Comorbidity among childhood anxiety disorders

This paper reports on 73 consecutive admissions to an outpatient anxiety disorder clinic for children and adolescents. Patients were evaluated with a structured diagnostic interview for primary and secondary disorders with DSM-III criteria in order to examine patterns of comorbidity. The most common primary diagnoses for the sample included separation anxiety disorder (33%), overanxious disorder (15%), social phobia of school (15%), and major depression (15%). Children with a primary diagnosis of separation anxiety disorders were most likely to receive a concurrent diagnosis of overanxious disorder. Alternatively, children with a primary diagnosis of overanxious disorder were most likely to receive an additional diagnosis indicative of a social anxiety problem, either social phobia or avoidant disorder. Children with a primary major depression most often exhibited social phobia and/or overanxious disorder. No clear-cut pattern of comorbidity emerged for the social phobic (school) group. These findings are discussed in terms of their comparability with results recently obtained from an adult anxiety clinic population.     

History of childhood abuse in panic disorder,social phobia,and generalized anxiety disorder

The authors examined the prevalence of self-reported childhood physical or sexual abuse in a sample of adult patients presenting for treatment of panic disorder, social phobia, or generalized anxiety disorder. Regardless of the presence of comorbid anxiety disorders or comorbid depression, patients with panic disorder had significantly higher rates of past childhood physical or sexual abuse than patients with social phobia. Patients with generalized anxiety disorder had intermediate rates of past physical or sexual abuse that were not significantly different from the other two diagnostic groups. Anxiety disorder patients with a history of childhood abuse were also more likely to have comorbid major depression than those without. These findings are discussed in terms of biological and behavioral factors that may influence the development of anxiety disorders after the experience of a traumatic event.     

A twin study of DSM-III-R anxiety disorders

The prevalence of anxiety disorders was studied in a sample of 20 monozygotic (MZ) and 29 dizygotic (DZ) co-twins of anxiety disorder probands. A comparison group of co-twins of 12 MZ and 20 DZ twin probands with other non-psychotic mental disorders was also studied. All subjects were personally interviewed with the Structured Clinical Interview for DSM-III-R Axis I (SCID-I). Panic disorder was significantly more prevalent in co-twins of panic probands. Generalized anxiety disorder (GAD) was more prevalent in co-twins of GAD probands with a history of mood disorder (NS). Post-traumatic stress disorder was significantly more prevalent in co-twins of anxiety probands and was more prevalent in MZ than in DZ co-twins. The prevalences of social and simple phobia were equal in co-twins of anxiety and comparison probands. For both panic disorder and generalized anxiety disorder the MZ:DZ concordance ratio was more than 2:1. The results support the hypothesis of a genetic contribution in the etiology of panic disorder, generalized anxiety disorder and post-traumatic stress disorder. The hypothesis that simple and social phobia are mainly caused by environmental experiences was also supported.     

Clinical characteristics and treatment outcomes of patients with major depressive disorder and comorbid anxiety disorders - results from a European multicenter study

This naturalistic European multicenter study aimed to elucidate the association between major depressive disorder (MDD) and comorbid anxiety disorders. Demographic and clinical information of 1346 MDD patients were compared between those with and without concurrent anxiety disorders. The association between explanatory variables and the presence of comorbid anxiety disorders was examined using binary logistic regression analyses. 286 (21.2%) of the participants exhibited comorbid anxiety disorders, 10.8% generalized anxiety disorder (GAD), 8.3% panic disorder, 8.1% agoraphobia, and 3.3% social phobia. MDD patients with comorbid anxiety disorders were characterized by younger age (social phobia), outpatient status (agoraphobia), suicide risk (any anxiety disorder, panic disorder, agoraphobia, social phobia), higher depressive symptom severity (GAD), polypsychopharmacy (panic disorder, agoraphobia), and a higher proportion receiving augmentation treatment with benzodiazepines (any anxiety disorder, GAD, panic disorder, agoraphobia, social phobia) and pregabalin (any anxiety disorder, GAD, panic disorder). The results in terms of treatment response were conflicting (better response for panic disorder and poorer for GAD). The logistic regression analyses revealed younger age (any anxiety disorder, social phobia), outpatient status (agoraphobia), suicide risk (agoraphobia), severe depressive symptoms (any anxiety disorder, GAD, social phobia), poorer treatment response (GAD), and increased administration of benzodiazepines (any anxiety disorder, agoraphobia, social phobia) and pregabalin (any anxiety disorder, GAD, panic disorder) to be associated with comorbid anxiety disorders. Our findings suggest that the various anxiety disorders subtypes display divergent clinical characteristics and are associated with different variables. Especially comorbid GAD appears to be characterized by high symptom severity and poor treatment response.     

Personality disorders and time to remission in generalized anxiety disorder, social phobia, and panic disorder

BACKGROUND: This investigation assessed the effect of personality disorders (PersDs) on time to remission in patients with generalized anxiety disorder, social phobia, or panic disorder. METHODS: Selected Axis I and II predictors of time to remission during 5 years of follow-up were assessed in 514 patients with 1 or more of these anxiety disorders who participated in the Harvard/Brown Anxiety Research Program, a multisite, prospective, longitudinal, naturalistic study. RESULTS: The presence of a PersD predicted a 30% lower likelihood of generalized anxiety disorder remission, a 39% lower likelihood of social phobia remission, and no difference in likelihood of panic disorder remission. More specifically, a lower likelihood of remission from generalized anxiety disorder was predicted by the presence of avoidant PersD (34% lower) and dependent PersD (14% lower). The presence of avoidant PersD predicted a 41% lower likelihood of social phobia remission. The presence of major depressive disorder did not account for these findings. CONCLUSIONS: Our findings provide new data on the pernicious effect of PersDs on the course of generalized anxiety disorder and social phobia but not panic disorder, suggesting that PersDs have a differential effect on the outcome of anxiety disorders.     

Memory deficits in children with and at risk for anxiety disorders

There are limited data on the neurocognitive correlates of childhood anxiety disorders. The objective of this study was to examine whether visual and verbal memory deficits of nonemotional stimuli are (1) a shared feature of three common childhood anxiety disorders (social phobia, separation anxiety disorder, and generalized anxiety disorder) or whether these deficits are restricted to specific anxiety disorders, and (2) present in offspring who possess at least one of the following established risk factors for anxiety disorders, parental history of panic disorder (PD), or major depressive disorder (MDD). One hundred and sixty offspring, ages 9-20 years, were recruited from parents with lifetime diagnoses of PD, MDD, PD plus MDD, or neither illness. Different clinicians blindly administered semistructured diagnostic interviews to offspring and parents. Verbal and visual memory subtests of the Wide Range Assessment of Memory and Learning were administered to offspring. The results showed that offspring with ongoing social phobia demonstrated reduced visual but not verbal memory scores compared to those without social phobia when controlling for offspring IQ, separation anxiety disorder, and generalized anxiety disorder. No other offspring anxiety disorder predicted memory performance. Neither parental PD nor parental MDD was associated with offspring memory performance. These findings are relevant to understanding the phenomenology of childhood anxiety disorders and may provide insights into the neural circuits underlying these disorders.     

Further evidence of an association between behavioral inhibition and anxiety disorders: results from a family study of children from a non-clinical sample

Behavioral inhibition to the unfamiliar, identifiable in early childhood and reflecting the tendency to exhibit withdrawal and excessive autonomic arousal to challenge or novelty, has been found to be prevalent in young offspring of parents with panic disorder and agoraphobia and associated with risk for anxiety disorders in these children. Using family study methodology, we now examine psychopathology in first degree relatives of children from a non-clinical longitudinal cohort identified at 21 months of age as inhibited (N = 22) or uninhibited (N = 19) and followed through the age of seven years for a study of preservation of temperamental characteristics in normal children. These assessments were compared with evaluations of the first degree relatives of 20 normal comparison children. Psychiatric assessments of parents (N = 110) and siblings (N = 72) were based on structured interviews conducted blindly to the temperamental classification of the index child. Parents of inhibited children, compared with parents of uninhibited and normal controls, had significantly higher risks for multiple (greater than or equal to 2) anxiety disorders, continuing anxiety disorders (both a childhood and adulthood anxiety disorder in the same parent), social phobia, and childhood avoidant and overanxious disorders. These findings provide additional support for the hypothesis linking behavioral inhibition with risk for anxiety disorder.     

Childhood antecedents to panic disorder in referred and nonreferred adults

OBJECTIVE: We used a recursive partitioning method to examine antecedent childhood anxiety disorders in large samples of referred and nonreferred subjects with and without panic disorder. METHODS: Referred subjects included adults treated for panic disorder (n = 131) and comparison adults with neither major anxiety nor mood disorders (n = 61). The nonreferred adult group derived from an opportunistic sample originally ascertained through family studies of probands with and without attention-deficit/hyperactivity disorder (ADHD), yielding 58 adults with panic disorder and 587 who were free of major anxiety and mood disorders. RESULTS: The majority of referred (65%) and nonreferred (52%) adults with panic disorder had antecedent childhood anxiety or disruptive behavior disorders. Classification and Regression Trees (CART) analysis showed that both separation anxiety disorder and overanxious disorder were independent predictors of subsequent panic disorder in both referred and nonreferred samples. CONCLUSIONS: These results confirm and extend previously reported findings by documenting that childhood anxiety disorders are important antecedent risk factors for panic disorder, independently of referral bias.     

Is childhood separation anxiety disorder a predictor of adult panic disorder and agoraphobia? A seven-year longitudinal study

OBJECTIVE: To examine whether separation anxiety disorder (SAD) in childhood is a risk factor for panic disorder and agoraphobia in adulthood. METHOD: Patients (n = 85) who had completed treatment for SAD, generalized anxiety disorder, and/or social phobia 7.42 years earlier (on average) were reassessed using structured diagnostic interviews. RESULTS: Subjects with a childhood diagnosis of SAD did not display a greater risk for developing panic disorder and agoraphobia in young adulthood than those with other childhood anxiety diagnoses. Subjects with a childhood diagnosis of SAD did not more frequently meet full diagnostic criteria for panic disorder and agoraphobia, generalized anxiety disorder, social phobia, or major depressive disorder in adulthood than subjects with childhood diagnoses of generalized anxiety disorder or social phobia, but were more likely to meet criteria for other anxiety disorders (i.e., specific phobia, obsessive compulsive disorder, posttraumatic stress disorder, and acute stress disorder). CONCLUSIONS: These results argue against the hypothesis that childhood SAD is a specific risk factor for adult panic disorder and agoraphobia.     

Anxiety disorders of childhood and adolescence: a critical review

The 1980s were a decade of advancement in the knowledge of anxiety disorders in children and adolescents; this sets the stage for research achievements in the 1990s. This review examines the anxiety disorders of childhood and adolescence (separation anxiety disorder, overanxious disorder, and avoidant disorder), including prevalence rates, demographic profiles, comparisons of clinical presentations in different developmental age groups, and comorbidity patterns. Fears and simple phobias, obsessive-compulsive disorder, post-traumatic stress disorder, and panic disorder in children and adolescents are also evaluated. The controversy of whether panic attacks occur in prepubertal children is addressed. A brief review of behavioral and pharmacological treatment studies is included. Future directions for research are suggested.     

Antecedents to panic disorder in nonreferred adults

OBJECTIVE: Previous work has shown that childhood anxiety disorders are unique antecedents for panic disorder. The current study examined both childhood and adult comorbid disorders as potential antecedent disorders to panic disorder in a large sample of nonreferred adults. METHODS: Subjects were 1018 adults with (N = 58) and without (N = 960) panic disorder who were derived from a sample originally ascertained through family studies of probands with and without attention-deficit/hyperactivity disorder (ADHD); data were obtained from 1988 to 1996. Classification and regression trees (CART) analysis was used to examine anxiety and nonanxiety disorders antecedent to panic disorder. RESULTS: CART analysis showed that separation anxiety disorder, social phobia, and simple phobia were unique predictors of subsequent panic disorder. CONCLUSION: These results support and expand previously reported findings in referred samples documenting that comorbid anxiety disorders are unique antecedent risk factors for panic disorder.     

Differential carbon dioxide sensitivity in childhood anxiety disorders and nonill comparison group

BACKGROUND: To examine the relationship between respiratory regulation and childhood anxiety disorders, this study considered the relationship between anxiety disorders and symptoms during carbon dioxide (CO(2)) exposure, CO(2) sensitivity in specific childhood anxiety disorders, and the relationship between symptomatic and physiological responses to CO(2). METHODS: Following procedures established in adults, 104 children (aged 9-17 years), including 25 from a previous study, underwent 5% CO(2) inhalation. The sample included 57 probands with an anxiety disorder (social phobia, generalized anxiety disorder, separation anxiety disorder, and panic disorder) and 47 nonill comparison subjects. Symptoms of anxiety were assessed before, during, and after CO(2) inhalation. RESULTS: All children tolerated the procedure well, experiencing transient or no increases in anxiety symptoms. Children with an anxiety disorder, particularly separation anxiety disorder, exhibited greater changes in somatic symptoms during inhalation of CO(2)-enriched air, relative to the comparison group. During CO(2) inhalation, symptom ratings were positively correlated with respiratory rate increases, as well as with levels of tidal volume, minute ventilation, end-tidal CO(2), and irregularity in respiratory rate during room-air breathing. CONCLUSIONS: Childhood anxiety disorders, particularly separation anxiety disorder, are associated with CO(2) hypersensitivity, as defined by symptom reports. Carbon dioxide hypersensitivity is associated with physiological changes similar to those found in panic disorder. These and other data suggest that certain childhood anxiety disorders may share pathophysiological features with adult panic disorder.     

Eating disorders and antecedent anxiety disorders: a controlled study

We compared the prevalence and age of onset of adult and childhood anxiety disorders relative to the primary diagnosis in 68 women with anorexia nervosa (AN), 116 women with bulimia nervosa (BN), 56 women with major depression with no eating disorder (MD) and 98 randomly selected controls (RC) in order to determine whether antecedent anxiety disorders are plausible risk factors for AN and BN. Comorbid anxiety disorders were common in all three clinical groups (AN, 60%; BN, 57%; MD, 48%). In 90% of AN women, 94% of BN women and 71 % of MD women, anxiety disorders preceded the current primary condition (P=0.01), although panic disorder tended to develop after the onset of AN, BN or MD. In multivariate logistic regressions, the odds ratios (ORs) for overanxious disorder (OR=13.4) and obsessive-compulsive disorder (OR=11.8) were significantly elevated for AN. The ORs for overanxious disorder and social phobia were significantly elevated for BN (OR_OAD,=4.9; OR_SP=15.5) and MD (OR_OAD,=6.1; OR_SP=6.4). These data suggest that certain anxiety disorders are non-specific risk factors for later affective and eating disorders, and others may represent more specific antecedent risk factors.     

The relationships among separation anxiety disorder,adult attachment style and agoraphobia in patients with panic disorder

Epidemiological studies indicate that separation anxiety disorder occurs more frequently in adults than children. It is unclear whether the presence of adult separation anxiety disorder (ASAD) is a manifestation of anxious attachment, or a form of agoraphobia, or a specific condition with clinically significant consequences. We conducted a study to examine these questions. A sample of 141 adult outpatients with panic disorder participated in the study. Participants completed standardized measures of separation anxiety, attachment style, agoraphobia, panic disorder severity and quality of life. Patients with ASAD (49.5% of our sample) had greater panic symptom severity and more impairment in quality of life than those without separation anxiety. We found a greater rate of symptoms suggestive of anxious attachment among panic patients with ASAD compared to those without ASAD. However, the relationship between ASAD and attachment style is not strong, and adult ASAD occurs in some patients who report secure attachment style. Similarly, there is little evidence for the idea that separation anxiety disorder is a form of agoraphobia. Factor analysis shows clear differentiation of agoraphobic and separation anxiety symptoms. Our data corroborate the notion that ASAD is a distinct condition associated with impairment in quality of life and needs to be better recognized and treated in patients with panic disorder.     

Prevalence of Panic Disorder and Other Subtypes of Anxiety Disorder and Their Background

Abstract: Two hundred and forty-four patients with various subtypes of DSM-IH anxiety disorder were found among 3,059 outpatients who visited our clinic consecutively for evaluation for five years. They included 53 patients with panic disorder comprising an outstanding number of patients, about a quarter of patients with anxiety disorder and 1.7% of the whole outpatient population, and 78 with generalized anxiety disorder. Differentiation between these two groups was difficult to make besides their specific clinical features whether the patient had panic attacks or chronic generalized anxiety. The patients with anxiety disorder were divided into two major groups– panic-generalized anxiety-simple phobia and social phobia-obsessive compulsive-agoraphobia–in respect to their age of onset of the illness, the duration of episode, separation from their parents, psychosocial stressors and response to pharmacotherapy. Social phobia and obsessive compulsive disorder comprised those patients with similar qualities to each other in terms of their demographic data and their social backgrounds, forming a distinct group apparently different from the panic-generalized anxiety group. They consisted predominantly of young male patients with an earlier onset of the illness, less separation experienced and a longer duration of the episode, while without meaningful psychosocial stressors preceding the present episode. These findings indicate that the prevalence of panic disorder in the Japanese population is as high as previously reported, although its discriminant factors from generalized anxiety disorder are ambiguous except for panic attacks.     

The relationship between anxiety disorders and suicide attempts: findings from the National Epidemiologic Survey on Alcohol and Related Conditions

Background: Previous work has suggested that anxiety disorders are associated with suicide attempts. However, many studies have been limited by lack of accounting for factors that could influence this relationship, notably personality disorders. This study aims to examine the relationship between anxiety disorders and suicide attempts, accounting for important comorbidities, in a large nationally representative sample. Methods: Data came from the National Epidemiologic Survey on Alcohol and Related Conditions Wave 2. Face‐to‐face interviews were conducted with 34,653 adults between 2004 and 2005 in the United States. The relationship between suicide attempts and anxiety disorders (panic disorder, agoraphobia, social phobia, specific phobia, generalized anxiety disorder, posttraumatic stress disorder (PTSD)) was explored using multivariate regression models controlling for sociodemographics, Axis I and Axis II disorders. Results: Among individuals reporting a lifetime history of suicide attempt, over 70% had an anxiety disorder. Even after adjusting for sociodemographic factors, Axis I and Axis II disorders, the presence of an anxiety disorder was significantly associated with having made a suicide attempt (AOR=1.70, 95% confidence interval (CI): 1.40–2.08). Panic disorder (AOR=1.31, 95% CI: 1.06–1.61) and PTSD (AOR=1.81, 95% CI: 1.45–2.26) were independently associated with suicide attempts in multivariate models. Comorbidity of personality disorders with panic disorder (AOR=5.76, 95% CI: 4.58–7.25) and with PTSD (AOR=6.90, 95% CI: 5.41–8.79) demonstrated much stronger associations with suicide attempts over either disorder alone. Conclusion: Anxiety disorders, especially panic disorder and PTSD, are independently associated with suicide attempts. Clinicians need to assess suicidal behavior among patients presenting with anxiety problems. Depression and Anxiety, 2010. © 2010 Wiley‐Liss, Inc.     

Patterns of comorbidity in panic disorder and major depression: findings from a nonreferred sample

Previous findings in referred adult samples document major depression as having important moderating effects on the patterns of comorbidity for panic disorder and major depression. This study evaluated whether these patterns of comorbidity are moderated by referral bias. Panic disorder (PD) and major depression (MD) were used to predict the risk for comorbid psychiatric disorders and functional outcomes using data from a large sample of adults who had not been ascertained on the basis of clinical referral (N=1,031). Participants were comprehensively assessed with structured diagnostic interview methodology to evaluate childhood and adult comorbid psychiatric disorders. PD increased the risk for anxiety disorders, independently of MD. MD increased the risk for mania, antisocial personality disorder, psychoactive substance use disorder, disruptive behavior disorders, overanxious disorder, social phobia, and generalized anxiety disorder, independently of PD. These results extend to nonreferred samples' previously reported findings documenting that MD has important moderating effects on patterns of comorbidity for PD and indicate that patterns of comorbidity for PD are not due to referral bias.     

Experience sampling and ecological momentary assessment for studying the daily lives of patients with anxiety disorders: A systematic review

Anxiety disorders are highly prevalent. Symptoms may occur unpredictably (e.g., panic attacks) or predictably in specific situations (e.g., social phobia). Consequently, it may be difficult to assess anxiety and related constructs realistically in the laboratory or by traditional retrospective questionnaires. Experience sampling methods (ESM) and ecological momentary assessment (EMA) can deepen the understanding of the course of anxiety disorders by frequently assessing symptoms and other variables in the natural environment. We review 34 ESM/EMA studies on adult panic disorder, generalized anxiety disorder, social phobia, post-traumatic stress disorder, and obsessive–compulsive disorder, as well as anxiety disorders in youth. Benefits of ESM/EMA for the study of anxiety disorders include generating insight into the temporal variability of symptoms and into the associations among daily affect, behaviors, and situational cues. Further, ESM/EMA has been successfully combined with ambulatory assessment of physiological variables and with treatment evaluations. We provide suggestions for future research, as well as for clinical applications.     

Psychiatric correlates of incest in childhood.

OBJECTIVE: The purpose of the study was to describe more precisely the type of psychiatric illness associated with incest during childhood. METHOD: The Diagnostic Interview Schedule was administered to 52 adult women who had been victims of incest during childhood and to 23 age- and race-matched comparison subjects from local self-help agencies. RESULTS: The prevalence of 19 psychiatric disorders was higher in the incest group than base population rates. Rates of anxiety disorders (panic disorder, agoraphobia, social and simple phobia), major depression, and alcohol abuse and dependence were significantly higher in the incest group than in the comparison group. More severe types of incestuous abuse were associated with a higher risk for the development of psychiatric disorders. CONCLUSIONS: There was an association between incest and psychiatric disorders in this community-based treatment population. All patients, especially those who present with these specific psychiatric disorders, should be queried about childhood sexual abuse during the history.     

Anxiety disorders and CRP in a population cohort study with 54,326 participants: The LifeLines study

Objectives: Growing evidence indicates that inflammatory processes may play a role in the pathogenesis of anxiety disorders. Nevertheless, much remains to be learned about the involvement of inflammation, including C-reactive protein (CRP), in specific anxiety disorders. This study examines the relation between anxiety disorders and CRP.

Methods: Associations of serum CRP with anxiety disorders were determined in a large population study (n?=?54,326 participants, mean age?=?47 years; 59% female), the LifeLines cohort. Depressive and anxiety disorders (generalized anxiety disorder, social anxiety phobia, panic disorder with or without agoraphobia and agoraphobia without panic disorder) were assessed using the Mini-International Neuropsychiatric Interview.

Results: Anxiety disorders, with the exception of social anxiety disorder, were significantly associated with increased CRP. After adjusting for demographics, life style factors, health factors, medication use, depression, and psychological stressors, CRP remained significantly associated with panic disorder with agoraphobia (β?=?0.01, P?=?.013). Moreover, CRP levels were significantly higher in people with panic disorder with agoraphobia compared to other anxiety disorders, independent of all covariates (F?=?3.00, df?=?4, P?=?.021).

Conclusions: Panic disorder with agoraphobia is associated with increased CRP, although the effect size of this association is small. This indicates that neuroinflammatory mechanisms may play a potential role in its pathophysiology.