Characteristics and putative mechanisms in boys at risk for drug abuse and aggression.
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Biomedical subjects
Publications and source records attributed to R O Pihl.
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Normal males received amino acid mixtures designed to raise or lower tryptophan availability, and thus to raise or lower brain serotonin synthesis. They also received alcoholic or non-alcoholic drinks. The subjects were tested in the Taylor Competitive Reaction Time Task in which they competed against a (non-existent) partner in a reaction time task. The magnitude of electric shocks that the subjects were willing to give to their bogus partner was used as a measure of aggression. Lowered tryptophan levels and ingestion of alcohol were associated with increased aggression. Our data support the idea that low serotonin levels may be involved in the etiology of aggression. They suggest that subjects with low brain serotonin levels may be particularly susceptible to alcohol-induced violence.
Alcoholics have previously been found to be more sensitive to painful stimulation than controls, and more sensitive to the pain-reducing effects of alcohol. The present study was designed to examine these effects in men at high familial-genetic risk for alcoholism and controls. Subjects were assigned to one of four alcohol doses [0.135 (active placebo), 0.50, 0.75, or 1.00 ml 95% USP alcohol/kg body weight]. Ratings of the amount of discomfort and pain experienced during an aversive shock procedure were taken immediately post-shock, both while subjects were sober and after they had consumed one of the four alcohol doses. High risk men were found to rate the experience of the shock as more uncomfortable and painful overall than the low risk controls. Pharmacologically significant levels of alcohol were found to reduce or eliminate these group differences, suggesting that alcohol has a "normalizing" effect on pain and discomfort perceptions in high risk men. Only the higher doses of alcohol were found significantly to dampen subjects' shock rating scores. High risk males' increased sensitivity to pain and discomfort, combined with the negatively reinforcing effects of reducing these perceptions at moderate to high alcohol doses, may play a role in predisposing high risk males for the development of alcoholism.
This study investigated the relationships between provocation, acute alcohol intoxication, impaired frontal-lobe function, and aggressive behavior. The authors ranked 114 men according to their performance on two neuropsychological tests associated with frontal-lobe function. Forty-eight men (24 with scores in the upper and 24 with scores in the lower performance quartiles) participated in the full study. Half completed and aggression task while intoxicated, the remainder while sober. Aggression was defined as shock intensity delivered to a sham opponent. Shock intensity significantly increased as a main effect of provocation, alcohol intoxication, and lower cognitive performance. Furthermore, provocation interacted significantly with test performance such that individuals in the lower cognitive performance quartile responded to increased provocation with heightened aggression.
Boys (average age = 12.1 years) from families with an extensive history of paternal alcoholism differed from controls of similar age and IQ on measures of cognitive function, cardiovascular reactivity, and parent-rated conduct problems. High-risk boys performed most poorly on neuropsychological tests of frontal lobe function. According to tests of temporal organization and conditional-associate learning, control over working memory was the frontal subfunction primarily affected. A mental arithmetic task also elicited greater heart rate increases and peripheral vasoconstriction among high-risk boys than among controls. After controlling for group status, significant correlations remained between frontal lobe test scores and disruptive behavior and between cardiovascular hyperreactivity and anxiety levels. The possible contribution of these findings to alcohol abuse was discussed.
Cognitive-neuropsychological tests were given to adolescent boys (N = 177) to investigate processes associated with physical aggression. Factor analysis yielded 4 factors representing verbal learning, incidental spatial learning, tactile-lateral ability, and executive functions. Physical aggression was assessed at ages 6, 10, 11, and 12, and 3 groups were created: stable aggressive, unstable aggressive, and nonaggressive. The authors found main effects for only the executive functions factor even when other factors were used as additional covariates in a step-down analysis; nonaggressive boys performed better than stable and unstable aggressive boys. The covariates family adversity and anxiety were both related only to the verbal learning factor. This study highlights the importance of deficits in executive function in the expression of physical aggression relative to other cognitive-neuropsychological functions.
Disruptive kindergarten boys from inner-city low socioeconomic neighborhood schools were randomly allocated to a preventive intervention and control condition. The 2-year prevention program included a home-based parent training component and a school-based social skills training component. Participants were followed up to mid-adolescence. Results indicated that a significantly greater percentage of treated boys remained in an age-appropriate regular classroom up to the end of elementary school and that the treated boys reported significantly less delinquent behaviors at yearly assessments from 10 to 15 years old, compared with controls. The preventive intervention appeared to have a significant long-term impact on the social development of the disruptive kindergarten boys. Earlier and more intensive intervention may be necessary for some cases, whereas for all disruptive boys, booster sessions between 12 and 15 years of age are recommended.
Both sons of male alcoholics with multigenerational family history of male alcoholism (MFH) and sons of essential hypertensives (HTs) exhibit elevated psychophysiological reactivity to stress when compared with male controls (FH-). MFHs also demonstrate a significant baseline heart rate increase and stress-response dampening following alcohol consumption. The present study investigates the specificity of this alcohol-induced psychophysiological response pattern by testing these two risk groups in a shock response paradigm, both sober and alcohol-intoxicated. A repeated measures analysis of variance on sober and alcohol-intoxicated heart rate reactivity yielded a significant risk by alcohol interaction, indicating that alcohol consumption led to a greater decrease in reactivity in the MFH group compared with the HT and FH- groups. Similar results were obtained for muscle tension measures. MFHs also displayed greater increases in resting baseline heart rate and muscle tension when alcohol intoxicated. The results may reflect a sensitivity to negatively and positively reinforcing effects of alcohol specific to individuals with multigenerational familial histories of alcoholism.
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Violence and drugs seem to mix readily. In this paper, relevant correlational studies are briefly reviewed and methodological issues are discussed. With a focus on alcohol, facts pointing to some type of causal relationship are presented both from crime and laboratory manipulative studies. Dose and rate-dependent anxiolytic, psychomotor stimulant and alteration in inhibitory and problem-solving cognitive functions are each in turn seen as precipatory to aggression. Drugs other than alcohol which interact with these systems are also discussed.
Individuals use and misuse alcohol (and other drugs) because of the pharmacologically mediated effects these substances have on the operation of 4 psychobiological systems, mediating response to motivationally relevant unconditioned and conditioned stimuli. These 4 systems have unique neuroanatomical structure, biochemical modes of operation, association with affect, behavior and cognition, and responsiveness to drugs of abuse. Individual variation in the operation of these systems determines individual susceptibility to initiation and maintenance of drug use and abuse. Sources of such variation differ, in a vitally important fashion, in various specific populations of individuals at heightened risk for drug abuse. Nonalcoholic sons of male alcoholics, with multigenerational family histories of male alcoholism, appear to be at heightened risk for the development of alcohol abuse because alcohol eliminates their heightened response to threat, and because they are hypersensitive to ethanol's psychomotor stimulant effects. Anxiety-sensitive individuals also appear attracted to alcohol for its anxiolytic properties. Many other important sources of idiosyncratic variability exist. Detailed analysis of such sources may lead to the development of more effective prevention and treatment programs.
Despite a relatively large body of literature on the role of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) in the regulation of alcohol intake, the functional significance of serotonergic neurotransmission and its relationship to alcohol intake, abuse, and dependence remains to be fully elucidated. In part two of this review, the experimental (animal) data is summarized along two lines: the effects of serotonergic manipulations on the intake of alcohol, and the effects of acute and chronic alcohol intake, as well as the withdrawal of chronic alcohol, on the serotonergic system. It is concluded that serotonin mediates ethanol intake as a part of its larger role in behavior modulation, such that increases in serotonergic functioning decrease ethanol intake, and decreased serotonergic functioning increases ethanol intake. Ethanol produces transient increases in serotonergic functioning that activate the mesolimbic dopaminergic reward system. The results are discussed in light of recent theories describing the regulatory role of serotonin in general behavior.
A large body of literature has emerged concerning the role of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) in the regulation of alcohol intake and the development of alcoholism. Despite the wealth of information, the functional significance of this neurotransmitter remains to be fully elucidated. This paper, part one of a two-part review, summarizes the available clinical research along two lines: the effects of alcohol on serotonergic functioning and the effects of pharmacological manipulation of serotonergic functioning on alcohol intake in normal (nonalcohol dependent) and alcohol-dependent individuals. It is concluded that considerable evidence exists to support the notion that some alcoholic individuals may have lowered central serotonin neurotransmission.
METHODS: Data from a large longitudinal study of boys who were between kindergarten and age 13 years were used to (1) test whether Gray's and Cloninger's personality dimensions measured in kindergarten predicted the early onset of stable, highly delinquent behavior; (2) test whether 1, 2, or 3 dimensions were needed; and (3) test the predictive value of a categorical approach. RESULTS: The impulsivity dimension was the best predictor of the early onset of stable, highly delinquent behavior. Anxiety and reward dependence made significant but weaker contributions. The categorical approach corroborated Cloninger's suggestion that boys who are high in impulsivity, low in anxiety, and low in reward dependence would be more at risk for delinquent involvement. Boys who were high in impulsivity and low in anxiety but high in reward dependence were much less at risk for delinquency. Differences in antisocial behavior among extreme kindergarten personality groups were stable from ages 11 to 13 years. CONCLUSIONS: The behavioral activating system appears to be the major dimension underlying the propensity toward early onset of antisocial behavior, but both the behavioral inhibition system and the need for social rewards play important roles. The behavioral style (personality) that results from the interplay of these systems is clearly in place by the kindergarten year. Preventive efforts should target preschool children with at-risk behavior profiles. However, longitudinal-experimental studies with at least yearly assessments between birth and school-entry age are needed to understand the extent to which the behavioral styles are antecedent to preschool disruptive behavior disorders.
The existence of a relationship between cardiovascular reactivity to signalled shock and alcohol consumption can be inferred from studies of males at increased familial risk for alcoholism. The present study examined two groups of nonalcoholic men--those with multigenerational histories (MGH) of alcoholism and family--history negative (FH-) controls-to determine whether reactivity was related to voluntary ethanol consumption in the context of a beverage taste test. High reactors, a significant majority of whom were MGH males, drank significantly more vodka and orange juice, rum and coke, and orange juice when asked to rate the flavor of three alcoholic and two nonalcoholic drinks. High reactors also consumed more alcohol on a weekly basis according to their self-report.
Acute alcohol intoxication has been shown to increase physical aggression in the laboratory as measured by the Taylor aggression paradigm with independent groups. Because it would be advantageous to use the Taylor paradigm in a repeated measures design to examine individual differences, the present study compared the performance of subjects on two counterbalanced occasions: when they were intoxicated and when they were sober. Order of testing significantly interacted with drug condition for the aggression measures and pain threshold. However, an analysis of the ratio of pain threshold to shock intensity, and to total aggression, revealed the procedure to be useful in understanding one aspect of how alcohol modulates aggression. The results suggest that acute alcohol intoxication interferes with the ability to integrate previously acquired knowledge in the formulation of behavioral strategies.