Search

Aim: This study aimed to investigate whether separation anxiety (SA) constitutes a dimension related to age at onset of panic disorder (PD), in homogeneous subgroups of outpatients with PD, based on their age of onset and symptom severity., Methods: A sample of 232 outpatients with PD was assessed with the Panic Disorder Severity Scale (PDSS) and the Sheehan Disability Scale (SDS) for functional impairments. Separation anxiety was evaluated using structured interviews and questionnaires. We applied a K-Means Cluster Analysis based on the standardized "PD age of onset" and "the PDSS total score" to identify distinct but homogeneous groups., Results: We identified three groups of patients: group 1 ("PD early onset/severe", N = 97, 42%, onset 23.2 ± 6.7 years), group 2 ("PD early onset/not severe", N = 76, 33%, onset 23.4 ± 6.0 years) and group 3 ("PD adult onset/not severe", N = 59, 25%, onset 42.8 ± 7.0 years). Patients with early onset/severe PD had significantly higher scores on all SA measures than PD late-onset/not severe. Regression analyses showed that SA scores, but not PDSS scores, were predictive of impairment in SDS work/school, social life, and family functioning domains., Conclusions: Our data indicate a significant relationship between SA and PD with an earlier age of onset and an impact on individual functioning. This may have important implications for implementing preventive interventions targeting early risk factors for the subsequent onset of PD., (© 2023 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Panic disorder (PD) is an acute paroxysmal anxiety disorder with poorly understood pathophysiology. The dorsal periaqueductal gray (dPAG) is involved in the genesis of PD. However, the downstream neurofunctional changes of the dPAG during panic attacks have yet to be evaluated in vivo. In this study, optogenetic stimulation to the dPAG was performed to induce panic-like behaviors, and in vivo positron emission tomography (PET) imaging with 18 F-flurodeoxyglucose ( 18 F-FDG) was conducted to evaluate neurofunctional changes before and after the optogenetic stimulation. Compared with the baseline, post-optogenetic stimulation PET imaging demonstrated that the glucose metabolism significantly increased (P < 0.001) in dPAG, the cuneiform nucleus, the cerebellar lobule, the cingulate cortex, the alveus of the hippocampus, the primary visual cortex, the septohypothalamic nucleus, and the retrosplenial granular cortex but significantly decreased (P < 0.001) in the basal ganglia, the frontal cortex, the forceps minor corpus callosum, the primary somatosensory cortex, the primary motor cortex, the secondary visual cortex, and the dorsal lateral geniculate nucleus. Taken together, these data indicated that in vivo PET imaging can successfully detect downstream neurofunctional changes involved in the panic attacks after optogenetic stimulation to the dPAG.

Plenty of evidence suggests that childhood separation anxiety (CSA) predisposes the subject to adult-onset panic disorder (PD). As well, panic is frequently comorbid with both anxiety and depression. The brain mechanisms whereby CSA predisposes to PD are but completely unknown in spite of the increasing evidence that panic attacks are mediated at midbrain's dorsal periaqueductal gray matter (DPAG). Accordingly, here we examined whether the neonatal social isolation (NSI), a model of CSA, facilitates panic-like behaviors produced by electrical stimulations of DPAG of rats as adults. Eventual changes in anxiety and depression were also assessed in the elevated plus-maze (EPM) and forced-swimming test (FST) respectively. Male pups were subjected to 3-h daily isolations from post-natal day 2 (PN2) until weaning (PN21) allotting half of litters in individual boxes inside a sound-attenuated chamber (NSI, n = 26) whilst siblings (sham-isolated rats, SHAM, n = 27) and dam were moved to another box in a separate room. Non-handled controls (CTRL, n = 18) remained undisturbed with dams until weaning. As adults, rats were implanted with electrodes into the DPAG (PN60) and subjected to sessions of intracranial stimulation (PN65), EPM (PN66) and FST (PN67-PN68). Groups were compared by Fisher's exact test (stimulation sites), likelihood ratio chi-square tests (stimulus-response threshold curves) and Bonferroni's post hoc t-tests (EPM and FST), for P<0.05. Notably, DPAG-evoked panic-like responses of immobility, exophthalmus, trotting, galloping and jumping were markedly facilitated in NSI rats relative to both SHAM and CTRL groups. Conversely, anxiety and depression scores either did not change or were even reduced in neonatally-handled groups relative to CTRL, respectively. Data are the first behavioral evidence in animals that early-life separation stress produces the selective facilitation of panic-like behaviors in adulthood. Most importantly, results implicate the DPAG not only in panic attacks but also in separation-anxious children's predispositions to the late development of PD.

Objective: Evidence suggests that childhood separation anxiety disorder may be associated with a heightened risk for the development of other disorders in adulthood. The authors conducted a meta-analysis to examine the relationship between childhood separation anxiety disorder and future psychopathology., Method: PubMed, PsycINFO, and Embase were searched for studies published through December 2011. Case-control, prospective, and retrospective cohort studies comparing children with and without separation anxiety disorder with regard to future panic disorder, major depressive disorder, any anxiety disorder, and substance use disorders were included in the analysis. Effects were summarized as pooled odds ratios in a random-effects model., Results: Twenty-five studies met all inclusion criteria (14,855 participants). A meta-analysis of 20 studies indicated that children with separation anxiety disorder were more likely to develop panic disorder later on (odds ratio=3.45; 95% CI=2.37-5.03). Five studies suggested that a childhood diagnosis of separation anxiety disorder increases the risk of future anxiety (odds ratio=2.19; 95% CI=1.40-3.42). After adjusting for publication bias, the results of 14 studies indicated that childhood separation anxiety disorder does not increase the risk of future depression (odds ratio=1.06; 95% CI=0.78-1.45). Five studies indicated that childhood separation anxiety disorder does not increase the risk of substance use disorders (odds ratio=1.27; 95% CI=0.80-2.03). Of the subgroup analyses performed, differences in comparison groups and sample type significantly affected odds ratio sizes., Conclusions: A childhood diagnosis of separation anxiety disorder significantly increases the risk of panic disorder and any anxiety disorder. These results support a developmental psychopathology conceptualization of anxiety disorders.

There is a need to explain the high level of comorbidity between separation anxiety disorder (SAD) in adulthood and panic disorder with agoraphobia (Pd-Ag). One possibility is that inadequate specification of symptom domains and/or diagnostic questions accounts for some of the comorbidity. The present anxiety clinic study examined responses of adult patients (n = 646) with SAD and/or Pd-Ag on eight symptom domains based on a previous factor analysis of a commonly used separation anxiety measure, the ASA-27, as well as on the Anxiety Sensitivity Index. We also examined questionnaire items that did not load on the factor structure. All separation anxiety domains distinguished strongly between SAD and Pd-Ag. Comparisons across three groups (SAD alone, Pd-Ag alone and comorbid SAD/Pd-Ag) revealed that two symptom domains (anxiety about embarking on trips, and sleep disturbances) showed some overlap between Pd-Ag and SAD. Two of the items of the ASA-27 that did not load with other items in the factor analysis also showed overlap with Pd-Ag, with both referring to anxieties about leaving home. Patients with SAD (with or without Pd-Ag) returned higher scores on anxiety sensitivity than those with Pd-Ag alone. The findings support the distinctiveness of the construct of SAD and the capacity of the ASA-27 to discriminate between that disorder and Pd-Ag. SAD appears to be a more severe form of anxiety than Pd-Ag. There may be a need to refine items to include the reasons for avoiding leaving home, reluctance to sleep alone and to embark on trips, to ensure accurate discrimination between Pd-Ag and SAD in adulthood., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Efficacy of treatments for panic disorder is well established, but not all patients respond. Adult separation anxiety has been found to predict poorer response to CBT, but its effect on response to medication has not been previously explored., Study Aim: The aim of this study is to investigate if panic-agoraphobic spectrum factors, including 'separation anxiety' factor predict treatment outcome in patients with panic disorder., Study Sample: Participants who met criteria for PD (n=57) completed baseline assessment and 12 months follow-up. Patients were administered the Panic Agoraphobic Spectrum Self-Report (PAS-SR, Lifetime and Last-Month Versions), and the Panic Disorder Severity Scale (PDSS). We examined patients who met the following criteria at baseline: 1) PDSS total score>7; 2) no current Axis I comorbidity with major depression; 3) no lifetime or current bipolar disorder. All patients were treated with evidence-based psychopharmacological treatment for panic disorder during the 12-month observation period., Results: Twenty eight patients (48.1%) achieved remission during the follow-up period. In a logistic regression model, controlling for baseline severity, gender and age, only the last-month PAS-SR 'separation anxiety' factor was associated with a lower likelihood of remission., Conclusions: Signs and symptoms of separation anxiety in adulthood, as assessed with the PAS-SR Last Month version, are predictors of poor treatment outcome in patients with PD. We submit that the assessment of panic-agoraphobic spectrum features, including adult separation anxiety, should become routine of clinical assessment of patients with PD. It is likely that a better psychopathological characterization of patients may inform treatment selection, and result in better treatment outcome., (Copyright © 2011 Elsevier B.V. All rights reserved.)

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 results of the authors' research efforts to date support the idea that the panic-agoraphobic spectrum is a robust and culturally transferable construct with important clinical implications for patients with mood and anxiety disorders. In particular, their findings suggest the need for alternate treatment strategies to treat mood patients with comorbid panic features [50,52]. They maintain that the spectrum approach could add to the knowledge of course and outcome of mood and anxiety disorders and inform treatment decisions. The spectrum concept has other potential implications. For the purposes of neurobiologic research, reliable identification of phenotypes that map [Figure 3: see text] onto specific brain processes in crucial. The definition of the diathesis phenotype is also important if we are to elucidate the cause and pathophysiology of mental disorders at a molecular level. A panic-agoraphobic spectrum assessment incorporate temperamental features and trait-like manifestations into a comprehensive symptom assessment to provide a detailed picture of the clinical features of PD. Such an approach holds some promise for progress in studies of neurobiologic basis of panic and may be useful in further efforts to overcome the nagging problem of the ambiguous boundaries of DSM diagnostic categories [53].

Panic disorder and agoraphobia have been postulated to occur when (1) fear is elicited by some automatic mechanism that requires catastrophic cognition, (2) there is a flaw in the physiology of fear, with special reference to the noradrenergic system, or (3) a putative suffocation alarm mechanism sends out false alarms. The presence of a suffocation alarm system has been supported by studies of children who lack this protective mechanism because they suffer from congenital central hypoventilation syndrome. Antidepressants with serotonin activity seem to control panic disorder by down-regulating the suffocation alarm system. Serotonin selective reuptake inhibitors (SSRIs) are among the most effective drugs for panic disorder, emphasizing the role of serotonin in respiratory regulation. Dyspnea and hyperventilation are the cardinal signs of a panic attack. Because carbon monoxide (CO) does not cause panic, it may sabotage the suffocation alarm system by acting as an inhibitory neurotransmitter within the carotid body.

Although juvenile separation anxiety disorder is maintained to be a predisposing factor to adult panic disorder in DSM-III-R, past research has failed to clarify (a) whether it is separation anxiety per se or school refusal that is the pathogenic risk factor and (b) whether affected youngsters are specifically at risk of developing panic disorder rather than symptoms of general anxiety or phobias in later life. The present study of 74 adults who responded to media publicity found that a measure of early separation anxiety but not a history of school refusal was associated with risk of adult panic disorder according to DSM-III-R criteria. In contrast, separation anxiety scores were not associated with the presence or absence of general anxiety symptoms or phobic-avoidance in adulthood. Subjects with higher separation anxiety scores were more likely to have either a sibling or child with school refusal. Although the present study is limited in its method to mailed survey responses and, in part, to retrospective data, the results do provide additional support for Klein's influential separation anxiety theory of panic disorder.