Carbon dioxide hypersensitivity in separation-anxious offspring of parents with panic disorder.

BACKGROUND: Similar patterns of vulnerability to carbon dioxide (CO(2)) inhalation have been reported in adults with panic disorder (PD) and children with separation anxiety disorder (SAD), suggesting a link between the adult and child conditions. This study examines the influence of familial risk for PD on CO(2) responses in children with SAD. We hypothesized that offspring with SAD of parents with PD would have distinct CO(2) responses. METHODS: Two hundred twelve 9- to 20-year-old offspring of parents with or without PD were exposed to maintained 5% CO(2) inhalation in the participants' homes. Anxiety symptoms, panic attacks, and respiratory physiology (respiratory frequency and tidal volume) were monitored during baseline and 15-min maintained CO(2) breathing. RESULTS: As hypothesized, significant offspring SAD x parent PD interactions were obtained for anxiety symptoms, respiratory frequency, tidal volume, and a panting index during CO(2) inhalation. Offspring with both SAD and parental PD exhibited more anxiety symptoms at termination of 5% CO(2) breathing than the other offspring groups and had the most extreme values on measures of respiratory physiology. CONCLUSIONS: Youth with both SAD and parental PD have respiratory responses to CO(2) similar to adult PD. They might be a subtype of SAD at particularly high risk for adult PD.

Amygdala and nucleus accumbens activation to emotional facial expressions in children and adolescents at risk for major depression.

OBJECTIVE: Offspring of parents with major depressive disorder face a threefold higher risk for major depression than offspring without such family histories. Although major depression is a significant cause of morbidity and mortality, neural correlates of risk for major depression remain poorly understood. This study compares amygdala and nucleus accumbens activation in children and adolescents at high and low risk for major depression under varying attentional and emotional conditions. METHOD: Thirty-nine juveniles, 17 offspring of parents with major depression (high-risk group) and 22 offspring of parents without histories of major depression, anxiety, or psychotic disorders (low-risk group) completed a functional magnetic resonance imaging study. During imaging, subjects viewed faces that varied in intensity of emotional expressions across blocks of trials while attention was unconstrained (passive viewing) and constrained (rate nose width on face, rate subjective fear while viewing face). RESULTS: When attention was unconstrained, high-risk subjects showed greater amygdala and nucleus accumbens activation to fearful faces and lower nucleus accumbens activation to happy faces (small volume corrected for the amygdala and nucleus accumbens). No group differences emerged in amygdala or nucleus accumbens activation during constrained attention. Exploratory analysis showed that constraining attention was associated with greater medial prefrontal cortex activation in the high-risk than in the low-risk group. CONCLUSIONS: Amygdala and nucleus accumbens responses to affective stimuli may reflect vulnerability for major depression. Constraining attention may normalize emotion-related neural function possibly by engagement of the medial prefrontal cortex; face-viewing with unconstrained attention may engage aberrant processes associated with risk for major depression.

Three-year medication prophylaxis in panic disorder: to continue or discontinue? A naturalistic study.

OBJECTIVE: Little is known about maintenance treatment for panic disorder. The purpose of this naturalistic study is to compare outcomes of remitted panic disorder patients continued on versus those successfully discontinued from maintenance medication. METHODS: After 3 years of sustained remission with medication in a naturalistic setting, 168 patients were continued on, whereas 37 successfully discontinued from medication. Continued and discontinued groups were followed for an additional 4 to 8 years and compared for differences in treatment outcome using chi(2) and Wilcoxon rank sum tests. Times to relapse were analyzed using the Kaplan-Meier product-limit method, and risk factors for relapse were assessed using Cox proportional hazards regression. RESULTS: The discontinued group was healthier at baseline but had a significantly worse outcome compared with the continued group. Panic-free survival probabilities for the continued group at 1, 2, 3, and 4 years were 0.87, 0.81, 0.71, and 0.64, respectively, and were significantly higher than respective probabilities of 0.53, 0.35, 0.29, and 0.15 for the discontinued group. Median survival time in the continued group was significantly longer, at 5.67 years, than in the discontinued group, at 1.17 years. Cognitive behavioral therapy significantly reduced hazard in the discontinued but not in the continued group. Residual symptoms in either group at time of assignment predicted poorer outcome. CONCLUSION: Our small study suggests that relapse of panic disorder in routine clinical practice occurs even after long-standing remission on maintenance medication, and that relapse risk appears to be markedly higher after medication discontinuation. Discontinuation may be more successful in candidates who received cognitive behavioral therapy and have minimal residual symptoms.

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.

Stress responsivity and HPA axis activity in juveniles: results from a home-based CO2 inhalation study.

OBJECTIVE: A previous laboratory-based study found elevated cortisol levels in anxious children susceptible to CO(2)-induced panic, but the effects of parent diagnosis were not considered. The current home-based study tested the hypothesis that parental panic disorder and offspring response to CO(2) are associated with elevated cortisol levels in juvenile offspring. METHOD: A total of 131 offspring (ages 9-19) of parents with panic disorder, major depression, and no mental disorder underwent CO(2) inhalation. Parent and child diagnoses were assessed. Salivary cortisol was assayed before and after CO(2) inhalation. RESULTS: Neither parents with panic disorder, parents with major depression, or offspring anxiety predicted offspring cortisol levels. Independent of parent and child diagnoses, anxiety response to CO(2) predicted elevated cortisol levels in offspring. CONCLUSIONS: As in adults, anxiety response to CO(2) in juveniles is associated with elevated cortisol levels, but elevated cortisol levels are not related to parent or child diagnoses.

School-based intervention for adolescents with social anxiety disorder: results of a controlled study.

Social anxiety disorder, whose onset peaks in adolescence, is associated with significant impairment. Despite the availability of effective treatments, few affected youth receive services. Transporting interventions into schools may circumvent barriers to treatment. The efficacy of a school-based intervention for social anxiety disorder was examined in a randomized wait-list control trial of 35 adolescents (26 females). Independent evaluators, blind to treatment condition, evaluated participants at preintervention, postintervention, and 9 months later. Adolescents in the intervention group demonstrated significantly greater reductions than controls in social anxiety and avoidance, as well as significantly improved overall functioning. In addition, 67% of treated subjects, compared to 6% of wait-list participants, no longer met criteria for social phobia following treatment. Findings support the possible efficacy of school-based intervention for facilitating access to treatment for socially anxious adolescents.

Face-emotion processing in offspring at risk for panic disorder.

OBJECTIVE: Panic disorder (PD) has been linked to perturbed processing of threats. This study tested the hypotheses that offspring of parents with PD and offspring with anxiety disorders display relatively greater sensitivity and attention allocation to fear provocation. METHOD: Offspring of adults with PD, major depressive disorder (MDD), or no disorder (ages 9-19) viewed computer-presented face photographs depicting angry, fearful, and happy faces. Offspring rated (1) subjectively experienced fear level, (2) how hostile the face appeared, and (3) nose width. Attention allocation was indexed by latency to perform ratings. RESULTS: Compared with offspring of parents without PD (n = 79), offspring of PD parents (n = 65) reported significantly more fear and had slower reaction times to rate fear, controlling for ongoing anxiety disorder in the offspring. Offspring with an anxiety disorder (n = 65) reported significantly more fear than offspring without an anxiety disorder but not when parental PD was controlled. Social phobia but no other anxiety disorder in offspring was associated with slower reaction times for fear ratings (but not greater fear ratings). Parental PD and offspring social phobia independently predicted slower reaction time. CONCLUSIONS: Results support an association between parental PD and offspring responses to fear provocation. Social phobia in children may have a specific relationship to allocation of attention to subjective anxiety during face viewing.

Response to 5% carbon dioxide in children and adolescents: relationship to panic disorder in parents and anxiety disorders in subjects.

BACKGROUND: Carbon dioxide (CO(2)) sensitivity is postulated to be a familial risk marker of panic disorder (PD). Exaggerated responses to CO(2) inhalation have been reported in adults with PD and their unaffected adult relatives, as well as in clinic-referred children with anxiety disorders. OBJECTIVE: To test in a family-based design whether CO(2) hypersensitivity is a familial risk marker for PD and associated with current anxiety disorders in children and adolescents. SETTING AND PARTICIPANTS: One hundred forty-two offspring (aged 9-19 years) of parents with PD, major depressive disorder, or no disorder. Forty-five (32%) had a current anxiety disorder, excluding specific phobia. DESIGN AND MAIN OUTCOME MEASURES: Parents and offspring received diagnostic assessments. Offspring underwent 5% CO(2) inhalation at home. Panic symptoms and panic attacks were rated with the Acute Panic Inventory at baseline, while anticipating CO(2) delivery ("threat"), and during CO(2) inhalation. Respiratory rate and volume were measured with spirometry. RESULTS: No group differences were found in Acute Panic Inventory ratings at baseline or in respiratory measures during threat. Risk for PD was not associated with CO(2) sensitivity (panic symptoms and respiratory physiologic response). During CO(2) inhalation, offspring with anxiety disorders, relative to offspring without anxiety disorders, experienced significantly more panic symptoms and panic attacks, as well as elevated respiratory rates. During threat, panic symptoms were significantly and independently associated with both parental PD and offspring anxiety disorders. CONCLUSIONS: No support was obtained for CO(2) hypersensitivity as a familial risk marker for PD in children and adolescents. Links between childhood anxiety disorders and CO(2) sensitivity were replicated. Familial risk for PD in children and adolescents may be associated with vulnerability to anticipatory anxiety.

Face-memory and emotion: associations with major depression in children and adolescents.

BACKGROUND: Studies in adults with major depressive disorder (MDD) document abnormalities in both memory and face-emotion processing. The current study used a novel face-memory task to test the hypothesis that adolescent MDD is associated with a deficit in memory for face-emotions. The study also examines the relationship between parental MDD and memory performance in offspring. METHODS: Subjects were 152 offspring (ages 9-19) of adults with either MDD, anxiety disorders, both MDD and anxiety, or no disorder. Parents and offspring were assessed for mental disorders. Collection of face-memory data was blind to offspring and parent diagnosis. A computerized task was developed that required rating of facial photographs depicting 'happy,"fearful,' or 'angry' emotions followed by a memory recall test. Recall accuracy was examined as a function of face-emotion type. RESULTS: Age and gender independently predicted memory, with better recall in older and female subjects. Controlling for age and gender, offspring with a history of MDD (n = 19) demonstrated significant deficits in memory selectively for fearful faces, but not happy or angry faces. Parental MDD was not associated with face-memory accuracy. DISCUSSION: This study found an association between MDD in childhood or adolescence and perturbed encoding of fearful faces. MDD in young individuals may predispose to subtle anomalies in a neural circuit encompassing the amygdala, a brain region implicated in the processing of fearful facial expressions. These findings suggest that brain imaging studies using similar face-emotion paradigms should test whether deficits in processing of fearful faces relate to amygdala dysfunction in children and adolescents with MDD.

Posttraumatic stress disorder and treatment seeking in a national screening sample.

The behavioral model of service use was employed to identify predictors of mental health treatment seeking and treatment readiness among individual with PTSD (N = 2,713) in data from the 1996 National Anxiety Disorders Screening Day (NADSD). This model examines the contribution of predisposing (age, sex, marital status, race/ethnicity, education), enabling (employment, geographic location), perceived need (interference of symptoms with daily life), and evaluated need (other diagnoses) factors to treatment seeking and treatment readiness for individuals with PTSD. Results indicate that although need factors (interference by anxiety symptoms with daily life, diagnosis of panic disorder) are related to both receiving and readiness for treatment, predisposing (age, marital status, minority race) factors influence which individuals receive treatment for PTSD.

Internal validity of an anxiety disorder screening instrument across five ethnic groups.

We tested the factor structure of the National Anxiety Disorder Screening Day instrument (n=14860) within five ethnic groups (White, Black, Hispanic, Asian, Native American). Conducted yearly across the US, the screening is meant to detect five common anxiety syndromes. Factor analyses often fail to confirm the validity of assessment tools' structures, and this is especially likely for minority ethnic groups. If symptoms cluster differently across ethnic groups, criteria for conventional DSM-IV disorders are less likely to be met, leaving significant distress unlabeled and under-detected in minority groups. Exploratory and confirmatory factor analyses established that the items clustered into the six expected factors (one for each disorder plus agoraphobia). This six-factor model fit the data very well for Whites and not significantly worse for each other group. However, small areas of the model did not appear to fit as well for some groups. After taking these areas into account, the data still clearly suggest more prevalent PTSD symptoms in the Black, Hispanic and Native American groups in our sample. Additional studies are warranted to examine the model's external validity, generalizability to more culturally distinct groups, and overlap with other culture-specific syndromes.

Helpseeking and access to mental health treatment for obsessive-compulsive disorder.

OBJECTIVE: To identify predictors of helpseeking and use of mental health treatment for obsessive-compulsive disorder (OCD) using the behavioral model of health service use. METHOD: Data were drawn from the 1996 National Anxiety Disorders Screening Day. Participants (n=14 860) completed screening measures providing information about demographics, mental disorders, helpseeking, and treatment experiences for OCD. RESULTS: Previous use of mental health treatment was associated with comorbid panic disorder [odds ratio (OR)=1.6 (1.3-1.98)], while minority racial status [OR=0.7 (0.5-0.9)] emerged as a barrier to receiving care among individuals with OCD. Among those who had never received mental health care, comorbid panic disorder [OR=2.0 (1.5-2.8)], post-traumatic stress disorder [OR=1.7 (1.3-2.4)], and suicidal ideation [OR=1.7 (1.2-2.3)] increased readiness to seek treatment while being employed [OR=0.7 (0.5-0.9)], and feeling one could handle the problem on his/her own [OR=0.5 (0.3-0.7)] decreased readiness to seek help for the first time. CONCLUSION: These data suggest that access to treatment for OCD may not be equally accessible to all in need by revealing non-disease related factors (e.g. race, health beliefs) that have a significant impact on decisions to seek and use mental health treatment.