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

Section on Development and Affective Neuroscience, National Institute of Mental Health Intramural Research Program, Bethesda, MD 20817, USA.
Archives of General Psychiatry (Impact Factor: 14.48). 02/2005; 62(1):73-80. DOI: 10.1001/archpsyc.62.1.73
Source: PubMed


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.
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.
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.
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.
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.
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.

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Available from: Rachel G Klein, Mar 17, 2015
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    • "Relatives of PD patients 35% CO 2 Perna et al., 1995 76 Relatives of PD patients 35% CO 2 Cavallini et al., 1998 77 Relatives of PD patients 35% CO 2 Perna et al., 1999 78 Relatives of PD patients 35% CO 2 Coryell et al., 1999 79 Relatives of PD patients 35% CO 2 van Beek et al., 2000 80 Relatives of PD patients 35% CO 2 Coryell et al., 2001 81 Relatives of PD patients 5% CO 2 Pine et al., 2005 82 Relatives of PD patients 5% CO 2 Coryell et al., 2006 83 Relatives of PD patients 5 and 35% CO 2 Roberson-Nay et al., 2010 84 Relatives of PD patients 5% CO 2 "
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    ABSTRACT: This systematic review assesses the current state of clinical and preclinical research on panic disorder (PD) in which the carbon dioxide (CO2) challenge was used as a trigger for panic attacks (PAs). A total of 95 articles published from 1984 to 2012 were selected for inclusion. Some hypotheses for PD evolved greatly due to the reproducibility of PAs in a controlled environment using the safe and noninvasive CO2 test. The 35% CO2 protocol was the method chosen by the majority of studies. Results of the test report specific sensitivity to hypercapnia in PD patients of the respiratory PD subtype. The CO2 challenge helped assess the antipanic effects of medication and non-pharmaceutical approaches such as physical exercise and cognitive behavioral therapy. The test was also used in studies about the genetic component of PD, in which twins and relatives of PD patients were analyzed.
    Revista Brasileira de Psiquiatria 07/2013; 35(3):318-31. DOI:10.1590/1516-4446-2012-1045 · 1.77 Impact Factor
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    • "Interestingly, current study found the association between anxiety sensitivity and separation anxiety to be as strong as that with panic disorder. This could be due to the common physiological symptoms and/or the shared developmental trajectory between separation anxiety and panic (Kossowsky et al., 2013; Pine et al., 2005). The results suggest that anxiety sensitivity might act as a shared risk factor for these problems. "
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    ABSTRACT: Anxiety sensitivity, a belief that symptoms of anxiety are harmful, has been proposed to influence development of panic disorder. Recent research suggests it may be a vulnerability factor for many anxiety subtypes. Moderate genetic influences have been implicated for both anxiety sensitivity and anxiety, however, little is known about the aetiology of the relationship between these traits in children. Self-reports of anxiety sensitivity and anxiety symptoms were collected from approximately 300 twin pairs at two time points. Partial correlations indicated that anxiety sensitivity at age 8 was broadly associated with most anxiety subtypes at age 10 (r=0.11-0.17, p<0.05). The associations were largely unidirectional, underpinned by stable genetic influences. Non-shared environment had unique influences on variables. Phenotypic results showed that anxiety sensitivity is a broad predictor of anxiety symptoms in childhood. Genetic results suggest that childhood is a developmental period characterised by genetic stability and time-specific environmental influences on anxiety-related traits.
    Journal of anxiety disorders 06/2013; 27(5):475-484. DOI:10.1016/j.janxdis.2013.05.008 · 2.68 Impact Factor
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    • "The importance of anxiety disorders has been widely recognized . Epidemiological studies of adult populations state high prevalence rates of anxiety disorders both in the USA (Kessler et al., 1994, 2005b) and in Europe (Le´pine, 2002; Wittchen and Jacobi, 2005). Aside from simple phobia, social anxiety disorder (SAnD) is reported to be the most common anxiety disorder and the third most common psychiatric disorder (Kessler et al., 1994). "
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    ABSTRACT: Anxiety disorders are common both in adults and children. While there have been major advances in understanding the neurobiology of anxiety disorders in adults, progress has been more limited in the elucidation of the mechanisms underlying these disorders in childhood. There is a need to delineate childhood biological models, since anxiety represents a significant clinical problem in children and is a risk factor for the subsequent development of anxiety and depression in adulthood. We conducted a review of the literature regarding pharmacological challenge tests and direct hypothalamic-pituitary-adrenal axis measurement in children with anxiety disorders, with emphasis on panic disorder and social anxiety disorder. Studies identified were contrasted with those in adult panic disorder and social anxiety disorder. Despite this broad approach few studies emerged in children, with only 22 studies meeting inclusion criteria. When contrasted with adult neurobiological models of panic disorder and social anxiety disorder, children studied showed some abnormalities which mirrored those reported in adults, such as altered baseline respiration, altered responses to CO(2) challenge tests and blunted growth hormone response to yohimbine. However, results differed from adults with panic disorder and social anxiety in some aspects of noradrenergic and serotonergic function. For endpoints studied in panic disorder children, unlike adults, displayed a lack of baseline end-tidal CO(2) abnormalities and a different hypothalamic-pituitary-adrenal pattern response under low-dose CO(2). The biology of these anxiety disorders in children may only partially mirror that of adult anxiety disorders. However, caution is required as the evidence is limited, and many studies combined patients with panic disorder and social anxiety disorder with other disorders or non-specific anxiety. Further research is required to fully understand the biology and progression of childhood anxiety disorders.
    Journal of Psychopharmacology 07/2010; 26(4):431-42. DOI:10.1177/0269881110372818 · 3.59 Impact Factor
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