A high risk study of young children of parents with panic disorder and agoraphobia with and without comorbid major depression

Using family study methodology and psychiatric assessments by blind raters, this study tested hypotheses about patterns of familial association between anxiety and depressive disorders among high risk children of clinically referred parents. The study design contrasted five groups of children defined by the presence or absence in a parent of (1) panic disorder and agoraphobia (PDAG) without comorbid major depressive disorder (MDD) (n = 14); (2) comorbid PDAG plus MDD (PDAG + MDD) (n = 25); (3) MDD without comorbid PDAG (n = 12); (4) other psychiatric disorders (n = 23); and (5) normal comparisons (n = 47). While the PDAG and PDAG + MDD groups had similarly elevated rates of anxiety disorders and MDD, offspring of MDD parents had an elevated rate of MDD but not of anxiety disorders. Among children of parents with PDAG + MDD, the presence of an anxiety disorder did not significantly increase the risk for MDD in the same child. Thus, anxiety and MDD did not cosegregate among children of PDAG parents. These findings indicate that parental PDAG, either alone or comorbidly with MDD, increases the risk for both anxiety and depressive disorders in offspring. In the absence of PDAG, however, parental MDD does not appear to place children at risk for anxiety disorders. These findings are most consistent with the hypothesis that PDAG and PDAG + MDD share common familial etiologic factors while MDD alone is an independent disorder. More studies are needed to confirm these preliminary findings as well as to identify mediating factors that influence the transition from childhood to adult anxiety disorders.     

A controlled study of behavioral inhibition in children of parents with panic disorder and depression

OBJECTIVE: "Behavioral inhibition to the unfamiliar" has been proposed as a precursor to anxiety disorders. Children with behavioral inhibition are cautious, quiet, introverted, and shy in unfamiliar situations. Several lines of evidence suggest that behavioral inhibition is an index of anxiety proneness. The authors sought to replicate prior findings and examine the specificity of the association between behavioral inhibition and anxiety. METHOD: Laboratory-based behavioral observations were used to assess behavioral inhibition in 129 young children of parents with panic disorder and major depression, 22 children of parents with panic disorder without major depression, 49 children of parents with major depression without panic disorder, and 84 children of parents without anxiety disorders or major depression (comparison group). A standard definition of behavioral inhibition based on previous research ("dichotomous behavioral inhibition") was compared with two other definitions. RESULTS: Dichotomous behavioral inhibition was most frequent among the children of parents with panic disorder plus major depression (29% versus 12% in comparison subjects). For all definitions, the univariate effects of parental major depression were significant (conferring a twofold risk for behavioral inhibition), and for most definitions the effects of parental panic disorder conferred a twofold risk as well. CONCLUSIONS: These results suggest that the comorbidity of panic disorder and major depression accounts for much of the observed familial link between parental panic disorder and childhood behavioral inhibition. Further work is needed to elucidate the role of parental major depression in conferring risk for behavioral inhibition in children.     

Patterns of abnormal processing of emotional information in panic disorder and major depression.

Studies showing interference with color naming threat-related words in patients with anxiety disorders suggest a bias towards processing threatening material in these patients. We assessed the specificity of this finding to anxiety disorders and to threatening stimuli by administering Stroop cards with a variety of types of emotional stimuli to 24 panic disorder patients with no history of major depression, 30 patients with major depression and no history of panic attacks and 25 controls with no history of an axis I disorder. Our findings suggest that the abnormal information processing seen in panic disorder may be characterized by a more general bias towards processing emotional stimuli than previously thought. They also suggest that this more general bias may illustrate differences in information processing in panic disorder and major depression.     

Clinical differentiation between major depression only, major depression with panic disorder and panic disorder only. Childhood, personality and personality disorder

A consecutive sample of 298 nonpsychotic psychiatric outpatients was classified according to DSM-III and divided into 4 diagnostic groups: pure major depression, mixed major depression/panic disorder, pure panic disorder and a remaining group of other disorders. The patients' report of childhood relationship to parents and siblings, family atmosphere, their own personality characteristics as children and precipitating events were compared in the various groups. In addition, differences in personality and frequencies of personality disorders were investigated by means of various instruments. Our results show that the type of relationship to parents in childhood differed in the various groups. The mother seems to be the most crucial person for the development of depression, the father for the development of panic disorder. Patients with major depression are more obsessive and patients with panic disorder more infantile and avoidant with less control of their personality. Finally, patients with mixed conditions are more in accordance with the DSM-III anxious personality disorder cluster.     

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.     

Personality disorder comorbidity in panic disorder patients with or without current major depression

To investigate the relationship between current or past major depressive disorder (MDD) on comorbid personality disorders in patients with panic disorder, we compared the comorbidity of personality disorders using the Structured Clinical Interview for DSM-III-R personality disorders (SCID-II) in 34 panic disorder patients with current MDD (current-MD group), 21 with a history of MDD but not current MDD (past-MD group), and 32 without lifetime MDD comorbidity (non-MD group). With regard to personality disorders, patients in the current-MD group met criteria for at least one personality disorder significantly more often than patients in the past-MD group or the non-MD group (82.4% vs. 52.4% and 56.3%, respectively). The current-MD group showed statistically significantly more borderline, dependent, and obsessive-compulsive personality disorders than the past-MD group or non-MD group. With stepwise regression analyses, number of MDD episodes emerged as an indicator of the comorbidity of cluster C personality disorder and any personality disorders. Future studies should determine whether aggressive treatment of comorbid personality disorders improves the outcome (e.g., lowers the likelihood of comorbid MDD) of patients with panic disorder.     

Platelet imipramine binding in patients with panic disorder and major familial depression

Platelet 3H-imipramine binding was investigated in 15 normal subjects, 17 patients with major depressive disorder and 43 patients with panic disorder, to further study the relationship between depressive and anxiety disorders. Whereas patients with major depression had a significantly lower mean Bmax value than healthy volunteers, mean Bmax values in patients with panic disorder did not differ significantly from normal controls. Furthermore, apparently normal Bmax values were observed even in those panic disorder patients who had concurrent major depression or a past history of depression. Thus, despite previous findings of an overlap between panic and depressive disorders, the present results suggest that the two syndromes may have distinct neurochemical substrates.     

Psychological features in panic disorder: a comparison with major depression

OBJECTIVE: We aim to evaluate the psychodynamic model for panic disorder (PD) formulated by Shear et al. (1993), comparing PD patients and major depression (MD) patients. METHOD: We evaluated these parameters in open interviews in 10 PD patients and 10 patients with MD (DSM-IV). The data were recorded on videotape and were examined by 5 diagnostic blind appraisers. RESULTS: The data allowed a comparative analysis that underscores the existence of a psychological model for PD vs MD: 1) the protracted symbiotic phase of development and the existence of problems with separation in PD patients; 2) patients with MD tended to have a particularly negative impression of relationship with the first objects; furthermore, they had remarkable experiences of loss; and 3) while the PD patients tended to be shy and inhibited in childhood, especially showing a clear difficulty in expressing aggressiveness, the depressed patients tended to disclose an impulsive aggressiveness from infancy to adulthood. CONCLUSION: Exposure to parental behaviours that augment fearfulness may result in disturbances in object relations and persistence of conflicts between dependence and independence may predispose to anxiety symptoms and fears of PD.     

Simultaneous major depression and panic disorder: treatment with electroconvulsive therapy.

BACKGROUND: Major depression and panic disorder commonly occur together. Patients with simultaneous depression and panic disorder may have a higher lifetime rate of suicide attempts and an overall worse prognosis than patients with either depression or panic disorder alone. In addition, preliminary work suggests that some of these patients may not respond satisfactorily to antidepressants. In this report, we describe the clinical courses of eight consecutive patients with simultaneous major depression and panic disorder who were referred for ECT at our institution. METHOD: Eight consecutive patients who met DSM-III-R criteria for simultaneous major depression and panic disorder received ECT. All eight patients were evaluated by a structured clinical interview and the patients' major depression and panic disorder were evaluated with a 7-point Clinical Global Impressions severity rating scale. RESULTS: Before ECT was begun, each subject's panic disorder and depression were rated as at least markedly ill. After receiving ECT, all eight showed improvement in their depression. In addition, none of the eight patients reported having a panic attack from the time of their fourth ECT treatment until discharge. CONCLUSION: In this report, eight consecutive patients with simultaneous major depression and panic disorder improved with ECT. Further work is required which examines the potential utility of ECT in treating these patients.     

Dopaminergic function in panic disorder: comparison with major and minor depression.

Several lines of evidence suggest that dopamine might be involved in anxiety states. In this study, we assessed the growth hormone (GH) response to apomorphine (a dopaminergic agonist) 0.5 mg SC in nine drug-free inpatients meeting Research Diagnostic Criteria (RDC) for panic disorder who were age-matched and gender-matched with nine major depressive, and nine minor depressive inpatients. The three groups differed significantly in their mean GH peak response: 5.29 +/- 2.75 ng/ml in major depressives, 26.27 +/- 12.71 ng/ml in minor depressives, and 37.28 +/- 10.58 ng/ml in panics, with a significantly higher response in panic than in either minor or major depressive patients. These results support dopaminergic overactivity in panic disorder as compared with major and minor depression.     

Immunity, major depression, and panic disorder comorbidity.

Because recent research reports indicated clinical and biological differences in major depression with and without comorbid Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) panic disorder, and as altered immune measures were reported in selected subgroups of depressive patients, we investigated 51 pairs of major depressive episode (MDE) subjects, and gender- and age-matched healthy controls in order to determine if T lymphocytes number and function abnormalities were associated with Panic Disorder comorbidty. We found that those MDE subjects with DSM-III-R panic disorder (PD) had greater numbers of T cells (p less than 0.05) and PHA mitogen (p less than 0.05) responses than depressive patients without PD, as well as increased phytohemagglutinin (PHA) (p less than 0.05) concanavalin A (ConA) (p less than 0.02) mitogen responses compared to their controls. These data suggest that panic disorder comorbidity significantly contributes to the variance of immunologic parameters in major depression and has to be carefully assessed within psychoimmunological studies of psychiatric patients with affective disorders.     

Clinical and psychobiological characteristics of simultaneous panic disorder and major depression

Simultaneous major depression and panic disorder appears to be a common occurrence in psychiatric patients. Patients with this condition present with more severe symptoms than patients with major depression only, respond less well to conventional antidepressants, and in general exhibit greater psychopathology over the course of their illness. Evidence suggesting a possible "dual diathesis," depression and panic, in these patients is reviewed from epidemiological, clinical, and biological perspectives. The importance of taking into account the combined symptoms in treatment planning and physiopathological studies is discussed.     

Panic disorder versus panic disorder with major depression: Defining and understanding differences in psychiatric morbidity

The present study examined the impact of comorbid major depressive disorder (MDD) on psychiatric morbidity, panic symptomatology and frequency of other comorbid psychiatric conditions in subjects with panic disorder (PD). Four hundred thirty-seven patients with PD were evaluated at intake as part of a multicenter longitudinal study of anxiety disorders; 113 of these patients were also in an episode of MDD. Patients were diagnosed by DSM-III-R criteria utilizing structured clinical interviews. The 113 PD/MDD patients were compared with the 324 remaining PD subjects regarding panic symptoms at intake, sociodemographic, quality of life and psychiatric morbidity variables. Differences in frequency of other comorbid Axis I psychiatric disorders were assessed at intake; personality disorders were evaluated twelve months after intake. The results revealed that PD/MDD patients exhibit increased morbidity and decreased psychosocial functioning as compared to PD patients. Personality disorders were more prevalent in the PD/MDD group at six month follow-up assessment; the PD/MDD group also had an increased frequency of posttraumatic stress disorder (PTSD) and more comorbid Axis I anxiety disorders as compared to the PD group. The total number and frequency of panic symptoms was highly consistent between the two patient groups. Depression and Anxiety 5:12–20, 1997. © 1997 Wiley-Liss, Inc.     

Divided and selective attention in panic disorder. A comparative study of patients with panic disorder,major depression and healthy controls

OBJECTIVE: While depression is definitely a condition with diminished attentional functioning, there is little evidence as to whether attention is also disturbed in panic disorder. In the present study patients with panic disorder and with depression were compared by means of neuropsychological tests which assess selective and divided attention. METHOD: Twenty-one inpatients with a Panic Disorder, 21 inpatients with a Major Depressive Disorder (DSM-IV diagnoses) and 20 healthy control subjects were investigated drug free. Neuropsychological standard tests were used to measure selective attention (Signal Detection, Wiener-Test-system) and divided attention (Gesichtsfeld-/Neglectprüfung, TAP), which allow the discrimination between left and right visual field stimulus processing. RESULTS: Patients with panic disorder and depression responded significantly slower than healthy control subjects in the test for divided attention, while no differences were found between the two groups of patients. In contrast, there were no differences among the groups of patients and control subjects in regard to reaction time in the test for selective attention. Stimulus presentations in the left and right visual fields did not affect the reaction times differently. CONCLUSIONS: Patients with panic disorder appeared as disturbed in their attentional functioning as patients with depression. Therefore, ignoring attentional deficits in patients with panic disorder is not justified.     

Children of depressed parents. Increased psychopathology and early onset of major depression

Data on the psychiatric diagnosis, overall functioning, and treatment of 220 6- to 23-year-old subjects who were at high or low risk for major depression are presented. The subjects' diagnoses were made by a child psychiatrist based on best-estimate evaluation of diagnostic information derived from structured interviews (Schedule for Affective Disorders and Schizophrenia for School-Aged Children, Epidemiologic Version) with the subjects and separately with their mothers about their children. The major findings were an increased overall prevalence of major depression and substance abuse, psychiatric treatment, poor social functioning, and school problems in the children of depressed proband parents compared with children of normal proband parents. Overall prepubertal depression was uncommon and the sex ratios were equal. After 12 years of age, there was an increasing preponderance of female subjects in the group with major depression. The mean age at onset of major depression was similar for male and female subjects. However, it was significantly earlier in the children of depressed probands (mean age at onset, 12 to 13 years) compared with the children of normal probands (mean age at onset, 16 to 17 years). Symptom profiles and additional types of diagnoses in the depressed children from either proband parent group did not differ. These children are being followed up longitudinally to determine the prognostic significance, persistence, recurrence, and recall of their symptoms. Several research and clinical strategies are suggested by these data.     

Caffeine challenge test in panic disorder and depression with panic attacks

Our aim was to observe if patients with panic disorder (PD) and patients with major depression with panic attacks (MDP) (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) respond in a similar way to the induction of panic attacks by an oral caffeine challenge test. We randomly selected 29 patients with PD, 27 with MDP, 25 with major depression without panic attacks (MD), and 28 healthy volunteers. The patients had no psychotropic drug for at least a 4-week period. In a randomized double-blind experiment performed in 2 occasions 7 days apart, 480 mg caffeine and a caffeine-free (placebo) solution were administered in a coffee form and anxiety scales were applied before and after each test. A total of 58.6% (n = 17) of patients with PD, 44.4% (n = 12) of patients with MDP, 12.0% (n = 3) of patients with MD, and 7.1% (n= 2) of control subjects had a panic attack after the 480-mg caffeine challenge test (chi(2)(3) = 16.22, P = .001). The patients with PD and MDP were more sensitive to caffeine than were patients with MD and healthy volunteers. No panic attack was observed after the caffeine-free solution intake. The patients with MD had a lower heart rate response to the test than all the other groups (2-way analysis of variance, group by time interaction with Greenhouse-Geisser correction: F(3,762) = 2.85, P = .026). Our data suggest that there is an association between panic attacks, no matter if associated with PD or MDP, and hyperreactivity to an oral caffeine challenge test.     

Treatment-emergent depression with antidepressants in panic disorder

Two patients with panic disorder received therapeutic doses of antidepressants. They developed endogenomorphic symptoms of major depression according to DSM-III-R criteria despite remission of their panic attacks. Treatment-emergent depression in panic disorder has been previously associated with high potency benzodiazepines. Whether antidepressant medications may unmask a depressive diathesis or are coincidentally associated with depression is discussed in this report.