Salivary cortisol is associated with diagnosis and severity of late-life generalized anxiety disorder

Age-associated alterations in hypothalamic-pituitary-adrenal (HPA) axis functioning may make individuals more susceptible to HPA dysregulation in the context of mood and anxiety disorders. Little to no research has been done to examine HPA axis function in generalized anxiety disorder (GAD), particularly in late-life GAD, the most prevalent anxiety disorder in the elderly. The study sample consisted of 71 GAD subjects and 40 nonanxious comparison subjects over 60 years of age. We examined the hypotheses that elderly individuals with GAD will have elevated salivary cortisol levels compared to nonanxious subjects, and that elevated cortisol levels in GAD will be associated with measures of symptom severity. We report that late-life GAD is characterized by elevated basal salivary cortisol levels, with higher peak cortisol levels and larger areas under the curve, compared to nonanxious subjects. Additionally, severity of GAD as measured by the GAD Severity Scale and the Penn State Worry Questionnaire are positively correlated with cortisol levels. These data demonstrate HPA axis dysfunction in late-life GAD and suggest the need for additional research on the influence of aging on HPA axis function in mood and anxiety disorders.     

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.     

Baseline cortisol measures and developmental pathways of anxiety in early adolescence

Objective: This study investigated whether baseline cortisol measures predicted future anxiety, and compared cortisol values of groups with different developmental pathways of anxiety. Method: Cortisol levels were assessed in 1768 individuals (10–12 years). Anxiety levels were assessed at the same age and 2 years later. Results: Cortisol measures did not predict future anxiety levels. Individuals with persistent anxiety problems did not show higher morning cortisol levels than those with persistently low, decreasing, or increasing anxiety levels. Instead, individuals with persistently high anxiety levels showed significantly lower evening cortisol levels than all other individuals. Further, participants with increasing anxiety levels showed higher morning cortisol levels (area under the curve; AUC) than individuals with persistently low anxiety levels. Conclusion: The extent to which the HPA‐axis – by itself – plays a role in the aetiology of anxiety is questionable. Interactions of the HPA‐axis with other biological or environmental factors may be more important.     

Childhood stressful events,HPA axis and anxiety disorders

Anxiety disorders are among the most common of all mental disorders and their pathogenesis is a major topic in psychiatry, both for prevention and treatment. Early stressful life events and alterations of hypothalamic pituitary adrenal (HPA) axis function seem to have a significant role in the onset of anxiety. Existing data appear to support the mediating effect of the HPA axis between childhood traumata and posttraumatic stress disorder. Findings on the HPA axis activity at baseline and after stimuli in panic disordered patients are inconclusive, even if stressful life events may have a triggering function in the development of this disorder. Data on the relationship between stress, HPA axis functioning and obsessive-compulsive disorder (OCD) are scarce and discordant, but an increased activity of the HPA axis is reported in OCD patients. Moreover, normal basal cortisol levels and hyper-responsiveness of the adrenal cortex during a psychosocial stressor are observed in social phobics. Finally, abnormal HPA axis activity has also been observed in generalized anxiety disordered patients. While several hypothesis have attempted to explain these findings over time, currently the most widely accepted theory is that early stressful life events may provoke alterations of the stress response and thus of the HPA axis, that can endure during adulthood, predisposing individuals to develop psychopathology. All theories are reviewed and the authors conclude that childhood life events and HPA abnormalities may be specifically and transnosographically related to all anxiety disorders, as well as, more broadly, to all psychiatric disorders.     

Twenty-four-hour cortisol secretion patterns in prepubertal children with anxiety or depressive disorders.

BACKGROUND: Previous studies found few abnormalities in hypothalamic-pituitary-adrenal (HPA) axis function in prepubertal children with anxiety or depressive disorders. In this study, we combined data from two independent, consecutive studies to achieve a larger sample size. Our goal was to identify potential alterations in the circadian pattern of cortisol secretion in anxious or depressed children. METHODS: A total of 124 prepubertal subjects from two independent samples (76 with major depressive disorder, 31 with anxiety disorders, and 17 healthy control subjects) were studied. Blood samples collected for cortisol at hourly intervals over a 24-hour period were examined. Analyses were performed aligning cortisol samples by clock-time. Additional analyses aligning samples by sleep-onset time were performed with a subsample of subjects. RESULTS: In the combined sample, significant findings emerged that were previously undetected. Anxious children exhibited significantly lower nighttime cortisol levels and an initially sluggish rise in cortisol during the nighttime when compared with depressed and healthy control children. In contrast, depressed children did not show a clear-cut pattern of differences compared with healthy control children. CONCLUSIONS: Anxious children seem to exhibit an altered pattern of nighttime cortisol secretion, with an initially sluggish or delayed nocturnal rise before reaching similar peak levels of cortisol near the time of awakening. These findings suggest subtle alterations in HPA axis function in prepubertal children with anxiety disorders.     

Prenatal anxiety predicts individual differences in cortisol in pre-adolescent children.

BACKGROUND: Animal studies suggest that prenatal stress is associated with long-term disturbance in hypothalamic-pituitary-adrenal (HPA) axis function, but evidence in humans is lacking. This study examined the long-term association between prenatal anxiety and measures of diurnal cortisol at age 10 years. METHODS: Measures of cortisol were collected at awakening, 30 min after awakening, and at 4 pm and 9 pm on 3 consecutive days in a sample of 10-year-olds (n = 74) from the Avon Longitudinal Study of Parents and Children, a prospective longitudinal cohort study of mothers and children on whom measures of anxiety and depression were collected in pregnancy and the postpartum period. Analyses examined the links between symptoms of prenatal anxiety and multiple indicators of cortisol, an index of HPA axis functioning. RESULTS: Prenatal anxiety was significantly associated with individual differences in awakening and afternoon cortisol after accounting for obstetric and sociodemographic risk (partial correlations were .32 and .25, p < .05). The effect for awakening cortisol remained significant after controlling for multiple postnatal assessments of maternal anxiety and depression. CONCLUSIONS: This study provides the first human evidence that prenatal anxiety might have lasting effects on HPA axis functioning in the child and that prenatal anxiety might constitute a mechanism for an increased vulnerability to psychopathology in children and adolescents.     

Children suffering from separation anxiety disorder (SAD) show increased HPA axis activity compared to healthy controls

Research questions

Separation anxiety disorder (SAD) is one of the most common mental disorders in childhood, and one of the earliest emerging. Little is known about the association between SAD and the hypothalamic-pituitary-adrenocortical (HPA) axis activity. Therefore, the present study aimed at investigating this association in children suffering from separation anxiety compared to healthy controls.

Methods

A total of 31 children with diagnosed SAD (mean age: 8.45; 17 females, 14 males) and 25 healthy controls (HC; mean age: 9.74; 12 females, 13 males) took part in the study. All participants underwent psycho-physiological testing for HPA axis challenge. Testing consisted of a separation and a social exposure paradigm. Saliva samples to assess HPA axis-related cortisol secretion were gathered in parallel.

Results

Compared to healthy controls, children with SAD showed greatly increased HPA axis activity, as reflected by an increased cortisol secretion throughout the entire period of investigation. The rise of cortisol was already observed in anticipation of, but not following the separation paradigm. No gender-related differences of cortisol secretion were observed.

Conclusions

Separation anxiety disorder (SAD) in children is reflected in greatly increased HPA axis activity. Compared to healthy controls, children with SAD showed increased cortisol values from the beginning of, and throughout, the entire investigation. This pattern of results suggests that both the anticipation of a separation and a persistent hyperactivity of the HPA axis system leads to an increased cortisol secretion.     

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.     

Salivary cortisol concentrations before and after carbon-dioxide inhalations in children.

BACKGROUND: Considerable research implicates over-activity of the hypothalamic-pituitary adrenal axis in the pathophysiology of adult mood and anxiety disorders. The current study evaluates the association between salivary cortisol concentrations and response to carbon-dioxide inhalation in children and adolescents with anxiety disorders, mood disorders, or no psychiatric illness. The central question was whether response to carbon-dioxide inhalation is associated with levels of hypothalamic-pituitary adrenal axis activation. If confirmed, this would relate hypothalamic-pituitary adrenal axis activation in juveniles, as in adults, and response to a well-studied respiratory procedure. METHODS: Serial salivary cortisol samples were examined in 98 subjects (ages 9-17 years), including 62 subjects with an anxiety and/or mood disorder and 36 nonpsychiatrically ill comparisons. Samples were obtained upon arrival at the laboratory, following a tilt test, then before and immediately after a standard 5% carbon dioxide inhalation procedure. RESULTS: Salivary cortisol levels pre-carbon-dioxide inhalation were significantly higher in patients sensitive to the anxiogenic effects of carbon dioxide (n = 20) than in patients who did not respond to carbon dioxide (n = 42) and in healthy subjects, none of whom were sensitive to carbon dioxide (n = 36); cortisol concentrations in the latter two groups were indistinguishable. Salivary cortisol did not increase during carbon-dioxide inhalation, irrespective of diagnostic group or degree of reactivity to the procedure. CONCLUSIONS: The current data resemble data from studies of laboratory-induced panic among adult patients. In both groups, activation of the hypothalamic-pituitary adrenal axis is associated with the response to a standardized stressor. Similarly, as in adults, carbon-dioxide inhalation in juveniles does not produce a significant change in hypothalamic-pituitary adrenal axis activation.     

Early sexual abuse and low cortisol

Post-traumatic stress disorder (PTSD) is a mental health disorder precipitated by a stressful event that produces fear or terror in the individual. Post-traumatic stress disorder studies, particularly in early sexual abuse, have been associated with neuroendocrine dysfunction, most notably the hypothalamic-pituitary-adrenal (HPA) axis. Since the literature on PTSD and neuroendocrine factors in young subjects has been sparse, the present studies were designed to look at the basal functioning of the HPA axis in response to early sexual abuse in girls aged 5 to 7 years. Morning salivary samples were collected for cortisol determination from subjects and controls who were scheduled for a physical exam by their pediatrician. The present study shows that subjects who had been abused within the last couple of months had significantly lower cortisol in comparison to control subjects (age, social economic status and race matched). The data suggest that children may have an impaired HPA axis after early trauma.     

Persistence of anxiety disorders and concomitant changes in cortisol

In a clinical sample of 116 children and adolescents we studied the relation between the course of an anxiety disorder during treatment and the concomitant changes in cortisol levels. Assessments at baseline, after three months, and at one-year follow-up were performed with the Anxiety Disorders Interview Schedule. When we compared cortisol levels at baseline and one-year follow-up, persistence of the anxiety disorder was associated with both increased daytime cortisol production (F=3.2, p=0.04) and a trend towards a decreased cortisol morning rise (F=2.4, p=0.09). At one-year follow-up daytime cortisol production was lowest in the early remitters (109.7±29.2 h mmol/l), higher in the late remitters (121.0±40.0 h mmol/l) and highest in the non-remitters (131.1±48.9 h mmol/l). Early remitters had the highest cortisol morning rise (1.1±1.5 h mmol/l), followed by the late remitters (0.8±1.8 h mmol/l), the non-remitters had the lowest cortisol morning rise (0.07±1.7 h mmol/l). Persistence of an anxiety disorder may thus lead to changes in HPA-axis functioning, underscoring the importance adequate treatment of anxiety disorders.     

Neuroendocrine responses to psychological stress in adolescents with anxiety disorder

Neurotransmitter-neuroendocrine and cardiovascular responses to the administration of a psychologically stressful mixed-model test (Mental Arithmetic, Stroop Color Word Interference Task, Trier Social Stress Test) were examined in 20 male peripubertal subjects affected by anxiety disorder (group A: 14 with generalized anxiety disorder, 6 with generalized anxiety disorder and separation anxiety disorder) and 20 junior school adolescents, matched for age, without overt psychological disorders (group B). Plasma levels of norepinephrine (NE), epinephrine (EPI), adrenocorticotropic hormone (ACTH), beta-endorphin (beta-EP), cortisol (CORT), growth hormone (GH), prolactin (PRL) and testosterone (Te) were measured immediately before the beginning of the tests and 30 min later at their end. Mean prestress values of GH, PRL, beta-EP and ACTH were significantly higher in anxious subjects than in controls. There was no difference in NE, EPI, CORT and Te prestress levels in the two groups. After the psychological stress session NE, GH and Te concentrations increased significantly in anxious subjects (A), but not in controls. In contrast, beta-EP and PRL decreased significantly during the psychological stress session in anxious subjects, and were unaffected by stress in the subjects without anxiety. No significant changes were found in ACTH, CORT and EPI during the challenge either in anxious subjects or in controls, which may be attributed to the late time of poststress blood sampling. In contrast to controls, heart rate and systolic blood pressure increased significantly in anxious subjects after psychological stress testing. Our data support the hypothesis that the hyperactivity of the noradrenergic system in response to stress is associated with anxiety disorders in adolescents and might influence the responses of GH and Te. High prestress basal values of stress hormones seem to be induced in anxious subjects by the anticipation of the task or by a persistent hyperactivity of the noradrenergic system. Further studies are needed to investigate in more detail the involvement of the HPA axis in anxious adolescents by a more refined resolution of time points of blood sampling.     

Temperament and character among Korean children and adolescents with anxiety disorders

The purpose of this study was to evaluate the temperament and character of children and adolescents with anxiety disorders in samples from Korean community. The study subjects were children and adolescents diagnosed with social phobia (n = 66), separation anxiety disorder (n = 47), specific phobia (n = 415), and obsessive–compulsive disorder (n = 42) with the diagnostic interview schedule for children, version IV (DISC-IV) in representative community samples. Among these, we excluded other psychiatric disorder comorbid samples, with the exception of externalizing disorders. We assessed the subjects of each anxiety group using the junior temperament and character inventory (JTCI). Social phobias were significantly associated with high harm avoidance and low self-directedness on the JTCI. The association of specific phobias with high harm avoidance, and obsessive–compulsive disorder with low self-directedness was also significant. Separation anxiety disorder was not associated with any temperament and character on the JTCI. Children and adolescents with anxiety disorders have different temperaments and character profiles in accordance with diagnostic groups, which implies the specific pathophysiological mechanism of each anxiety disorder.     

Daytime cortisol and stress reactivity in the offspring of parents with bipolar disorder

The hypothalamic-pituitary-adrenal (HPA) axis is compromised in major depression and bipolar disorder (BD). It is not known however whether HPA abnormalities predate the onset of these disorders. Preliminary data indicated that the adolescent offspring of parents with BD (high-risk), as compared to adolescents of parents with no mental disorder (low-risk), had higher levels of daytime salivary cortisol. The present study re-examined the cortisol increase after awakening and basal cortisol levels in a larger sample, and tested the hypothesis that high-risk offspring are more reactive to psychosocial stress than low-risk offspring. Saliva samples were collected from 58 adolescents, 29 high-risk (14 male/15 female, 16.8 years) and 29 (14 male/15 female, 16.6 years) low-risk, in their natural environment during at least two days. Twenty-five high-risk (13 male/12 female) and 25 low-risk (13 male/12 female) youth completed a child adaptation (15 years) or the standard version of the “Trier Social Stress Test”. Consistent with our previous finding, high-risk offspring had higher daytime levels of cortisol in their natural environment than low-risk offspring, and the difference was unrelated to clinical symptoms or other known confounds. Irrespective of risk status, female participants had higher daytime levels of cortisol than male participants. In contrast, there were no group differences in the cortisol response to the laboratory psychosocial stressor. The offspring of parents with BD show evidence of increased daytime basal HPA functioning with normal reactivity to psychosocial stress.     

Salivary cortisol and psychopathology in children bereaved by the september 11, 2001 terror attacks.

BACKGROUND: Studies suggest that stressful events increase risk for childhood anxiety and depression and hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This prospective longitudinal study evaluated relationships among severe psychosocial stress, psychiatric morbidity, and HPA axis function in children. METHODS: Forty-five children (mean age: 8.9 +/- 2.9 years) suffering parent death from September 11, 2001 terror attacks and 34 nonbereaved children (mean age: 9.3 +/- 2.5 years) were evaluated prospectively at 6-month intervals in this 2-year study. Assessments involved diagnostic interviews (Child Schedule for Affective Disorders and Schizophrenia [K-SADS]) for psychopathology and 3 days of baseline salivary cortisol and a salivary dexamethasone suppression test for HPA axis function. RESULTS: Bereaved children, but not nonbereaved children, had significantly increased rates of psychiatric disorders involving anxiety disorders, especially posttraumatic stress disorder (PTSD), after September 11, 2001 compared with retrospective assessments before September 11, 2001. Morning (AM) and 4:00 pm baseline cortisol were significantly and persistently higher for bereaved than nonbereaved children. Compared with bereaved children without psychopathology, bereaved children with PTSD had significantly lower 4:00 pm baseline cortisol and significantly greater 4:00 pm cortisol suppression. Children with generalized anxiety disorder had significantly less AM cortisol suppression than children without psychopathology. CONCLUSIONS: Children bereaved by sudden, unexpected parent death had persistent psychological dysfunction and HPA axis dysregulation in this study.     

Co-occurring manic symptomatology influences HPA axis alterations in depression

Although dysfunctioning of the HPA axis is considered to be a core pathophysiological process in mood disorders, the evidence with regard to depression remains conflicting. This could partly be due to the large heterogeneity within mood disorders, since HPA axis abnormalities may also be associated with the extent of co-occurring manic symptomatology as is seen in bipolar disorder. In this study, patients with depressive disorder and bipolar spectrum disorders were studied with regard to their HPA axis functioning. In 304 healthy controls, 1134 patients with pure unipolar depressive disorder (UP), and 133 bipolar spectrum disorder patients (BD spectrum), cortisol was measured in 7 saliva samples to determine the 1 h cortisol awakening response (CAR), evening cortisol levels and cortisol suppression after a 0.5 mg dexamethasone suppression test. Both patient groups had overall higher CAR levels compared to controls, but only UP patients showed a higher increase over time in the CAR. A linear association was found between increasing bipolarity and cortisol diurnal slope: BD spectrum patients had a significantly higher diurnal slope than UP patients. Dexamethasone suppression did not differ between mood disorder diagnoses. The heterogeneity in HPA axis functioning in patients with depression can partially be explained by co-existing manic symptomatology, since an increase in the CAR appears to be more specific for pure depression whereas the presence of bipolarity is associated with an increase in the diurnal slope of cortisol.     

Higher cortisol awakening response in young adolescents with persistent anxiety problems

OBJECTIVE: The aims of the present study were to test the association between current anxiety problems and basal cortisol levels in a large population sample of young preadolescents, and to test if HPA-axis activity differs between individuals with no, only current, or persistent anxiety problems. METHOD: Cortisol levels of 10- to 12-year olds (n = 1,768) from the general population were measured on three time points during the day. A self-report questionnaire (RCADS) was used to assess current anxiety, a parent-report questionnaire (TPBQ) to assess anxiety problems at age 4. RESULTS: Associations between cortisol levels and current anxiety problems were not found. However, individuals with persistent anxiety problems had higher morning cortisol levels and a higher cortisol awakening response. CONCLUSION: Apparently, only persistent, and not current, anxiety problems are associated with higher HPA-axis activity. Alterations in HPA-axis activity might underlie persistent anxiety problems, or result from the stress accompanied by persistent anxiety problems.     

HPA system regulation and adult attachment anxiety: individual differences in reactive and awakening cortisol

Early life experiences can influence hypothalamus–pituitary–adrenal (HPA) axis regulation in adulthood, in both animals and humans. In humans, they have also been shown to influence adult attachment styles. However, the relationship between adult attachment styles and HPA axis regulation is largely unexplored. The present study investigated the relationship among varying levels of attachment anxiety and avoidance with both the cortisol response to acute stress (CRS) and the cortisol response to awakening (CRA) in 48 adult women. Attachment-unrelated stress was induced by a laboratory stress task. Saliva for free cortisol assessment was sampled before and after the stress task in the laboratory and at home on 2 consecutive days in the morning after awakening. We found that attachment anxiety but not attachment avoidance was associated with cortisol measures. Attachment anxiety was positively correlated with CRS and negatively with CRA. Finally, the two cortisol parameters were negatively associated with one another. The results are discussed with respect to (1) recent findings suggesting that the HPA system and hippocampus are programmed during critical development periods, establishing a certain trajectory of physiological responsiveness throughout life, and (2) a model that links development of the hippocampus with self development.     

High levels of cortisol among adolescent offspring of parents with bipolar disorder: a pilot study

The hypothalamic-pituitary-adrenal (HPA) axis is compromised at several levels in major depressive and bipolar disorder (BD). However, it is not known whether HPA abnormalities predate the onset of these disorders. We conducted a pilot study comparing salivary cortisol levels of 10 adolescent offspring of parents with BD and 10 offspring of parents with no mental disorder (NMD). For two days, samples were collected at awakening and during the day in the adolescents' natural environment. The offspring of parents with BD had higher mean cortisol levels in the mornings and afternoons than the offspring of parents with NMD. When controlling for age, group differences in cortisol persisted in the afternoon, but not morning samples. None of the adolescents met diagnostic criteria for anxiety, affective, attention-deficit, or conduct disorders. Although preliminary, the results suggest that there is an early abnormality in the HPA system of the offspring of parents with BD.     

Somatic symptoms in children and adolescents with anxiety disorders

ObjectiveTo evaluate the prevalence of somatic symptoms (SSs) in children and adolescents with anxiety disorders; the relationship between SSs and anxiety severity, impairment, and child global functioning; and the impact of fluvoxamine (FLV) versus pill placebo (PBO) on reducing SSs.MethodAs part of a double-blind, placebo-controlled trial, 128 children (mean age, 10.8 years; range, 6-17) with DSM-IV anxiety disorders (i.e., social, separation, and generalized anxiety) were assessed by expert clinicians on 16 SSs using the Pediatric Anxiety Rating Scale.ResultsThe most common SSs at baseline were restlessness (74%), stomachaches (70%), blushing (51%), palpitations (48%), muscle tension (45%), sweating (45%), and trembling/shaking (43%). Older children (age 12 and older) reported more SSs than younger children, boys and girls reported similar numbers of SSs, and SSs were higher among children with than without generalized anxiety disorder. SSs were significantly and positively correlated with anxiety severity, impairment, and global functioning. Pre-/postreductions in SSs were statistically significant in both PBO and FLV conditions; however, FLV was superior to PBO in reducing SSs.ConclusionsSSs are highly prevalent among children and adolescents with anxiety disorders and are associated with greater anxiety severity and impairment. Treatment with FLV was effective in reducing rather than increasing SSs. The high rates of SSs in youths with each of the three anxiety disorders suggest a re-evaluation of SSs in the DSM-IV diagnostic criteria for the most common anxiety disorders among children and adolescents.