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Journal ArticleDOI: 10.1016/J.PNPBP.2020.110059

The neurobiology of human aggressive behavior: Neuroimaging, genetic, and neurochemical aspects.

02 Mar 2021-Progress in Neuro-psychopharmacology & Biological Psychiatry (Elsevier)-Vol. 106, pp 110059
Abstract: In modern societies, there is a strive to improve the quality of life related to risk of crimes which inevitably requires a better understanding of brain determinants and mediators of aggression. Neurobiology provides powerful tools to achieve this end. Pre-clinical and clinical studies show that changes in regional volumes, metabolism-function and connectivity within specific neural networks are related to aggression. Subregions of prefrontal cortex, insula, amygdala, basal ganglia and hippocampus play a major role within these circuits and have been consistently implicated in biology of aggression. Genetic variations in proteins regulating the synthesis, degradation, and transport of serotonin and dopamine as well as their signal transduction have been found to mediate behavioral variability observed in aggression. Gene-gene and gene-environment interactions represent additional important risk factors for aggressiveness. Considering the social burden of pathological forms of aggression, more basic and translational studies should be conducted to accelerate applications to clinical practice, justice courts, and policy making.

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Topics: Genetics of aggression (62%), Aggression (58%), Poison control (50%)

13 results found

Open access
Laura Bevilacqua1, Stéphane Doly2, Jaakko Kaprio3, Jaakko Kaprio1  +17 moreInstitutions (6)
01 Jan 2010-
Abstract: Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behaviour. The complex origins of impulsivity hinder identification of the genes influencing it and the diseases with which it is associated. Here we perform exon-focused sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B was identified that is common (minor allele frequency > 1%) but exclusive to Finnish people. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon, which was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviours in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioural phenotypes using founder populations, and indicates a role for HTR2B in impulsivity.

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Topics: Impulsivity (59%), Population (54%), Minor allele frequency (51%)

218 Citations

Open access
Jari Tiihonen1, M-R Rautiainen1, Hanna Ollila1, Eila Repo-Tiihonen2  +12 moreInstitutions (5)
12 Jun 2015-
Abstract: In developed countries, the majority of all violent crime is committed by a small group of antisocial recidivistic offenders, but no genes have been shown to contribute to recidivistic violent offending or severe violent behavior, such as homicide. Our results, from two independent cohorts of Finnish prisoners, revealed that a monoamine oxidase A (MAOA) low-activity genotype (contributing to low dopamine turnover rate) as well as the CDH13 gene (coding for neuronal membrane adhesion protein) are associated with extremely violent behavior (at least 10 committed homicides, attempted homicides or batteries). No substantial signal was observed for either MAOA or CDH13 among non-violent offenders, indicating that findings were specific for violent offending, and not largely attributable to substance abuse or antisocial personality disorder. These results indicate both low monoamine metabolism and neuronal membrane dysfunction as plausible factors in the etiology of extreme criminal violent behavior, and imply that at least about 5–10% of all severe violent crime in Finland is attributable to the aforementioned MAOA and CDH13 genotypes.

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110 Citations

Open accessJournal ArticleDOI: 10.1097/HRP.0000000000000282
David S Im1Institutions (1)
Abstract: Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by markedly impaired social interaction, impaired communication, and restricted/repetitive patterns of behavior, interests, and activities. In addition to challenges caused by core symptoms, maladaptive behaviors such as aggression can be associated with ASD and can further disrupt functioning and quality of life. For adults with ASD, these behaviors can portend adverse outcomes (e.g., harm to others or to the individual with ASD, hindering of employment opportunities, criminal justice system involvement). This article reviews the scientific literature to provide an update on evidence-based interventions for aggression in adults with ASD. Method A search of the electronic databases CINAHL, EMBASE, and PsycINFO was conducted using relevant search terms. After reviewing titles, abstracts, full-length articles, and reference lists, 70 articles were identified and reviewed. Results The strongest (controlled trial) evidence suggests beneficial effects of risperidone, propranolol, fluvoxamine, vigorous aerobic exercise, and dextromethorphan/quinidine for treating aggression in adults with ASD, with lower levels of evidence supporting behavioral interventions, multisensory environments, yokukansan, and other treatments. Conclusions Additional randomized, controlled trials using consistent methodology that adequately addresses sources of bias are needed to determine which treatments are reliably effective in addressing aggression in adults with ASD. In the meantime, considering efficacy and adverse effect/long-term risk profiles, a practical approach could start with functional assessment-informed behavioral interventions along with encouragement of regular, vigorous aerobic exercise to target aggression in adults with ASD, with pharmacotherapy employed if these interventions are unavailable or inadequate based on symptom acuity.

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Topics: Aggression (54%), Autism spectrum disorder (53%)

3 Citations

Journal ArticleDOI: 10.1016/J.APPDEV.2021.101331
Abstract: Both family and school environments are considered important proximal microsystems for young children's social and behavioral development. Numerous studies have reported associations between child-caregiver interactions in both family and school and child outcomes. The benefits of quality child-caregiver interactions across home and classroom contexts to child development may be maximized when positive interactional experiences in the home and classrooms are mutually supportive. Recent research employed multilevel models to examine the association between maternal supportive parenting and preschool children's development of social skills and problem behaviors, as well as the cross-level moderating effects of teachers' emotional support. The study took place in Guangdong province, China. A total of 388 children (Mage = 4.07, SD = 0.41) from 59 preschool classrooms and their mothers participated in this study. Results indicated that higher supportive parenting was associated with children's gains in social skills and decreases in problem behaviors; teachers' emotional support strengthened the effects of supportive parenting on children's development of social skills, but not for their problem behaviors. These findings revealed the importance of both providing young children supportive parenting at home and quality teacher-child interactions in classrooms, as family and schools work together to optimize children's social development.

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Topics: Social skills (54%), Child development (53%), Social change (53%)

2 Citations

Open accessJournal Article
Abstract: Cerebral dopamine (DA) transmission is thought to be an important modulator for the development and occurrence of aggressive behavior. However, the link between aggression and DA transmission in humans has not been investigated using molecular imaging and standardized behavioral tasks. We investigated aggression as a function of DA transmission in a group of (N = 21) healthy male volunteers undergoing 6-[18F]-fluoro-l-DOPA (FDOPA)-positron emission tomography (PET) and a modified version of the Point Subtraction Aggression Paradigm (PSAP). This task measures aggressive behavior during a monetary reward-related paradigm, where a putative adversary habitually tries to cheat. The participant can react in three ways (i.e., money substraction of the putative opponent [aggressive punishment], pressing a defense button, or continuing his money-making behavior). FDOPA-PET was analyzed using a steady-state model yielding estimates of the DA-synthesis capacity (K), the turnover of tracer DA formed in living brain (kloss), and the tracer distribution volume (Vd), which is an index of DA storage capacity. Significant negative correlations between PSAP aggressive responses and the DA-synthesis capacity were present in several regions, most prominently in the midbrain (r = −0.640; p = 0.002). Lower degrees of aggressive responses were associated with higher DA storage capacity in the striatum and midbrain. Additionally, there was a significant positive correlation between the investment into monetary incentive responses on the PSAP and DA-synthesis capacity, notably in the midbrain (r = +0.618, p = 0.003). The results suggest that individuals with low DA transmission capacity are more vulnerable to reactive/impulsive aggression in response to provocation.

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2 Citations


417 results found

Journal ArticleDOI: 10.1016/S1364-6613(00)01483-2
George Bush1, Phan Luu2, Michael I. Posner3Institutions (3)
Abstract: Anterior cingulate cortex (ACC) is a part of the brain’s limbic system. Classically, this region has been related to affect, on the basis of lesion studies in humans and in animals. In the late 1980s, neuroimaging research indicated that ACC was active in many studies of cognition. The findings from EEG studies of a focal area of negativity in scalp electrodes following an error response led to the idea that ACC might be the brain’s error detection and correction device. In this article, these various findings are reviewed in relation to the idea that ACC is a part of a circuit involved in a form of attention that serves to regulate both cognitive and emotional processing. Neuroimaging studies showing that separate areas of ACC are involved in cognition and emotion are discussed and related to results showing that the error negativity is influenced by affect and motivation. In addition, the development of the emotional and cognitive roles of ACC are discussed, and how the success of this regulation in controlling responses might be correlated with cingulate size. Finally, some theories are considered about how the different subdivisions of ACC might interact with other cortical structures as a part of the circuits involved in the regulation of mental and emotional activity.

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Topics: Cingulate cortex (59%), Error-related negativity (58%), Anterior cingulate cortex (57%) ... show more

5,550 Citations

Journal ArticleDOI: 10.1126/SCIENCE.274.5292.1527
Klaus-Peter Lesch1, D. Bengel2, Armin Heils1, Sue Z. Sabol2  +6 moreInstitutions (2)
29 Nov 1996-Science
Abstract: Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships.

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Topics: Serotonin transporter (61%), rs6311 (57%), Rs6313 (56%) ... show more

4,947 Citations

Open accessJournal ArticleDOI: 10.1073/PNAS.85.14.5274
G. Di Chiara1, Assunta ImperatoInstitutions (1)
Abstract: The effect of various drugs on the extracellular concentration of dopamine in two terminal dopaminergic areas, the nucleus accumbens septi (a limbic area) and the dorsal caudate nucleus (a subcortical motor area), was studied in freely moving rats by using brain dialysis. Drugs abused by humans (e.g., opiates, ethanol, nicotine, amphetamine, and cocaine) increased extracellular dopamine concentrations in both areas, but especially in the accumbens, and elicited hypermotility at low doses. On the other hand, drugs with aversive properties (e.g., agonists of kappa opioid receptors, U-50,488, tifluadom, and bremazocine) reduced dopamine release in the accumbens and in the caudate and elicited hypomotility. Haloperidol, a neuroleptic drug, increased extracellular dopamine concentrations, but this effect was not preferential for the accumbens and was associated with hypomotility and sedation. Drugs not abused by humans [e.g., imipramine (an antidepressant), atropine (an antimuscarinic drug), and diphenhydramine (an antihistamine)] failed to modify synaptic dopamine concentrations. These results provide biochemical evidence for the hypothesis that stimulation of dopamine transmission in the limbic system might be a fundamental property of drugs that are abused.

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Topics: Dopamine receptor (63%), Mesolimbic pathway (62%), Dopaminergic (62%) ... show more

4,392 Citations

Journal ArticleDOI: 10.1126/SCIENCE.1072290
02 Aug 2002-Science
Abstract: We studied a large sample of male children from birth to adulthood to determine why some children who are maltreated grow up to develop antisocial behavior, whereas others do not. A functional polymorphism in the gene encoding the neurotransmitter-metabolizing enzyme monoamine oxidase A (MAOA) was found to moderate the effect of maltreatment. Maltreated children with a genotype conferring high levels of MAOA expression were less likely to develop antisocial problems. These findings may partly explain why not all victims of maltreatment grow up to victimize others, and they provide epidemiological evidence that genotypes can moderate children's sensitivity to environmental insults.

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4,031 Citations

Journal ArticleDOI: 10.1038/277093A0
John W. Kebabian1, Donald B. Calne1Institutions (1)
11 Jan 1979-Nature
Abstract: Pharmacological and biochemical criteria can be used to separate those dopamine receptors which are linked to the enzyme adenylyl cyclase and those which are not.

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Topics: Dopamine binding (67%), Dopamine receptor D3 (65%), Dopamine receptor binding (65%) ... show more

3,712 Citations

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