Measuring anxiety: parent-child reporting differences in clinical samples

This study examines parent-child reporting differences for childhood anxiety in normal controls (n = 16) and in children with diagnosed anxiety disorders (ANX; n = 15), attention-deficit hyperactivity disorder (ADHD; n = 15), and comorbid ANX and ADHD (n = 16). Correspondence between child reports of anxiety on two self-report inventories and diagnosis based on structured parent interview was assessed for all four groups. Parent-child agreement did not appear to be measurement dependent but did differ by diagnostic group, with poorer agreement for clinical groups. Though needing replication, these findings suggest that it is inadvisable to rely exclusively on self-report measures when assessing childhood anxiety, especially in clinical populations. Such measures can be useful in monitoring clinical progress, however, provided parent and child reports are examined separately.     

Attention bias to threat faces in children with bipolar disorder and comorbid lifetime anxiety disorders.

BACKGROUND: Although comorbid anxiety disorders are common in children with bipolar disorder (BD), it is unclear how this comorbidity impacts the pathophysiology of the illness. METHODS: Pediatric BD with lifetime anxiety (BD+ANX, n = 20), BD without lifetime anxiety (BD-ANX, n = 11), and controls (n = 14) were administered the visual-probe paradigm, which assesses attention bias to threat faces. RESULTS: Bipolar disorder +ANX demonstrated a stronger bias toward threat relative to BD-ANX and controls; the latter two did not differ from each other. CONCLUSIONS: Bipolar disorder +ANX showed a bias toward threat while, in two previous studies, anxious children showed a bias away from threat faces. Future studies should compare the pathophysiology of BD with and without a comorbid anxiety disorder and anxiety disorders presenting alone.     

Peri-sleep-onset cortisol levels in children and adolescents with affective disorders.

BACKGROUND: Changes in the hypothalamic-pituitary-adrenal (HPA) axis, as evidenced by patterns of cortisol secretion, have been of interest in understanding depression and anxiety disorders across the life span. Previous studies of pediatric depression have pointed to the period around sleep onset as a key time point for observing alterations in cortisol secretion associated with affective disorders. Evidence also indicates that pubertal development may influence the expression of HPA dysregulation. We hypothesized that adolescents with depression and youth with anxiety disorders exhibit elevated peri-sleep-onset cortisol. METHODS: Plasma cortisol was sampled every 20 min around sleep onset from children and adolescents with major depressive disorder (n = 116), anxiety disorders (n = 32), or no history of psychiatric disorder (control; n = 76). Sleep onset was determined by polysomnography. Classification of participants as children or adolescents was based on Tanner staging of pubertal maturation. RESULTS: Children with anxiety disorders had higher peri-sleep-onset cortisol than children with depression or control children. Adolescents with depression had marginally higher peri-sleep-onset cortisol than control adolescents and significantly higher peri-sleep-onset cortisol than children with depression. CONCLUSIONS: Depression and anxiety are associated with altered cortisol secretion around sleep onset, and these changes appear to be influenced by pubertal maturation.     

Relaxation and guided imagery program in patients with breast cancer undergoing radiotherapy is not associated with neuroimmunomodulatory effects

OBJECTIVE: Treatment of breast cancer is usually associated with significant psychological stress. In this study, we examined the effects of relaxation and visualization therapy (RVT) on psychological distress, cortisol levels, and immunological parameters of breast cancer patients undergoing radiotherapy. METHODS: Participants were randomly assigned to either the experimental (n=20) who underwent group RVT for 24 consecutive days or control group (n=14) who were on radiotherapy only. Psychological scores (stress, anxiety, and depression) were measured by structured clinical interviews. Salivary cortisol was assessed along the day. Lymphocytes were isolated and cultured to measure T-cell proliferation and sensitivity to glucocorticoids (GCs). RESULTS: RVT was effective to reduce stress, anxiety, and depression scores (all P<.05). However, cortisol levels as well as proliferation remained unchanged following RVT. Although T cells of experimental group were more sensitive to GCs than cells of controls at baseline, no changes were noted following RVT. Cortisol levels were positively correlated to anxiety and depression scores and inversely correlated to T-cell proliferation and sensitivity to GCs. CONCLUSION: We conclude that the psychological intervention was capable to attenuate the emotional distress presented during radiotherapy treatment. A longer RVT or worse psychological morbidity at baseline may be necessary to translate psychological into biological changes.     

Hypochondriasis, somatoform disorders, and anxiety disorders: sociodemographic variables, general psychopathology, and naturalistic treatment effects

The question of whether hypochondriasis (HYP) should be considered a somatoform disorder (SFD) or classified as an anxiety disorder (ANX) has recently been raised. To empirically provide information on this issue, we compared patients with HYP (n = 65) with those with other SFDs (n = 94) and those with ANX (n = 224) regarding sociodemographic and biographical variables, general psychopathology, and naturalistic cognitive-behavioral therapy treatment effects. Compared with SFD, patients with HYP were younger and had fewer comorbid affective disorders and less impaired life domains, suggesting a closer connection between HYP and ANX. Regarding cognitive-behavioral therapy treatment effects, all diagnostic groups showed comparable significant improvement (d = 0.44-0.64). According to level of anxiety, the SFD sample had significantly lower pretreatment scores than did the ANX and the HYP samples. The results suggest that patients with HYP have an interim position between SFD and ANX, with slightly closer connections to ANX.     

The sounds of silence: language, cognition, and anxiety in selective mutism

OBJECTIVES: To determine whether oral language, working memory, and social anxiety differentiate children with selective mutism (SM), children with anxiety disorders (ANX), and normal controls (NCs) and explore predictors of mutism severity. METHOD: Children ages 6 to 10 years with SM (n = 44) were compared with children with ANX (n = 28) and NCs (n = 19) of similar age on standardized measures of language, nonverbal working memory, and social anxiety. Variables correlating with mutism severity were entered in stepwise regressions to determine predictors of mute behavior in SM. RESULTS: Children with SM scored significantly lower on standardized language measures than children with ANX and NCs and showed greater visual memory deficits and social anxiety relative to these two groups. Age and receptive grammar ability predicted less severe mutism, whereas social anxiety predicted more severe mutism. These factors accounted for 38% of the variance in mutism severity. CONCLUSIONS: Social anxiety and language deficits are evident in SM, may predict mutism severity, and should be evaluated in clinical assessment. Replication is indicated, as are further studies of cognition and of intervention in SM, using large, diverse samples.     

Moderate versus severe early life stress: associations with stress reactivity and regulation in 10-12-year-old children

Early life stress (ELS) is expected to increase reactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis; however, several recent studies have shown diminished cortisol reactivity among adults and children with ELS exposure. The goal of this study was to examine cortisol activity in 10-12-year-old internationally adopted children to determine if moderate and severe ELS have different impacts on the HPA axis. Salivary cortisol and two measures of autonomic activity were collected in response to the Trier Social Stress Test for Children (TSST-C). Three groups reflecting moderate, severe, and little ELS were studied: early adopted children who came predominantly from foster care overseas (early adopted/foster care (EA/FC), n=44), later adopted children cared for predominantly in orphanages overseas (late adopted/post-institutionalized (LA/PI), n=42) and non-adopted (NA) children reared continuously by their middle- to upper-income parents in the United States (n=38). Diminished cortisol activity was noted for the EA/FC group (moderate ELS), while the LA/PI group (severe ELS) did not differ from the NA group. Overall, few children showed cortisol elevations to the TSST-C in any group. The presence/absence of severe growth delay at adoption proved to be a critical predictive factor in cortisol activity. Regardless of growth delay, however, LA/PI children exhibited higher sympathetic tone than did NA children. These results suggest that moderate ELS is associated with diminished cortisol activity; however, marked individual differences in cortisol activity among the LA/PI children suggest that child factors modify the impact of severe ELS. Lack of effects of severe ELS even for growth delayed children may reflect the restorative effects of adoption or the generally low responsiveness of this age group to the TSST-C.     

Effect of comorbid anxiety disorders on the hypothalamic-pituitary-adrenal axis response to a social stressor in major depression.

BACKGROUND: Major depressive disorder (MDD) is often complicated by anxiety symptoms, and anxiety disorders occur in approximately 30% of mood cases. This study examined the influence of anxiety comorbidity on the hypothalamic-pituitary-adrenal (HPA) axis response to stress in patients with MDD. METHODS: Untreated subjects with pure MDD (n = 15), MDD with comorbid anxiety disorders (n = 18), and pure anxiety disorders (n = 15) were recruited by advertising. Age- and gender-matched control subjects were recruited for each subject with a psychiatric diagnosis (n = 48). All subjects underwent a social stressor, the Trier Social Stress Test (TSST), and blood was collected for adrenocorticotropic hormone (ACTH) and cortisol assay. RESULTS: When all depressed patients (n = 33) were compared with their matched control subjects (n = 33), they showed a significantly greater ACTH response to the stressor; however, this exaggerated ACTH response was exclusively due to the depressed group with comorbid anxiety disorders. A similar but nonsignificant effect was observed in the cortisol response. Subjects with pure mood or pure anxiety disorders showed normal ACTH and cortisol responses to the TSST. All patient groups showed similar levels of TSST-induced anxiety. CONCLUSIONS: Comorbid anxiety disorders might play a role in the increased activation of the HPA axis observed in patients with major depression.     

A distinctive interaction between chronic anxiety and problem solving in asymptomatic APOE e4 homozygotes

We correlated measures of problem solving (Wisconsin Card Sorting Test [WCST] categories, total errors, and perseverative errors) and chronic anxiety (Personality Assessment Inventory Anxiety Scale [ANX]) in asymptomatic apolipoprotein E (APOE) e4 homozygotes (HMZs), heterozygotes, and noncarriers (NC) (n = 42 in each group) matched for age, education, and gender. Differences between HMZ and NC in the slope of the regression of WCST scores on ANX reached statistical significance on all three WCST measures. Chronic anxiety adversely affects cognitive skills in all groups, and is associated with significantly greater decline in problem solving skills in cognitively normal APOE e4 HMZ.     

Parsing the comorbidity between bipolar disorder and anxiety disorders: a familial risk analysis

BACKGROUND: A growing literature suggests that anxiety disorders (ANX) co-occur with bipolar disorder (BPD), but the nature of this overlap is unknown. Thus, we investigated the familial association between BPD and ANX among the first-degree relatives of children with BPD with and without comorbid ANX. METHODS: We compared relatives of four proband groups defined by the presence or absence of BPD and ANX in the proband: (1) BPD + ANX (n = 23 probands, 74 relatives), (2) BPD without ANX (n = 11 probands, 38 relatives), (3) ANX without BPD (n = 48 probands, 167 relatives), and (4) controls without BPD or ANX (n = 118 probands, 385 relatives). All subjects were evaluated with structured diagnostic interviews. Diagnoses of relatives were made blind to the diagnoses of probands. RESULTS: The results show high rates of both BPD and ANX in relatives of children with BPD + ANX. Moreover, BPD and ANX cosegregated among the relatives of children with BPD + ANX. Although relatives of both ANX proband groups (with and without BPD) had high rates of ANX, and relatives of both BPD proband groups (with and without ANX) had high rates of BPD, the combined condition BPD + ANX was the predominant form of BPD among relatives of probands with BPD + ANX. CONCLUSIONS: These family-genetic findings suggest that the comorbid condition BPD+ANX may be a distinct clinical entity. More work is needed to evaluate whether the presence of comorbid ANX may be a marker of very early onset BPD.     

ACTH and beta-endorphin responses to physical exercise in adolescent women tested for anxiety and frustration.

Thirty healthy adolescent women (age: 14 years), high school students without clinical signs of psychiatric or major affective disorders, received psychological and endocrinological examinations. Two psychological tests were used: the Anxiety Score Test for Adolescents and the Pictures Frustration Test for Adolescents of Rosenzweig. On the basis of the results of these tests, subjects were divided into two groups: A (n = 21), normal subjects; B (n = 9), subjects with evidence of anxiety (n = 1), frustration (n = 1), or both (n = 7). Plasma levels of adrenocorticotropic hormone (ACTH) and beta-endorphin were measured under basal conditions and after physical exercise (Step Test) in all subjects. Hormonal responses in groups A and B were compared. Basal concentrations of ACTH and cortisol were similar in the two groups, whereas basal beta-endorphin levels were significantly higher in group B than in group A. Exercise induced a slight but significant increase in plasma concentrations of both ACTH (32% increase) and beta-endorphin (60% increase) in group A. A striking increase in plasma ACTH (100% increment) and a slight increase of beta-endorphin (60% increment) levels were observed in group B after exercise. Absolute levels of ACTH and beta-endorphin after physical exercise were significantly higher in group B than in group A. These findings indicate increased levels of adrenocorticotropic and opioid activity in adolescent women with high scores on psychological measures of anxiety and frustration.     

Objective sleep in pediatric anxiety disorders and major depressive disorder

OBJECTIVE: To examine objective and subjective sleep problems in early-onset anxiety and depression. METHOD: Children and adolescents (46% female, ages 7 to 17 years) with anxiety disorders (n = 24), major depressive disorder (MDD) without comorbid anxiety disorders (n = 128), or no history of psychiatric disorder (n = 101) spent two consecutive nights in a sleep laboratory and completed self-reports of sleep quality. RESULTS: On objective measures, the anxiety group exhibited more awakenings than the MDD group, less slow-wave sleep than the control or MDD group, and greater night 2 sleep latency than the MDD or control group. The anxiety group exhibited no decrease in rapid eye movement latency from the first night to the second. The MDD group exhibited less time awake than the control group and less stage 1 sleep than the anxiety or control group. On subjective measures, young people with anxiety reported greater sleep latency on the second night and no decrease in sleep latency. Age was covaried in analyses. CONCLUSIONS: Findings provide objective and subjective evidence of sleep disturbance in children and adolescents with anxiety disorders and replicate findings of limited objective sleep disturbance in those with MDD. Sleep problems are an important consideration when treating young people with anxiety.     

Dichotic listening and response inhibition in children with comorbid anxiety disorders and ADHD

OBJECTIVE: To compare children with comorbid anxiety disorders (ANX) and attention-deficit hyperactivity disorder (ADHD) with children with either pure disorder and normal controls on 2 cognitive measures to elucidate the cognitive basis of this comorbidity. METHOD: Four groups of children aged 8 to 12 years (n = 64 total) were assessed: ANX, ADHD, both conditions (comorbid group), and neither condition (normal control group). Groups were compared on 2 cognitive measures: a measure of auditory emotional perception (dichotic listening task) and a measure of response inhibition (stop task), chosen for their relative specificity for ANX and ADHD, respectively, in previous studies. RESULTS: Multivariate analyses of variance revealed significant group differences on the dichotic listening task (p < .05), with the comorbid group differing from the control group on emotion targets (p < .01) and the ADHD group differing from the control group on word targets (p < .05). On the stop task, the ADHD group appeared slower than the other diagnostic groups on both go and stop-signal reaction times, but differences were not significant. CONCLUSIONS: In this study, children with comorbid ANX and ADHD showed reduced auditory emotion recognition relative to controls but did not show response inhibition deficits. Thus they appeared cognitively distinct from children with either pure disorder.     

A pilot study of noradrenergic and HPA axis functioning in PTSD vs. panic disorder

The biological literature in the anxiety disorders has focused on comparisons between patient groups and normal volunteers, with relatively little comparative study of the anxiety disorders. We therefore conducted this pilot study to compare a group of patients with post-traumatic stress disorder (PTSD) (n=7) to a contiguously studied panic disorder group (n=17) and healthy control subjects (n=16) on baseline levels of cortisol and 3-methoxy-4-hydroxyphenylglycol (MHPG), and response to clonidine challenge. Despite the small sample size, highly significant differences were found on the following measures: PTSD patients had lower cortisol, lower MHPG, reduced MHPG volatility to clonidine challenge, and marginally reduced cortisol volatility compared to patients with panic disorder. These biological findings support existing clinical, epidemiologic, family study, and clinical trial findings that distinguish these two disorders as distinct syndromes.     

Performance monitoring and response inhibition in anxiety disorders with and without comorbid ADHD

Anxiety disorder (ANX) is characterized by heightened arousal, psychosocial and academic difficulties, and comorbidity with other disorders, in particular, attention-deficit/hyperactivity disorder (ADHD). The heightened arousal contributes to cognitive impairment by adversely affecting executive control of cognition. The nature of the effect on executive control is poorly understood. Research in this area could inform intervention, diagnostic, and etiological research. Our objective was to characterize children with ANX on measures of executive functioning, while controlling for comorbid ADHD. We compared children ages 6-14 with ANX (N=21), ADHD (N=78), ANX+ADHD (N=38), and normal controls (NC; N=40) on the stop task, a measure of performance monitoring and response inhibition. No difference was observed between NC and ANX groups in performance monitoring. Compared to the NC group, the three clinical groups showed inhibition deficits, and both ADHD and ANX+ADHD groups monitored less after responses. ANX was not associated with performance monitoring or inhibition deficits once comorbid ADHD was considered. This emphasizes the importance of controlling for comorbid ADHD in studies of cognition and anxiety.     

Social anxiety,depression, and PTSD in Vietnam veterans

Many Vietnam veterans with PTSD report a high level of social anxiety and avoidance. Many traumatized individuals also suffer from symptoms of depression, which is often associated with significant problems in social functioning. In order to explore the relationship between social anxiety, depression, and PTSD, we recruited a group of Vietnam veterans with PTSD (n = 27), veterans with other mental disorders (n = 20), and veterans with no mental disorders (n = 35). Participants were administered diagnostic interviews and some of the most commonly used social anxiety instruments. Although the groups did not differ in their rates of social phobia, veterans with PTSD scored highest in most social anxiety measures. Veterans with PTSD were also more likely to be clinically depressed than veterans without PTSD at the time of the assessment. When controlling for the level of depression, the three groups no longer differed in any of the social anxiety measures. Furthermore, level of depression was the best predictor for group membership. These findings suggest that social anxiety in Vietnam combat veterans with PTSD is closely associated with mood disturbance, social withdrawal, and isolation associated with depression.     

How is the Beads Task related to intolerance of uncertainty in anxiety disorders?

Intolerance of uncertainty (IU) is a cognitive bias associated with anxiety disorders that has only been reliably measured using self-report instruments. The current study investigated relationships between a probabilistic inference task – the Beads Task – and self-report IU. Individuals with anxiety disorders (ANX) and non-anxious controls (NAC) completed self-report measures as well as the Beads Task at three levels of difficulty. The Beads Task successfully induced task-related uncertainty as the decision became more difficult. While the two groups did not differ on the observable performance related measures, the ANX group was significantly more distressed during the task than were the NACs. Moreover, among the ANX group, self-reported IU was correlated with draws to decision and distress during the task. The Beads Task appears to provoke distress associated with uncertainty for anxious individuals, rather than altering their behavioral responses; thus, clinical implications and avenues for future research are discussed.     

Preliminary evidence for sleep complaints among children referred for anxiety

BACKGROUND AND PURPOSE: Clinical observation suggests that sleep complaints are common among youth with anxiety disorders though empirical data documenting this co-occurrence of symptoms are generally unavailable. PATIENTS AND METHODS: Based on retrospective chart reviews, the current study examined rates of several types of parent-reported sleep complaints among a sample of (n=35) purely anxious children and adolescents (ANX). Sleep complaints were examined in terms of age (children versus adolescents) and type of anxiety diagnosis (generalized anxiety versus other anxious diagnoses). Rates of sleep complaints among anxious youth also were compared to those among (n=38) healthy control children and (n=33) children referred for sleep problems. RESULTS: The presence of at least one intermittent sleep complaint was reported by 83% of parents of ANX, with almost half reporting at least one frequent sleep complaint. Rates of sleep complaints among anxious children versus adolescents were similar. Children with generalized anxiety disorder (GAD) had a significantly greater number of sleep complaints than children with other types of anxiety disorders, though rates for specific items varied. Although parents of sleep-referred children reported the highest rates of sleep complaints overall, the frequency of several specific types of sleep complaints was highly similar among ANX and sleep-referred children. CONCLUSIONS: Findings indicate that certain sleep complaints are common among ANX. The need for appropriate assessment practices is discussed.     

Treatment of childhood anxiety disorders: a preliminary comparison between cognitive-behavioral group therapy and a psychological placebo intervention

The present study examined the efficacy of group cognitive-behavioral therapy (CBT) in the treatment of childhood anxiety disorders. Thirty high-anxious children (aged 9-12 years) were assigned to either (a) group CBT (n = 10), (b) a psychological placebo intervention (i.e., emotional disclosure [ED]; n = 10), or (c) a no-treatment control condition (n = 10). Therapy outcome measures (i.e., children's self-report of anxiety disorders symptoms, depression, and trait anxiety) were obtained three months before treatment, at pretreatment, and at posttreatment. Results showed that levels of psychopathological symptoms remained relatively stable during the three months preceding treatment. Most importantly, pretreatment-posttreatment comparisons indicated that CBT was superior to ED and the no-treatment control condition. That is, only in the CBT condition significant reductions of anxiety disorders symptoms, trait anxiety, and depression were observed. These findings can be taken as further evidence for the efficacy of CBT in the treatment of childhood anxiety disorders.     

Physiological and behavioral adaptation to relocation stress in differentially reared rhesus monkeys: hair cortisol as a biomarker for anxiety-related responses

Increased hair cortisol concentrations have been associated with stress exposure in both human and nonhuman primates, and hair cortisol is now gaining attention as a biomarker for stress-related health problems. The present study examined the behavioral and physiological reactions of rhesus monkey (Macaca mulatta) infants reared in three different rearing environments to the major stressor of relocation. Infant monkeys (n=61) were studied from birth through 2 years of age. For the first 8 months of life, infants were either with their mothers and peers (MPR, n=21) or reared in a nursery using either peer-rearing (PR, n=20) or surrogate-peer-rearing (SPR, n=20). At approximately 8 months of age, infants were removed from their rearing group, simultaneously placed into a large social environment consisting of infants from all three rearing conditions, and observed for the next 16 months. Behavior was recorded twice per week from 1 to 24 months, and composite anxiety scores were calculated for each monkey. Monkeys were initially shaved at the nape of the neck on day 14 to remove any prenatal effects on hair cortisol deposition. Hair samples were then collected by re-shaving at 6, 12, 18 and 24 months and analyzed for cortisol content. MPR monkeys were the least affected by the stressor, showing smaller increases in anxious behavior than the other groups and more rapid physiological adaptation as assessed using hair cortisol. PR monkeys showed heightened and prolonged anxious behavior, had the highest cortisol levels prior to relocation, and their cortisol levels did not decline until more than a year later. SPR monkeys exhibited more rapid behavioral adaptation than PR monkeys, showing heightened but not prolonged anxious behavior. However, the SPR group showed a marked increase in cortisol in response to the relocation, and like the PR group, their physiological adaptation was slower than that of the MPR group as indicated by elevated cortisol levels at 18 months. By 24 months of age (16 months after relocation), all rearing groups were indistinguishable from one another physiologically and behaviorally. Spearman rank correlation revealed that hair cortisol taken at month 6 was not correlated with composite anxiety scores from months 6 to 8 (just before the relocation), but was positively correlated with composite anxiety scores between months 8 and 12 (immediately after relocation) for PR infants only (r(s)=0.75, p<0.001). Month 6-hair cortisol tended to positively correlate with composite anxiety scores for the following 6 months (months 12-18) for PR monkeys only (r(s)=0.47, p=0.037), which exhibited more anxious behavior than MPR and SPR infants during this period (ANOVA: F((2,60))=14.761, p<0.001) This is the first study to show that elevated hair cortisol early in life is a biomarker for the later development of anxious behavior in response to a major life stressor, particularly for infant monkeys exposed to early life adversity in the form of peer-rearing.