MESSAGE FROM THE EDITOR
Neurology: Violence at Home
O
ne of us (SLH) recently spent an evening with Jeremy Richman and Jennifer Hensel, parents of Avielle Richman, a sparkling eyed 6 year old who was one of 20 children, with 6 teachers, killed at the Sandy Hook school shooting last October. It is simply not possible to put into words the poignancy of this meeting with her grieving parents. Of the 20 children murdered, Avielle was the only one who was also an only child. Her father is a neuropharmacologist with a background in synaptic biology and developing drugs for neurologic diseases; her mother is an immunologist, and shares our interest in B-cells and their signaling pathways. We’ve also been stunned by the recent shotgun and stabbing deaths of Creighton University child neurologist Roger Brumback, murdered with his wife Mary in their home. Roger was an internationally renowned figure in child neurology and neuropathology, and among many accomplishments was founding Editor-in-Chief of the Journal of Child Neurology, a position that he continued to hold for more than a quarter-century. Mary was an attorney and Roger’s partner in many professional activities – including the Journal. They were inseparable and intensely devoted to each other. Roger and Mary leave a rich legacy, not only in the example of their lives but also in their children. There is yet another recent premature death in the neurosciences community. Autumn Klein, a neurologist at the University of Pittsburgh, an expert on women’s health issues including pregnancy related disorders, and the mother of a 6 year old daughter, was found dead in her home after her husband, the well-known neuroscientist Dr. Robert Ferrante, called 911 to report that she had suffered a stroke. The true cause of death was cyanide poisoning. At the time of this writing, Dr. Ferrante remains jailed without bond in Pittsburgh, pending a rescheduled preliminary hearing for 23 September 2013. In medicine, as in civilian life, we are accustomed to death and human tragedy. In these pages we’ve not infrequently eulogized the passing of our colleagues, remembering their impact on our profession.1 Our words are usually tempered with an understanding, implicit or explicit, that life is transient, and that its end is predestined. What is truly shocking, and enormously unsettling, is to witness a cluster in our own professional
community of premature, painful, and totally unnecessary deaths caused by meaningless violence. Violence is nothing new, of course and, as the Klein case clearly reminds us, guns are by no means the only source of violent deaths in the Western world or elsewhere. However, it is worth reviewing the numbers. As detailed in a recent Institute of Medicine (IOM) report on gun violence,2 in 2010 there were more than 105,000 injuries from firearms; about a third of these were fatal. Not all represent violent crimes, as about 60% of the total number resulted from attempted or successful suicide. Firearms are responsible for the vast majority of murders in the US, and each year an estimated 600,000 people are robbed at gunpoint. There are about as many firearms in the US as there are people; given this statistic, it is not surprising that firearm-related homicides are 20 fold higher in the US than in other industrialized nations. There has been vigorous debate over whether the widespread availability of guns in the US makes sense in the 21st century. Should the right to bear arms, cited in the second amendment of the US Constitution but originally intended to protect 18th C. militia, be interpreted as a carte blanche to extend firearm ownership to all citizens in 2013? Should this free-range policy include highly lethal semiautomatic weapons, the weapons of choice in many mass murders, unknown at the time of the Founding Fathers? Unfortunately, arguments on all sides are unlikely to be shaped by much data, given current governmental restrictions on research into firearmrelated violence. The Gun Control Act of 1968 prohibits the federal government from creating a database of gun owners, other Congressional action in 1996 bans the CDC from conducting firearm injury research and, amazingly, in 2011 a similar ban was enacted across the entire US Department of Health and Human Services (housing the NIH)! Clarifying the biology of maladaptive behaviors, and developing evidence to improve prevention, risk stratification, and treatment of violent behaviors, is a wonderful research priority for the neuroscience community. Associations with poor mental health, drug and alcohol use, impulsivity and aggressive behavior, recent active military service, stress and PTSD, among other associations, need C 2013 American Neurological Association V A5
ANNALS
of Neurology
to be better understood – are they causal, and through which molecular and neuronal pathways do they operate? Can we define the consequences of widespread violence (and glorification of the offenders) in the media, in movies, video games, and music? Defining the molecular events by which stressful events shape later aggressive behaviors is one area that is likely to be particularly informative. For example, in humans early (but not late) traumatic experiences can induce long-lasting epigenetic changes in an FK506 binding protein gene (FKBP5) in individuals who carry a particular intronic variant; this change increases the hormonal response to stress throughout life.3 A population of progesterone receptor-containing neurons in the ventromedial hypothalamus was very recently found to control sexual behaviors in male and female mice, but also aggression in males;4 other insights into the biology of aggressive behaviors are appearing regularly.5,6 We should be careful, of course, not to overextrapolate the significance of single gene analyses, artificial animal model paradigms, or imaging studies of network activity in humans to the complex social issues at hand.7 However, the power of behavioral neuroscience, and the very best tools of genomics, imaging and animal models, provides us with an unprecedented opportunity to address a problem in brain function that is arguably as important as any “traditional” neurologic disease. As clinical neuroscientists, we are uniquely qualified to provide real-life context and relevance to the artificial paradigms emerging from the laboratories. With advocacy, this issue might also become a priority for the Obama
A6
administration’s BRAIN initiative. The opportunity is great, as the problem of violence, and the social ills that surround and engender it, is certain to remain a big part of our world even when it is not at the doorstep of our neurologic community. Stephen L. Hauser, MD S Claiborne Johnston, MD, PhD Editors
References 1.
Hauser SL, Johnston SC. Fred Plum and the founding of the Annals of Neurology. Ann Neurol 68: A5, 2010.
2.
Leshner AI, Altevogt BM, Lee AF, McCoy MA, Kelley PW, Editors. Priorities for Research to Reduce the Threat of Firearm-Related Violence. Institute of Medicine and National Research Council of the National Academies. The National Academies Press. Washington, DC 2013.
3.
Klengel T et al. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nature Nsci. 16:33, 2013.
4.
Yang CF et al. Sexually dimorphic neurons in the ventromedial hypothalamus govern mating in both sexes and aggression in males. Cell 153:896, 2013.
5.
Audero E et al. Suppression of serotonin neuron firing increases aggression in mice. J Nsci 33:8678, 2013.
6.
Prince JEA et al. Kirrel3 is required for the coalescence of volmeronasal sensory neuron axons into glomeruli and for male-male aggression. Development 140:2398, 2013.
7.
For a highly critical, but entertaining, assessment of the fMRI literature, interested readers are referred to: Satel S and Lilienfield SO. Brainwashed. The Seductive Appeal of Mindless Neuroscience. Basic Books New York 2013.
DOI: 10.1002/ana.23979
Volume 74, No. 2
Neurology: Violence at Home
O
ne of us (SLH) recently spent an evening with Jeremy Richman and Jennifer Hensel, parents of Avielle Richman, a sparkling eyed 6 year old who was one of 20 children, with 6 teachers, killed at the Sandy Hook school shooting last October. It is simply not possible to put into words the poignancy of this meeting with her grieving parents. Of the 20 children murdered, Avielle was the only one who was also an only child. Her father is a neuropharmacologist with a background in synaptic biology and developing drugs for neurologic diseases; her mother is an immunologist, and shares our interest in B-cells and their signaling pathways. We’ve also been stunned by the recent shotgun and stabbing deaths of Creighton University child neurologist Roger Brumback, murdered with his wife Mary in their home. Roger was an internationally renowned figure in child neurology and neuropathology, and among many accomplishments was founding Editor-in-Chief of the Journal of Child Neurology, a position that he continued to hold for more than a quarter-century. Mary was an attorney and Roger’s partner in many professional activities – including the Journal. They were inseparable and intensely devoted to each other. Roger and Mary leave a rich legacy, not only in the example of their lives but also in their children. There is yet another recent premature death in the neurosciences community. Autumn Klein, a neurologist at the University of Pittsburgh, an expert on women’s health issues including pregnancy related disorders, and the mother of a 6 year old daughter, was found dead in her home after her husband, the well-known neuroscientist Dr. Robert Ferrante, called 911 to report that she had suffered a stroke. The true cause of death was cyanide poisoning. At the time of this writing, Dr. Ferrante remains jailed without bond in Pittsburgh, pending a rescheduled preliminary hearing for 23 September 2013. In medicine, as in civilian life, we are accustomed to death and human tragedy. In these pages we’ve not infrequently eulogized the passing of our colleagues, remembering their impact on our profession.1 Our words are usually tempered with an understanding, implicit or explicit, that life is transient, and that its end is predestined. What is truly shocking, and enormously unsettling, is to witness a cluster in our own professional
community of premature, painful, and totally unnecessary deaths caused by meaningless violence. Violence is nothing new, of course and, as the Klein case clearly reminds us, guns are by no means the only source of violent deaths in the Western world or elsewhere. However, it is worth reviewing the numbers. As detailed in a recent Institute of Medicine (IOM) report on gun violence,2 in 2010 there were more than 105,000 injuries from firearms; about a third of these were fatal. Not all represent violent crimes, as about 60% of the total number resulted from attempted or successful suicide. Firearms are responsible for the vast majority of murders in the US, and each year an estimated 600,000 people are robbed at gunpoint. There are about as many firearms in the US as there are people; given this statistic, it is not surprising that firearm-related homicides are 20 fold higher in the US than in other industrialized nations. There has been vigorous debate over whether the widespread availability of guns in the US makes sense in the 21st century. Should the right to bear arms, cited in the second amendment of the US Constitution but originally intended to protect 18th C. militia, be interpreted as a carte blanche to extend firearm ownership to all citizens in 2013? Should this free-range policy include highly lethal semiautomatic weapons, the weapons of choice in many mass murders, unknown at the time of the Founding Fathers? Unfortunately, arguments on all sides are unlikely to be shaped by much data, given current governmental restrictions on research into firearmrelated violence. The Gun Control Act of 1968 prohibits the federal government from creating a database of gun owners, other Congressional action in 1996 bans the CDC from conducting firearm injury research and, amazingly, in 2011 a similar ban was enacted across the entire US Department of Health and Human Services (housing the NIH)! Clarifying the biology of maladaptive behaviors, and developing evidence to improve prevention, risk stratification, and treatment of violent behaviors, is a wonderful research priority for the neuroscience community. Associations with poor mental health, drug and alcohol use, impulsivity and aggressive behavior, recent active military service, stress and PTSD, among other associations, need C 2013 American Neurological Association V A5
ANNALS
of Neurology
to be better understood – are they causal, and through which molecular and neuronal pathways do they operate? Can we define the consequences of widespread violence (and glorification of the offenders) in the media, in movies, video games, and music? Defining the molecular events by which stressful events shape later aggressive behaviors is one area that is likely to be particularly informative. For example, in humans early (but not late) traumatic experiences can induce long-lasting epigenetic changes in an FK506 binding protein gene (FKBP5) in individuals who carry a particular intronic variant; this change increases the hormonal response to stress throughout life.3 A population of progesterone receptor-containing neurons in the ventromedial hypothalamus was very recently found to control sexual behaviors in male and female mice, but also aggression in males;4 other insights into the biology of aggressive behaviors are appearing regularly.5,6 We should be careful, of course, not to overextrapolate the significance of single gene analyses, artificial animal model paradigms, or imaging studies of network activity in humans to the complex social issues at hand.7 However, the power of behavioral neuroscience, and the very best tools of genomics, imaging and animal models, provides us with an unprecedented opportunity to address a problem in brain function that is arguably as important as any “traditional” neurologic disease. As clinical neuroscientists, we are uniquely qualified to provide real-life context and relevance to the artificial paradigms emerging from the laboratories. With advocacy, this issue might also become a priority for the Obama
A6
administration’s BRAIN initiative. The opportunity is great, as the problem of violence, and the social ills that surround and engender it, is certain to remain a big part of our world even when it is not at the doorstep of our neurologic community. Stephen L. Hauser, MD S Claiborne Johnston, MD, PhD Editors
References 1.
Hauser SL, Johnston SC. Fred Plum and the founding of the Annals of Neurology. Ann Neurol 68: A5, 2010.
2.
Leshner AI, Altevogt BM, Lee AF, McCoy MA, Kelley PW, Editors. Priorities for Research to Reduce the Threat of Firearm-Related Violence. Institute of Medicine and National Research Council of the National Academies. The National Academies Press. Washington, DC 2013.
3.
Klengel T et al. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nature Nsci. 16:33, 2013.
4.
Yang CF et al. Sexually dimorphic neurons in the ventromedial hypothalamus govern mating in both sexes and aggression in males. Cell 153:896, 2013.
5.
Audero E et al. Suppression of serotonin neuron firing increases aggression in mice. J Nsci 33:8678, 2013.
6.
Prince JEA et al. Kirrel3 is required for the coalescence of volmeronasal sensory neuron axons into glomeruli and for male-male aggression. Development 140:2398, 2013.
7.
For a highly critical, but entertaining, assessment of the fMRI literature, interested readers are referred to: Satel S and Lilienfield SO. Brainwashed. The Seductive Appeal of Mindless Neuroscience. Basic Books New York 2013.
DOI: 10.1002/ana.23979
Volume 74, No. 2
