Bidirectional and interactive effects of child temperament and parenting in early childhood on the trajectory of social anxiety in adolescence.

INTRODUCTION: Research suggests that certain parenting behaviors are best suited to promote optimal child development, depending on a child's distinctive temperamental presentation. This multimethod, longitudinal study examines the interactive effect of parenting and temperament in early childhood on the developmental trajectory of social anxiety in adolescence. METHODS: Longitudinal growth modeling was used to examine the developmental trajectory of child social anxiety from age 9-15 and the interactive effect of parenting and child temperament at 36 months on the developmental trajectory of child social anxiety from age 9-15. RESULTS: The slope of social anxiety from age 9-15 suggested a decrease in social anxiety throughout early adolescence. Furthermore, 36-month behavioral inhibition (BI) predicted the trajectory of child social anxiety from age 9-15 when parents displayed low and high levels of dismissive and supportive parenting (at 36 months). CONCLUSIONS: Results support an interactive effect of infant temperament and parenting in early childhood (at 36 months) on the developmental trajectory of child social anxiety from age 9-15. Specifically, results suggest that engaging highly inhibited children with high supportive and low dismissive parenting may help reduce social anxiety over time in adolescence. Furthermore, parenting needs may differ for children high or low in BI to impact the developmental trajectory of social anxiety in adolescence, such that children who are high BI seem to benefit from low dismissive and high supportive parenting, and children who are low in BI seem to benefit more from high dismissive parenting.

Do I really feel better? Effectiveness of emotion regulation strategies depends on the measure and social anxiety.

BACKGROUND: Effective emotion regulation (ER) is important to long-term healthy functioning, but little is known about what constitutes effective ER in the moment or how social anxiety symptoms and different strategies influence short-term effectiveness outcomes. METHODS: Intensive ecological momentary data from N = 124 college students illustrate how different ways of operationalizing ER effectiveness leads to different conclusions about the short-term effectiveness of different strategies in daily life. RESULTS: When effectiveness is operationalized as the degree to which participants judged that their ER attempts made them feel better, social anxiety severity was negatively associated with effectiveness, and avoidance-oriented strategies were judged to be less effective than engagement-oriented strategies. In contrast, when effectiveness is operationalized as the degree of change in self-reported affect following ER attempts, social anxiety severity was not related to effectiveness, and avoidance-oriented strategies were more effective than engagement-oriented strategies. Social anxiety and ER strategy type did not interact in either model, regardless of how effectiveness was measured. CONCLUSIONS: The study highlights discrepancies when examining two common but distinct ways of measuring the same overarching effectiveness construct, and raises intriguing questions about how forms of psychopathology that are intimately tied to emotion dysregulation, like social anxiety, moderate different ways of measuring the effectiveness of ER attempts.

Limbic and prefrontal neural volume modulate social anxiety in children at temperamental risk.

BACKGROUND: Clinical levels of a social anxiety disorder (SAD) often appear during childhood and rise to a peak during late adolescence. The temperament trait behavioral inhibition (BI), evident early in childhood, has been linked to increased risk for SAD. Functional and structural variations in brain regions associated with the identification of, and response to, fear may support the BI-SAD relation. Whereas relevant functional studies are emerging, the few extant structural studies have focused on adult samples with mixed findings. METHODS: A moderated-mediation model was used to examine the relations between BI, SAD symptoms, and brain-volume individual differences in a sample of children at risk for anxiety (ages 9-12; N = 130, 52 BI). RESULTS: Our findings indicate that at higher levels of BI, children with smaller anterior insula volumes showed stronger correlations between BI and SAD. In addition, larger ventrolateral prefrontal cortex (vlPFC) volumes were associated with fewer SAD symptoms. CONCLUSIONS: These findings support previous reports linking SAD levels with variations in volume and reactivity in both limbic (insula) and prefrontal (vlPFC) regions. These findings set the foundation for further examination of networks of neural structures that influence the transition from BI to SAD across development, helping further clarify mechanisms of risk and resilience.

Early childhood social reticence and neural response to peers in preadolescence predict social anxiety symptoms in midadolescence.

BACKGROUND: Early childhood social reticence (SR) and preadolescent social anxiety (SA) symptoms increase the risk for more severe SA in later adolescence. Yet, not all at-risk youth develop more severe SA. The emergence of distinct patterns of neural response to socially evocative contexts during pivotal points in development may help explain this discontinuity. We tested the extent to which brain function during social interactions in preadolescence influenced the effects of SA and early childhood SR on predicting SA symptoms in midadolescence. METHODS: Participants (N = 53) were assessed for SR from ages 2 to 7. At age 11, SA symptoms were assessed and brain function was measured using functional magnetic resonance imaging (fMRI) as participants anticipated social evaluation from purported peers with a reputation for being unpredictable, nice, and mean. At age 13, SA symptoms were re-assessed. Moderated-mediation models tested the extent to which early childhood SR, preadolescent SA, and preadolescent brain function predicted midadolescent SA. RESULTS: In individuals with preadolescent SA, the presence of early childhood SR and SR-linked differences in brain activation predicted more severe SA in midadolescence. Specifically, in those who exhibited preadolescent SA, greater early childhood SR was associated with enhanced bilateral insula engagement while anticipating unpredictable-versus-nice social evaluation in preadolescence, and more severe SA in midadolescence. CONCLUSIONS: SR-linked neural responses to socially evocative peer interactions may predict more severe SA symptoms in midadolescence among individuals with greater preadolescent SA symptoms and childhood SR. This same pattern of neural response may not be associated with more severe SA symptoms in youth with only one risk factor.

Moderating effect of comorbid anxiety disorders on treatment outcome in a randomized controlled psychotherapy trial in early-onset persistently depressed outpatients.

BACKGROUND: Persistent depressive disorder (PDD) is associated with high rates of comorbid psychiatric disorders, mostly anxiety disorders (ADs). Comorbid AD was found to be associated with poorer treatment outcome in PDD patients. The effect of comorbid AD on disorder-specific treatment for PDD (Cognitive Behavioral Analysis System of Psychotherapy [CBASP]) has not been studied yet. METHODS: We analyzed whether the presence of a comorbid AD was moderating the effectiveness of disorder-specific (CBASP) versus nonspecific psychotherapy (supportive therapy [SP]) on depressive symptoms (24-item Hamilton Rating Scale for Depression [HRSD-24]) in a sample of unmedicated early-onset PDD outpatients (N = 268). Secondary outcomes were response and remission of depressive symptoms and the extent of interpersonal problems (Inventory of Interpersonal Problems [IIP-64]). RESULTS: The superiority of CBASP over SP was significantly stronger in PDD patients with comorbid AD compared to patients without AD (in HRSD-24 and IIP-64). There was no significant moderation for remission or response of depressive symptoms. DISCUSSION: Our hypothesis of a moderating effect of comorbid AD was confirmed. The main limitation might be the exclusion criteria of our sample limiting the generalizability. The major strength is the systematic analysis of the effect of AD in treating early-onset PDD with high quality of psychotherapy in both arms of this trial. CONCLUSION: Patients suffering from PDD comorbid with AD might experience greater benefit when they are treated with specific as opposed to unspecific therapy. Analyzing subgroups of patients with PDD seems worthwhile to improve treatment effectiveness even within disorder-specific treatment programms.

Association between attention bias to threat and anxiety symptoms in children and adolescents.

BACKGROUND: Considerable research links threat-related attention biases to anxiety symptoms in adults, whereas extant findings on threat biases in youth are limited and mixed. Inconsistent findings may arise due to substantial methodological variability and limited sample sizes, emphasizing the need for systematic research on large samples. The aim of this report is to examine the association between threat bias and pediatric anxiety symptoms using standardized measures in a large, international, multi-site youth sample. METHODS: A total of 1,291 children and adolescents from seven research sites worldwide completed standardized attention bias assessment task (dot-probe task) and child anxiety symptoms measure (Screen for Child Anxiety Related Emotional Disorders). Using a dimensional approach to symptomatology, we conducted regression analyses predicting overall, and disorder-specific, anxiety symptoms severity, based on threat bias scores. RESULTS: Threat bias correlated positively with overall anxiety symptoms severity (ß = 0.078, P = .004). Furthermore, threat bias was positively associated specifically with social anxiety (ß = 0.072, P = .008) and school phobia (ß = 0.076, P = .006) symptoms severity, but not with panic, generalized anxiety, or separation anxiety symptoms. These associations were not moderated by age or gender. CONCLUSIONS: These findings indicate associations between threat bias and pediatric anxiety symptoms, and suggest that vigilance to external threats manifests more prominently in symptoms of social anxiety and school phobia, regardless of age and gender. These findings point to the role of attention bias to threat in anxiety, with implications for translational clinical research. The significance of applying standardized methods in multi-site collaborations for overcoming challenges inherent to clinical research is discussed.

Brain activation during fear extinction predicts exposure success.

BACKGROUND: Exposure therapy, a gold-standard treatment for anxiety disorders, is assumed to work via extinction learning, but this has never been tested. Anxious individuals demonstrate extinction learning deficits, likely related to less ventromedial prefrontal cortex (vmPFC) and more amygdala activation, but the relationship between these deficits and exposure outcome is unknown. We tested whether anxious individuals who demonstrate better extinction learning report greater anxiety reduction following brief exposure. METHODS: Twenty-four adults with public speaking anxiety completed (1) functional magnetic resonance imaging during a conditioning paradigm, (2) a speech exposure session, and (3) anxiety questionnaires before and two weeks postexposure. Extinction learning was assessed by comparing ratings to a conditioned stimulus (neutral image) that was previously paired with an aversive noise against a stimulus that had never been paired. Robust regression analyses examined whether brain activation during extinction learning predicted anxiety reduction two weeks postexposure. RESULTS: On average, the conditioning paradigm resulted in acquisition and extinction effects on stimulus ratings, and the exposure session resulted in reduced anxiety two weeks post-exposure. Consistent with our hypothesis, individuals with better extinction learning (less negative stimulus ratings), greater activation in vmPFC, and less activation in amygdala, insula, and periaqueductal gray reported greater anxiety reduction two weeks postexposure. CONCLUSION: To our knowledge, this is the first time that the theoretical link between extinction learning and exposure outcome has been demonstrated. Future work should examine whether extinction learning can be used as a prognostic test to determine who is most likely to benefit from exposure therapy.

Vortioxetine versus placebo in major depressive disorder comorbid with social anxiety disorder.

BACKGROUND: Major Depressive Disorder (MDD) and Social Anxiety Disorder (SAD) are highly comorbid, yet the combined condition has not been subject to any placebo-controlled treatment trials. This study reports a trial of vortioxetine, an antidepressant that has also shown benefit in Generalized Anxiety Disorder (GAD), in patients meeting DSM-5 criteria for both MDD and SAD. METHODS: The study was a 12-week double-blind, placebo-controlled comparison of vortioxetine 10-20 mg/day or placebo administered on a 1:1 ratio. The study was designed to include 40 male or female outpatients aged 18-70 years. The primary endpoint was the "composite" Clinical Global Impression of Improvement (CGI-I) responder rate, factoring in improvement in both MDD and SAD features. Major secondary outcome measures were changes on the Montgomery Asberg Depression Rating Scale (MADRS) and Liebowitz Social Anxiety Scale (LSAS). RESULTS: On the composite CGI-I, 10 of 20 (50%) vortioxetine and six of 20 (30%) placebo-treated patients were rated as responders, a non-significant difference. However, vortioxetine-treated patients did show significantly greater improvement than those on placebo on both the MADRS (effect size 0.672) and LSAS (effect size 0.714). Efficacy in depression was seen before improvement in SAD. Adverse effects were similar to those previously reported. CONCLUSIONS: In this preliminary trial vortioxetine appears safe and effective for patients with MDD comorbid with SAD, with robust effect sizes on dimensional measures of both depression and social anxiety, but failure to separate from placebo on the primary outcome measure of composite responder rate. More studies of patients with comorbid conditions are needed, as this mirrors what is often seen in clinical practice.

Amygdala-Cortical Connectivity: Associations with Anxiety, Development, and Threat.

BACKGROUND: Amygdala-prefrontal cortex (PFC) functional connectivity may be influenced by anxiety and development. A prior study on anxiety found age-specific dysfunction in the ventromedial PFC (vmPFC), but not amygdala, associated with threat-safety discrimination during extinction recall (Britton et al.). However, translational research suggests that amygdala-PFC circuitry mediates responses following learned extinction. Anxiety-related perturbations may emerge in functional connectivity within this circuit during extinction recall tasks. The current report uses data from the prior study to examine how anxiety and development relate to task-dependent amygdala-PFC connectivity. METHODS: Eighty-two subjects (14 anxious youths, 15 anxious adults, 25 healthy youths, 28 healthy adults) completed an extinction recall task, which directed attention to different aspects of stimuli. Generalized psychophysiological interaction analysis tested whether task-dependent functional connectivity with anatomically defined amygdala seed regions differed across anxiety and age groups. RESULTS: Whole-brain analyses showed significant interactions of anxiety, age, and attention task (i.e., threat appraisal, explicit threat memory, physical discrimination) on left amygdala functional connectivity with the vmPFC and ventral anterior cingulate cortex (Talairach XYZ coordinates: -16, 31, -6 and 1, 36, -4). During threat appraisal and explicit threat memory (vs. physical discrimination), anxious youth showed more negative amygdala-PFC coupling, whereas anxious adults showed more positive coupling. CONCLUSIONS: In the context of extinction recall, anxious youths and adults manifested opposite directions of amygdala-vmPFC coupling, specifically when appraising and explicitly remembering previously learned threat. Future research on anxiety should consider associations of both development and attention to threat with functional connectivity perturbations.

Effect of as-needed use of intranasal PH94B on social and performance anxiety in individuals with social anxiety disorder.

BACKGROUND: There are no medications approved for as-needed use for feared situations for individuals with social anxiety disorder (SAD). In the present study, intranasal PH94B was provided for use as needed during stressful events. METHODS: Twenty-two subjects were randomized (double-blind) to 2 weeks of treatment with intranasal PH94B or placebo. Following self-administration of medication prior to a feared event, peak levels of anxiety were recorded using the Subjective Units of Distress Scale (SUDS). After 2 weeks, subjects were crossed over to the opposite treatment for 2 weeks. Average peak SUDS during treatment with PH94B and placebo were compared using a paired t-test. RESULTS: Significant differences in favor of PH94B were found on the primary outcome measure: mean peak SUDS change from baseline for all subjects receiving PH94B was 15.6 points versus 8.3 points for placebo (paired t = 3.09, P = .006, effect size of .658). PH94B showed less superiority over placebo when placebo was given second rather than first, likely due to a carryover effect. Looking between groups at just the first 2 weeks of treatment, PH94B also showed trend superiority to placebo on the Liebowitz Social Anxiety Scale (LSAS) (P = .07) and a significant difference on the Patient Global Impression of Change (P = .024) and the LSAS Avoidance subtotal (P = .02). CONCLUSIONS: While further study is needed, these results, combined with earlier findings, suggest that PH94B could represent a useful as-needed treatment for SAD, and continue to validate the nasal chemosensory system as a novel mechanism for medication delivery.

AUGMENTATION STRATEGIES FOR TREATMENT-RESISTANT ANXIETY DISORDERS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: A systematic review and meta-analysis was conducted to explore the efficacy of medication augmentation strategies compared to control treatments in patients who have had a partial or no response to initial treatment for generalized anxiety disorder, social anxiety disorder, and panic disorder. METHODS: Double-blind controlled trials of medication augmentation in adult treatment-resistant anxiety disorders conducted between January 1990 and January 2015 were systematically reviewed and evaluated by two independent raters. The search identified 625 articles; 610 were excluded following abstract review and 15 had full-text screening. Studies had to include a definition of treatment resistance, exclude concomitant medications, and have a parallel or crossover design. Data extraction forms were completed in duplicate. RESULTS: Six studies were included in the meta-analysis. Effect estimates were calculated using random effects modeling; heterogeneity was assessed and subgroup and sensitivity analyses were completed. Primary outcome was response, defined by Clinical Global Impression-Improvement score of ≤2. Augmentation was not associated with an increased risk of response, as compared with placebo (RR = 1.08, 95% CI = 0.94-1.24). A small significant effect was found in reduction in symptom severity: standard mean difference = -0.32, 95% CI = -0.56 to -0.08. No significant differences between augmentation with medication versus placebo were found in ratings of functional impairment and dropouts due to adverse events. CONCLUSIONS: Augmentation does not appear to be beneficial in treatment-resistant anxiety disorders. These results may be limited by small study samples, and a small number of overall studies in the analysis.

Anxiety disorders are independently associated with suicide ideation and attempts: propensity score matching in two epidemiological samples.

BACKGROUND: Research suggests that suicidal behavior in individuals with anxiety disorders is attributable to co-occurring risk factors, such as depression. We argue that these conclusions are founded primarily in statistical adjustments that may obscure independent associations. We explored independent associations between specific anxiety disorders and suicide attempts and ideation by means of propensity score matching, a process that simulates a case-control study by creating matched groups that differ in group status (e.g., diagnosis of a specific anxiety disorder) but that are statistically equivalent on observed covariates. METHODS: We made use of the National Comorbidity Survey Replication (NCS-R) and the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), which include a total of 43,935 adults. Diagnoses included agoraphobia without panic disorder, generalized anxiety disorder, panic disorder with or without agoraphobia, posttraumatic stress disorder, social anxiety disorder, and specific phobia. RESULTS: Each anxiety disorder was (95% confidence intervals) associated with increased odds of lifetime suicide attempts (odds ratios 3.57-6.64 [NCS-R], 3.03-7.00 [NESARC]) and suicidal ideation (odds ratios 2.62-4.87 [NCS-R], 3.34-10.57 [NESARC]). Odds ratios for each disorder remained statistically significant after matching on diagnostic status of dysthymia, major depressive disorder, alcohol abuse/dependence, substance abuse/dependence, bipolar disorder I, bipolar disorder II, all other anxiety disorders, and on sociodemographic variables. CONCLUSIONS: This is the first report to present evidence that each anxiety disorder is associated with suicide ideation and suicide attempts beyond the effects of co-occurring mental disorders. These findings warrant consideration in assessment, intervention, and related policies.

Anxiety and depression in adolescents with a visible difference: A systematic review and meta-analysis.

Living with a visible difference can entail challenging social situations, associated with psychosocial symptoms. However, it is not clear whether adolescents with a visible difference experience more anxiety and depression than unaffected peers. We aim to determine whether adolescents with a visible difference experience more symptoms of anxiety and depression than unaffected peers. A literature search was conducted in Embase, Medline Ovid, Web of Science, Cochrane CENTRAL, PsycINFO Ovid, and Google Scholar. Meta-analyses were done using random-effects models to calculate a standardised mean difference. Analyses for subgroups were used to study causes of visible difference. Eleven studies were identified (n = 1075, weighted mean age = 15.80). Compared to unaffected peers, adolescents with a visible difference experience more symptoms of anxiety (SMD = 0.253, 95 % CI [0.024, 0.482], p = .030), but not depression (SMD = 0.236, 95 % CI [-0.126, 0.599], p = .202). Adolescents with a skin condition did not experience more symptoms of anxiety (SMD = 0.149, 95 % CI [-0.070, 0.369], p = .182) or depression (SMD = 0.090, 95 % CI [-0.082, 0.262], p = .305) when compared to unaffected peers. Overall, more symptoms of anxiety are found in adolescents with a visible difference compared to peers. No differences in anxiety or depression were found for skin differences. Screening for anxiety is recommended.

The relationship between dorsolateral prefrontal activation and speech performance-based social anxiety using functional near infrared spectroscopy.

Functional near-infrared (fNIR) spectroscopy is a promising new technology that has demonstrated utility in the study of normal human cognition. We utilized fNIR spectroscopy to examine the effect of social anxiety and performance on hemodynamic activity in the dorsolateral prefrontal cortex (DLPFC). Socially phobic participants and non-clinical participants with varying levels of social anxiety completed a public speaking task in front of a small virtual audience while the DLPFC was being monitored by the fNIR device. The relationship between anxiety and both blood volume (BV) and deoxygenated hemoglobin (Hb) varied significantly as a function of speech performance, such that individuals with low social anxiety who performed well showed an increase in DLPFC activation relative to those who did not perform well. This result suggests that effortful thinking and/or efficient top-down inhibitory control may have been required to complete an impromptu speech task with good performance. In contrast, good performers who were highly socially anxious showed lower DLPFC activation relative to good performers who were low in social anxiety, suggesting autopilot thinking or less-effortful thinking. In poor performers, slight increases in DLPFC activation were observed from low to highly anxious individuals, which may reflect a shift from effortless thinking to heightened self-focused attention. Heightened self-focused attention, poor inhibitory control resulting in excessive fear or anxiety, or low motivation may lower performance. These results suggest that there can be different underlying mechanisms in the brain that affect the level of speech performance in individuals with varying degrees of social anxiety. This study highlights the utility of the fNIR device in the assessment of changes in DLPFC in response to exposure to realistic phobic stimuli, and further supports the potential utility of this technology in the study of the neurophysiology of anxiety disorders.

The Effects of a Brief Acceptance-Based Behavioral Treatment Versus Traditional Cognitive-Behavioral Treatment for Public Speaking Anxiety: An Exploratory Trial Examining Differential Effects on Performance and Neurophysiology.

Individuals with public speaking anxiety (PSA) experience fear and avoidance that can cause extreme distress, impaired speaking performance, and associated problems in psychosocial functioning. Most extant interventions for PSA emphasize anxiety reduction rather than enhancing behavioral performance. We compared the efficacy of two brief cognitive-behavioral interventions, a traditional cognitive-behavior treatment (tCBT) and an acceptance-based behavior treatment (ABBT), on public speaking performance and anxiety in a clinical sample of persons with PSA. The effects of treatment on prefrontal brain activation were also examined. Participants (n = 21) were randomized to 90 min of an ABBT or a tCBT intervention. Assessments took place at pre- and post-treatment and included self-rated anxiety and observer-rated performance measures, a behavioral assessment, and prefrontal cortical activity measurements using functional near-infrared spectroscopy (fNIRS). Exploratory results indicated that participants in the ABBT condition experienced greater improvements in observer-rated performance relative to those in the tCBT condition, while those in the tCBT condition experienced greater reductions in subjective anxiety levels. Individuals in the ABBT condition also exhibited a trend toward greater treatment-related reductions in blood volume in the left dorsolateral prefrontal cortex relative to those who received tCBT. Overall, these findings preliminarily suggest that acceptance-based treatments may free more cognitive resources in comparison with tCBT, possibly resulting in greater improvements in objectively rated behavioral performances for ABBT interventions.