Pediatric Generalized Anxiety Disorder Research Articles

Exploring volumetric abnormalities in subcortical L-HPA axis structures in pediatric generalized anxiety disorder

Background Pediatric generalized anxiety disorder (GAD) is debilitating and increasingly prevalent, yet its etiology remains unclear. Some believe the disorder to be propagated by chronic dysregulation of the limbic-hypothalamic-pituitary-adrenal (L-HPA) axis, but morphometric studies of implicated subcortical areas have been largely inconclusive. Recognizing that certain subcortical subdivisions are more directly involved in L-HPA axis functioning, this study aims to detect specific abnormalities in these critical areas. Methods Thirty-eight MRI scans of preschool children with (n = 15) and without (n = 23) GAD underwent segmentation and between-group volumetric comparisons of the basolateral amygdala (BLA), ventral hippocampal subiculum (vSC), and mediodorsal medial magnocellular (MDm) area of the thalamus. Results Children with GAD displayed significantly larger vSC compared to healthy peers, F(1, 31) = 6.50, pFDR = .048. On average, children with GAD presented with larger BLA and MDm, Fs(1, 31) ≥ 4.86, ps FDR ≤ .054. Exploratory analyses revealed right-hemispheric lateralization of all measures, most notably the MDm, F(1, 31) = 8.13, pFDR = .024, the size of which scaled with symptom severity, r = .83, pFDR = .033. Conclusion The BLA, vSC, and MDm are believed to be involved in the regulation of anxiety and stress, both individually and collectively through the excitation and inhibition of the L-HPA axis. All were found to be enlarged in children with GAD, perhaps reflecting hypertrophy related to hyperexcitability, or early neuronal overgrowth. Longitudinal studies should investigate the relationship between these early morphological differences and the long-term subcortical atrophy previously observed.

The effectiveness of using escitalopram in pediatric generalized anxiety disorder and the methods to predict the treatment response: A systematic review and meta-analysis

Background Generalized Anxiety Disorder (GAD) affects approximately 10–15% of children and adolescents. Selective Serotonin Reuptake Inhibitors (SSRIs) are among the main treatment options. Escitalopram, an SSRI for adult anxiety, is being studied for pediatric use. Predicting the treatment response could optimize interventions. This systematic review aimed to understand the safety and efficacy of escitalopram in the treatment of pediatric GAD and to determine potential treatment response indicators. Methods Searches for randomized controlled trials (RCTs) on escitalopram’s effectiveness in pediatric GAD were conducted across six databases. Two reviewers selected the trials, extracted data, and evaluated the trial quality independently. A third reviewer resolved the discrepancies. Outcomes were presented as mean differences (MDs) with 95% confidence intervals (CIs), while the Cochrane risk of bias tool was used to gauge evidence quality. Results Five RCTs including 401 patients were analyzed. Escitalopram showed a greater reduction in The Pediatric Anxiety Rating Scale PARS score than placebo (MD -6.1, 95% CI [-8.75 to -3.44] (P = 0.09, I2 = 65%)). Multiple methods have been used to predict escitalopram treatment responses, such as reaction time changes, executive functions, and Amygdala Functional Connectivity, including the CYP2C19 metabolizer phenotype. The data indicated that neuroimaging was the most effective predictor of the treatment response. Conclusion Escitalopram notably reduced PARS scores in pediatric patients with GAD. Neuroimaging, as a biomarker, is a valuable predictor of treatment response and provides insights into the neurological aspects of anxiety disorders, offering the potential for groundbreaking treatment advancements.

Treating Pediatric Generalized Anxiety Disorder with Mindfulness: A Case Series

ABSTRACT Mindfulness interventions have been shown to be effective in the treatment of anxiety for both adolescent and adult populations. However, little research has investigated and tested the use of mindfulness as an intervention for child anxiety. This may be in part due to the question of the developmental appropriateness of mindfulness techniques for this age group, given children’s limited capacity for attention and abstract thinking. This case series discusses the format and effectiveness of a pilot mindfulness intervention for children ages 9 to 12 with Generalized Anxiety Disorder (GAD). The treatment is comprised of developmentally tailored, concrete exercises using the senses to teach mindful awareness of the present moment. This case series describes four children who received a 6-session, individual intervention with parental involvement. Outcome data and qualitative case descriptions are presented. Results indicated improvements in the clinical severity of GAD from pre- to post-treatment, as well as at the 8-week follow-up assessment, for each participant. The treatment also demonstrated high feasibility and acceptability to families. Overall, the study provides promising preliminary support for a mindfulness-based pilot treatment specifically tailored for children with GAD.

Short-term Ambient Fine Particulate Matter and Anxiety Symptoms in Adolescents with Generalized Anxiety Disorder

Background: Short-term ambient fine particulate matter has been associated with exacerbations of psychiatric disorders in children and adolescents as measured by psychiatric emergency department utilizations. It is currently unknown if a similar association is seen with a continuous measure of symptom severity. We sought to determine if anxiety symptoms in adolescents with moderate-to-severe generalized anxiety disorder (GAD) were related to short-term ambient fine particulate matter concentrations.Methods: An analysis of participants receiving a placebo in an ongoing clinical trial (FiESTAA; clinicaltrials.gov identifier: NCT02818751) designed to test the efficacy of a medication in pediatric GAD was conducted. The severity of anxiety symptoms was assessed weekly over 8 weeks using the Pediatric Anxiety Rating Scale (PARS) score administered by a psychiatrist. Participants’ geocoded residential addresses and PARS assessment dates were used to estimate short-term ambient concentrations of particulate matter smaller than 2.5 µm (PM2.5) using a previously validated spatiotemporal model. A Poisson fixed effects regression model with a participant-specific intercept was used to estimate the increase in PARS corresponding to a doubling in total ambient PM2.5 concentrations two and three days prior to PARS assessment while adjusting for temperature and humidity.Results: A subset of FiESTAA participants with currently available data (n = 5) representing 33 total PARS assessments were analyzed. A doubling of the total ambient PM2.5 concentrations two and three days prior to the assessment were associated with a 1.21 fold increase (95% CI: 0.98, 1.48) in the PARS score.Conclusions: These results will be replicated using the full FiESTAA dataset and within an additional clinical trial for GAD when all data is available. Initial results suggest that short-term ambient air pollution may influence the severity of anxiety symptoms in adolescents with GAD and future work should examine the impact of ambient air pollution on the pathoetiology of anxiety disorders.

Greater Dynamic and Lower Static Functional Brain Connectivity Prospectively Predict Placebo Response in Pediatric Generalized Anxiety Disorder.

Objectives: Placebo response is one of the most significant barriers to detecting treatment effects in pediatric (and adult) clinical trials focusing on affective and anxiety disorders. We sought to identify neurofunctional predictors of placebo response in adolescents with generalized anxiety disorder (GAD) by examining dynamic and static functional brain connectivity. Methods: Before randomization to blinded placebo, adolescents, aged 12-17 years, with GAD (N = 25) underwent resting state functional magnetic resonance imaging. Whole brain voxelwise correlation analyses were used to determine the relationship between change in anxiety symptoms from baseline to week 8 and seed-based dynamic and static functional connectivity maps of regions in the salience and ventral attention networks (amygdala, dorsal anterior cingulate cortex [dACC], and ventrolateral prefrontal cortex [VLPFC]). Results: Greater dynamic functional connectivity variability in amygdala, dACC, VLPFC, and regions within salience, default mode, and frontoparietal networks was associated with greater placebo response. Lower static functional connectivity between amygdala and dorsolateral prefrontal cortex, amygdala and medial prefrontal cortex, dACC and posterior cingulate cortex and greater static functional connectivity between VLPFC and inferior parietal lobule were associated with greater placebo response. Conclusion: Placebo response is associated with a distinct dynamic and static connectivity fingerprint characterized by "variable" dynamic but "weak" static connectivity in the salience, default mode, frontoparietal, and ventral attention networks. These data provide granular evidence of how circuit-based biotypes mechanistically relate to placebo response. Finding biosignatures that predict placebo response is critically important in clinical psychopharmacology and to improve our ability to detect medication-placebo differences in clinical trials.

A Diagnostic Biomarker for Pediatric Generalized Anxiety Disorder Using the Error-Related Negativity.

The error-related negativity (ERN) is a negative deflection in the event-related potential following a mistake that is a putative biomarker of anxiety. The study assessed the ERN as a diagnostic biomarker using receiver operating characteristic (ROC) analyses in 96 cases with anxiety disorders (AD) and 96 matched healthy controls (HC) ages 8 to 18years. Forty-one cases had generalized anxiety disorder (GAD); 55 cases had other anxiety disorders (OAD) without GAD. ERN amplitude was significantly increased in AD cases compared to HC. The area under the curve (AUC) in the ROC analysis was 0.64, indicating the ERN is an inadequate diagnostic test for AD altogether. The ERN was significantly increased in cases with either GAD or OAD compared to HC. The AUC in ROC analyses with GAD and OAD was 0.75 and 0.56, respectively, suggesting the ERN provides an adequate diagnostic test for GAD but not for OAD.

Novel pharmacological treatments for generalized anxiety disorder: Pediatric considerations.

Pediatric anxiety disorders such as generalized anxiety disorder (GAD) are common, impairing, and often undertreated. Moreover, many youth do not respond to standard, evidence-based psychosocial or psychopharmacologic treatment. An increased understanding of the gamma-aminobutyric acid (GABA) and glutamate neurotransmitter systems has created opportunities for novel intervention development for pediatric GAD. This narrative review examines potential candidates for pediatric GAD: eszopiclone, riluzole, eglumegad (LY354740), pimavanserin, agomelatine. The pharmacology, preclinical data, clinical trial findings and known side effects of eszopiclone, riluzole, eglumegad (LY354740), pimavanserin, agomelatine, are reviewed, particularly with regard to their potential therapeutic relevance to pediatric GAD. Notwithstanding numerous challenges, some of these agents represent potential candidate drugs for pediatric GAD. Further treatment development studies of agomelatine, eszopiclone, pimavanserin and riluzole for pediatric GAD also have the prospect of informing the understanding of GABAergic and glutamatergic function across development.

Recognizing, diagnosing, and treating pediatric generalized anxiety disorder.

Generalized anxiety disorder (GAD), characterized by excessive worry or apprehension, can lead to significant distress or impairment in patients' social or occupational function but commonly is overlooked by primary care providers. GAD and other anxiety disorders are among the most common mental health disorders affecting children. Without treatment, children with GAD are at higher risk for academic underperformance, substance abuse, other mental health disorders, and poor outcomes in adulthood. This article reviews screening and assessment for GAD in children and pharmacologic and nonpharmacologic recommendations for management.

Stress system dysregulation in pediatric generalized anxiety disorder associated with comorbid depression.

Because chronic stress is an important risk factor for anxiety states and depressive disorders, we studied hypothalamus-pituitary-adrenal (HPA) axis and sympathetic system activity via changes in cortisol and alpha amylase activity levels in pediatric generalized anxiety disorder (GAD) patients (n=26) with comorbid depression and a healthy comparison group (n=26). Morning plasma cortisol and diurnal profiles of salivary cortisol and salivary alpha amylase (sAA) activity were assessed, also reactivity of HPA-axis, sAA activity, and heart rate following a psychosocial stressor (Trier Social Stress Test for children). GAD patients with comorbid depression showed increased morning plasma and salivary cortisol levels, ameliorating throughout in-patient treatment, and higher sAA activity in their diurnal profile. Both HPA and sympathetic activity positively correlated with the severity of anxiety and depression. We also demonstrated a blunted HPA and sympathetic response to acute stress in patients. This pattern of neuroendocrine and sympathetic changes seems to be distinct from the one previously reported in pediatric patients with only social anxiety or depressive disorders. We propose morning plasma and saliva cortisol levels as potential physiological indicators for supporting the evaluation of symptoms' severity and treatment progress in children with GAD and comorbid depressive disorder.

Pharmacotherapy for Pediatric Generalized Anxiety Disorder: A Systematic Evaluation of Efficacy, Safety and Tolerability.

Randomized controlled trials consistently support the efficacy of antidepressants in treating youth with generalized anxiety disorder (GAD), although integrated examinations of efficacy, safety, and tolerability of psychotropic medications in GAD, specifically, are rare. With this in mind, we sought to describe the efficacy, safety, and tolerability of psychopharmacologic interventions in pediatric patients with GAD. Randomized, double-blind, placebo-controlled, prospective trials of psychopharmacologic interventions in youth with GAD were identified through a PubMed/Medline (1966-2015) search. Both authors manually reviewed trials and, to evaluate comparative efficacy and tolerability across medications, numbers needed to treat (NNT) [based on Pediatric Anxiety Rating Scale (PARS) remission criteria (PARS≤8)] and number needed to harm (NNH) for selected treatment-emergent adverse events (TEAEs) were calculated. Finally, treatment-emergent suicidality and taper-emergent/post-study adverse events are reported descriptively. Five trials that involved 1186 patients and evaluated four medications were reviewed and efficacy data were extracted with regard to dimensional measures of anxiety. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) demonstrated efficacy in the reduction of anxiety symptoms with NNTs ranging from 2.8 to 9.3. TEAEs varied considerably between studies but tended to be mild and generally did not lead to discontinuation. Data from five trials of SSRI/SNRI in youth with GAD, many of whom had co-occurring separation and social anxiety disorders, suggest superiority to placebo and favorable tolerability profiles.

Stress and anxiety in children and young people: A future epidemic?

Nurse PrescribingVol. 12, No. 10 NewsStress and anxiety in children and young people: A future epidemic?Maria AnguitaMaria AnguitaSearch for more papers by this authorMaria AnguitaPublished Online:9 Oct 2014https://doi.org/10.12968/npre.2014.12.10.474AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Department of Health (2011) No health without mental health. www.gov.uk/government/uploads/system/uploads/attachment_data/file/213761/dh_124058.pdf (accessed 26 September 2014) Google ScholarKeeton CP, Kolos AC, Walkup JT (2009) Pediatric generalized anxiety disorder: epidemiology, diagnosis and management. Paediatr Drugs 11(3): 171–83. doi: https://doi.org/10.2165/00148581-200911030-00003 Crossref, Google ScholarNational Institute for Health and Care Excellence (2013) Social anxiety disorder: recognition, assessment and treatment. www.nice.org.uk/guidance/cg159 (accessed 29 September 2014) Google ScholarNuffield Foundation (2013) Social trends and mental health: introducing the main findings. Nuffield Foundation, London Google ScholarOffice for National Statistics (2011) Social trends 41. ONS, London Google ScholarPrice C (2013) IAPT programme struggling to achieve targets. Also available at: http://www.pulsetoday.co.uk/clinical/therapy-areas/mental-health/iapt-programme-struggling-toachieve-targets/20004817.article#.VCVDZSikpaU (accessed 26 September 2014) Google ScholarYoungMinds (2014a) Mental health statistics. http://www.youngminds.org.uk/training_services/policy/mental_health_statistics (accessed 26 September 2014) Google ScholarYoungMinds (2014b) About school work and exam stress. http://www.youngminds.org.uk/for_parents/worried_about_your_child/schoolwork_exam_stress/about_schoolwork_exam_stress (accessed 26 September 2014) Google Scholar FiguresReferencesRelatedDetailsCited ByPedagogy, Culture & Society, Vol. 27, No. 4 2 October 2014Volume 12Issue 10ISSN (print): 1479-9189ISSN (online): 2052-2924 Metrics Downloaded 25 times History Published online 9 October 2014 Published in print 2 October 2014 Information© MA Healthcare LimitedPDF download

Pediatric Generalized Anxiety Disorder

Pediatric Generalized Anxiety Disorder

A Pilot Study of Anterior Cingulate Cortex Neurochemistry in Adolescents with Generalized Anxiety Disorder

Background/Aims: This study used proton magnetic resonance spectroscopy (¹H MRS) to evaluate the neurochemistry of the anterior cingulate cortex (ACC) in adolescents with generalized anxiety disorder (GAD). Methods: Adolescents with GAD (n = 10) and healthy subjects (n = 10) underwent a ¹H MRS scan at 4 T. Glutamate (Glu), N-acetyl aspartate, creatine (Cr) and myo-inositol concentrations were measured in the ACC and were compared between untreated adolescents with GAD and age- and sex-matched healthy subjects. Results: Glu/Cr ratios in the ACC correlated with the severity of both generalized anxiety symptoms on the Pediatric Anxiety Rating Scale and with total anxiety symptom severity as measured by the Hamilton Anxiety Rating Scale, but did not differ between adolescents with GAD and healthy subjects. In addition, no differences in N-acetyl aspartate, Cr, or myo-inositol were detected between groups. Conclusion: These findings suggest that Glu/Cr in untreated adolescents with GAD may relate to the severity of anxiety symptoms and raise the possibility that dysregulation of Glu within the ACC may be linked to the pathophysiology of pediatric GAD.

ESTABLISHING THE NEUROBIOLOGIC BASIS OF TREATMENT IN CHILDREN AND ADOLESCENTS WITH GENERALIZED ANXIETY DISORDER

Generalized anxiety disorder (GAD) is associated with significant morbidity in children and adolescents, yet only recently have the neuropharmacology and neurophysiology of this condition been studied in youth. Accumulating data suggest structural and functional abnormalities within the brain's fear networks in youth with GAD. Additionally, seven studies examined the efficacy of medications that modulate this system and, in some cases, the direct effects of these medications on structures within these networks (e.g. amygdala, ventrolateral prefrontal cortex [VLPFC]). In this review, we summarize the extant functional, functional connectivity, and structural neuroimaging data in children and adolescents with GAD. In addition, data concerning selective serotonin reuptake inhibitors (SSRIs), selective serotonin norepinephrine reuptake inhibitors (SSNRIs), atypical anxiolytics, benzodiazepines, and psychotherapy are reviewed in the context of the neurophysiology of pediatric GAD. The existing data suggest abnormal activity within the amygdala, VLPFC, and anterior cingulate cortex, as well as the possibility of impaired connectivity among these brain regions. In addition to numerous cognitive behavioral therapy (CBT) trials, five randomized, controlled psychopharmacologic trials primarily in youth with GAD suggest that SSRIs and SSNRIs are effective for this condition. These findings also raise the possibility that functional activity within the amygdala and VLPFC may be altered following successful treatment.

Pediatric Generalized Anxiety Disorder

Pediatric generalized anxiety disorder (GAD) is characterized by excessive and uncontrollable worry about a variety of events and is accompanied by physical symptoms such as headaches, tension, restlessness, gastrointestinal distress, and heart palpitations. Symptoms impose marked distress and interfere with social, emotional, and educational functioning. GAD occurs in over 10% of children and adolescents, has an average age of onset of 8.5 years, and is more often reported in girls. Common co-occurring conditions include separation anxiety disorder and social phobia. Assessment involves a multi-informant, multi-method approach involving the child, parents, and school teachers. A clinical interview should be conducted to assess for the three primary ways anxiety presents: behaviors, thoughts, and somatic symptoms. Several semi-structured diagnostic interviews are available, and the Anxiety Disorders Interview Schedule is increasingly used. Rating scales completed by the patient, caregivers, and teachers provide useful information for diagnosis and symptom monitoring. Several scales are available to assess patients for the Diagnostic and Statistical Manual of Mental Disorders (4th Edition) GAD diagnosis; however, instruments generally cannot distinguish children with GAD from children with similar anxiety disorders. Both cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) have demonstrated efficacy for the treatment of pediatric anxiety disorders including GAD. Evidence suggests that the combination of CBT plus sertraline offers additional benefit compared with either treatment alone. With pharmacotherapy, systematic tracking of treatment-emergent adverse events such as headaches, stomach aches, behavioral activation, worsening symptoms, and emerging suicidal thoughts is important. Recommended starting doses are fluvoxamine 25 mg/day, fluoxetine 10 mg/day, and sertraline 25 mg/day, though lower starting doses are possible. Dosing can be adjusted as often as weekly with the goal of achieving a high-quality response, while minimizing side effects. Long-term treatment with medication has not been well studied; however, to achieve optimal long-term outcome extended use of medication may be required. It is recommended to continue medication for approximately 1 year following remission in symptoms, and when discontinuing medication to choose a stress-free time of the year. If symptoms return, medication re-initiation should be considered seriously.

Amygdala and Ventrolateral Prefrontal Cortex Activation to Masked Angry Faces in Children and Adolescents With Generalized Anxiety Disorder

Vigilance for threat is a key feature of generalized anxiety disorder (GAD). The amygdala and the ventrolateral prefrontal cortex constitute a neural circuit that is responsible for detection of threats. Disturbed interactions between these structures may underlie pediatric anxiety. To date, no study has selectively examined responses to briefly presented threats in GAD or in pediatric anxiety. To investigate amygdala and ventrolateral prefrontal cortex activation during processing of briefly presented threats in pediatric GAD. Case-control study. Government clinical research institute. Youth volunteers, 17 with GAD and 12 without a psychiatric diagnosis. We used functional magnetic resonance imaging to measure blood oxygenation level-dependent signal. During imaging, subjects performed an attention-orienting task with rapidly presented (17 milliseconds) masked emotional (angry or happy) and neutral faces. When viewing masked angry faces, youth with GAD relative to comparison subjects showed greater right amygdala activation that positively correlated with anxiety disorder severity. Moreover, in a functional connectivity (psychophysiological interaction) analysis, the right amygdala and the right ventrolateral prefrontal cortex showed strong negative coupling specifically to masked angry faces. This negative coupling tended to be weaker in youth with GAD than in comparison subjects. Youth with GAD have hyperactivation of the amygdala to briefly presented masked threats. The presence of threat-related negative connectivity between the right ventrolateral prefrontal cortex and the amygdala suggests that the prefrontal cortex modulates the amygdala response to threat. In pediatric GAD, amygdala hyperresponse occurs in the absence of a compensatory increase in modulation by the ventrolateral prefrontal cortex.

Efficacy and Safety of Extended-Release Venlafaxine in the Treatment of Generalized Anxiety Disorder in Children and Adolescents: Two Placebo-Controlled Trials

The authors evaluated the efficacy, safety, and tolerability of extended-release venlafaxine in the treatment of pediatric generalized anxiety disorder. Two randomized, double-blind, placebo-controlled trials were conducted at 59 sites in 2000 and 2001. Participants 6 to 17 years of age who met DSM-IV criteria for generalized anxiety disorder received a flexible dosage of extended-release venlafaxine (N=157) or placebo (N=163) for 8 weeks. The primary outcome measure was the composite score for nine delineated items from the generalized anxiety disorder section of a modified version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children, and the primary efficacy variable was the baseline-to-endpoint change in this composite score. Secondary outcome measures were overall score on the nine delineated items, Pediatric Anxiety Rating Scale, Hamilton Anxiety Rating Scale, Screen for Child Anxiety Related Emotional Disorders, and the severity of illness and improvement scores from the Clinical Global Impression scale (CGI). The extended-release venlafaxine group showed statistically significant improvements in the primary and secondary outcome measures in study 1 and significant improvements in some secondary outcome measures but not the primary outcome measure in study 2. In a pooled analysis, the extended-release venlafaxine group showed a significantly greater mean decrease in the primary outcome measure compared with the placebo group (-17.4 versus -12.7). The response rate as indicated by a CGI improvement score <3 was significantly greater with extended-release venlafaxine than placebo (69% versus 48%). Common adverse events were asthenia, anorexia, pain, and somnolence. Statistically significant changes in height, weight, blood pressure, pulse, and cholesterol levels were observed in the extended-release venlafaxine group. Extended-release venlafaxine may be an effective, well-tolerated short-term treatment for pediatric generalized anxiety disorder.

Efficacy and Safety of Extended-Release Venlafaxine in the Treatment of Generalized Anxiety Disorder in Children and Adolescents: Two Placebo-Controlled Trials

Objective: The authors evaluated the efficacy, safety, and tolerability of extended-release venlafaxine in the treatment of pediatric generalized anxiety disorder. Method: Two randomized, double-blind, placebo-controlled trials were conducted at 59 sites in 2000 and 2001. Participants 6 to 17 years of age who met DSM-IV criteria for generalized anxiety disorder received a flexible dosage of extended-release venlafaxine (N=157) or placebo (N=163) for 8 weeks. The primary outcome measure was the composite score for nine delineated items from the generalized anxiety disorder section of a modified version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children, and the primary efficacy variable was the baseline-to-endpoint change in this composite score. Secondary outcome measures were overall score on the nine delineated items, Pediatric Anxiety Rating Scale, Hamilton Anxiety Rating Scale, Screen for Child Anxiety Related Emotional Disorders, and the severity of illness and improvement scores from the Clinical Global Impression scale (CGI). Results: The extended-release venlafaxine group showed statistically significant improvements in the primary and secondary outcome measures in study 1 and significant improvements in some secondary outcome measures but not the primary outcome measure in study 2. In a pooled analysis, the extended-release venlafaxine group showed a significantly greater mean decrease in the primary outcome measure compared with the placebo group (–17.4 versus –12.7). The response rate as indicated by a CGI improvement score <3 was significantly greater with extended-release venlafaxine than placebo (69% versus 48%). Common adverse events were asthenia, anorexia, pain, and somnolence. Statistically significant changes in height, weight, blood pressure, pulse, and cholesterol levels were observed in the extended-release venlafaxine group. Conclusions: Extended-release venlafaxine may be an effective, well-tolerated short-term treatment for pediatric generalized anxiety disorder.

Abnormal Attention Modulation of Fear Circuit Function in Pediatric Generalized Anxiety Disorder

Considerable work implicates abnormal neural activation and disrupted attention to facial-threat cues in adult anxiety disorders. However, in pediatric anxiety, no research has examined attention modulation of neural response to threat cues. To determine whether attention modulates amygdala and cortical responses to facial-threat cues differentially in adolescents with generalized anxiety disorder and in healthy adolescents. Case-control study. Government clinical research institute. Fifteen adolescents with generalized anxiety disorder and 20 controls. Blood oxygenation level-dependent signal as measured via functional magnetic resonance imaging. During imaging, participants completed a face-emotion rating task that systematically manipulated attention. While attending to their own subjective fear, patients, but not controls, showed greater activation to fearful faces than to happy faces in a distributed network including the amygdala, ventral prefrontal cortex, and anterior cingulate cortex (P<.05, small-volume corrected, for all). Right amygdala findings appeared particularly strong. Functional connectivity analyses demonstrated positive correlations among the amygdala, ventral prefrontal cortex, and anterior cingulate cortex. This is the first evidence in juveniles that generalized anxiety disorder-associated patterns of pathologic fear circuit activation are particularly evident during certain attention states. Specifically, fear circuit hyperactivation occurred in an attention state involving focus on subjectively experienced fear. These findings underscore the importance of attention and its interaction with emotion in shaping the function of the adolescent human fear circuit.

Cerebellar Volumes in Pediatric Maltreatment-Related Posttraumatic Stress Disorder

The results of previous studies suggest structural brain differences in pediatric maltreatment-related posttraumatic stress disorder (PTSD) However, posterior fossa volumes were not examined, despite the consensus that the cerebellum is important in emotional and cognitive development. We investigated the relationship between structural volumes of the cerebellum hemispheres, vermis, brainstem, and clinical variables in pediatric maltreatment-related PTSD. Fifty-eight psychotropic-naïve maltreated children and adolescents with DSM-IV PTSD were compared with two groups of pediatric subjects who had no DSM-IV criteria A trauma histories: 1) 13 with pediatric generalized anxiety disorder, and 2) 98 healthy non-abused children and adolescents. Subjects underwent a comprehensive psychiatric assessment and an anatomical magnetic resonance image brain scan. Unadjusted means of the left, right, and total cerebellum were smaller in the PTSD group. The group differences remained significant in the left cerebellum, right cerebellum, and total cerebellum in the analyses adjusted for cerebral volume, sociodemographic, and IQ variables. Cerebellar volumes positively correlated with age of onset of the trauma that lead to PTSD and negatively correlated with the duration of the trauma that lead to PTSD. Cerebellar volumes were larger in boys versus girls, but there was no group x gender interaction. There were significant positive correlations between IQ measures and volumetric variables. The results support cerebellar volume differences in maltreated children and adolescents with PTSD. Further studies are warranted.