Journal Article•
The impact of dopamine on aggression: An [18F]FDOPA PET study
TL;DR: In this article, a modified version of the Point Subtraction Aggression Paradigm (PSAP) was used to measure aggressive behavior during a monetary reward-related paradigm, where a putative adversary habitually tried to cheat.
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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TL;DR: In this paper , the authors carried out a systematic review of studies that assess underlying biological markers (e.g., genes, brain, psychophysiological, and hormonal) of reactive and proactive aggression.
6 citations
Dissertation•
01 Jan 2019
5 citations
01 Jan 2019
TL;DR: The resulting neurobiological portrait of IED is of a person with a lifelong history of angry outbursts, with evidence of disturbed, stress-related 5-HT signaling, which worsens the very system that can regulate stress reactivity.
Abstract: According to the SEIP/predictive coding framework, neurotransmitters and neuromodulators have a role as signaling molecules in circuits that enable social interaction. Depending on the balance of stress demands on the system and its biological vulnerabilities, variability can be seen in the balance of facilitation versus restraining of aggression. Neurobiological research has pointed to disturbed serotonin signaling in impulsive aggression. Impulsive aggression is indeed caused by serotonin dysregulation but in distinct, receptor-specific pathways. Recent research has not provided evidence to the contrary, but has rather expanded the network of connections to serotonin to distributed brain circuits and even out into the body in immune and intracellular signaling cascades. In total, the resulting neurobiological portrait of IED is of a person with a lifelong history of angry outbursts, with evidence of disturbed, stress-related 5-HT signaling. This 5-HT dysfunction worsens the very system that can regulate stress reactivity, centered on hubs in the prefrontal cortex. Contributing to this positive feedback loop may be an overtaxed immune system, tasked with cleaning up the metabolically costly synaptic downsides of stress. Despite progress in understanding the basic biological mechanism of IED, many unanswered questions remain regarding the role of neurotransmitters and neuromodulators. The task is daunting, because the brain is an enormously complicated system; its functions are not captured simply. System-based approaches have increasingly been called on in the treatment of other complex medical disorders and will likely be required to understand and treat IED. Neurotransmitter and neuromodulator signaling systems have a key role in how brain circuits learn about social interaction over time. This work can be considered as part of the larger effort to understand IED as a brain-based disorder of interpersonal reactivity.
4 citations
TL;DR: A non-mammal model is developed that provides novel insights for developing appropriate intervention strategies to prevent psychological disorders among individuals, especially those who experienced prenatal stress, by controlling dietary tryptophan and medication therapy during pregnancy.
Abstract: Tryptophan, as the sole precursor of serotonin, mainly derived from diets, is essential for neurodevelopment and immunomodulation. Gestational tryptophan fluctuation may account for the maternal-fetal transmission in determining neuroembryogenesis with long-lasting effects on psychological development. Personality disorders and social exclusion are related to psychosocial problems, leading to impaired social functioning. However, it is not clear how the fluctuation in mother-child transmission regulates the neuroendocrine development and gut microbiota composition in progeny due to that tryptophan metabolism in pregnant women is affected by multiple factors, such as diets (tryptophan-enriched or -depleted diet), emotional mental states (anxiety, depression), health status (hypertension, diabetes), and social support as well as stresses and management skills. Recently, we have developed a non-mammal model to rationalize those discrepancies without maternal effects. This perspective article outlines the possibility and verified the hypothesis in bully-victim research with this novel model: (1). Summarizes the effects of the maternal tryptophan administration on the neuroendocrine and microbial development in their offspring; (2). Highlights the inconsistency and limitations in studying the relationship between gestational tryptophan exposure and psychosocial development in humans and viviparous animals; and (3). Evidences that embryonic exposure to tryptophan and its metabolite modify bullying interactions in the chicken model. With the current pioneer researches on the biomechanisms underlying the bully-victim interaction, the perspective article provides novel insights for developing appropriate intervention strategies to prevent psychological disorders among individuals, especially those who experienced prenatal stress, by controlling dietary tryptophan and medication therapy during pregnancy.
2 citations
TL;DR: In this paper , the effects of early-life cecal microbiota transplantation (CMT) on the host's microbial composition, brain serotonergic activity, and aggressive behavior of recipient chickens were investigated.
Abstract: Accumulating evidence from human trials and rodent studies has indicated that modulation of gut microbiota affects host physiological homeostasis and behavioral characteristics. Similarly, alterations in gut microbiota could be a feasible strategy for reducing aggressive behavior and improving health in chickens. The study was conducted to determine the effects of early-life cecal microbiota transplantation (CMT) on cecal microbial composition, brain serotonergic activity, and aggressive behavior of recipient chickens.Chicken lines 63 and 72 with nonaggressive and aggressive behavior, respectively, were used as donors and a commercial strain Dekalb XL was used as recipients for CMT. Eighty-four 1-d-old male chicks were randomly assigned to 1 of 3 treatments with 7 cages per treatment and 4 chickens per cage (n = 7): saline (control, CTRL), cecal solution of line 63 (63-CMT), and cecal solution of line 72 (72-CMT). Transplantation was conducted via oral gavage once daily from d 1 to 10, and then boosted once weekly from week 3 to 5. At weeks 5 and 16, home-cage behavior was recorded, and chickens with similar body weights were assigned to paired aggression tests between the treatments. Samples of blood, brain, and cecal content were collected from the post-tested chickens to detect CMT-induced biological and microbiota changes.63-CMT chickens displayed less aggressive behavior with a higher hypothalamic serotonergic activity at week 5. Correspondingly, two amplicon sequence variants (ASVs) belonging to Lachnospiraceae and one Ruminococcaceae UCG-005 ASV were positively correlated with the levels of brain tryptophan and serotonin, respectively. 72-CMT chickens had lower levels of brain norepinephrine and dopamine at week 5 with higher levels of plasma serotonin and tryptophan at week 16. ASVs belonging to Mollicutes RF39 and GCA-900066225 in 72-CMT chickens were negatively correlated with the brain 5-hydroxyindoleacetic acid (5-HIAA) at week 5, and one Bacteroides ASV was negatively correlated with plasma serotonin at week 16.Results indicate that CMT at an early age could regulate aggressive behavior via modulating the cecal microbial composition, together with central serotonergic and catecholaminergic systems in recipient chickens. The selected CMT could be a novel strategy for reducing aggressive behavior through regulating signaling along the microbiota-gut-brain axis.
References
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TL;DR: Recent neurophysiological studies reveal that neurons in certain brain structures carry specific signals about past and future rewards, and the optimal use of rewards in voluntary behavior would benefit from interactions between the signals.
2,478 citations
TL;DR: The ability to quantify the variance of the human brain as a function of age in a large population of subjects for whom data is also available about their genetic composition and behaviour will allow for the first assessment of cerebral genotype-phenotype-behavioural correlations in humans to take place in a population this large.
Abstract: Motivated by the vast amount of information that is rapidly accumulating about the human brain in digital form, we embarked upon a program in 1992 to develop a four–dimensional probabilistic atlas and reference system for the human brain. Through an International Consortium for Brain Mapping (ICBM) a dataset is being collected that includes 7000 subjects between the ages of eighteen and ninety years and including 342 mono– and dizygotic twins. Data on each subject includes detailed demographic, clinical, behavioural and imaging information. DNA has been collected for genotyping from 5800 subjects. A component of the programme uses post–mortem tissue to determine the probabilistic distribution of microscopic cyto– and chemoarchitectural regions in the human brain. This, combined with macroscopic information about structure and function derived from subjects in vivo , provides the first large scale opportunity to gain meaningful insights into the concordance or discordance in micro– and macroscopic structure and function. The philosophy, strategy, algorithm development, data acquisition techniques and validation methods are described in this report along with database structures. Examples of results are described for the normal adult human brain as well as examples in patients with Alzheimer's disease and multiple sclerosis. The ability to quantify the variance of the human brain as a function of age in a large population of subjects for whom data is also available about their genetic composition and behaviour will allow for the first assessment of cerebral genotype–phenotype–behavioural correlations in humans to take place in a population this large. This approach and its application should provide new insights and opportunities for investigators interested in basic neuroscience, clinical diagnostics and the evaluation of neuropsychiatric disorders in patients.
2,094 citations
TL;DR: This study reports the development of the Reactive-Proactive Aggression Questionnaire (RPQ), and the differential correlates of these two forms of aggression, and demonstrates that this brief but reliable and valid self-report instrument can be used to assess proactive and reactive aggression in child and adolescent samples.
Abstract: This study reports the development of the Reactive–Proactive Aggression Questionnaire (RPQ), and the differential correlates of these two forms of aggression. Antisocial, psychosocial and personality measures were obtained at ages 7 and 16 years in schoolboys, while the RPQ was administered to 334 of the boys at age 16 years. Confirmatory factor analysis indicated a significant fit for a two-factor proactive–reactive model that replicated from one independent subsample to another. Proactive aggression was uniquely characterized at age 7 by initiation of fights, strong-arm tactics, delinquency, poor school motivation, poor peer relationships, single-parent status, psychosocial adversity, substance-abusing parents, and hyperactivity, and at age 16 by a psychopathic personality, blunted affect, delinquency, and serious violent offending. Reactive aggression was uniquely characterized at age 16 by impulsivity, hostility, social anxiety, lack of close friends, unusual perceptual experiences, and ideas of reference. Findings confirm and extend the differential correlates of proactive–reactive aggression, and demonstrate that this brief but reliable and valid self-report instrument can be used to assess proactive and reactive aggression in child and adolescent samples.
1,357 citations
TL;DR: Of the groups studied, impulsive violent offenders who had attempted suicide had the lowest 5HIAA levels, which may be a marker of impulsivity rather than violence.
1,285 citations
TL;DR: The findings indicate that when rewards are predictable, brain regions recruited during expectation are, in part, dissociable from areas responding to reward receipt.
1,085 citations