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Aggressive behavior in schizophrenia: relationship to age of onset and cortical atrophy.

Aggressive behavior is a common feature of schizophrenia and is associated with the presence of 'soft' neurological signs. Since early age of onset of schizophrenia has been found to be associated with the negative syndrome, which according to Crow (1982) is related to structural brain abnormalities, I predicted that early age of onset may be a biological risk factor for aggressive behavior in the disease. To test this hypothesis, I investigated in 52 chronic institutionalized schizophrenic patients (mean age = 32.8 years; SD = 8.0), the association between age of onset of the disease and the severity of belligerent behavior. The age of onset was judged from the patient's histories as the age at which florid symptoms first emerged. Patients with early onset schizophrenia had a significantly higher belligerent score compared to those with later-onset schizophrenia (p < .05). These findings support the hypothesis of an association between early age of onset of schizophrenia and the risk of aggressive behavior and suggest, furthermore, that schizophrenic symptoms which emerge early may predict a higher risk of aggressive behavior. Furthermore, this study suggest that the neurochemical mechanisms which underlie the early emergence of symptoms may also predispose to aggressive behavior in schizophrenia. Specifically, since aggressive behavior has been linked to impairment of serotonergic (5-HT) functions, I propose that the timing of onset of schizophrenia may be partly associated with dysregulation of the 5-HT system. In a second study, I investigated whether schizophrenic patients with aggressive (suicide) behavior are characterized by more extensive brain damage and hence greater degree of cerebral atrophy on CT scan. The study, which involved 26 schizophrenic patients (mean age: 31.3 years; SD = 6.8), revealed that patients with aggressive behavior had a significantly greater degree of parieto-occipital atrophy on CT scan (p < .05). In contrast, ventricular size and prefrontal cortical atrophy did not distinguish aggressive from nonaggressive patients. These findings suggest that cortical atrophy may be a neuroradiological marker of aggressive behavior in schizophrenia.

Adult↗

Maternal and mating-induced aggression is associated with elevated citrulline immunoreactivity in the paraventricular nucleus in prairie voles.

Lactating female rodents are fiercely aggressive against intruders when they are rearing and protecting pups. In monogamous prairie voles, Microtus ochrogaster, males are parental and exhibit a dramatic increase in aggression, termed mating-induced aggression, in association with reproduction. In mice, the gas, nitric oxide (NO), inhibits male aggression, but may have an excitatory role in the production of maternal aggression. In this study, we combined aggressive behavioral testing of female and male prairie voles with immunohistochemistry for citrulline, a marker of NO synthesis, to examine NO synthesis indirectly during maternal and mating-induced aggression. A significant increase in the number of citrulline-positive cells was identified in the paraventricular nucleus (PVN) of the hypothalamus in aggressive lactating females compared with unstimulated lactating females. A significant increase in the number of citrulline-positive cells was also observed in the PVN of aggressive mated males compared with nonaggressive unmated males and unstimulated mated males. Both nonaggressive unmated males and unstimulated mated males show similar levels of citrulline immunoreactivity in the PVN. In other regions of the brain, no changes in the number of citrulline-positive cells were observed. These results suggest that NO is released specifically in the PVN during both maternal and mating-induced aggression in prairie voles.

Aggression↗

Effects of alcoholic beverage, instigation, and inhibition on expectancies of aggressive behavior.

To investigate the role of alcohol expectancy, situational factors, and personality variables in predicting postdrinking aggression, two questionnaire studies were conducted. Subjects were randomly assigned to imagine themselves and their responses in a scenario situation, which was a combination of different beverages (soda vs. alcohol), instigation, and inhibition conditions. Both studies found significant 3-way interactions of personality aggression proneness (Buss-Durkee Hostility Inventory Assault scale) by beverage condition and by situational cue condition on subjects' reported likelihood of engaging in aggressive behavior. Expected aggression was strongly associated with greater aggression proneness in the nonalcoholic condition when there was a situational cue (low inhibition in Study 1, high instigation in Study 2) invoking aggression, but not when the situational cue was absent. This relationship between aggression proneness and expected aggression, however, was attenuated in the alcoholic drink conditions in both studies. In general, it was found that the effect of alcohol on expected aggression was minor relative to the large and significant effects of aggression proneness, instigation, and inhibition.

Adolescent↗

The effects of alcohol and provocation on aggressive behavior in men and women.

OBJECTIVE: The purpose of this study was to investigate the manner in which acute alcohol consumption and provocation affect aggressive behavior in men and women. METHOD: Subjects were 102 (56 men) healthy social drinkers between 21 and 35 years of age. Aggression was measured using a modified version of the Taylor Aggression Paradigm, in which electric shocks are received from and administered to a fictitious opponent during a competitive task. RESULTS: Provocation was a stronger elicitor of aggression than either gender or alcohol. Under low provocation, men were more aggressive than were women. Under high provocation, men and women were equally aggressive, except in the case of extreme aggression, in which men again exhibited higher levels than did women. Alcohol increased aggression for men but not for women. CONCLUSIONS: These results are important because there now appears to be some convergence among studies indicating that, whereas provocation and alcohol are effective in lifting inhibitions against the expression of aggression for men, only provocation seems to be an effective aggression-elicitor for women.

Adult↗

Marital and severe parent-to-adolescent physical aggression in clinic-referred families: mother and adolescent reports on co-occurrence and links to child behavior problems.

This study examined the interplay of marital and severe parental physical aggression, and their links to child behavior problems, in 232 families of clinic-referred adolescents. Combined reports from mothers and adolescents indicated that two thirds of adolescents exposed to marital aggression in the past year had also experienced parental aggression. Mothers and fathers who used and/or were victims of marital aggression were both more likely to direct aggression toward their adolescent. Mother and youth reports of marital aggression were tied to each party's report of greater externalizing problems and to youth reports of greater internalizing problems. Severe parental aggression uniquely predicted maternal reports of both behavior problems, after controlling for marital aggression; the reverse was not true. Also, adolescents exposed to both types of family aggression did not display greater maladjustment than those subjected to only one type of family aggression.

Adolescent↗

[Characteristics of patient aggression in a psychiatric hospital in Switzerland].

Characteristics of patient aggression in a psychiatric hospital in Switzerland Patient aggression in psychiatry is a prominent problem for all concerned. In this prospective survey we registered and analysed all violent incidents of patients in a cantonal psychiatric hospital in Switzerland in order to determine the characteristics of aggression. The Staff Observation Aggression Scale Revised (SOAS-R) was utilised. During the study period 815 patients were admitted to the hospital. 71 (63.4%) of the 110 violent incidents were perpetrated by male patients. The majority of aggressive incidents were perpetrated in the vicinity of the rooms of the patients and were triggered mainly by the refusal to adhere to the demands of the patient or by patients' use of toxic substances. The most frequent type of aggression was of a verbally aggressive nature and the principal target was nursing personnel who felt threatened in most of the cases. In order to terminate the aggression the most predominant measure was communication with the patient and coercive measures. This study demonstrates clearly that aggression concerns psychiatric nursing personnel and points to the recommendation to reinforce measures of security and to predictive measures to ameliorate the management of aggression.

Adolescent↗

Inhibition of positively rewarding behavior by the heightened aggressive state evoked either by pain-inducing stimulus or septal lesion.

Using a footshock elicited aggression paradigm, aggressive responses were scored in normal and in septal-lesioned adult male Wistar rats. Septal lesions were made electrolytically to include the medial and lateral septal nuclei. The lesion was confirmed by behavioral criteria (septal aggression) and post-mortem histology. The aggressive response types (threat, attack) of the septal animals were compared with their corresponding age and weight matched controls. Results showed a statistically significant increase (P = 0.05) in the number of attack responses but not the threat responses in septal animals. The modulatory role of the aggressive experience on responsiveness to positively rewarding or hedonic stimuli was assessed by quantifying the intracranial self-stimulation (SS) rates that were obtained before and after an aggression schedule. For testing the SS behavior bipolar electrodes were implanted in the ventral tegmental area--substantia nigra (VTA-SN). Results showed a decrease in SS pedal press rates in post-aggression schedule as compared to the pre-aggression period in the normal subjects. This depressing effect lasted for over a week. In septal lesioned rats the SS rates were virtually abolished even without having an aggressive schedule. These experiments revealed the effect of environment and of a brain area in provoking aggressive mood and its inhibitory consequence on responding for positive experience.

Aggression↗

[Genetic analysis of predator aggressiveness in mice].

The character of inheritance of mouse predatory aggression towards crickets and locusts was investigated. The percentage of aggressive animals in the group and the latency of attack were indices of aggression. The hybridological analysis included obtaining reciprocal F1 and F2 hybrids and backcrosses of CBA and DD mice lines exhibiting polar parameters in predatory tests. Examination of hybrids and backcrosses showed that the high level of aggressiveness is dominant. Sex differences in aggression were seen neither in parent strains, nor in hybrids, reciprocal effects being also absent. The results of the hybridological analysis indicated that the predatory aggressions are under control of a small number of genes with a pronounced dominant effect. As a result of diallele analysis in three strains of mice, BALB/c, C57BL/6, DD and all combinations of first generation hybrids, it was found that almost all hybrids exhibited greater aggressiveness than that of parent strains or that it was similar to the indices of highly aggressive parents. Analysis of a strain combinative ability showed that the genotypic component is conditioned by a specific combinative ability, the influence of the total combinating ability and of the reciprocal effects being not significant. It was once more confirmed that the predatory aggression in mice is inherited as a high level dominancy of aggression and genes influencing its manifestation are localized in autosomes.

Aggression↗

Effects of cigarette smoking on human aggressive behavior.

Nicotine administered by smoking experimental cigarettes produced decreases in two types of aggressive responses elicited by low and high frequency subtractions of money which were attributed to another "person". The suppressing effects of smoking different doses of nicotine on aggressive responses was dose-dependent, in that smoking the high dose of nicotine produced more suppression than smoking the low dose. The ostensible subtraction of money from another "person", the more aggressive response option available to research subjects, was generally more sensitive to the suppressing effects of nicotine than aggressive noise delivery responses. Although this effect could be attributed to another constituent of tobacco, the dose-dependent effect observed with these cigarettes which contained the same amount of tar suggest the effects are due to nicotine. The relatively selective suppression of aggressive behavior observed in humans in the present study is highly consistent with the effects of nicotine observed in a number of infrahuman species. Nicotine has been found to suppress aggressive behavior in ants (Kostowski 1968), rats (Silverman 1971), and cats (Berntson et. al. 1976). In addition, nicotine has been observed to suppress shock elicited fighting in rats (Driscoll, Baettig 1981; Rodgers 1979; Waldbillig 1980) as well as shock elicited biting in monkeys (Hutchinson, Emley 1973). The importance of determining specificity of drug action on aggressive behavior has been repeatedly emphasized in the field of behavioral pharmacology (Sidman 1959; Cook, Kelleher 1963; Thompson, Boren 1977; Miczek, Krsiak 1979). One method employed to evaluate drug specificity and identify a general non-specific excitatory or depressant drug effect is to determine the drug effect on more than one response option which is available to the subject (Sidman 1959). In this study, the same doses of nicotine which suppressed aggressive responding increased nonaggressive monetary reinforcement responses. This indicates that the suppressing effects of nicotine on human aggressive responses was not due to a non-specific and generalized depression action. This selective action is similar to that observed by Hutchinson and Emley (1973) when they observed that nicotine decreased shock-elicited biting in monkeys while increasing anticipatory manual responses preceding shock. The highly selective and specific suppressing effect of nicotine on aggressive behavior provides a consistent observation in species ranging from insects to man.

Aggression↗

Sex differences in aggression: a rejoinder and reprise.

A meta analysis of observational studies of peer-directed aggression by children aged 6 and younger yields a highly significant sex difference. Out of 32 studies, z values reflected higher male aggression in 24, no difference in 8, higher female aggression in none. Furthermore, boys' aggression is most often displayed in the presence of male partners. Evidence is presented that the sex difference is probably not merely an artifact of higher rates of male activity or social interaction. Existing cross-cultural evidence also shows higher rates of male aggression, as does most of the work on free-living primates. Specifically, the 3 observational studies of chimpanzees show considerably more aggression in males. Evidence for a hormonal contribution to male aggression is clear in animals and inconclusive in human beings, although the existing human findings are consistent with such a contribution. Recent evidence on the differential socialization of boys and girls supports our earlier view: that boys do not receive more reinforcement for aggression than girls, and that rates of punishment are also similar once the differential base rates in aggression are taken into account. The role of self-socialization (including choice of same-sex models) is discussed, and the view is expressed that this probably depends upon the development of certain cognitions about sex identity which normally do not develop until a later age than the age at which a consistent sex difference in aggression first appears.

Adolescent↗

The use of anticonvulsants in aggression and violence.

Aggression and violence are not univariate concepts. A key to research into the effects of anticonvulsants on aggression and violence is using a nosology that provides a theoretical basis for the clinical use of anticonvulsants and leads to meaningful criterion measures for their evaluation. It is proposed that aggression can be divided into three broad categories: (1) medically related--the aggression is a symptom secondary to a psychiatric, neurological, or other medical disorder; (2) premeditated or planned--the aggressive act is an instrumental response; (3) impulsive--this is a hair-trigger response, that is, the subject does not process information in an adaptive way during the temper outburst. It is hypothesized that selected anticonvulsants (e.g., phenytoin and carbamazepine) will have a therapeutic effect on impulsive aggression. Preliminary data from our research indicate that phenytoin does decrease impulsive aggressive acts. Possible pharmacodynamic mechanisms for these results are briefly discussed within the context of electrophysiological measures at different levels of the central nervous system (event-related potentials, kindling, and ion channel functions). It is further proposed that the equivocal findings in the early studies of the effects of phenytoin on aggression were due to poor criterion measures and inappropriate inclusion/exclusion criteria for subjects (especially failure to document psychiatric or neurological disorders). The early results of our research on carbamazepine are encouraging, but not enough data have been gathered to document its effects on impulsive aggression. The therapeutic use of anticonvulsants to control aggressive and violent behaviors has a long and controversial history (Monroe 1975).(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗

Use of fluoxetine to treat dominance aggression in dogs.

OBJECTIVE: To evaluate fluoxetine for the treatment of owner-directed dominance aggression in dogs. DESIGN: Prospective study. ANIMALS: 9 dogs of various breeds, ages, and either sex determined to have owner-directed dominance aggression. PROCEDURE: Placebo and fluoxetine (1 mg/kg of body weight) were compared for the treatment of owner-directed dominance aggression in a single-blind crossover study. Owners were instructed to record aggressive and nonaggressive responses of their dogs daily on a canine-overt aggression chart for the 5-week duration of the study. Total aggression scores (linear and geometric) were calculated for each week of the study. The frequency of individual responses was also analyzed independently. RESULTS: Fluoxetine resulted in a significant (P = 0.01) reduction in owner-directed dominance aggression after 3 weeks of treatment. No particular aggressive response accounted for the overall reduction in aggression. CLINICAL IMPLICATIONS: Fluoxetine may be useful in the management of dominance aggression in dogs.

Aggression↗

Attributional bias and reactive aggression.

This article looks at a cognitive behavioral intervention designed to reduce minority youths' (Latino and African-American boys) levels of reactive peer-directed aggression. The BrainPower Program trains aggressive boys to recognize accidental causation in ambiguous interactions with peers. The objective of this research is to evaluate the effectiveness of this attribution retraining program in reducing levels of reactive, peer-directed aggression. This research hypothesizes that aggressive young boys' tendency to attribute hostile intentions to others in ambiguous social interactions causes display of inappropriate, peer-directed aggression. A reduction in attributional bias should produce a decrease in reactive physical and verbal aggression directed toward peers. A 12-session, attributional intervention has been designed to reduce aggressive students' tendency to infer hostile intentions in peers following ambiguous peer provocations. The program trains boys to (1) accurately perceive and categorize the available social cues in interactions with peers, (2) attribute negative outcomes of ambiguous causality to accidental or uncontrollable causes, and (3) generate behaviors appropriate to these retrained attributions. African-American and Latino male elementary-school students (N = 384), in grades four-six, served as subjects in one of three groups: experimental attribution retraining program, attention training, and no-attention control group. Three broad categories of outcome data were collected: teacher and administrator reports of behavior, independent observations of behavior, and self-reports from participating students. Process measures to assess implementation fidelity include videotaped training sessions, observations of intervention sessions, student attendance records, and weekly team meetings. The baseline data indicated that students who were evenly distributed across the four sites were not significantly different on the baseline indicators: student cognitions, teacher perceptions of behavior, and student suspension rates. Substantial evidence has shown that aggressive boys tend to attribute hostile intentions to peers, often resulting in inappropriate retaliatory aggression. The BrainPower Program was designed to determine whether psychoeducational strategies in a school context are effective in reducing attributional bias and whether such reductions significantly reduce aggressive behavior.

Black or African American↗

Reactive and proactive aggression differentially predict later conduct problems.

This study tested whether proactive and reactive aggression were differently predictive of later externalizing problems such as delinquency and DSM-related disruptive behaviors (i.e. oppositional defiant and conduct disorders). It also tested whether these two subtypes of aggressive behaviors interacted in predicting externalizing problems. A community sample of low SES boys participated in the study. Proactive and reactive aggression were rated by teachers when boys were 12 years old. Delinquency, oppositional disorders, and conduct disorders were assessed during mid-adolescence. Proactive but not reactive aggression predicted delinquency and disruptive behaviors. Moreover, high levels of reactive aggression weakened the link between proactive aggression and delinquency. Reactive aggression, however, did not moderate the link between proactive aggression and disruptive behaviors. We conclude that reactive and proactive aggression are two types of aggressive behaviors with different predictive abilities. We also offer tentative explanations to account for the present findings.

Adolescent↗

An association between the 4G polymorphism in the PAI-1 promoter and the development of aggressive fibromatosis (desmoid tumor) in familial adenomatous polyposis patients.

Aggressive fibromatosis is a mesenchymal neoplasm associated with mutations resulting in beta-catenin mediated transcriptional activation. Plasminogen activator inhibitor-1 (PAI-1) is expressed at a high level in aggressive fibromatosis, and using transgenic mice, we found that PAI-1 plays an important role in aggressive fibromatosis tumor formation. Familial adenomatous polyposis is associated with Adenomatous Polyposis Coli gene mutations resulting in beta-catenin mediated transcriptional activation, yet only some patients develop aggressive fibromatosis. Since PAI-1 expression is influenced by a promoter 4G/5G polymorphism, we investigated the incidence of this polymorphism in familial adenomatous polyposis patients who did and who did not develop aggressive fibromatosis, as well as sporadic aggressive fibromatosis patients. There was a trend towards association of the 4G allele (associated with high PAI-1 expression) with the development of aggressive fibromatosis in familial adenomatous polyposis patients (50% vs. 19%, P = 0.1). In familial adenomatous polyposis patients who did not develop aggressive fibromatosis, there was a significantly lower proportion of patients with a 4G allele compared to the healthy control (19% vs. 51%, P = 0.0286). The lower incidence of 4G polymorphism in the PAI-1 promoter may be preventive against the development of aggressive fibromatosis. This data provides additional evidence supporting an important role for PAI-1 in the pathogenesis of aggressive fibromatosis.

Adenomatous Polyposis Coli↗

Host defense factors, tumor aggressiveness, and prognosis associated with carcinomas of the breast.

Analysis of disease-free survival rates in 405 women with operable breast cancers was undertaken in a five-year retrospective study; tumor aggressiveness and host defense factors ( HDF ) were evaluated by a histologic method. Tumors were classified as slightly, moderately, or highly aggressive carcinomas by a scoring method that takes into account several histologic features. The presence of absence of HDF was determined by nodal sinus histiocytosis in the regional axillary lymph nodes and by stromal mononuclear reaction in the primary tumor. Overall, women with positive HDF had better cumulative five-year survival rates (76 per cent) than women with negative HDF (49 per cent). The combination of highly aggressive tumors, metastatic lymph nodes, and negative HDF was associated with extremely poor five-year survival rates (1 per cent) compared with those observed for women with aggressive tumors, nodal metastases, and positive HDF (30 percent), P less than 0.001. In this group, patients with four or fewer metastatic nodes showed a recurrence rate of 28 per cent; however, if five or more nodes were involved, the recurrence rate was 93 per cent. This pattern in disease-free survival rates related to HDF was not found in slightly or moderately aggressive tumors with or without metastases or in aggressive tumors without metastases. In addition, there was no relation between the number of metastatic nodes and survival in patients with slightly or moderately aggressive tumors or with aggressive tumors and negative HDF . It is concluded that HDF influence survival only in aggressive tumors with metastases and that the inherent aggressiveness of the tumor is the main factor that determines prognosis.

Breast Neoplasms↗

Aggressive warming reduces blood loss during hip arthroplasty.

UNLABELLED: We evaluated the effects of aggressive warming and maintenance of normothermia on surgical blood loss and allogeneic transfusion requirement. We randomly assigned 150 patients undergoing total hip arthroplasty with spinal anesthesia to aggressive warming (to maintain a tympanic membrane temperature of 36.5 degrees C) or conventional warming (36 degrees C). Autologous and allogeneic blood were given to maintain a priori designated hematocrits. Blood loss was determined by a blinded investigator based on sponge weight and scavenged cells; postoperative loss was determined from drain output. Results were analyzed on an intention-to-treat basis. Average intraoperative core temperatures were warmer in the patients assigned to aggressive warming (36.5 degrees +/- 0.3 degrees vs 36.1 degrees +/- 0.3 degrees C, P< 0.001). Mean arterial pressure was similar in each group preoperatively, but was greater intraoperatively in the conventionally warmed patients: 86+/-12 vs 80+/-9 mm Hg, P<0.001. Intraoperative blood loss was significantly greater in the conventional warming (618 mL; interquartile range, 480-864 mL) than the aggressive warming group (488 mL; interquartile range, 368-721 mL; P: = 0.002), whereas postoperative blood loss did not differ in the two groups. Total blood loss during surgery and over the first two postoperative days was also significantly greater in the conventional warming group (1678 mL; interquartile range, 1366-1965 mL) than in the aggressively warmed group (1,531 mL; interquartile range, 1055-1746 mL, P = 0.031). A total of 40 conventionally warmed patients required 86 units of allogeneic red blood cells, whereas 29 aggressively warmed patients required 62 units (P = 0.051 and 0.061, respectively). We conclude that aggressive intraoperative warming reduces blood loss during hip arthroplasty. IMPLICATIONS: Aggressive warming better maintained core temperature (36.5 degrees vs 36.1 degrees C) and slightly decreased intraoperative blood pressure. Aggressive warming also decreased blood loss by approximately 200 mL. Aggressive warming may thus, be beneficial in patients undergoing hip arthroplasty.

Adult↗

Synaptic Proteome Divergence in the Prefrontal Cortex of Tame and Aggressive Red Foxes (Vulpes vulpes).

The biological mechanisms behind aggressive and affiliative behaviors are difficult to pinpoint. In the Farm-Fox Experiment, conventional foxes were selectively bred since 1959 in two different directions, one for tame and another for aggressive response to humans. The distinct differences in social behavior of tame, aggressive, and conventional populations are genetically based and the three populations live in conditions that control for factors that could impact social reactions, such as environment and social experiences. Genomic and transcriptomic studies of genetic differences among the fox populations have highlighted genes involved in synaptic processes in the prefrontal cortex. To investigate how the synaptic mechanisms differ between the three fox populations, synaptosomes were isolated from prefrontal and premotor cortex extracts of sixteen female foxes. Tandem mass tags with liquid chromatography tandem mass spectrometry (LC-MS) were used to identify and quantify the relative abundance of the proteins. The results were sorted into protein groups and compared between populations using a limma analysis to determine proteins with differential expression (DE). In the tame versus aggressive comparison, 174 protein groups were found to be DE, while only five were found in the conventional versus aggressive comparison. Most DE protein groups had lower fold expression in the aggressive population compared to tame and aggressive populations. ADGRB2 was found to be the most DE protein group, with 11-fold higher expression in aggressive foxes than in tame foxes. ADGRB2 was previously shown to affect depression-like behavior in mice and is involved in the vascular endothelial growth factor signaling pathway, that is known to influence neurogenesis. Enrichment analyses on the DE protein groups found gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were enriched in the tame versus aggressive comparison, including multiple, highly enriched terms involving ribosome and translation. Local translation at synapses plays an important role in synaptic plasticity and, as a result, can profoundly influence behavior. This study highlighted potential mechanisms that could underly the behavioral differences between tame and aggressive foxes.

Journal Article↗