and investigate between-group differences in intra-/inter-network functional network connectivity (FNC). Furtherly, we explored the associations of FNC abnormalities with clinical characteristics, and assessed their ability to discriminate SAD from HC using support vector machine analyses. RESULTS: SAD patients showed widespread intra-network FNC abnormalities in the default mode network, the subcortical network and the perceptual system (i.e. sensorimotor, auditory and visual networks), and large-scale inter-network FNC abnormalities among those high-order and primary RSNs. Some aberrant FNC signatures were correlated to disease severity and duration, suggesting pathophysiological relevance. Furthermore, intrinsic FNC anomalies allowed individual classification of SAD v. HC with significant accuracy, indicating potential diagnostic efficacy. CONCLUSIONS: SAD patients show distinct patterns of functional synchronization abnormalities both within and across large-scale RSNs, reflecting or causing a network imbalance of bottom-up response and top-down regulation in cognitive, emotional and sensory domains. Therefore, this could offer insights into the neurofunctional substrates of SAD.

Internet-delivered therapist-assisted cognitive therapy for adolescent social anxiety disorder (OSCA): a randomised controlled trial addressing preliminary efficacy and mechanisms of action.

BACKGROUND: Cognitive therapy for SAD (CT-SAD) is a first-line recommended treatment for adult social anxiety disorder (SAD) and shows considerable promise for youth. However, the high prevalence of adolescent SAD and limited number of therapists presents an implementation challenge. Delivery of CT-SAD via the Internet may offer part of the solution. METHOD: Forty-three youth (14-18 years) with SAD recruited through schools were randomly allocated to therapist-assisted Internet-delivered CT-SAD (called OSCA) or waitlist for 14 weeks (ISRCTN15079139). RESULTS: OSCA outperformed waitlist on all measures and was associated with large effects that were maintained at 6-month follow-up. In the OSCA arm, 77% of adolescents lost their SAD diagnosis at post (vs. 14% in the waitlist arm), increasing to 91% at 6-months. Beneficial effects of OSCA were mediated through changes in cognitions and safety behaviours as predicted by cognitive models of SAD. OSCA was associated with high credibility and therapeutic alliance. CONCLUSIONS: This preliminary trial suggests OSCA holds promise as an effective, accessible treatment for adolescent SAD. Future definitive trials could compare OSCA to active comparators to examine specificity of effects.