بررسی مرز بین خلق و خو و اختلال اضطراب فراگیر: گیرنده عامل تجزیه و تحلیل مشخصه

Studies of individuals with an increased tendency to experience negative emotions such as fear, sadness, and anger have documented links between this temperamental trait and anxiety disorders. There exists debate, however, concerning the degree to which high levels of a temperamental trait are a necessary and/or sufficient component of a DSM diagnosis. In this study, receiver operating characteristic (ROC) analyses assessed the relations between levels of harm avoidance (HA) and generalized anxiety disorder (GAD) diagnoses in 334 children and their parents. Analyses revealed HA scores to be highly predictive of GAD diagnoses in children (AUC = .791, P < .001) and adults (AUC = .818, P < .001). However, there were many individuals with high HA scores who did not qualify for a GAD diagnosis. These findings suggest that while there are strong associations between HA and GAD, high levels of HA are neither necessary nor sufficient in the formation of clinically significant anxiety symptoms.

The interface between temperament and psychopathology has received increased interest of late as researchers continue to find strong links between temperamental traits and a wide array of psychiatric disorders (Nigg & Goldsmith, 1998; Rettew & McKee, 2005). The degree of association has stirred both methodological and theoretical debate about the distinction between these supposedly independent domains (Frick, 2004). Complicating matters further is the fact that the definition of temperament remains somewhat elusive (Rothbart, 2004), although there is at least some consensus that temperament refers to individual differences in emotional reactivity and regulation that can be observed early, are moderately stable, and under at least some genetic influence (Goldsmith et al., 1987). Some researchers have postulated temperament as a subclinical variant of psychiatric disorders (von Zerssen & Akiskal, 1998) with temperament and corresponding psychopathology existing along a single continuum (Carey, 1999; Graham & Stevenson, 1987). Under this view, more extreme levels of a particular temperamental trait would be a necessary although not sufficient element of a corresponding psychiatric disorder. A large twin study conducted in Australia (Jardine, Martin, & Henderson, 1984) reported the genetic correlation between neuroticism and anxiety to be approximately .8. Hettema, Prescott, and Kendler (2004) recently found evidence that not only is there a high degree of correlation between neuroticism and generalized anxiety disorder (GAD) but that the two conditions may involve some of the same genes. Others, however, view temperamental dimensions as one of many risk factors for later psychopathology (Schwartz, Snidman, & Kagan, 1999) and something qualitatively distinct between psychopathology itself. Anxiety disorders have been particularly linked to temperamental dimensions. Kagan (1994) and coworkers have proposed the temperamental dimension of behavior inhibition (BI) to describe children who become overly fearful and reticent when confronted with novel situations and people. BI as a toddler has been found to predict later psychopathology, particularly anxiety disorders (Biederman et al., 1993 and Schwartz et al., 1999). Other measures of related temperamental or personality traits, variably named neuroticism, negative affectivity, or negative emotionality have also been found to have strong associations with anxiety disorders (Anthony, Lonigan, Hooe, & Phillips, 2002; Caspi, 2000; Kuo, Chih, Soong, Yang, & Chen, 2004). Using Cloninger's framework, the related dimension of harm avoidance (HA) appears to be strongly linked to many anxiety and affective disorders in both children and adults (Öngür, Farabaugh, Iosifescu, Perlis, & Fava, 2005; Pelissolo et al., 2002; Rettew, Copeland, Stanger, & Hudziak, 2004). Many hypotheses concerning the temperament/psychopathology boundary are now able to be tested and quantified using modern data analytic techniques. One type of analysis that holds promise in quantifying the relations between two variables is receiver operating characteristic (ROC) analysis. This procedure has typically been applied to quantifying the association between a continuous test variable and a binary outcome variable at varying cut-off points of the test variable. ROC analyses allow the investigator not only to calculate the sensitivity and specificity of the test variable at different cut-off levels but also an overall area under the curve (AUC): a more general measure of the ability to optimize both sensitivity and specificity at each point of the test variable. Williamson and colleagues (2005) performed ROC analyses in adults using a composite measure from multiple questionnaires, including the neuroticism scale from the Eysenck Personality Questionnaire (EPQ-N; Eysenck, Eysenck, & Barrett, 1985), to predict the presence of a mood or anxiety disorder, as determined through a telephone structured interview. The AUC for this composite measure was found to be good (.869), and the authors concluded that neuroticism represents a vulnerability factor for later depressive and anxiety disorders. The goal of this study was to provide a quantitative evaluation of the degree of overlap between the temperamental trait of harm avoidance and generalized anxiety disorder in both children and adults. GAD is a highly distressing disorder characterized by chronic, excessive worry surrounding various aspects of one's life. The HA dimension was chosen because of its previously mentioned links particularly with mood and anxiety disorders, although other temperament dimensions such as low novelty seeking and reward dependence have also been implicated (Öngür et al., 2005 and Pelissolo et al., 2002). Both HA and GAD share features of feeling habitually tense and worried. While we expected a high degree of overlap, we were particularly interested to investigate the degree to which temperamental traits can exist without a psychiatric disorder and vice versa. To improve validity of both temperament and diagnosis, this study utilizes a multiple informant approach. We hypothesized that although HA scores would be highly predictive of GAD, there would be many individual cases in which high HA scores were not associated with GAD. Alternately, we expected some cases in which an individual with GAD had low or moderate HA scores. We expected, however, that the former case (tested as a sensitivity question) would be more common than the latter (tested as a specificity question). In other words, we predicted that it would be more common for an individual to express high levels of harm avoidance in the absence of GAD relative to the existence of individuals with GAD expressing low levels of harm avoidance. Support for these hypotheses would be expected to challenge the theory that a clinical diagnosis of GAD belongs to a fundamental continuum of neurotic temperament. To our knowledge, this is the first application of this statistical procedure to the overlap between temperament and psychopathology in a sample that includes children and adolescents. 2. Methods 2.1. Subjects 2.1.1. Subject recruitment Participants came from a family study conducted in the northeastern United States that was designed to examine the genetic and environmental contributions to attention and aggression. Details of the study design are presented elsewhere (Hudziak, Copeland, Stanger, & Wadsworth, 2004); however, we will summarize some of the procedures. Potential families were recruited from local pediatricians and psychiatrists in a university-based outpatient clinic based on a review of clinical records. Local newspaper advertisements and posters were also used. Families were initially screened over the telephone for the following demographic inclusion criteria: (1) proband child between the ages of 6 and 18; (2) proband child living with at least one biological parent; and (3) proband child with at least one sibling between the ages of 6 and 18. If a family met those requirements, they were then sent parent-rater Child Behavior Checklists (Achenbach, 1991) to assess levels of behavior problems. Four target groups of probands were sought based on the CBCL, including subjects with (1) T scores greater than 67 on the attention problems (AP) scale and less then 60 on the aggressive behavior (AG) scale; (2) T scores greater than 67 on AG but less than 60 on AP; (3) T scores greater than 67 on both scales; and (4) T scores less than 60 on both scales. Siblings were not subject to any of the T score restrictions placed on probands. A total of 206 families were recruited into the family study. From these families, there were 458 children (195 girls, 263 boys); 197 mothers, and 101 fathers who agreed to participate in the study. The sample was almost exclusively Caucasian with an average score of 6.38 (S.D. = 2.15) on the Hollinghead SES scale (Hollingshead, 1975).