Int J Adolesc Med Health 2015; aop
Kathleen Pajer*, Robert Hoffman, William Gardner, Chien-Ni Chang, David Boley and Wei Wang
Endothelial dysfunction and negative emotions in adolescent girls Keywords: adolescent girls; endothelial function; hopelessness; negative emotions.
Abstract Background: Endothelial dysfunction predicts adult cardiovascular disorder and may be associated with negative emotions in adolescents. This study was conducted to determine if hopelessness, hostility, and depressive, anxiety, or conduct disorders were associated with compromised endothelial function and whether those associations were mediated by health risk behaviors. Methods: Endothelial function, assessed through brachial artery reactive hyperemia, was measured in a psychopathology enriched sample of 60 15–18-year-old girls. The correlations between hopelessness, hostility, and depressive, anxiety, or conduct disorders and the percent change in forearm vascular resistance (PCFVR) were measured. Possible mediation effects of health risk behaviors were tested. Results: Hopelessness was negatively associated with PCFVR, controlling for race and body mass index. Conduct disorder without any anxiety disorder was associated with better endothelial function. The other negative emotions were not associated with PCFVR. Risky health behaviors were associated with conduct disorder and hopelessness, but not with PCFVR, so there was no evidence of mediation. Conclusions: The main finding was that hopelessness in adolescent girls was associated with endothelial dysfunction. This may indicate that when present, hopelessness places a girl at risk for later cardiovascular disease, whether she has a psychiatric disorder or not. Possible mechanisms for this finding are examined and the surprising finding that conduct disorder is associated with better endothelial function is also discussed. Suggestions for future research are presented. *Corresponding author: Dr. Kathleen Pajer, Professor of Psychiatry, University of Ottawa Faculty of Medicine, Children’s Hospital of Eastern Ontario (CHEO) Chief, Department of Psychiatry, 401 Smyth Road Ottawa, ON K1H 8L1 Canada, Phone: 613 737-7600 x2723, Fax: 613 737-2257, E-mail: [email protected] Robert Hoffman, Chien-Ni Chang and Wei Wang: Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, USA William Gardner: CHEO Research Institute, Ottawa, Ontario, Canada David Boley: Johns Hopkins University, College of Nursing, Baltimore, Maryland, USA
DOI 10.1515/ijamh-2014-0080 Received November 5, 2014; accepted January 1, 2015
Introduction Although cardiovascular disease (CVD) normally manifests in middle to late adulthood, some children and adolescents have signs of pathophysiologic changes. For example, endothelial dysfunction, now recognized as an early stage in the pathogenesis of atherosclerosis (1), has been reported in multiple studies of children and adolescents. These studies often use youths with adult risk factors for cardiovascular disease, e.g., diabetes or hyperlipidemia (2, 3), but several investigations of “healthy” children or adolescents also report evidence of endothelial dysfunction (4, 5). If such changes are present in a “healthy” group, then early prevention may reduce later CVD. However, we need to better determine who in this “non-diseased” group might be at risk. This would improve the cost-effectiveness of early prevention and also increase our understanding of the atherosclerotic process. Up to 40% of adults who develop atherosclerotic disease do not have traditional risk factors, indicating that other factors are involved (6). Mounting evidence suggests that negative emotions such as hopelessness, hostility, anxiety, or depression may be important (7, 8), as well as antisocial behavior (9). Although both hopelessness and hostility occur in the context of depression, they are also independent predictors of adult CVD (10, 11) and can be found in other psychiatric disorders, such as antisocial behavior disorders (12). Persistent states of these negative emotions often first manifest in mid-to late adolescence, when the psychoneuroendocrinological milieu and psychosocial environment change dramatically. Two studies have reported associations between negative emotions and endothelial function in children or
Brought to you by | Carleton University OCUL Authenticated Download Date | 7/21/15 4:21 PM
2 Pajer et al.: Endothelial dysfunction and negative emotions
adolescents. Poorer endothelial function correlated with scores on a depression inventory in 15–19-year-old females (13). However, the sample was selected on the basis of participants having no clinical depression; the average score for the sample was quite low. This makes it difficult to draw conclusions about clinical or general populations. Osika and colleagues measured levels of depression, anxiety, anger, disruptive behavior, and self-concept in 248 public school youths, ages 7–18 years. In girls, depression, anxiety, and anger were associated with poorer endothelial function (14). Boys’ endothelial function was positively correlated with externalizing behavior, i.e., the more disruptive a boy, the better his endothelial function. This study raises interesting questions, but does not easily translate into recommendations for clinical populations. The mechanism of the relationship in adults between negative emotions and endothelial dysfunction is poorly understood, but a frequently proposed hypothesis is mediation by health risk behaviors (e.g., poor eating habits, sedentary lifestyle, smoking) (15, 16). Mid-to late adolescence is a time period during which health risk behaviors increase dramatically. Thus, it is possible that a negative emotions/endoethlial dysfunction relationship in adolescents could be explained by health risk behaviors. This is an untested hypothesis. In summary, two studies of negative emotions and endothelial dysfunction in children and adolescents suggest that there may be a pre-adult association. Neither of these studies examined youths who had clinical disorders of mood, anxiety, or antisocial behaviors, and neither tested the associations between hopelessness or hostility and endothelial function. The purpose of this study was to extend our knowledge by examining these questions and to test whether health risk behaviors mediated any correlations we found. To optimize the clinical relevance, our sample was enriched for psychopathology by including participants with recent histories of depressive disorders, anxiety disorders, or conduct disorder, in addition to youths who had no lifetime history of psychiatric disorders.
Materials and methods Design and participants Using a cross-sectional design, we recruited 15–18-year-old girls from a concurrent larger, longitudinal project [Girls Coping with Stress Study (GCSS)] examining stress response system function and psychopathology. We limited our study to girls because there are gender differences in endothelial function (17) and anxiety and depression
are higher in girls. Studying just one gender gave us more statistical power. GCSS participants were recruited by newspaper and radio ads. Based on a comprehensive research diagnostic interview, 205 girls were enrolled into one of three groups: – an internalizing disorder (INT) [depressive or anxiety disorder (except for specific phobia)]; – conduct disorder (CD); – no lifetime psychiatric disorder (ND). In an effort to make the sample representative of the clinical population, half the girls in the CD group were recruited with a comorbid internalizing disorder. None of the girls in the INT group had a comorbid disruptive behavior disorder. The study was explained to girls or parents calling in response to an ad, and an intake appointment was arranged, during which consent and assent were obtained. Separate interviews were conducted with girls and parents. Psychiatric diagnoses were made with the computerized Diagnostic Interview Schedule for Children (C-DISC), Parent and Youth Versions (18). The girls also completed the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) (19), as well as several other tests for exclusion criteria (see below). Families received transportation/parking costs, and parent and girl each received $20. The study described in this paper used an additional recruitment and consent/assent process. Letters describing the study were sent to randomly selected GCSS girls from each of the three diagnostic groups. Based on a previous study of endothelial function by coauthor RH (4), we estimated that approximately 60 girls were needed for the sample. Seventy-two letters were sent out. When a girl called in, the study was explained, and if she wanted to participate, she was instructed to call the staff as soon as she started her next menstrual period. Exclusion criteria for this study were pregnancy, age other than 15–18 years, pubertal stage
Kathleen Pajer*, Robert Hoffman, William Gardner, Chien-Ni Chang, David Boley and Wei Wang
Endothelial dysfunction and negative emotions in adolescent girls Keywords: adolescent girls; endothelial function; hopelessness; negative emotions.
Abstract Background: Endothelial dysfunction predicts adult cardiovascular disorder and may be associated with negative emotions in adolescents. This study was conducted to determine if hopelessness, hostility, and depressive, anxiety, or conduct disorders were associated with compromised endothelial function and whether those associations were mediated by health risk behaviors. Methods: Endothelial function, assessed through brachial artery reactive hyperemia, was measured in a psychopathology enriched sample of 60 15–18-year-old girls. The correlations between hopelessness, hostility, and depressive, anxiety, or conduct disorders and the percent change in forearm vascular resistance (PCFVR) were measured. Possible mediation effects of health risk behaviors were tested. Results: Hopelessness was negatively associated with PCFVR, controlling for race and body mass index. Conduct disorder without any anxiety disorder was associated with better endothelial function. The other negative emotions were not associated with PCFVR. Risky health behaviors were associated with conduct disorder and hopelessness, but not with PCFVR, so there was no evidence of mediation. Conclusions: The main finding was that hopelessness in adolescent girls was associated with endothelial dysfunction. This may indicate that when present, hopelessness places a girl at risk for later cardiovascular disease, whether she has a psychiatric disorder or not. Possible mechanisms for this finding are examined and the surprising finding that conduct disorder is associated with better endothelial function is also discussed. Suggestions for future research are presented. *Corresponding author: Dr. Kathleen Pajer, Professor of Psychiatry, University of Ottawa Faculty of Medicine, Children’s Hospital of Eastern Ontario (CHEO) Chief, Department of Psychiatry, 401 Smyth Road Ottawa, ON K1H 8L1 Canada, Phone: 613 737-7600 x2723, Fax: 613 737-2257, E-mail: [email protected] Robert Hoffman, Chien-Ni Chang and Wei Wang: Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, USA William Gardner: CHEO Research Institute, Ottawa, Ontario, Canada David Boley: Johns Hopkins University, College of Nursing, Baltimore, Maryland, USA
DOI 10.1515/ijamh-2014-0080 Received November 5, 2014; accepted January 1, 2015
Introduction Although cardiovascular disease (CVD) normally manifests in middle to late adulthood, some children and adolescents have signs of pathophysiologic changes. For example, endothelial dysfunction, now recognized as an early stage in the pathogenesis of atherosclerosis (1), has been reported in multiple studies of children and adolescents. These studies often use youths with adult risk factors for cardiovascular disease, e.g., diabetes or hyperlipidemia (2, 3), but several investigations of “healthy” children or adolescents also report evidence of endothelial dysfunction (4, 5). If such changes are present in a “healthy” group, then early prevention may reduce later CVD. However, we need to better determine who in this “non-diseased” group might be at risk. This would improve the cost-effectiveness of early prevention and also increase our understanding of the atherosclerotic process. Up to 40% of adults who develop atherosclerotic disease do not have traditional risk factors, indicating that other factors are involved (6). Mounting evidence suggests that negative emotions such as hopelessness, hostility, anxiety, or depression may be important (7, 8), as well as antisocial behavior (9). Although both hopelessness and hostility occur in the context of depression, they are also independent predictors of adult CVD (10, 11) and can be found in other psychiatric disorders, such as antisocial behavior disorders (12). Persistent states of these negative emotions often first manifest in mid-to late adolescence, when the psychoneuroendocrinological milieu and psychosocial environment change dramatically. Two studies have reported associations between negative emotions and endothelial function in children or
Brought to you by | Carleton University OCUL Authenticated Download Date | 7/21/15 4:21 PM
2 Pajer et al.: Endothelial dysfunction and negative emotions
adolescents. Poorer endothelial function correlated with scores on a depression inventory in 15–19-year-old females (13). However, the sample was selected on the basis of participants having no clinical depression; the average score for the sample was quite low. This makes it difficult to draw conclusions about clinical or general populations. Osika and colleagues measured levels of depression, anxiety, anger, disruptive behavior, and self-concept in 248 public school youths, ages 7–18 years. In girls, depression, anxiety, and anger were associated with poorer endothelial function (14). Boys’ endothelial function was positively correlated with externalizing behavior, i.e., the more disruptive a boy, the better his endothelial function. This study raises interesting questions, but does not easily translate into recommendations for clinical populations. The mechanism of the relationship in adults between negative emotions and endothelial dysfunction is poorly understood, but a frequently proposed hypothesis is mediation by health risk behaviors (e.g., poor eating habits, sedentary lifestyle, smoking) (15, 16). Mid-to late adolescence is a time period during which health risk behaviors increase dramatically. Thus, it is possible that a negative emotions/endoethlial dysfunction relationship in adolescents could be explained by health risk behaviors. This is an untested hypothesis. In summary, two studies of negative emotions and endothelial dysfunction in children and adolescents suggest that there may be a pre-adult association. Neither of these studies examined youths who had clinical disorders of mood, anxiety, or antisocial behaviors, and neither tested the associations between hopelessness or hostility and endothelial function. The purpose of this study was to extend our knowledge by examining these questions and to test whether health risk behaviors mediated any correlations we found. To optimize the clinical relevance, our sample was enriched for psychopathology by including participants with recent histories of depressive disorders, anxiety disorders, or conduct disorder, in addition to youths who had no lifetime history of psychiatric disorders.
Materials and methods Design and participants Using a cross-sectional design, we recruited 15–18-year-old girls from a concurrent larger, longitudinal project [Girls Coping with Stress Study (GCSS)] examining stress response system function and psychopathology. We limited our study to girls because there are gender differences in endothelial function (17) and anxiety and depression
are higher in girls. Studying just one gender gave us more statistical power. GCSS participants were recruited by newspaper and radio ads. Based on a comprehensive research diagnostic interview, 205 girls were enrolled into one of three groups: – an internalizing disorder (INT) [depressive or anxiety disorder (except for specific phobia)]; – conduct disorder (CD); – no lifetime psychiatric disorder (ND). In an effort to make the sample representative of the clinical population, half the girls in the CD group were recruited with a comorbid internalizing disorder. None of the girls in the INT group had a comorbid disruptive behavior disorder. The study was explained to girls or parents calling in response to an ad, and an intake appointment was arranged, during which consent and assent were obtained. Separate interviews were conducted with girls and parents. Psychiatric diagnoses were made with the computerized Diagnostic Interview Schedule for Children (C-DISC), Parent and Youth Versions (18). The girls also completed the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) (19), as well as several other tests for exclusion criteria (see below). Families received transportation/parking costs, and parent and girl each received $20. The study described in this paper used an additional recruitment and consent/assent process. Letters describing the study were sent to randomly selected GCSS girls from each of the three diagnostic groups. Based on a previous study of endothelial function by coauthor RH (4), we estimated that approximately 60 girls were needed for the sample. Seventy-two letters were sent out. When a girl called in, the study was explained, and if she wanted to participate, she was instructed to call the staff as soon as she started her next menstrual period. Exclusion criteria for this study were pregnancy, age other than 15–18 years, pubertal stage
