Childhood separation anxiety and separation events in women with agoraphobia with or without panic disorder.

OBJECTIVE: This study aimed to investigate the association between separation anxiety and actual separation events during childhood in adult patients with agoraphobia with or without panic disorder (PD). METHOD: Forty-two women with agoraphobia with or without PD participated in long-term follow-ups after exposure-in-vivo treatment. We assessed separation anxiety and separation events from age 0 to 18 years, as well as adult separation from a spouse. RESULTS: Childhood separation experiences (55%) and separation anxiety were significantly higher in patients than in healthy subjects, but both conditions were not associated with each other. Childhood separation anxiety was related to adult separation events. CONCLUSIONS: Retrospective measures of childhood separation anxiety appear to be confounded by adult separation events. Thus the conclusion of whether childhood anxiety is a consequence of actual childhood separation events cannot be drawn, owing to a lacking association between both ratings.     

Separation anxiety and actual separation experiences during childhood in patients with panic disorder.

OBJECTIVE: The association between separation anxiety in childhood and actual separation experiences during childhood has not yet been investigated in patients with panic disorder. METHODS: In 115 patients with panic disorder with or without agoraphobia and in 124 control subjects without a history of psychiatric illness, we assessed separation anxiety during childhood, retrospectively, using DSM-IV and ICD-10 criteria and the Separation Anxiety Symptom Inventory (SASI). In addition, actual separation experiences from age 0 to 15 years were assessed, retrospectively. RESULTS: A total of 22.6% of the patients and 4.8% of the control subjects fulfilled both DSM-IV and ICD-10 criteria for childhood separation anxiety (chi 2 = 11.8; P < 0.0001). Further, 57.4% of the patients and 37.9% of the control subjects reported actual separation experiences during their childhood (chi 2 = 9.09, P < 0.003). Separation anxiety and actual separation experiences, however, were independent of each other. CONCLUSION: These results suggest that separation anxiety during childhood is not a consequence of actual traumatic separation experiences in panic disorder patients.     

Childhood history of anxiety disorders among adults with social phobia: rates, correlates, and comparisons with patients with panic disorder.

We examined the rates and correlates of a childhood history of anxiety disorders in 100 adults with a primary diagnosis of social phobia (social anxiety disorder). Adulthood and childhood disorders were assessed by experienced clinicians with structured clinical interviews. Rates of childhood anxiety disorders were evaluated to diagnostic comorbidity and a comparison group of patients with panic disorder. Onset of social phobia occurred before age 18 in 80% of the sample. Over half of the sample (54%) met criteria for one or more childhood anxiety disorders other than social phobia: 47% for overanxious disorder, 25% for avoidant disorder, 13% for separation anxiety disorder, and 1% for childhood agoraphobia. A history of childhood anxiety was associated with an early age of onset of social phobia, greater severity of fear and avoidance of social situations, greater fears of negative evaluation, and greater anxiety and depression morbidity. Rates of childhood social phobia, overanxious disorder, and avoidant disorder were significantly higher in patients with social phobia relative to our panic-disordered comparison group. We found approximately equal rates of a childhood history of separation anxiety disorder in patients with social phobia and panic disorder, providing further evidence against a unique relationship between separation anxiety disorder and panic disorder.     

Agoraphobia with panic attacks. Development, diagnostic stability, and course of illness

A structured psychiatric interview was used to examine the symptom history of 55 patients meeting DSM-III criteria for agoraphobia with panic attacks and five patients meeting DSM-III criteria for panic disorder. Anticipatory anxiety and generalized anxiety occurred in over 80% of the patients, and these anxiety states together with panic attacks and phobic avoidances had courses that were chronic and unremitting. Major depression occurred in 70% of the patients and had an episodic course that differentiated it from the anxiety states. Other frequently reported disorders were childhood separation disorder (18%), alcoholism (17%), and obsessive compulsive disorder (17%). An initial nonspontaneous first panic attack and separation anxiety was associated with earlier onset and longer duration of agoraphobia and panic disorder. An inaccurate cognitive appraisal of the initial panic attack frequently led to the rapid development of subsequent agoraphobia. Caffeine consumption exacerbated anxiety in 54% of the patients and triggered panic attacks in 17%. Fifty-one percent of female agoraphobics experienced premenstrual exacerbation of anxiety symptoms.     

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.     

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.     

Moderating effects of major depression on patterns of comorbidity in patients with panic disorder

Given the high rate of co-occurring major depression in patients with panic disorder, it is unclear whether patterns of comorbidity in individuals with panic disorder reported in the literature are associated with panic disorder or with the presence of major depression. Subjects were 231 adult subjects with panic disorder and major depression (n=102), panic disorder without comorbid major depression (n=29), major depression without comorbid panic disorder (n=39), and neither panic disorder nor major depression (n=61). Subjects were comprehensively assessed with structured diagnostic interviews that examined psychopathology across the life cycle. Panic disorder, independently of comorbidity with major depression, was significantly associated with comorbid separation anxiety disorder, simple phobia, obsessive-compulsive disorder, generalized anxiety disorder, and agoraphobia. Major depression, independently of comorbidity with panic disorder, was significantly associated with comorbidity with psychoactive substance use disorders and childhood disruptive behavior disorders. Overanxious disorder was associated with both panic disorder and major depression. Major depression has important moderating effects on patterns of comorbidity of panic disorder in referred adults.     

Childhood and family characteristics in panic and generalized anxiety disorders

The author compared 32 patients who had generalized anxiety disorders with 29 patients who had panic disorder and agoraphobia with panic attacks. He observed that patients with generalized anxiety disorder more often had lost their fathers and/or mothers before the age of 16 years, whereas patients with panic disorder and agoraphobia with panic attacks had more often experienced chronic anxiety in childhood. More parents and siblings of patients with panic disorder had affective disorders and alcohol abuse than did parents and siblings of patients with anxiety disorders.     

Relationship between panic disorder and agoraphobia. A family study

A family study of patients with agoraphobia (n = 40), panic disorder (n = 40), and nonanxious controls (n = 20) showed that the morbidity risk for panic disorder was increased among the relatives of agoraphobics (8.3%) and the relatives of patients with panic disorder (17.3%). The morbidity risk for agoraphobia was also increased among the relatives of agoraphobics (11.6%) but not the relatives of panic disorder patients (1.9%). Male relatives of agoraphobics were shown to be at higher risk for alcohol disorders (30.8%). No greater risk for primary affective disorders was found among the relatives of agoraphobic or panic disorder patients or among the relatives of probands with secondary depression compared with relatives of probands without secondary depression. Probands and relatives with agoraphobia reported an earlier onset of illness, more persistent and disabling symptoms, more frequent complications, and a less favorable outcome than probands and relatives with panic disorder. The findings suggest that agoraphobia is a more severe variant of panic disorder. They also lend support to the separation between anxiety disorders and affective disorders.     

Developmental trajectories of anxiety disorders in offspring at high risk for panic disorder and major depression

The objective of this study was to evaluate the longitudinal course of psychiatric disorders in children of parents with and without panic disorder and major depression as they transition through the period of risk from early to late childhood. Over a 5-year follow-up, we compared the course of psychiatric disorders in offspring of parents with panic disorder, major depression, or neither disorder. Subjects consisted of 233 offspring (from 151 families) with baseline and follow-up assessments. Subjects were comprehensively assessed with structured diagnostic interviews. Anxiety disorders at baseline were used to predict anxiety disorders and major depression at follow-up using stepwise logistic regression. Separation anxiety disorder significantly increased the risk for the subsequent development of specific phobia, agoraphobia, panic disorder, and major depression, even after parental panic and depression were covaried. Agoraphobia significantly increased the risk for subsequent generalized anxiety disorder. These findings suggest that separation anxiety disorder is a major antecedent disorder for the development of panic disorder and a wide range of other psychopathological outcomes, and that it increases the risk for subsequent psychopathology even among children already at high familial risk for anxiety or mood disorder.     

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.     

The developmental psychopathology of social anxiety in adolescents

To evaluate a developmental psychopathology approach for understanding adolescent social anxiety, parent-reported predictors of social anxiety were examined in a nonclinical sample of adolescents. Structured diagnostic interviews were obtained from biological parents of 770 participants. Potential risk factors assessed included child characteristics: negative affect, shyness, separation anxiety disorder, and childhood chronic illness, as well as parent characteristics: major depression, panic disorder, and agoraphobia. Adolescent social anxiety was measured multiple times during high school. Findings indicate stability in social anxiety symptoms across time. Parent-reported, childhood negative affect, shyness, and chronic illness as well as parental panic disorder or agoraphobia were associated with adolescent social anxiety. Interactions were observed between parent-reported childhood shyness and gender and between parent-reported childhood shyness and parent-reported childhood chronic illness in the prediction of social anxiety. Parent-reported childhood shyness was a stronger predictor of adolescent social anxiety in females compared to males. The combined effect of subjects being positive for both parent-reported childhood shyness and parent-reported childhood chronic illness was greater than would be expected based on additive effects. This study provides support for a multifactorial and developmentally informed understanding of adolescent social anxiety.     

Pathological worry, anxiety disorders and the impact of co-occurrence with depressive and other anxiety disorders

The Penn State Worry Questionnaire (PSWQ) was administered to 123 outpatients with principal diagnoses of generalized anxiety disorder (GAD), social anxiety disorder (SAD), panic disorder with agoraphobia, and panic disorder without agoraphobia (PD) to examine the specificity of pathological worry for GAD. The mean PSWQ scores in patients with GAD and SAD were significantly higher than the mean PSWQ scores in patients with PD, while not differing significantly in the subgroups without any co-occurring depressive or anxiety disorders. Patients with any co-occurring depressive or anxiety disorder scored significantly higher on the PSWQ. In a logistic regression analysis, high PSWQ scores independently predicted only GAD and SAD diagnoses. The study suggests that pathological worry is specific not only for GAD, and indicates that a significant relationship exists between pathological worry, GAD and SAD, and that depressive and anxiety disorders co-occurrence increases levels of pathological worry in patients with anxiety disorders.     

An examination of syndromal validity and diagnostic subtypes in social phobia and panic disorder.

BACKGROUND: We investigated whether patients with DSM-III-R panic disorder and patients with social phobia could be distinguished on the basis of selected demographic variables and by several commonly used anxiety and phobia rating scales. METHOD: Sixty-six patients with social phobia and 60 patients with panic disorder (42 with and 18 without agoraphobia) were studied. Subjects completed a battery of self-report measures that assessed phobic fears, avoidance, and related problems. RESULTS: Social phobic patients showed an earlier age at onset than the panic disorder group, and there was a trend for more social phobics to have never married. Social phobics reported significantly greater levels of social phobic avoidance and distress, fear of negative evaluation, and avoidance of social situations than the panic disorder patients who reported more overall anxiety and rated themselves as significantly more avoidant of situations involving exposure to public places and to blood or injury. Discriminant function analyses showed that social phobic and panic disorder patients can be reliably discriminated on these scales. CONCLUSION: The results of this study lend further support for the validity of the DSM-III-R nosologic distinctions between social phobia and panic disorder. Furthermore, generalized social phobia appears to be remarkably different from discrete social phobia on these measures. This study provides less support for considering panic disorder with agoraphobia to be distinct from panic disorder without agoraphobia.     

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.     

Thyroid hormones in panic disorder, panic disorder with agoraphobia, and generalized anxiety disorder

Fifty-two patients with generalized anxiety disorder who had symptoms persisting for at least 6 months, 41 patients suffering from either panic disorder (32 patients) or panic disorder with agoraphobia (9 patients), and 14 control subjects were screened for thyroid disease. Total serum thyroxine (TT4), serum-free thyroxine index (FT4I), and triiodothyronine resin uptake (T3RU), were examined for the entire sample, using a one-way analysis of variance (ANOVA). No significant differences were found in TT4 (p = .24), FT4I (p = .24), and T3RU (p = .19). Thyroid-stimulating hormone (TSH) was examined in a subsample of 10 patients with generalized anxiety disorder, 11 with panic disorder or panic disorder with agoraphobia, and 10 controls. One-way ANOVA again showed no significant differences, although there was a trend (p = .07). This is the first report that compares generalized anxiety disorder patients, panic disorder patients, and patients with panic disorder and agoraphobia with controls on measures of thyroid function. It is also the first to report normal values in the thyroid indices of generalized anxiety disorder patients.     

Panic disorder with and without agoraphobia: comorbidity within a half-year of the onset of panic disorder

The present study was performed to compare the clinical features of patients with panic disorder with and without agoraphobia. The subjects were 233 outpatients with panic disorder (99 males and 134 females) diagnosed according to DSM-IV criteria. Sixty-three patients met the criteria for panic disorder without agoraphobia, and 170 met the criteria for panic disorder with agoraphobia. Patients with agoraphobia showed a significantly longer duration of panic disorder and higher prevalence of generalized anxiety disorder. However, there were no significant differences in prevalence of major depressive episodes, in current severity of panic attacks, or in gender ratio between the two groups. The second aim of the present study was to investigate the effects of onset age and sex differences on the development of agoraphobia within a half-year. The subjects were divided into two groups according to their self-report: patients who did or did not develop agoraphobia within 24 weeks of onset of panic disorder. A total of 40.6% of the patients developed agoraphobia within 24 weeks of the onset of panic disorder, and onset age and sex differences had no robust effect on the development of agoraphobia within 24 weeks.     

Comparing panic disorder uncomplicated and panic disorder with agoraphobia in cardiology patients with atypical or nonanginal chest pain

Thirty-eight cardiology patients with either atypical or nonanginal chest pain and current panic disorder were divided into two groups, those with agoraphobia (N = 8) and those without agoraphobia (N = 30). The agoraphobia group reported marginally longer duration of panic disorder (17.0 ± 21.1 years vs. 3.0 ± 3.2 years) and significantly more panic symptoms (10.6 ± 3 vs. 7.3 ± 2.2) during the last major attack. The agoraphobia group also scored significantly higher on measures of anxiety, depression, phobic avoidance, somatization, interpersonal sensitivity, and psychoticism and also scored higher on three of three global measures of distress. This agoraphobia group differed from previously reported agoraphobics with panic attacks in that they all had current panic disorder, while previously reported groups were categorized according to DSM-III, which required only a history of panic attacks. These findings suggest that patients who have current panic disorder and agoraphobia are more symptomatic. Of interest is the low proportion of agoraphobics compared to nonagoraphobics found in this panic disorder population.     

Prodromal symptoms in panic disorder with agoraphobia

Of 20 patients suffering from panic disorder with agoraphobia, 18 reported experiencing agoraphobic avoidance, generalized anxiety, and/or hypochondriacal fears and beliefs before the first panic attack. The prevalence of these symptoms in the patients was significantly higher than the prevalence in 20 healthy control subjects. The results indicate that phobic avoidance in panic disorder with agoraphobia may not be secondary to the panic attacks, a finding that runs counter to the current DSM-III-R classification of anxiety disorders.     

Parent-reported predictors of adolescent panic attacks

OBJECTIVE: To identify parent-reported risk factors for adolescent panic attacks. METHOD: Structured diagnostic interviews were obtained from 770 parents of participants in a school-based risk factor study for adolescent panic. Parent-reported risk factors assessed included characteristics of the child (negative affect, separation anxiety disorder [SAD], childhood chronic illness, and childhood loss) as well as characteristics of the parent (parental panic disorder or agoraphobia [PDA], parental major depression, and parental chronic illness). RESULTS: Bivariate predictors of adolescent panic attacks included parent history of PDA, parent history of chronic illness, child negative affect, and child SAD. Using signal detection methods, three subgroups of participants at risk for panic attacks were identified. Fifty-eight percent of adolescents with panic attacks belonged to one of these high-risk groups. Adolescents with a positive parental history of PDA were at highest risk: 24% of this group experienced panic attacks. Among those without a positive parental history of PDA, those with high childhood negative affect or history of SAD were at increased risk for panic attacks (14% and 20%, respectively). CONCLUSIONS: The use of parent-reported data provides cross-validation for previously identified risk factors of adolescent panic attacks. Signal detection results suggest there are multiple paths (equifinality) to the development of adolescent panic attacks.