Hormonal and behavioral homeostasis in boys at risk for substance abuse
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.
References (88)
- et al.
The adolescent outcome of hyperactive children diagnosed by research criteria, I: An 8-year prospective follow-up study
J. Am. Acad. Child Adolesc. Psychiatry
(1990) - et al.
Is ADHD a risk factor for Psychoactive Substance Use Disorder? Findings from a four-year prospective follow-up study
J. Am. Acad. Child Adolesc. Psychiatry
(1997) - et al.
Emerging diversities in the mechanism of action of steroid hormones
J. Steroid Biochem.
(1995) - et al.
Young adult drug use and delinquency: Childhood antecedents and adolescent mediators
J. Am. Acad. Child Adolesc. Psychiatry
(1996) - et al.
Serrotonin function in human subjects: Intercorrelations among central 5-HI indices and aggressiveness
Psychiatry Res.
(1997) - et al.
Fluoxetinne and impulsive aggressive behaviour in personality-disordered subjects
Arch. Gen. Psychiatry
(1997) - et al.
Testosterone and aggression in children
J. Am. Acad. Child Adolesc. Psychiatry
(1993) - et al.
Behavioral self-regulation: Correlates and 2-year follow-up for boys at risk for substance abuse
Drug Alcohol Depend.
(1997) - et al.
Serotonin, aggression, and parental psychopathology in children with attention-deficit hyperactivity disorder
J. Am. Acad. Child Adol. Psychiatry
(1997) - et al.
Mechanisms of stress: A dynamic overview of hormonal and behavioral homeostasis
Neurosci. Biobehav. Rev.
(1992)
Salivary cortisol in psychoneuroendocrine research: Recent developments and applications
Psychoneuroendocrinology
Genetic mechanisms in childhood psychiatric disorders
J. Am. Acad. Child Adolesc. Psychiatry
Substance use and risky sexual behavior in female adolescents
Drug Alcohol Depend.
Salivary cortisol responses and the risk for substance abuse in prepubertal boys
Biol. Psychiatry
Diverse pathways to deficient self-regulation: Implications for disinhibitory psychopathology in children
Clin. Psychol. Rev.
Retrospective assessment of prepubertal major depression with the Kiddie-SADS-E
J. Am. Acad. Child Adolesc. Psychiatry
Catecholamines in ADHD: A postscript
J. Am. Acad. Child Adolesc. Psychiatry
Catecholamines in Attention-Deficit Hyperactivity Disorder: Current perspectives
J. Am. Acad. Child Adolesc. Psychiatry
Psychopathology in children of alcoholics
J. Am. Acad. Child Adolesc. Psychiatry
Testicular function, social rank and personality among wild baboons
Psychoneuroendocrinology
Salivary testosterone and cortisol in disruptive children: Relationship to aggressive, hyperactive, and internalizing behaviors
J. Am. Acad. Child Adolesc. Psychiatry
Male testosterone linked to high social dominance but low physical aggression in early adolescence
J. Am. Acad. Child Adolesc. Psychiatry
Antisocial symptoms in preadolescent boys and their parents: Associations with cortisol
Psychiatry Res.
Manual for the Child Behavior Checklist and Revised Child Behavior Profile
Child/adolescent behavioral and emotional problems: Implications of cross-informant correlations for situational specificity
Psychol. Bull.
Mother–child interactions in ADHD and comparison boys: Relationships with overt and covert externalizing behavior
J. Abnorm. Child Psychol.
The influence of testosterone on human aggression
Br. J. Psychol.
Types of alcoholics, I. Evidence for an empirically derived typology based on indicators for an empirically derived typology based on indicators of vulnerability and severity
Arch. Gen. Psychiatry
Direct inhibitory effect of glucocorticoids upon testicular luteinizing hormone receptor and steroidogenesis in vivo and in vitro
Endocrinology
Adolescents with attention deficit hyperactivity disorder: Mother–adolescent interactions, family beliefs and conflicts, and maternal psychopathology
J. Abnorm. Child Psychol.
Influences of seratonin and testosterone in aggression and dominance: convergence with social psychology
Current Directions in Psychosocial Science
A prospective 4-year follow-up study of attention-deficit hyperactivity and related disorders
Arch. Gen. Psychiatry
The relationship between substance use disorders, impulse control disorders, and pathological aggression
Am. J. Addict.
Are adolescents the victims of raging hormones: Evidence for activational effects of hormones on moods and behavior at adolescence
Psychol. Bull.
Behavioral observations at age 3 year predict adult psychiatric disorders: Longitudinal evidence from a birth cohort
Arch. Gen. Psychiatry
Cerebrospinal fluid vasopressin levels: Correlates with aggression and serotonin function in personality-disordered subjects
Arch. Gen. Psychiatry
Effects of stress on gonadal function
J. Endocrinol. Invest.
Acute suppression of circulating testosterone by cortisol in men
J. Clin. Endocrinol. Metab.
Salivary testosterone and cortisol among late adolescent male offenders
J. Abnorm. Child Psychol.
The neurobiology of stress: Understanding regulation of affect during female biological transitions
Semin. Reprod. Endocrinol.
The relationship between high and low trait psychological stress, serum testosterone, and serum cortisol
Experientia
Hyperactive boys almost grown up: I. Psychiatric status
Arch. Gen. Psychiatry
Disinhibitory psychopathology: A new perspective and model for research
Psychol. Rev.
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2013, Biological PsychologyCitation Excerpt :While expected stress dampening effects on cortisol were found among low risk drinkers, this was not the case among at risk drinkers. Attenuated HPA response to stress on the no alcohol day found in high risk drinkers is consistent with previous studies with alcoholics (Errico et al., 1993; Bernardy et al., 1996; Lovallo et al., 2000) and in subjects with a family history of alcoholism (Dawes et al., 1999; Sorocco et al., 2006). These observations were generally in agreement with previous work examining individual differences in hormonal stress response following alcohol intake (Dai et al., 2007; Croissant et al., 2008).