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Role of the serotoninergic system in the acceleration of sexual maturation in wild Norway rats selected for reduced aggressiveness toward humans.

The role of the serotoninergic system in acceleration of the sexual development of domesticated rats (Rattus norvegicus) was assessed. The onset of age-related changes in hypothalamic serotonin during prepubertal period occurred earlier in domesticated than in aggressive male rats. Blockade of the serotoninergic system after p-chlorophenylalanine (PCPA) administration on days 40 and 44 delayed the development of the reproductive system in both aggressive and domesticated males. In 60-day-old rats treated with PCPA, levels of testosterone in plasma and the number of mature spermatozoa in epididymis were decreased compared to controls. At the same time, the administration of PCPA on days 30 and 34 did not modify basal testosterone secretion and other parameters in 60-day-old aggressive rats and produced a decrease similar to PCPA injections on days 40 and 44, although less pronounced, in the weights of testes in domesticated animals. Administration of 5-hydroxytryptophan (5-HTP), a precursor of serotonin synthesis, on days 30, 32, 34, 36 and 38 increased plasma testosterone levels and weights of the sex organs in 60-day-old domesticated males, but did not significantly affect the development of reproductive system in aggressive animals. These data indicate that serotonin stimulates sexual development of males during prepubertal period and this activating effect of serotonin occurs earlier in domesticated than in aggressive males. They also suggest that the acceleration in sexual maturation of domesticated rats could result from changes in the ontogenetic dynamic of hypothalamic serotonin induced by a selection for low aggressiveness towards man.

5-Hydroxytryptophan↗

The serotonin reuptake inhibitor fluoxetine reduces sex steroid-related aggression in female rats: an animal model of premenstrual irritability?

The aggressive behavior displayed by some (but not all) female Wistar rats when an unfamiliar rat is being introduced into their home cage (the resident intruder paradigm) was found to be higher in non-receptive phases (metestrus, diestrus) than in the receptive phases (proestrus, estrus) of the estrus cycle, and effectively reduced by ovariectomy. When removal of the ovaries was followed by administration of estradiol and progesterone, in a regimen mimicking the normal cyclical release of these hormones, aggressive behavior was elicited, two days after estrus, in animals that had displayed aggressive behavior before ovariectomy, but not in those that had not. Short-term administration of a serotonin reuptake inhibitor (fluoxetine hydrochloride; 10 mg/kg, i.p.; 4-5 days) reduced both the aggressive behavior displayed during the diestrus phase by normally cycling rats, and the aggressive behavior elicited by administration of estradiol plus progesterone after ovariectomy. It is suggested that the aggressive behavior displayed by the female Wistar rat in the resident intruder paradigm may serve as an animal model of premenstrual dysphoria.

Aggression↗

Tryptophan depletion, executive functions, and disinhibition in aggressive, adolescent males.

Low serotonin has been associated with aggressive behavior and impulsivity. Executive functions (cognitive abilities involved in the initiation/maintenance of goal attainment) have also been related to aggression. We tested whether dietary depletion of tryptophan, the amino acid precursor of serotonin, would increase disinhibition (impulsivity) in aggressive male adolescents. Cognitive-neuropsychological variables predictive of disinhibition were explored. Stable aggressive and nonaggressive adolescent men received balanced and tryptophan-depleted, amino acid mixtures separately (counterbalanced, double-blind). Commission errors on a go/no-go learning task (i.e., failures to inhibit responding to stimuli associated with punishment/nonreward) measured disinhibition. Aggressive adolescent males made more commission errors as compared to nonaggressives. Lower executive functioning was significantly related to commission errors over and above conventional memory abilities. Tryptophan depletion had no effect on commission errors in the aggressive adolescents, possibly because of a ceiling effect.

Adolescent↗

Plasma monoamine metabolites and aggression: two studies of normal and oppositional defiant disorder children.

In two studies the relationship between plasma monoamine metabolites and different parameters of aggression were examined in children suffering from severe aggression and antisocial behavior. No prior studies have related measures of serotonergic function to experimentally elicited aggression and only a few included healthy comparison groups. Plasma 5-HIAA, HVA and MHPG were measured in 15 boys with a oppositional defiant disorder (ODD) and 25 normal controls (NC) (study 1), and 22 ODD and 25 NC children (study 2). On a separate occasion each subject had the opportunity to behave aggressively towards an opponent. 5-HIAA and HVA were significantly lower in the ODD than NC group and both parameters were significantly inversely correlated with aggression and delinquency. These findings were replicated in the second study: The results of the study support a role for serotonergic functioning in persistent antisocial and aggressive behavior in young children.

Aggression↗

Aggression and personality: association with amino acids and monoamine metabolites.

Associations in 52 normal individuals were examined between plasma and cerebrospinal fluid (CSF) concentrations of tryptophan (Trp) and tyrosine, and concentrations of monoamine metabolites in the CSF, and scores on an aggression questionnaire, the Kinsey Institute Reaction List II, and the Eysenck Personality Questionnaire. There was a significantly positive correlation between CSF 5-hydroxyindoleacetic acid (5-HIAA) levels and extroverted aggression scores, and a significantly negative correlation between CSF 5-HIAA levels and introverted aggression scores. Males showed higher plasma Trp concentrations than females, and significantly positive correlations between plasma Trp concentrations and scores on extroverted aggression and the Eysenck E scale. Males, furthermore, showed a significantly negative correlation between CSF Trp levels and scores on the Eysenck P scale, and a significantly positive correlation between concentrations of 3-methoxy-4-hydroxy-phenylglycol in CSF and scores on moral aggression. These results suggest that central serotonin influences aggression in normal individuals through effects on personality.

Adult↗

Serotonergic and cognitive impairment in impulsive aggressive personality disordered offenders: are there implications for treatment?

BACKGROUND: Reduced serotonin (5-HT) function and deficits on neuropsychological tasks have been separately reported in antisocial populations. We investigated whether these impairments are independent or associated factors underlying impulsivity in aggressive personality disordered (PD) offenders and healthy controls and whether there are associated changes in quantitative brain measures. METHODS: This study reports on the findings from a sample of 51 PD offenders and 24 controls, recruited from maximum security psychiatric hospitals, who were characterized using the Special Hospital Assessment of Personality and Socialisation (SHAPS). Subjects underwent assessment of 5-HT function (prolactin response to D-fenfluramine challenge), neuropsychological testing and had a diagnostic MRI scan. Of this sample 19 controls and 24 patients also had quantitative measurement of frontal and temporal lobe volumes on magnetic resonance imaging (MRI). RESULTS: Non-psychopathic (low-impulsive) aggressive PDs had enhanced 5-HT function compared with controls and highly impulsive aggressive psychopaths. Primary and secondary psychopaths had poorer executive/frontal, but not memory/temporal neuropsychological function than controls and non-psychopaths. There were no significant group differences in frontal or temporal lobe brain volumes. Although impulsivity and aggression are correlated constructs impulsivity appeared to be related to both executive function and 5-HT function, while aggression only correlated inversely with executive/frontal and memory/temporal function. 5-HT did not directly correlate with frontal or temporal volume or function. CONCLUSION: Impulsivity appears to be contributed to by both impaired neuropsychological function and 5-HT function. Impaired neuropsychological function alone makes a contribution to aggression. Treatment needs to take account of the neuropsychological and biochemical deficits in this challenging population.

Adult↗

A longitudinal behavioral genetic analysis of the etiology of aggressive and nonaggressive antisocial behavior.

Developmental studies of antisocial behavior (ASB) have found two subgroups of behaviors, roughly described as aggressive and nonaggressive ASB. Theoretical accounts predict that aggressive ASB, which shows greater stability, should have high heritability. In contrast, nonaggressive ASB is very common in adolescence, shows less continuity, and should be influenced both by genes and shared environment. This study explored the genetic and environmental influences on aggressive and nonaggressive ASB in over 1,000 twin pairs aged 8-9 years and again at 13-14 years. Threshold models were fit to the data to incorporate the skew. In childhood, aggressive ASB was highly heritable and showed little influence of shared environment, whereas nonaggressive ASB was significantly influenced both by genes and shared environment. In adolescence, both variables were influenced both by genes and shared envirnmment. The continuity in aggressive antisocial behavior symptoms from childhood to adolescence was largely mediated by genetic influences, whereas continuity in nonaggressive antisocial behavior was mediated both by the shared environment and genetic influences. These data are in agreement with the hypothesis that aggressive ASB is a stable heritable trait as compared to nonaggressive behavior, which is more strongly influenced by the environment and shows less genetic stability over time.

Adolescent↗

Accelerated longitudinal comparisons of aggressive versus delinquent syndromes.

Accelerated longitudinal analyses revealed both similarities and differences between the developmental trajectories of empirically based aggressive versus delinquent syndromes in childhood and adolescence. Syndromes were scored from standardized ratings obtained from parents five times at 2-year intervals for seven birth cohorts of Dutch children initially assessed at ages 4 to 10 years. Scores for both the aggressive and delinquent syndromes declined from ages 4 to 10. After about age 10 years, scores for the aggressive syndrome continued to decline, but scores for the delinquent syndrome increased until about age 17. The aggressive syndrome was significantly more stable than the delinquent syndrome. Long-term predictive correlations between matched subjects from different cohorts were as high as predictive correlations between scores obtained by the same subjects, thus supporting the validity of accelerated longitudinal analyses. The results highlight important developmental distinctions between aggressive versus delinquent conduct problems. Failure to distinguish between aggressive and delinquent conduct problems could generate misleading conclusions about their respective developmental courses and limit the generalizability of results.

Adolescent↗

The 5-HTTPR polymorphism confers liability to a combined phenotype of psychotic and aggressive behavior in Alzheimer disease.

BACKGROUND: Psychotic symptoms in subjects with Alzheimer disease (AD+psychosis, AD+P) are a marker for a distinct phenotype characterized by more rapid cognitive and functional decline and a liability to aggressive behaviors. We recently found that AD subjects homozygous for long alleles (l) of an insertion/deletion polymorphism in the promoter region of the serotonin transporter (5-HTTPR) had elevated rates of aggressive behavior. OBJECTIVE: To examine whether the 5-HTTPR ll genotype confers an increased risk of AD+P, and of the combined AD+P/aggressive phenotype. METHODS: The 5-HTTPR genotype was determined in 332 subjects diagnosed with possible or probable AD. All subjects received structured psychiatric assessments and were categorized with regard to their history of aggressive behaviors and psychotic symptoms. RESULTS: Consistent with other reports, AD+P was associated with a significant increased risk for aggressive behavior. AD+P and aggression were both significantly associated with 5-HTTPR ll genotype and with an increased l allele frequency. Subjects with the combined behavioral phenotype (AD+P and aggressive behavior) had the highest rate of ll genotype and highest l allele frequency. CONCLUSION: The 5-HTTPR l allele appears to confer risk for the combined AD+P/aggressive phenotype. Confirmation of this association in a similar behaviorally well-characterized independent sample is needed.

Aged↗

Acute and long-term effects of a single dose of MDMA on aggression in Dark Agouti rats.

MDMA causes selective depletion of serotonergic terminals in experimental animals and the consequent decrease in synaptic 5-HT may, inter alia, increase impulsivity. To study the effects of MDMA upon brain function, the behaviour of male Dark Agouti rats exposed to MDMA (15 mg/kg i.p.), two 5-HT1B agonists (CGS-12066A and CP-94,253, both 5 mg/kg i.p.) or saline were investigated in the resident-intruder test. Studies were performed in drug-naive rats and also in rats exposed to MDMA (15 mg/kg i.p.) 21 d earlier. In parallel experiments the functional neuroanatomy of MDMA effects were assessed using 2-deoxyglucose imaging of local cerebral metabolic rate of glucose utilization (LCMRGlu) and neurotoxicity was assessed by measuring [3H]paroxetine binding. There was no significant difference in aggressive behaviour (biting, boxing, wrestling and their latencies) between drug-naive rats and rats previously exposed to MDMA 21 d earlier, despite reduced social behaviour, decreased LCMRGlu in several brain areas involved in aggression, and reductions in paroxetine binding by 30-60% in the forebrain. CGS-12066A, CP-94,253 and acute MDMA produced marked decreases in aggressive behaviours, especially in biting, boxing and kicking found in drug-naive rats. In animals previously exposed to the drug, acute anti-aggressive effects of MDMA were, in general, preserved as were MDMA-induced increases in LCMRGlu. Our studies provide evidence that in the resident-intruder test, where social isolation is a requirement, aggressive behaviour and acute anti-aggressive effects of MDMA and 5-HT1B receptor agonists remain intact 3 wk after a single dose of the drug despite significant damage to the serotonergic system.

Adrenergic Uptake Inhibitors↗

Reactive and proactive aggression: predictions to physical violence in different contexts and moderating effects of parental monitoring and caregiving behavior.

This study aimed at (a) comparing the links of proactive and reactive aggression at 13 years of age to delinquency-related violence and dating violence at ages 16 and 17, and (b) examining the moderating effects of parental supervision, and mother's and father's warmth and caregiving behaviors on these links. Based on a sample of 525 Caucasian boys, the results showed that proactive aggression uniquely predicted delinquency-related violence, whereas reactive aggression uniquely predicted later dating violence. The relation between proactive aggression and delinquency-related violence, however, was moderated by parental supervision. The relation between reactive aggression and dating violence was moderated by mother's warmth and caregiving behavior. The implications of the findings for the theoretical and practical distinction between proactive and reactive aggression are discussed.

Adolescent↗

Relationship quality of aggressive children and their siblings: a multiinformant, multimeasure investigation.

Sibling influence on the learning and enactment of aggressive behavior has been consistently demonstrated in studies of sibling relationships. Available evidence suggests that, compared with nonaggressive children's sibling interactions, the sibling interactions of aggressive children are marked by more frequent, intense, and prolonged aggressive behaviors. Although research on normative and aggressive children's sibling interactions has increased recently, a number of limitations in this literature were addressed in this study by: (1) including both an aggressive and nonaggressive comparison group, (2) examining both positive and negative features of sibling relationships, (3) employing a multimethod/multiinformant approach to data collection, and (4) utilizing an improved self-report method. In support of our hypotheses and consistent with previous research, results showed that aggressive children's sibling relationships were marked by higher levels of observed conflict and lower levels of self-reported positive features. When gender was examined, results showed that older brother/younger sister dyads were characterized by higher levels of negative features and lower levels of positive features.

Aggression↗

Anxiolytic and anxiogenic effects of diazepam in male mice with different experience of aggression.

Effects of diazepam (0.5 mg/kg intraperitoneally) on aggressive and anxious behavior were studied on male C57Bl/6J mice with different experience of aggression. Diazepam reduced aggression in animals with previous 3- and 20-day experience of aggression, but the plus-maze test revealed an anxiogenic effect of this drug in the former group and anxiolytic effect in the latter group. It was hypothesized that previous aggression experience modified animal sensitivity to diazepam. The effect of the drug depends on psychoemotional status of experimental animals, and this status differs in male mice with short- and long-term experience of aggression.

Aggression↗

Assessing aggressive and depressed children's social relations with classmates and friends: a matter of perspective.

This study examined aggressive, depressed, and aggressive-depressed children's peer relations from the children's own and from their peers' perspective. Participants were 819 fourth through sixth graders (50.2% girls) who were assessed twice during the same school year. Measures included children's aggression and depression, self-rated and peer-rated social acceptance, number of reciprocal friends, and self-rated and friend-rated friendship quality. Analyses revealed different patterns, depending on the perspective considered. Depression but not aggression was significantly related to difficulties with the peer group and with dyadic friends from the children's own perspective, whereas the opposite pattern was found according to the peers' view. The co-occurrence of aggression and depression entailed significant difficulties with peers regardless of perspective. The implications of these results for the links between children's aggression and depression and their interpersonal relationships are discussed.

Adolescent↗

Emotional competence and aggressive behavior in school-age children.

Examined emotional competence in 87 children, aged 7-10 years, who varied with respect to reports of aggressive behavior to determine whether individual differences in emotional competence characterize children with higher levels of aggressive behavior. Emotional competence was assessed during a 1-hr lab visit that included (a) an observational period consisting of a modified disappointment paradigm, (b) assessment of cognitive and language abilities, and (c) 2 structured emotion interviews. Children with higher levels of aggressive behavior exhibited more intense and frequent expressions of anger, both as reported by mothers and as observed during the disappointment paradigm. Less sophisticated ability to identify the causes of emotion also characterized children with higher levels of aggressive behavior. Gender moderated the relation between aggressive behavior and type of emotion identified such that reports of happiness (in response to receiving a disappointing prize) were associated with lower levels of reported aggressive behavior for boys. The value of assessing children's emotional competence in the context of an emotionally arousing situation is suggested by these findings.

Adaptation, Psychological↗

Behavioral rehabilitation and the reduction of aggressive and self-injurious behaviors with cognitively impaired, chronic psychiatric inpatients.

Aggressive behavior has been identified as a significant concern and occupational hazard in psychiatric inpatient settings. Several factors, including lax or unclear ward structure, have been identified as contributing to the exhibition of aggressive behavior. Token economies are effective in increasing ward structure and reducing aggressive behavior. This study evaluated the effects of rehabilitation programming, based on Gordon Paul's social learning approach (SLA), on rates of aggressive and self-injurious behaviors in a group of cognitively impaired, chronic psychiatric inpatients, compared to three long-term wards of similar patients. While no differences were found between the two groups prior to implementing SLA procedures, lower rates of aggression and self-injurious behavior were observed at one and two years on the Paul-derived ward. These results support the use of Paul's approach with multiply-impaired psychiatric inpatients in reducing patient aggression.

Adult↗

Associations between clinic-referred boys and their fathers on childhood inattention-overactivity and aggression dimensions.

The question asked in this study of 70 clinically referred 6- to 12-year-old boys with behavior problems was whether or not childhood inattention-overactivity and aggression are transmitted specifically from biological fathers to sons. Fathers' self-reported childhood inattention-overactivity on a retrospectively valid measure was exclusively associated with parents' ratings of their sons' current attention problems on the Mothers' Operational Measure for Subgrouping (MOMS), the Revised Child Behavior Checklist (RCBCL), and an approximated DSM-IV inattention dimension. Fathers' self-reported childhood aggression was not associated with ratings of their sons' aggression on the MOMS or DADS (a parallel instrument for fathers), nor on DSM-III oppositional or conduct disorder dimensions, but it was exclusively associated with RCBCL ratings of sons' aggressive and delinquent behavior. None of the nonspecific correlations (father inattention-overactivity with son aggression or father aggression with son inattention-overactivity) was significant.

Aggression↗

Social-cognitive and behavioral correlates of aggression and victimization in boys' play groups.

A contrived play group procedure was utilized to examine the behavioral and social-cognitive correlates of reactive aggression, proactive aggression, and victimization via peers. Eleven play groups, each of which consisted of six familiar African-American 8-year-old boys, met for 45-min sessions on five consecutive days. Social-cognitive interviews were conducted following the second and fourth sessions. Play group interactions were videotaped and examined by trained observers. High rates of proactive aggression were associated with positive outcome expectancies for aggression/assertion, frequent displays of assertive social behavior, and low rates of submissive behavior. Reactive aggression was associated with hostile attributional tendencies and frequent victimization by peers. Victimization was associated with submissive behavior, hostile attributional bias, reactive aggression, and negative outcome expectations for aggression/assertion. These results demonstrate that there is a theoretically coherent and empirically distinct set of correlates associated with each of the examined aggression subtypes, and with victimization by peers.

Black or African American↗