Hormonal and behavioral homeostasis in boys at risk for substance abuse

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Abstract

This study modeled the influences of cortisol reactivity, androgens, age-corrected pubertal status, parental personality, family and peer dysfunction on behavioral self-regulation (BSR), in boys at high (HAR) and low average risk (LAR) for substance abuse. Differences between risk groups in cortisol and androgen concentrations, and cortisol reactivity were also examined. Subjects were 10- through 12-year-old sons of substance abusing fathers (HAR; n=150) and normal controls (LAR; n=147). A multidimensional construct of BSR was developed which utilized multiple measures and multiple informants. Boys reported on family dysfunction and deviant behavior among their peers. Parents reported on their propensity to physically abuse their sons, and their own number of DSM-III-R Antisocial Personality Disorder symptoms. Endocrine measures included plasma testosterone, dihydrotestosterone, and salivary cortisol. HAR boys, compared to LAR boys, had lower mean concentrations for testosterone, dihydrotestosterone, salivary cortisol prior to evoked related potential testing, and lower cortisol reactivity. The number of maternal Antisocial Personality Disorder symptoms, parental potential for physical abuse, degree of family dysfunction, and peer delinquency were significantly associated with BSR. Parental aggression antisocial personality symptoms and parental physical abuse potential are likely to influence sons’ behavioral dysregulation and homeostatic stress reactivity. These key components of liability are posited to increase the likelihood of developing suprathreshold Psychoactive Substance Use Disorder (PSUD).

Introduction

Empirical findings (Reich et al., 1993, Martin et al., 1994, Dawes et al., 1997, Mezzich et al., 1997a, Mezzich et al., 1997b), as well as theoretical literature (Gorrenstein and Newman, 1980, Tarter et al., 1989, Newman and Wallace, 1993) indicate that specific behavioral characteristics increase the likelihood of developing a Psychoactive Substance Use Disorder (PSUD; DSM-III-R, American Psychiatric Association, 1987). Disorders of inattention, impulsivity, and hyperactivity (Barkley et al., 1990, Biederman et al., 1996), childhood aggressivity (Kellam and Brown, 1982, Brook et al., 1996), and conduct disorder (Kandel et al., 1986, Robins and McEvoy, 1990), have been shown to increase the risk for PSUD. Converging evidence suggests that Conduct Disorder often mediates the Attention Deficit Hyperactivity Disorder (ADHD)–PSUD relationship (Gittelman et al., 1985, Hechtman and Weiss, 1986, Barkley et al., 1990, Mannuzza et al., 1991, Babor et al., 1992, Biederman et al., 1997). It is posited that these behavioral characteristics constitute a core disorder of behavioral self-regulation (BSR). BSR is defined herein as the degree to which an individual can control their activity and reactivity to environmental challenges. Only recently has the extent to which BSR increases risk for PSUD and related behaviors been examined. Dawes et al. (1997), in an earlier study using the same subjects described in Section 2.1, demonstrated predictive validity of BSR for family, peer, and school problems in young adolescence at 2-year follow-up. Disturbances in these three domains of psychosocial functioning are posited to increase the risk for substance abuse (Hawkins et al., 1992). Mezzich et al., 1997a, Mezzich et al., 1997b, employing definitions and procedures similar to those used by Martin et al. (1994), but in a separate sample of female adolescent substance abusers, developed a latent construct of behavioral dysregulation that included measures of hyperactivity, impulsivity, and inattention. Mezzich et al. (1997a) showed behavioral dysregulation, negative affectivity, and family impairment influence violence in substance abusing female adolescents. In a second study, Mezzich et al. (1997b) demonstrated that behavioral dysregulation, negative affectivity, and childhood victimization predicted substance use and risky sexual behavior in substance abusing female adolescents. Caspi et al. (1996), in a third study of a different sample, reported that undercontrolled 3-year-old boys were at greater risk of developing Antisocial Personality Disorder and Alcohol Dependence by age 21. Taken together, the concurrent and predictive validity of measures similar to BSR is supported by the three above described studies.

Johnson et al. (1992), in their review of the hormonal and behavioral homeostasis (Greek for ‘steady state’) literature, define ‘stress’ as a state of threatened homeostasis. Hormonal and behavioral homeostasis can be perturbed by physical and psychological stressors, induced by family dysfunction, abusive parenting, and deviant peer affiliation (Johnson et al., 1992, Moss et al., 1995). Johnson et al. (1992) suggest that these chronic contextual stressors can suppress both androgen and cortisol concentrations. The mechanisms by which chronic environmental stress influences circulating levels of androgens and cortisol include direct modulation by the Hypopituitary Gonadal Axis (HPG) and indirect modulation by the Hypopituitary Adrenal Axis (HPA) (Bambino and Hsueh, 1981, Francis, 1981, Collu et al., 1984, Sapolsky, 1991, Sapolsky, 1992, Johnson et al., 1992). Moreover, previous experience (Archer, 1991, Rubinow and Schmidt, 1996), social interactions (Mazur, 1985), and social rank (Schaal et al., 1996) are thought to influence androgen (Archer, 1991, Rubinow and Schmidt, 1996) and cortisol (Buchanan et al., 1992, Susman et al., 1997) levels, as well as hormone–behavior associations. Studies on non-human primates and adult humans have shown that both the HPG and HPA axes, but particularly the HPA axis, are sensitive to physical and psychological stress. Studies on human youths, however, have generally shown hyporesponsivity of cortisol in chronic environmental stress situations. In a small sample of prepubertal youth, Constantino et al., (1993) failed to find abnormal levels of testosterone in aggressive subjects. Moss et al. (1995), in the same baseline assessment of preadolescent sample as described herein in Section 2.1, have shown that decreased cortisol reactivity to an anticipated stressor in sons of substance abusing fathers is associated with Child Behavior Checklist (CBCL; Achenbach and Edelbrock, 1983) problem behaviors, and commission error scores on a computerized task (Schneider and Detweiler, 1987). Moreover, Moss et al. (in press), also in longitudinal follow-up of the same sample as described in Section 2.1, have reported that lower preadolescent cortisol level prior to an anticipated stress was associated prospectively with regular monthly cigarette and marijuana use, but not with regular alcohol use during middle adolescence.

Cross-sectional studies on hormone–behavior relations in peripubertal and pubertal youth have shown significant positive (Olweus, 1987), negative (Dabbs et al., 1991), and no (Susman et al., 1987, Inoff-Germain et al., 1988) associations. Positive associations have been shown between androgen concentration and level of verbal (Olweus, 1987) and physical (Olweus, 1987) aggression, as well as peer-nominated dominance (Schaal et al., 1996). Testosterone has been associated with other behaviors that are posited to be linked to BSR in adolescents, including smoking, drinking, and sex (Udry, 1990). Dabbs et al. (1991) reported a significant interaction between testosterone and cortisol levels; that is, they found that the testosterone–aggression association was greater among subjects having a low cortisol level. Scerbo and Kolko (1994) did not confirm this finding in a separate sample. The longitudinal relations among testosterone–aggression and low cortisol in these samples have not been reported. Inoff-Germain et al. (1988) and Susman et al. (1987), in a sample of peripubertal youth, failed to observe a significant correlation between plasma androgen level and negative affect, maternal reports of delinquency and oppositional behavior, and direct observation measures of irritability and assertiveness.

Longitudinal data suggest that the hormone reactivity may be more sensitive to environmental stressors at particular developmental transitions, such as the peripubertal period (Johnson et al., 1992, Susman et al., 1997). For example, Susman et al. (1997) show that in a small sample of healthy adolescents, over a 1-year period, distress behavior for both sexes in a challenging situation decreases, whereas, for girls cortisol level decreases, while for boys, cortisol level increases. This study, however, does not relate the magnitude, timing, or chronicity of environmental stressors during the follow-up period. Hence, interpretation of these sex differences in cortisol level at longitudinal follow-up is problematic. In a separate sample of males, followed from ages 6 to 13, testosterone levels were positively associated with high social dominance and social success, whereas males with a history of high physical aggression had lower testosterone levels, compared to boys with no history of physical aggression (Schaal et al., 1996, Tremblay et al., 1997). Schaal et al. (1996) speculate that chronic activation of the adrenal axis may explain the relative suppression of the HPG axis in this sample. This study also does not relate the magnitude, timing, or chronicity of environmental stressors during the longitudinal follow-up. Although speculative, these chronically aggressive boys most probably matured in environments where they experienced high degrees of physical and psychological stressors, including family dysfunction, abusive parenting from angry and aggressive parents, and deviant peer affiliation.

From a multifactorial epigenetic perspective of etiology of substance abuse, inclusion of measures of behavioral and hormonal homeostastis, and of the environmental stressors that may perturb homeostasis, in a longitudinal study of sons and daughters of substance abusing fathers is likely to help elucidate the mechanisms leading to PSUD outcomes (Tarter and Vanyukov, 1994, Vanyukov et al., 1994, Moss et al., in press). The extent to which measures of hormonal profile (e.g. androgens, cortisol) and hormonal homeostasis (e.g. cortisol reactivity), interact with concurrent environmental stressors (e.g. specific parental aggressive antisocial personality characteristics, as well as family and peer dysfunction), to modulate BSR in high risk youth (e.g. behavioral homeostasis) heretofore has not been investigated in sons of substance abusing fathers. It is posited that measures of hormonal and behavioral homeostasis have a greater magnitude of covariation in sons of substance abusing fathers, compared to normal control sons, during the peripubertal period. Empirical evidence has yet to document the preadolescent covariation of hormonal and behavioral homeostasis in sons of substance abusing fathers and in controls, or the direction and magnitude of these associations in these comparison groups.

This investigation tested two cross-sectional hypotheses. The first hypothesis was that concentrations of plasma testosterone, plasma dihydrotestosterone, and salivary cortisol, as well as cortisol reactivity, were lower in preadolescent high average risk (HAR) boys, compared to preadolescent low average risk (LAR) boys; these associations are posited to be due in part to chronic homeostatic stress experienced from the family and peer environment prior to baseline assessment. The second hypothesis was that in these preadolescent boys, cortisol reactivity would be negatively associated with BSR (e.g. low cortisol reactivity would be associated with high behavioral dysregulation), while parent antisociality, family dysfunction and deviant peer affiliation would be significantly positively associated with BSR (e.g. high degree of environmental stressors would be associated with high behavioral dysregulation).

Section snippets

Subjects

The sample consisted of baseline assessment of two groups of 10- through 12-year-old boys, classified according to their biological father’s diagnostic status of lifetime DSM-III-R Psychoactive Substance Use Disorder (PSUD). This baseline sample was accrued between 1989 and 1997, and is a portion of the first wave on an ongoing longitudinal study. One-hundred fifty high average risk (HAR) boys had fathers who qualified for PSUD. Low average risk (LAR) boys (n=147) had fathers who were not

Test of differences in hormone levels and risk group status

MANOVA of hormone concentrations and cortisol reactivity between risk groups was significant (Wilk’s λ=0.93, F(5, 211)=3.28, P=0.007, η2=0.07), controlling for age-corrected Tanner stage and household SES. Table 4 presents results for simple factorial ANOVAs of differences in hormone levels in HAR and LAR boys. Age-corrected Tanner genital status was significantly positively correlated with testosterone level (T; r=0.56, P<0.001) and dihydrotestosterone (DHT; r=0.57, P<0.001). Cortisol prior to

Discussion

Our first hypothesis, that baseline assessment concentrations of testosterone, dihydrotestosterone, cortisol, and cortisol reactivity would be significantly lower in HAR boys, compared to LAR boys, was supported. Our second hypothesis, that cortisol reactivity, parent personality characteristics, family dysfunction, and peer delinquency would be significantly associated with BSR was only partially supported. These findings nevertheless extend results reported by Vanyukov et al. (1993) and Moss

Acknowledgements

This work was supported in part by a center grant from the National Institute on Drug Abuse (DA 05606), and a Mentored Clinical Scientist Development Award (1K08 DA-299) from the National Institute on Drug Abuse. We thank the families who participated in this research. Special appreciation is expressed to Dr Galina P. Kirillova for performing the hormone assays and Brion Maher for his technical assistance.

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