Subtypes of aggression and their relevance to child psychiatry.

OBJECTIVE: To review the evidence for qualitatively distinct subtypes of human aggression as they relate to childhood psychopathology. METHOD: Critical review of the pertinent literature. RESULTS: In humans, as well as in animals, the term aggression encompasses a variety of behaviors that are heterogeneous for clinical phenomenology and neurobiological features. No simple extrapolation of animal subtypes to humans is possible, mainly because of the impact of complex cultural variables on behavior. On the whole, research into subtypes of human aggression has been rather limited. A significant part of it has been conducted in children. Clinical observation, experimental paradigms in the laboratory, and cluster/factor-analytic statistics have all been used in an attempt to subdivide aggression. A consistent dichotomy can be identified between an impulsive-reactive-hostile-affective subtype and a controlled-proactive-instrumental-predatory subtype. Although good internal consistency and partial descriptive validity have been shown, these constructs still need full external validation, especially regarding their predicting power of comorbidity, treatment response, and long-term prognosis. CONCLUSIONS: Our understanding and treatment of children and adolescents with aggressive behavior can benefit from research on subtypes of aggression. The differentiation between the impulsive-affective and controlled-predatory subtype as qualitatively different forms of aggressive behavior has emerged as the most promising construct. Specific therapeutic hypotheses could be tested in this context and contribute to a full validation of these concepts.

A synthesis of current findings regarding neurobiological correlates and treatment of suicidal behavior.

Considerable progress has been made in the study of neurobiological correlates of suicidal behavior. These studies have confirmed the link between reduced serotonergic function and serious suicidal acts. They have localized the changes to the ventral prefrontal cortex and suggested how genetics, childhood rearing, alcoholism, substance abuse, gender, age, and cholesterol intake can modulate suicide rates through effects on the serotonergic system. Future studies need to apply this knowledge in the development of in vivo brain imaging and molecular genetic probes for study of high-risk patients. Identification of high-risk groups is essential for the conduct of controlled treatment trials, which are presently almost entirely lacking in suicidal populations. Previous clinical trials of medications and psychotherapies have targeted axis I or axis II disorders but not the predisposition to suicidal acts. Controlled treatment in high-risk patients must be undertaken to identify interventions that can reduce the propensity for suicidal acts. Such interventions will supplement current treatment strategies that target the associated psychiatric illness and reduce the opportunities to attempt suicide in high-risk patients by hospitalization.

Ethical issues in biological psychiatric research with children and adolescents.

OBJECTIVE: This article reviews, discusses, and elaborates considerations and recommendations summarized by the biological research working group at the May 1993 NIMH conference on ethical issues in mental health research on children and adolescents. METHOD: Notes from the conference were summarized and supplemented by a computer search of relevant literature. Drafts were circulated for comment to national and international experts, some of whom joined as coauthors. RESULTS: Issues addressed include possible overprotection by policy makers and institutional review boards arising out of the recognition of children's special vulnerability without equal recognition of their need for research; the definition of minimal risk, which has often been equated with no risk in the case of children; assessment of the risk-benefit ratio; procedures for minimization of risk, such as improved technology, "piggybacking" onto clinical tests, and age-appropriate preparation; the difficulty of justifying risk for normal controls; age-graded consent; special considerations about neuroimaging; "coercive" inducement, both material and psychological; disposition of unexpected or unwanted knowledge about individuals, including the subject's right not to know and parent's right not to tell; and socioeconomic status and cultural/ethnic equity. CONCLUSIONS: The working group adopted a position of advocacy for children's right to research access while recognizing that this advocacy must be tempered by thoughtful protections for child and adolescent subjects.

Distinguishing instrumental and hostile aggression: does it make a difference?

An analogue task of instrumental and hostile aggression during a competitive game, modified to minimize overlap between aggressive responses, was evaluated in 8- to 14-year-old clinically referred boys (n = 33). Postgame interviews indicated that the hostile response, an aversive noise, was perceived by over 80% of subjects as hostile and not instrumental. In contrast, the instrumental response, blocking the opponent's game, was perceived about equally as having instrumental and hostile functions. The hostile aggressive response was uniquely correlated with continuous performance task impulsive commission errors (r = .51), which supported the theoretical relation of hostile aggression to poor impulse control. These results suggest that instrumental and hostile aggression can be distinguished and when precisely defined are distinct in theoretically important ways.

Instrumental and hostile aggression in childhood disruptive behavior disorders.

An analogue task of instrumental and hostile aggression during a competitive game was evaluated in a sample of clinically-referred 8- to 12-year-old aggressive boys. Similar to a prior task in a normative sample (Hoving, Wallace, & La Forme, 1979), both types of aggression increased during provocation as compared to baseline, indicating the success of the provocation manipulation, with moderate correlations between the two aggressive responses. The aggressive group with attention-deficit hyperactivity disorder (ADHD) and the aggressive group without ADHD each had higher rates of instrumental aggression than controls. Only the aggressive/ADHD group had higher rates of hostile aggression than controls. Parent Child Behavior Checklist ratings indicated a modest but significant unique relationship between instrumental aggression and delinquency. The high rate of both types of aggression in the aggressive/ADHD group suggests that comorbid ADHD and aggression may result in qualitative differences in aggressive behavior. The high rate of hostile aggression in the aggressive-ADHD group supports theoretical assumptions regarding the relationship of hostile aggression to poor impulse control.

Neuroendocrine responses to challenge with dl-fenfluramine and aggression in disruptive behavior disorders of children and adolescents.

Prolactin (PRL) and cortisol (CORT) responses to a single oral administration (1.0 mg/kg) of the indirect serotonin agonist dl-fenfluramine were assessed in unmedicated prepubertal and adolescent males with disruptive behavior disorders (DBD). Neuroendocrine responses were correlated with scores on aggression rating scales in prepubertal and adolescent DBD patients and compared with those of matched adolescent normal control subjects. Net dl-fenfluramine-induced PRL and CORT release was not correlated with aggression rating scores in prepubertal and adolescent DBD patients and did not differ significantly between adolescent DBD patients and normal control subjects. Although the present study does not demonstrate a serotonergic abnormality in aggression or DBD, this may be more a reflection of limitations of the neuroendocrine challenge test procedures or the methods used than evidence that serotonergic function in the central nervous system is normal in aggression.

Test-retest reliability of the prolactin and cortisol responses to D,L-fenfluramine challenge in disruptive behavior disorders.

We examined the intraindividual stability of plasma prolactin (PRL) and cortisol responses to D,L-fenfluramine challenges (1.0 mg/kg, p.o.), at a 1-week interval, in boys with disruptive behavior disorders. Two acute administrations of fenfluramine produced consistent and predictable effects on net prolactin responses (peak delta PRL, area under the curve delta PRL), but variable and unpredictable effects on net cortisol responses. The time course and magnitude of fenfluramine blood levels, not nor-fenfluramine, paralleled net PRL responses to fenfluramine. These data indicate that the PRL response to fenfluramine shows continuity within individuals over the course of 1 week, providing a reliable index to reflect the overall function of the serotonin system in the limbic-hypothalamus.

Reliability of subtle (soft) neurological signs in children.

Reliability and stability of neurological "subtle" ("soft") signs were assessed in 54 psychiatric patients and 25 normal children, aged 5-17 years, using the revised Neurological Examination for Subtle Signs (NESS). Acceptable interrater reliability (kappa greater than or equal to 0.50, or intraclass correlation coefficient greater than or equal to 0.70) was found for 40 of the 64 items tested. Test-retest reliability at 2 weeks was unsatisfactory for most of the categorically scored items, including some "classic" subtle signs such as overflows or dysrhythmias. Continuous items, such as time needed to perform 20 consecutive movements, remained mostly stable at retest. A practicing effect was evident only in the graphesthesia test. Overall internal consistency was good (Cronbach's alpha = 0.74). Given the poor stability of overflows and dysrhythmias, researchers and clinicians should rely more on subtle signs that can be assessed on continuous scales.

Elevated platelet MAO is related to impulsivity in disruptive behavior disorders.

Platelet monoamine oxidase (MAO) activity was measured in 32 drug-free prepubertal boys with externalizing symptoms of disruptive behavior disorders and 47 boys with no DSM-III-R diagnoses, and correlated to questionnaire and laboratory performance measures of impulsivity. A subgroup of boys with high MAO activity exhibited significantly poorer performance (i.e., more impulsivity) than a subgroup of low MAO activity on laboratory tasks requiring response inhibition. High MAO patients were more impulsive than high MAO controls on some performance tasks and elevated platelet MAO was unrelated to personality questionnaire measures of impulsivity or to patient status. These data suggest that biological markers such as MAO activity may correlate better with performance than clinical questionnaire measures. Abnormally high platelet MAO activity may not be sufficient to produce externalizing symptoms in children, perhaps interacting with an underlying behavioral dimension of impulsivity.

Decrease in plasma tryptophan after tryptophan-free amino acid mixtures in man.

Male healthy subjects, fasting 12 hours, ingested increasing amounts of a mixture containing a fixed proportion of seven essential amino acids (L-isoleucine 11.5%, L-leucine 18.0%, L-lysine 13.1%, L-methionine 18.0%, L-phenylalanine 18.0%, L-threonine 8.2%, L-valine 13.1%) and lacking tryptophan. The diets produced a rapid fall in plasma tryptophan which was proportional to the total amount of the amino acids ingested. Following the highest dose administered (36.6 g) plasma tryptophan fell to a minimum of about 35% the initial level and remained markedly reduced at 6 hours after treatment. The mechanism of this decrease and its potential clinical relevance are discussed.

Reduction of (3H)-imipramine binding sites on platelets of conduct-disordered children.

Binding characteristics of tritiated imipramine on blood platelets were determined in daytime hospitalized prepubertal children who had mixed diagnoses of conduct disorder (CD) plus attention deficit disorder hyperactivity (ADDH) and in inpatient adolescents who had a history of aggressive behavior. The number of (3H)-imipramine maximal binding sites (Bmax) was significantly lower in the prepubertal patient group of CD plus ADDH; the dissociation constant (Kd) was not significantly different. There were significant negative correlations between Bmax and the Externalizing or Aggressive factors of the Child Behavior Checklist when the CD plus ADDH prepubertal patients were combined with their matched controls and within the adolescent inpatient group. We propose that a decreased platelet imipramine binding Bmax value, as an index of disturbed presynaptic serotonergic activity, is not specific to depression and may be used as a biologic marker for the lack of behavioral constraint in heterogeneous. populations of psychiatric patients.

Pharmacogenetics of phenylethylamine: determination of heritability and genetic transmission of locomotor effects in recombinant inbred strains of mice.

beta-Phenylethylamine (PEA) is an amphetamine-like compound that is postulated to be a possible endogenous psychotogen. We studied locomotor response to PEA in two inbred progenitor strains of mice (C57BL/6 By and BALB/c By), their reciprocal F1 hybrids (B6CF1 and CB6F1), and seven recombinant inbred strains (CXBD, CXBE, CXBG, CXBH, CXBI, CXGJ, and CXBK). Univariate and multivariate statistical analyses were done. Heritability of the response to PEA was 82%. The strain distribution pattern was suggestive of the inheritance of the trait through a single major gene locus.

Effects of combined administration of imipramine and chlorpromazine on beta- and alpha 2-adrenergic receptors in rat cerebral cortex.

Administration of the combination of antidepressant and neuroleptic drugs has been reported to have a synergistic effect in the treatment of delusional depression. The effects of chronic coadministration of imipramine (IMIP) and chlorpromazine (CPZ) on beta-adrenergic and alpha 2-adrenergic binding sites in rat cerebral cortex were studied. The combination caused the same reduction in the number of beta-adrenergic receptors as IMIP alone. No changes in alpha 2-adrenergic receptors were observed with IMIP and/or CPZ.

Interstrain comparison of avoidance behavior and neurochemical parameters of brain cholinergic function.

Five rat strains (Long-Evans Hooded, Zivic Miller, Lewis, Buffalo and Fischer-344) were tested in a shuttlebox conditioned avoidance task and the differences in the performance levels among the strains were noted. In parallel experiments using naive rats, the acetylcholine concentrations in eight brain regions and the acetylcholine turnover rate in five brain regions were determined for these strains. Interstrain differences in these parameters were found but no correlation between avoidance performance and either of these measures was apparent in any brain region studied. In separate experiments, no differences were found in the hippocampal acetylcholine concentration or the turnover rate among good performing Hooded, poor performing Hooded or untested Hooded rats. Similarly, no differences in regional acetylcholine turnover rates were found between naive rats of the Iowa Reactive and Nonreactive strains. [3H]-QNB (quinuclidinyl benzilate) binding was studied in three brain regions in the five strains, but no large interstrain differences in binding characteristics were found. In contrast to interpretations of other workers based on less direct assay methods involving fewer strains, we conclude that no strong correlation exists between avoidance performance ability and basal levels of brain cholinergic activity.