Association of serotonin transporter promoter gene polymorphism with violence: relation with personality disorders, impulsivity, and childhood ADHD psychopathology.
Retz W, Retz-Junginger P, Supprian T, Thome J, Rösler M.
Source
Institute for Forensic Psychology and Psychiatry, University of the Saarland, Homburg/Saar, Germany. [email protected]
Abstract
There is evidence that disturbances in central serotonin (5-HT) function have a role in impulsive aggression, violence, and criminality. A deletion/insertion polymorphism within the 5-HT transporter (5-HTT) promoter gene (5-HTT gene-linked polymorphic region, 5-HTTLPR) is thought to be associated with several psychopathological phenotypes related to disturbed impulse control, anxiety and depression. This study examined the association of the 5-HTTLPR with violent behavior in a sample of 153 male Caucasians referred for a forensic psychiatric examination. We found a significant excess of the short (s) allele and the s/s genotype in patients characterized by recurrent and overt physical violent behavior. This genetic variance explained 5% of the variance of violent behavior. When controlled for the impact of several psychopathologies related to violent behavior, this association was observed in individuals with a history of childhood attention deficit/hyperactivity disorder (ADHD)-related symptoms, but not presenting with personality disorder or increased impulsiveness. In conclusion, the results (i). suggest an association between serotonergic dysfunction and violent behavior, (ii). provide evidence for an-at least partial-genetic regulation of violent behavior in a subgroup of male offenders, and (iii). suggest a significant role for 5-HT transporter functionality for violent behavior.
The neuropsychopharmacology of criminality and aggression.
Lee R, Coccaro E.
Source
Clinical Neurosciences and Psychopharmacology Research Unit, Department of Psychiatry, University of Chicago, 5841 South Maryland Ave, MC 3077, Chicago, IL 60637, USA.
Abstract
Although the idea that aggression has biological components is not a new one, recent research in genetics, neuropsychopharmacology, and neuroimaging has helped clarify the biological contributions to aggression. Studies to date have focused on serotonergic function and impulsive aggression. Reduced levels of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) are associated with impulsive aggression. Pharmacochallenge studies have found decreased serotonergic responsiveness associated with impulsive aggression. Neuroimaging studies suggest a role for the prefrontal cortex, along with other regions of the brain, in the expression of aggression. Serotonin is not the only aspect of brain function implicated in impulsive aggression, and further work is being done on other neurotransmitters and neuropeptides.
Serotonin transporter genotype (5-HTTLPR) predicts utilitarian moral judgments.
Marsh AA, Crowe SL, Yu HH, Gorodetsky EK, Goldman D, Blair RJ.
Source
Department of Psychology, Georgetown University, Washington, District of Columbia, United States of America. [email protected]
Abstract
BACKGROUND:
The psychological and neurobiological processes underlying moral judgment have been the focus of extensive recent research. Here we show that serotonin transporter (5-HTTLPR) genotype predicts responses to moral dilemmas featuring foreseen harm to an innocent.
METHODOLOGY/PRINCIPAL FINDINGS:
Participants in this study judged the acceptability of actions that would unintentionally or intentionally harm an innocent victim in order to save others' lives. An analysis of variance revealed a genotype × scenario interaction, F(2, 63) = 4.52, p = .02. Results showed that, relative to long allele homozygotes (LL), carriers of the short (S) allele showed particular reluctance to endorse utilitarian actions resulting in foreseen harm to an innocent individual. LL genotype participants rated perpetrating unintentional harm as more acceptable (M = 4.98, SEM = 0.20) than did SL genotype participants (M = 4.65, SEM = 0.20) or SS genotype participants (M = 4.29, SEM = 0.30). No group differences in moral judgments were observed in response to scenarios featuring intentional harm.
CONCLUSIONS/SIGNIFICANCE:
The results indicate that inherited variants in a genetic polymorphism that influences serotonin neurotransmission influence utilitarian moral judgments as well. This finding is interpreted in light of evidence that the S allele is associated with elevated emotional responsiveness.
Who's flying the plane: serotonin levels, aggression and free will.
Siegel A, Douard J.
Source
Department of Neurology and Neuroscience, NJ Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
Abstract
The present paper addresses the philosophical problem raised by current causal neurochemical models of impulsive violence and aggression: to what extent can we hold violent criminal offenders responsible for their conduct if that conduct is the result of deterministic biochemical processes in the brain. This question is currently receiving a great deal of attention among neuroscientists, legal scholars and philosophers. We examine our current knowledge of neuroscience to assess the possible roles of deterministic factors which induce impulsive aggression, and the extent to which this behavior can be controlled by neural conditioning mechanisms. Neural conditioning mechanisms, we suggest, may underlie what we consider the basis of responsible (though not necessarily moral) behavior: the capacity to give and take reasons. The models we first examine are based in part upon the role played by the neurotransmitter, serotonin, in the regulation of violence and aggression. Collectively, these results would appear to argue in favor of the view that low brain serotonin levels induce impulsive aggression which overrides mechanisms related to rational decision making processes. We next present an account of responsibility as based on the capacity to exercise a certain kind of reason-responsive control over one's conduct. The problem with such accounts of responsibility, however, is that they fail to specify a neurobiological realization of such mechanisms of control. We present a neurobiological, and weakly determinist, framework for understanding how persons can exercise guidance control over their conduct. This framework is based upon classical conditioning of neurons in the prefrontal cortex that allow for a decision making mechanism that provides for prefrontal cortical control of the sites in the brain which express aggressive behavior that include the hypothalamus and midbrain periaqueductal gray. The authors support the view that, in many circumstances, neural conditioning mechanisms provide the basis for the control of human aggression in spite of the presence of brain serotonin levels that might otherwise favor the expression of impulsive aggressive behavior. Indeed if those neural conditioning mechanisms underlie the human capacity to exercise control, they may be the neural realization of reason-responsiveness generally.
Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17433-8. Epub 2010 Sep 27.
Serotonin selectively influences moral judgment and behavior through effects on harm aversion.
Crockett MJ, Clark L, Hauser MD, Robbins TW.
Source
Department of Experimental Psychology, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, United [email protected]
Abstract
Aversive emotional reactions to real or imagined social harms infuse moral judgment and motivate prosocial behavior. Here, we show that the neurotransmitter serotonin directly alters both moral judgment and behavior through increasing subjects' aversion to personally harming others. We enhanced serotonin in healthy volunteers with citalopram (a selective serotonin reuptake inhibitor) and contrasted its effects with both a pharmacological control treatment and a placebo on tests of moral judgment and behavior. We measured the drugs' effects on moral judgment in a set of moral 'dilemmas' pitting utilitarian outcomes (e.g., saving five lives) against highly aversive harmful actions (e.g., killing an innocent person). Enhancing serotonin made subjects more likely to judge harmful actions as forbidden, but only in cases where harms were emotionally salient. This harm-avoidant bias after citalopram was also evident in behavior during the ultimatum game, in which subjects decide to accept or reject fair or unfair monetary offers from another player. Rejecting unfair offers enforces a fairness norm but also harms the other player financially. Enhancing serotonin made subjects less likely to reject unfair offers. Furthermore, the prosocial effects of citalopram varied as a function of trait empathy. Individuals high in trait empathy showed stronger effects of citalopram on moral judgment and behavior than individuals low in trait empathy. Together, these findings provide unique evidence that serotonin could promote prosocial behavior by enhancing harm aversion, a prosocial sentiment that directly affects both moral judgment and moral behavior.
I fear for you: A role for serotonin in moral behavior
Heike Tosta and Andreas Meyer-Lindenbergb1
aClinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892; and
bDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, 68159 Mannheim, Germany
1To whom correspondence should be addressed. E-mail: [email protected].
Contributed by
Author contributions: H.T. and A.M.-L. wrote the paper.
See the article"Serotonin selectively influences moral judgment and behavior through effects on harm aversion" on page 17433.
This article has been cited by other articles in PMC.
Other Sections▼
Decision making in the face of conflicting ethical demands has intrigued mankind for millennia. A long philosophical tradition has placed emphasis on reasoning, about utilitarian outcomes, for example, in such decisions (1). However, recent work in social neuroscience (2, 3) has identified brain circuits active during moral judgment that have been linked to prosocial emotions such as empathy, guilt, and pity. Using an innovative combination of behavioral research and pharmacological intervention, a study in this issue of PNAS (4) suggests a role for the neurotransmitter serotonin in the neural substrate of ethical decision making.
Neurobiology of escalated aggression and violence.
Miczek KA, de Almeida RM, Kravitz EA, Rissman EF, de Boer SF, Raine A.
Source
Department of Psychology, Tufts University, Medford, Massachusetts 02155, USA. [email protected]
Abstract
Psychopathological violence in criminals and intense aggression in fruit flies and rodents are studied with novel behavioral, neurobiological, and genetic approaches that characterize the escalation from adaptive aggression to violence. One goal is to delineate the type of aggressive behavior and its escalation with greater precision; second, the prefrontal cortex (PFC) and brainstem structures emerge as pivotal nodes in the limbic circuitry mediating escalated aggressive behavior. The neurochemical and molecular work focuses on the genes that enable invertebrate aggression in males and females and genes that are expressed or suppressed as a result of aggressive experiences in mammals. The fruitless gene, immediate early genes in discrete serotonin neurons, or sex chromosome genes identify sexually differentiated mechanisms for escalated aggression. Male, but not female, fruit flies establish hierarchical relationships in fights and learn from previous fighting experiences. By manipulating either the fruitless or transformer genes in the brains of male or female flies, patterns of aggression can be switched with males using female patterns and vice versa. Work with Sts or Sry genes suggests so far that other genes on the X chromosomes may have a more critical role in female mouse aggression. New data from feral rats point to the regulatory influences on mesocortical serotonin circuits in highly aggressive animals via feedback to autoreceptors and via GABAergic and glutamatergic inputs. Imaging data lead to the hypothesis that antisocial, violent, and psychopathic behavior may in part be attributable to impairments in some of the brain structures (dorsal and ventral PFC, amygdala, and angular gyrus) subserving moral cognition and emotion.
Retz W, Retz-Junginger P, Supprian T, Thome J, Rösler M.
Source
Institute for Forensic Psychology and Psychiatry, University of the Saarland, Homburg/Saar, Germany. [email protected]
Abstract
There is evidence that disturbances in central serotonin (5-HT) function have a role in impulsive aggression, violence, and criminality. A deletion/insertion polymorphism within the 5-HT transporter (5-HTT) promoter gene (5-HTT gene-linked polymorphic region, 5-HTTLPR) is thought to be associated with several psychopathological phenotypes related to disturbed impulse control, anxiety and depression. This study examined the association of the 5-HTTLPR with violent behavior in a sample of 153 male Caucasians referred for a forensic psychiatric examination. We found a significant excess of the short (s) allele and the s/s genotype in patients characterized by recurrent and overt physical violent behavior. This genetic variance explained 5% of the variance of violent behavior. When controlled for the impact of several psychopathologies related to violent behavior, this association was observed in individuals with a history of childhood attention deficit/hyperactivity disorder (ADHD)-related symptoms, but not presenting with personality disorder or increased impulsiveness. In conclusion, the results (i). suggest an association between serotonergic dysfunction and violent behavior, (ii). provide evidence for an-at least partial-genetic regulation of violent behavior in a subgroup of male offenders, and (iii). suggest a significant role for 5-HT transporter functionality for violent behavior.
The neuropsychopharmacology of criminality and aggression.
Lee R, Coccaro E.
Source
Clinical Neurosciences and Psychopharmacology Research Unit, Department of Psychiatry, University of Chicago, 5841 South Maryland Ave, MC 3077, Chicago, IL 60637, USA.
Abstract
Although the idea that aggression has biological components is not a new one, recent research in genetics, neuropsychopharmacology, and neuroimaging has helped clarify the biological contributions to aggression. Studies to date have focused on serotonergic function and impulsive aggression. Reduced levels of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) are associated with impulsive aggression. Pharmacochallenge studies have found decreased serotonergic responsiveness associated with impulsive aggression. Neuroimaging studies suggest a role for the prefrontal cortex, along with other regions of the brain, in the expression of aggression. Serotonin is not the only aspect of brain function implicated in impulsive aggression, and further work is being done on other neurotransmitters and neuropeptides.
Serotonin transporter genotype (5-HTTLPR) predicts utilitarian moral judgments.
Marsh AA, Crowe SL, Yu HH, Gorodetsky EK, Goldman D, Blair RJ.
Source
Department of Psychology, Georgetown University, Washington, District of Columbia, United States of America. [email protected]
Abstract
BACKGROUND:
The psychological and neurobiological processes underlying moral judgment have been the focus of extensive recent research. Here we show that serotonin transporter (5-HTTLPR) genotype predicts responses to moral dilemmas featuring foreseen harm to an innocent.
METHODOLOGY/PRINCIPAL FINDINGS:
Participants in this study judged the acceptability of actions that would unintentionally or intentionally harm an innocent victim in order to save others' lives. An analysis of variance revealed a genotype × scenario interaction, F(2, 63) = 4.52, p = .02. Results showed that, relative to long allele homozygotes (LL), carriers of the short (S) allele showed particular reluctance to endorse utilitarian actions resulting in foreseen harm to an innocent individual. LL genotype participants rated perpetrating unintentional harm as more acceptable (M = 4.98, SEM = 0.20) than did SL genotype participants (M = 4.65, SEM = 0.20) or SS genotype participants (M = 4.29, SEM = 0.30). No group differences in moral judgments were observed in response to scenarios featuring intentional harm.
CONCLUSIONS/SIGNIFICANCE:
The results indicate that inherited variants in a genetic polymorphism that influences serotonin neurotransmission influence utilitarian moral judgments as well. This finding is interpreted in light of evidence that the S allele is associated with elevated emotional responsiveness.
Who's flying the plane: serotonin levels, aggression and free will.
Siegel A, Douard J.
Source
Department of Neurology and Neuroscience, NJ Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
Abstract
The present paper addresses the philosophical problem raised by current causal neurochemical models of impulsive violence and aggression: to what extent can we hold violent criminal offenders responsible for their conduct if that conduct is the result of deterministic biochemical processes in the brain. This question is currently receiving a great deal of attention among neuroscientists, legal scholars and philosophers. We examine our current knowledge of neuroscience to assess the possible roles of deterministic factors which induce impulsive aggression, and the extent to which this behavior can be controlled by neural conditioning mechanisms. Neural conditioning mechanisms, we suggest, may underlie what we consider the basis of responsible (though not necessarily moral) behavior: the capacity to give and take reasons. The models we first examine are based in part upon the role played by the neurotransmitter, serotonin, in the regulation of violence and aggression. Collectively, these results would appear to argue in favor of the view that low brain serotonin levels induce impulsive aggression which overrides mechanisms related to rational decision making processes. We next present an account of responsibility as based on the capacity to exercise a certain kind of reason-responsive control over one's conduct. The problem with such accounts of responsibility, however, is that they fail to specify a neurobiological realization of such mechanisms of control. We present a neurobiological, and weakly determinist, framework for understanding how persons can exercise guidance control over their conduct. This framework is based upon classical conditioning of neurons in the prefrontal cortex that allow for a decision making mechanism that provides for prefrontal cortical control of the sites in the brain which express aggressive behavior that include the hypothalamus and midbrain periaqueductal gray. The authors support the view that, in many circumstances, neural conditioning mechanisms provide the basis for the control of human aggression in spite of the presence of brain serotonin levels that might otherwise favor the expression of impulsive aggressive behavior. Indeed if those neural conditioning mechanisms underlie the human capacity to exercise control, they may be the neural realization of reason-responsiveness generally.
Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17433-8. Epub 2010 Sep 27.
Serotonin selectively influences moral judgment and behavior through effects on harm aversion.
Crockett MJ, Clark L, Hauser MD, Robbins TW.
Source
Department of Experimental Psychology, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge CB2 3EB, United [email protected]
Abstract
Aversive emotional reactions to real or imagined social harms infuse moral judgment and motivate prosocial behavior. Here, we show that the neurotransmitter serotonin directly alters both moral judgment and behavior through increasing subjects' aversion to personally harming others. We enhanced serotonin in healthy volunteers with citalopram (a selective serotonin reuptake inhibitor) and contrasted its effects with both a pharmacological control treatment and a placebo on tests of moral judgment and behavior. We measured the drugs' effects on moral judgment in a set of moral 'dilemmas' pitting utilitarian outcomes (e.g., saving five lives) against highly aversive harmful actions (e.g., killing an innocent person). Enhancing serotonin made subjects more likely to judge harmful actions as forbidden, but only in cases where harms were emotionally salient. This harm-avoidant bias after citalopram was also evident in behavior during the ultimatum game, in which subjects decide to accept or reject fair or unfair monetary offers from another player. Rejecting unfair offers enforces a fairness norm but also harms the other player financially. Enhancing serotonin made subjects less likely to reject unfair offers. Furthermore, the prosocial effects of citalopram varied as a function of trait empathy. Individuals high in trait empathy showed stronger effects of citalopram on moral judgment and behavior than individuals low in trait empathy. Together, these findings provide unique evidence that serotonin could promote prosocial behavior by enhancing harm aversion, a prosocial sentiment that directly affects both moral judgment and moral behavior.
I fear for you: A role for serotonin in moral behavior
Heike Tosta and Andreas Meyer-Lindenbergb1
aClinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892; and
bDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, 68159 Mannheim, Germany
1To whom correspondence should be addressed. E-mail: [email protected].
Contributed by
Author contributions: H.T. and A.M.-L. wrote the paper.
See the article"Serotonin selectively influences moral judgment and behavior through effects on harm aversion" on page 17433.
This article has been cited by other articles in PMC.
Other Sections▼
Decision making in the face of conflicting ethical demands has intrigued mankind for millennia. A long philosophical tradition has placed emphasis on reasoning, about utilitarian outcomes, for example, in such decisions (1). However, recent work in social neuroscience (2, 3) has identified brain circuits active during moral judgment that have been linked to prosocial emotions such as empathy, guilt, and pity. Using an innovative combination of behavioral research and pharmacological intervention, a study in this issue of PNAS (4) suggests a role for the neurotransmitter serotonin in the neural substrate of ethical decision making.
Neurobiology of escalated aggression and violence.
Miczek KA, de Almeida RM, Kravitz EA, Rissman EF, de Boer SF, Raine A.
Source
Department of Psychology, Tufts University, Medford, Massachusetts 02155, USA. [email protected]
Abstract
Psychopathological violence in criminals and intense aggression in fruit flies and rodents are studied with novel behavioral, neurobiological, and genetic approaches that characterize the escalation from adaptive aggression to violence. One goal is to delineate the type of aggressive behavior and its escalation with greater precision; second, the prefrontal cortex (PFC) and brainstem structures emerge as pivotal nodes in the limbic circuitry mediating escalated aggressive behavior. The neurochemical and molecular work focuses on the genes that enable invertebrate aggression in males and females and genes that are expressed or suppressed as a result of aggressive experiences in mammals. The fruitless gene, immediate early genes in discrete serotonin neurons, or sex chromosome genes identify sexually differentiated mechanisms for escalated aggression. Male, but not female, fruit flies establish hierarchical relationships in fights and learn from previous fighting experiences. By manipulating either the fruitless or transformer genes in the brains of male or female flies, patterns of aggression can be switched with males using female patterns and vice versa. Work with Sts or Sry genes suggests so far that other genes on the X chromosomes may have a more critical role in female mouse aggression. New data from feral rats point to the regulatory influences on mesocortical serotonin circuits in highly aggressive animals via feedback to autoreceptors and via GABAergic and glutamatergic inputs. Imaging data lead to the hypothesis that antisocial, violent, and psychopathic behavior may in part be attributable to impairments in some of the brain structures (dorsal and ventral PFC, amygdala, and angular gyrus) subserving moral cognition and emotion.
