Neurobehavior disinhibition in childhood predicts suicide potential and substance use disorder by young adulthood.

The objectives of this study were to (a) determine whether two factors that are established components of the risk for substance use disorder (SUD) also impact on the risk for suicide; and (2) evaluate whether SUD manifest by early adulthood predicts suicide propensity. Neurobehavior disinhibition assessed in 227 boys at ages 10-12 and 16 and parental history of SUD were prospectively evaluated to determine their association with the risk for SUD and suicide propensity between ages 16 and 19. The results indicated that neurobehavior disinhibition at age 16 predicts suicide propensity between ages 16 and 19 (p = .04). A trend was observed (p = .08) for SUD manifest between ages 16 and 19 to predict suicide propensity during the same period. Maternal SUD is directly associated with son's SUD risk but not suicide propensity. Paternal SUD predicts son's neurobehavior disinhibition that, in turn, predisposes to SUD. A direct relation between paternal SUD and son's suicide propensity was not observed. These findings suggest that neurobehavior disinhibition, a component of the liability of SUD, is also associated with suicide risk. These results are discussed within a neurobehavioral framework in which prefrontal cortex dysfunction is hypothesized to underlie the risk for these two outcomes.

Concordance between verbal report and urine screen of recent marijuana use in adolescents.

This study compared the concordance of self-report for recent marijuana use with results obtained from urine drug screen. The sample consisted of adolescent sons of fathers with DSM-III-R lifetime substance use disorder (SUD) [high average risk (HAR); N= 75] and sons of fathers with no Axis 1 psychiatric or SUD [low average risk (LAR); N= 125]. To avoid recall bias, and to ensure that the timeframe for accurate detection was restricted to promote accuracy, urine drug screen results were compared to self-reported marijuana use during the prior 48 h using an interview format. The HAR group of adolescents reported a higher rate of recent cannabis use and also had a higher rate of cannabis detection as measured in urine. The two groups did not differ with respect to either over or under-reporting marijuana use. Overall, of 19 participants who obtained positive urine cannabis results, six (31.5%) verbally denied that they used marijuana within the previous 2 days. Among the 181 participants who obtained a negative urine drug screen, 20 subjects (11.5%) inaccurately asserted that they had used marijuana within the prior 2 days. In total, 13% of the participants (26/200) inaccurately reported recent cannabis use. These results underscore the need for caution in interpreting the results of self-report methods documenting the prevalence of drug use among youth.

Impact of parental substance use disorder and child neglect severity on substance use involvement in male offspring.

Two child self-report scales were developed to measure parental neglect (emotional distance and parental involvement) in a sample of 344 boys between 10 and 12 years of age. Psychometric analyses of the parental emotional distance and involvement scales demonstrated their unidimensionality; construct, concurrent, and predictive validity; and reliability. Cross-sectional analyses indicated that neglect was more severe among boys who had a parent with a DSM-III-R lifetime substance use disorder (SUD) compared to youth whose parents had no Axis I psychiatric disorder. In addition, children reported more severe neglect by the mother than the father. Longitudinal analyses of a subsample (n = 99) revealed that child neglect at ages 10-12 predicted significant variance on a composite measure of substance use involvement and severity of substance use as well as increased the risk for SUD at age 19.

Developmental sources of variation in liability to adolescent substance use disorders.

This review provides a synthesis of the literature on the complex sequence of maturational, psychosocial, and neuroadaptive processes that lead to substance use disorders (SUD) in adolescence. A brief overview introduces the concepts of liability to SUD and epigenesis. A theory is presented explaining how affective, cognitive, and behavioral dysregulation in late childhood is exacerbated during early and middle adolescence by family and peer factors, as well as puberty, leading to substance use. Continued exacerbation of the three components of dysregulation by drug and non-drug stressors during late adolescence is posited to result in neuroadaptations that increase the likelihood of developing SUD, particularly in high-risk individuals. Implications for etiologic research as well as clinical and preventive interventions are discussed.

Antisociality, substance dependence, and the DRD5 gene: a preliminary study.

A pilot population-based study of a microsatellite polymorphism at the DRD5 locus in adult European-Americans showed its association with childhood symptom counts for oppositional defiant disorder (ODD) in males and females and adult antisocial personality disorder (ASPD) in females. No association with childhood conduct disorder symptom count was observed. ODD mediated the genotype-ASPD relationship in females. Neither ODD nor ASPD significantly mediated the relationship between the genotype and the liability to substance dependence (SD). The data suggest involvement of the DRD5 locus in the variation and sexual dimorphism of SD liability and antisociality and in the developmental continuity of antisociality.

Genetic studies of substance abuse.

Genetic studies of substance abuse indicate that variation in the risk for the disorder in the population is contributed by differences in both individual genotypes and environment. Recent developments in genetics raise the possibility of disentangling the complex system of genotype-environment interaction that determines the development of the individual behavioral phenotype. This paper reviews the concepts, methods and results pertaining to genetic investigation of substance abuse.

Individual traits and family contexts predict sons' externalizing behavior and preliminary relative risk ratios for conduct disorder and substance use disorder outcomes.

An ontogenetic framework for elucidating the etiology of substance use disorders (SUD) requires identifying how individual traits and family contexts combine to increase risk for SUD outcomes. In this study, we examine individual traits in family context to identify processes that account for the relationship between fathers' SUD + status and sons' externalizing behaviors. Results obtained from SUD + (n = 89) and SUD - (n = 139) families show that fathers' abusive propensities toward their sons mediated the relationship between fathers' SUD + status and sons' externalizing behavior scale (EBS) scores 2 years later. Moreover, individual traits, family contextual variables and deviant peer affiliations accounted for 58% of the variance on sons' EBS scores. Also, high risk cluster (HRC) and low risk cluster (LRC) memberships were derived from cluster analyses of the continuous risk factor scores that predicted sons' EBS scores. Preliminary relative risk ratios show that sons classified into the HRC at age 10-12 were at greater risk for DSM-III-R conduct disorder and SUD outcomes at age 16 than sons assigned to the LRC, SUD + or SUD - groups. Implications for selected family-based prevention initiatives are presented.

Family and peer correlates of behavioral self-regulation in boys at risk for substance abuse.

Behavioral self-regulation (BSR), defined herein as the degree to which one can control one's own activity and reactivity to environmental stimuli, has been posited to be salient to the onset of adolescent substance abuse. The goal of this study was to clarify particular family and peer correlates of BSR in at-risk sons. Subjects were 10-through 12-year-old sons of substance-abusing fathers (high-average risk [HAR]; n = 176) and normal controls (low-average risk [LAR]; n = 199). A BSR latent trait was developed using multiple measures and multiple informants. Analyses included separate hierarchical linear regressions for HAR and LAR groups. In the hierarchical linear model for HAR sons, family dysfunction and deviant peer affiliation were significantly associated with BSR, whereas for LAR sons, only peer affiliation was significantly associated with BSR. The above family and peer correlates differed in proportions of variance explained for BSR in HAR and LAR sons. These findings extend previous studies by showing that, in a hierarchical linear model, BSR in HAR sons is associated with specific interpersonal, family, and peer factors. These findings suggest that empirical, theory-guided interventions to prevent worsening of BSR in HAR boys should address specific interpersonal, family, and peer factors.

Hormonal and behavioral homeostasis in boys at risk for substance abuse.

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).

Association between hyperactivity and executive cognitive functioning in childhood and substance use in early adolescence.

OBJECTIVE: To determine whether deficient executive cognitive functioning (ECF) in association with high behavioral activity level comprise components of the liability to substance abuse. METHOD: A high-risk (HR) group having fathers with a lifetime DSM-III-R diagnosis of a psychoactive substance use disorder was compared with a low-average-risk (LAR) group whose fathers had neither psychoactive substance use disorder nor another adult Axis I psychiatric disorder. ECF and behavioral activity were measured using neuropsychological tests, activity monitor, diagnostic interview, and informant ratings when the subjects were 10 to 12 years of age. Alcohol, tobacco, and cannabis use were measured at 2-year follow-up. RESULTS: At baseline, the HR group had a significantly higher behavioral activity level and exhibited poorer performance on ECF tests than the LAR group. By early adolescence, HR subjects had a higher lifetime rate of tobacco and cannabis use and earlier age at onset of cannabis use. ECF capacity, but not behavioral activity level, predicted tobacco and cannabis use, total number of drugs ever tried, and severity of drug involvement. ECF accounted for additional variance beyond the effects of conduct problems on these outcomes. CONCLUSION: Whereas behavioral activity and ECF capacity in late childhood distinguishes HR from LAR youth, childhood ECF capacity is the more salient predictor of drug use in early adolescence.

Etiology of early age onset substance use disorder: a maturational perspective.

The etiology of early age onset substance use disorder (SUD), an Axis I psychiatric illness, is examined from the perspective of the multifactorial model of complex disorders. Beginning at conception, genetic and environment interactions produce a sequence of biobehavioral phenotypes during development which bias the ontogenetic pathway toward SUD. One pathway to SUD is theorized to emanate from a deviation in somatic and neurological maturation, which, in the context of adverse environments, predisposes to affective and behavioral dysregulation as the cardinal SUD liability-contributing phenotype. Dysregulation progresses via epigenesis from difficult temperament in infancy to conduct problems in childhood to substance use by early adolescence and to severe SUD by young adulthood.

Quality of life following liver transplantation.

This article reviews a program of research using a newly developed questionnaire, the Quality of Life Inventory, to describe the effects of liver transplantation. Although recovery does not return to premorbid level, liver transplantation is effective in reversing cognitive, emotional, behavioral and physical capacity disturbances.

Executive cognitive functioning, temperament, and antisocial behavior in conduct-disordered adolescent females.

The authors assessed whether low executive cognitive functioning (ECF) and a difficult temperament are related to aggressive and nonaggressive forms of antisocial behavior (ASB) in 249, 14-18-year-old, conduct-disordered females and controls. ECF was measured using neuropsychological tests; temperament was measured using the Dimensions of Temperament Survey-revised; and ASB was assessed using psychiatric symptom counts for conduct disorder. The conduct-disordered females exhibited lower ECF capacity and a greater difficult temperament compared with the controls. The combined influence of low ECF and difficult temperament was significantly related to both forms of ASB. In comparison with low ECF, difficult temperament was more strongly related to nonaggressive ASB, whereas in comparison with difficult temperament, low ECF was more strongly related to aggressive ASB. Last, ECF mediated the relation between difficult temperament and aggressive ASB.

Isometric muscle strength in alcoholic and nonalcoholic liver-transplantation candidates.

Intensity of isometric muscle contractions was measured in alcoholic subjects with cirrhosis (N = 42), nonalcoholic subjects with cirrhosis (N = 33), and normal controls (N = 31). Muscle strength and endurance were comparable in the alcoholic and nonalcoholic cirrhotic subjects for all variables. Both cirrhotic groups were inferior to normal controls for all variables. The quantity x frequency (Q x F) index reported for the period during peak alcohol consumption correlated with 6 muscle-force variables, accounting for 9-20% of the variance. Alcoholic and nonalcoholic cirrhotic subjects did not differ in Quality of Life Inventory (QOLI) scales. Significant correlations, however, were found for the alcoholic cirrhotic subjects but not for the nonalcoholic cirrhotic subjects between quality-of-life indices and muscle strength and endurance. Muscle weakness is thus differentially associated with quality of life in alcoholic cirrhotic subjects as compared with nonalcoholic subjects with cirrhosis even though level of strength and endurance in the two groups is comparable.

Disruptive, delinquent and aggressive behavior in female adolescents with a psychoactive substance use disorder: relation to executive cognitive functioning.

OBJECTIVE: This study had four objectives: (1) to determine whether female adolescents with a psychoactive substance use disorder are more impaired than controls on a battery of neuropsychological tests of Executive Cognitive Functioning (ECF); (2) to determine whether these individuals exhibit higher levels of disruptive, delinquent and aggressive behavior compared with controls; (3) to determine whether ECF is related to disruptive, delinquent and aggressive behavior in this population; and (4) to determine whether these relations are moderated by drug use. METHOD: Multiple indicators of ECF, and disruptive, delinquent and aggressive behavior, as well as drug use, were used to test these relations in a sample of 188 female adolescents who qualified for a DSM-III-R diagnosis of a psychoactive substance use disorder (PSUD) and 95 normal controls between the ages of 14-18 years (N = 283). RESULTS: Hierarchical multiple regression equations determined that ECF was related to disruptive, delinquent and aggressive behavior even when chronological age, SES and drug use were accounted for. The final regression models suggested that drug use was more strongly related to disruptive and delinquent behavior, whereas ECF was more strongly related to aggression. Drug use did not moderate any relation between ECF and the dependent measures. CONCLUSIONS: One implication of these results is that violence prevention and treatment outcomes may be ameliorated by incorporating cognitive habilitation of ECF as an integral component of multimodel interventions.

An association between a microsatellite polymorphism at the DRD5 gene and the liability to substance abuse: pilot study.

We have conducted a population-based association study of substance abuse and a microsatellite at the dopamine D5 receptor locus (DRD5) in a sample of European-American males and females with substance dependence (SA) or without any psychiatric disorder. Overrepresentation of the most frequent allele (148 bp) was found in males in the SA group (OR = 2.2, P = .02); this finding was reproduced in females (OR = 5.4, p < .001). The difference in the frequencies of this allele between SA males and SA females was statistically significant. The genotype coded in accordance with the dose of this allele correlated with substance abuse liability in males and females (stronger in females) and with novelty seeking in females. There was no evidence of correlation between the genotypes of spouses that could be induced by assortative mating for the liability to substance abuse. The data suggest that the DRD5 locus is involved in the variation and sex dimorphism of substance abuse liability.

Adolescent versus adult onset and the development of substance use disorders in males.

This study examines the influence of adolescent age of onset on the development of substance use disorders (SUD) by comparing adult males (n = 181) with SUD categorized into adolescent-onset, early-adult onset and late-adult onset groups on patterns of substance use and related disorders, time course of the development of substance dependence and rates of comorbid mental disorders. A sample of male adolescents (n = 81) with SUD was also included as a comparison group. The subjects were recruited from intervention programs in the community and participated in semistructured interviews with diagnoses determined by the best estimate method. Adolescent-onset adults, compared with other adult-onset groups, had higher lifetime rates of cannabis and hallucinogen use disorders, shorter times from first exposure to dependence, shorter times between the development of their first and second dependence diagnoses and higher rates of disruptive behavior disorders and major depression. Adolescents were similar to adolescent-onset adults. While the findings must be interpreted in light of methodological limitations, these results suggest that adolescent-onset SUD is a distinct subtype involving different substances and more rapid development than adult-onset SUD.

Violence, suicidality, and alcohol/drug use involvement in adolescent females with a psychoactive substance use disorder and controls.

This study had three aims: (1) to determine the relations between behavioral dysregulation, negative affectivity, and familial impairment with violence and suicidality (i.e., severity of ideation and attempts) in a sample of adolescent females with a psychoactive substance use disorder and controls; (2) to determine whether these relations are mediated by internalizing (depression/anxiety) and externalizing (nonviolent antisocial behavior) symptomatology; and (3) to determine whether severity of alcohol/drug use involvement moderates the relations between the mediating variables with violence and suicidality. Multiple behavioral, psychiatric interview, and self-report measures were used to index behavioral dysregulation, negative affectivity, familial impairment, internalizing and externalizing symptomatology, and violence and suicidality in one hundred sixty-one 14- to 18-year-old adolescent females with a psychoactive substance use disorder and in 80 controls. Structural equation modeling was used to determine the proposed relations. Results indicated that behavioral dysregulation, negative affectivity, and familial impairment were related to violence, whereas only familial impairment was related to suicidality. Internalizing symptomatology mediated the relation between familial impairment and suicidality, and was related to violence, whereas externalizing symptomatology mediated the relations between behavioral dysregulation, negative affectivity, and familial impairment with violence. Severity of alcohol/drug use involvement did not moderate the relations between internalizing or externalizing symptomatology with suicidality or violence. Nevertheless, the relation between internalizing symptomatology and suicidality was stronger in females with a greater degree of alcohol/drug use involvement, compared with those with a milder degree of involvement. Therefore, from a prevention standpoint, behavioral dysregulation, negative affectivity, familial impairment, as well as internalizing and externalizing symptoms, may serve as clinical "points of intervention" for altering the development of violence and suicidality in high risk and substance abusing youth.