Remote warfare – Buzzword or Buzzkill?

The debates around remote warfare have grown significantly over the last decade, leading to the term acquiring a certain buzz in the media, think-tank, and policy discourse. The lack of any serious attempt to reflect and take stock of this body of scholarship informs the scope of this special issue, in general, and of this article in particular. This paper addresses this former gap and, in doing so, serves a threefold purpose. First, to provide a state-of-the-art review of this emerging debate. Second, to both categorise what properties make a buzzword and to make the case for why existing remote warfare scholarship should be approached in this way. Third, to introduce how the various contributions to this special issue extend the debate’s conceptual, theoretical, and empirical parameters

Brain monoamine oxidase A activity predicts trait aggression

The genetic deletion of monoamine oxidase A (MAO A), an enzyme that breaks down the monoamine neurotransmitters norepinephrine, serotonin, and dopamine, produces aggressive phenotypes across species. Therefore, a common polymorphism in the MAO A gene (MAOA, Mendelian Inheritance in Men database number 309850, referred to as high or low based on transcription in non-neuronal cells) has been investigated in a number of externalizing behavioral and clinical phenotypes. These studies provide evidence linking the low MAOA genotype and violent behavior but only through interaction with severe environmental stressors during childhood. Here, we hypothesized that in healthy adult males the gene product of MAO A in the brain, rather than the gene per se, would be associated with regulating the concentration of brain amines involved in trait aggression. Brain MAO A activity was measured in vivo in healthy nonsmoking men with positron emission tomography using a radioligand specific for MAO A (clorgyline labeled with carbon 11). Trait aggression was measured with the multidimensional personality questionnaire (MPQ). Here we report for the first time that brain MAO A correlates inversely with the MPQ trait measure of aggression (but not with other personality traits) such that the lower the MAO A activity in cortical and subcortical brain regions, the higher the self-reported aggression (in both MAOA genotype groups) contributing to more than one-third of the variability. Because trait aggression is a measure used to predict antisocial behavior, these results underscore the relevance of MAO A as a neurochemical substrate of aberrant aggression

Gene by Disease Interaction on Orbitofrontal Gray Matter in Cocaine Addiction

Chronic cocaine use has been associated with structural deficits in brain regions having dopamine receptive neurons. However, the concomitant use of other drugs and common genetic variability in monoamine regulation present additional structural variability. We therefore examined variations in gray matter volume (GMV) as a function of lifetime drug use and the monoamine oxidase A (MAOA) genotype in cocaine use disorders (CUD) and healthy controls

Clinical Trials in Head Injury

Traumatic brain injury (TBI) remains a major public health problem globally. In the United States the incidence of closed head injuries admitted to hospitals is conservatively estimated to be 200 per 100,000 population, and the incidence of penetrating head injury is estimated to be 12 per 100,000, the highest of any developed country in the world. This yields an approximate number of 500,000 new cases each year, a sizeable proportion of which demonstrate signficant long-term disabilities. Unfortunately, there is a paucity of proven therapies for this disease. For a variety of reasons, clinical trials for this condition have been difficult to design and perform. Despite promising pre-clinical data, most of the trials that have been performed in recent years have failed to demonstrate any significant improvement in outcomes. The reasons for these failures have not always been apparent and any insights gained were not always shared. It was therefore feared that we were running the risk of repeating our mistakes. Recognizing the importance of TBI, the National Institute of Neurological Disorders and Stroke (NINDS) sponsored a workshop that brought together experts from clinical, research, and pharmaceutical backgrounds. This workshop proved to be very informative and yielded many insights into previous and future TBI trials. This paper is an attempt to summarize the key points made at the workshop. It is hoped that these lessons will enhance the planning and design of future efforts in this important field of research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63185/1/089771502753754037.pd

An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology

BACKGROUND: In humans, serotonin has typically been investigated as a neurotransmitter. However, serotonin also functions as a hormone across animal phyla, including those lacking an organized central nervous system. This hormonal action allows serotonin to have physiological consequences in systems outside the central nervous system. Fluctuations in estrogen levels over the lifespan and during ovarian cycles cause predictable changes in serotonin systems in female mammals. DISCUSSION: We hypothesize that some of the physiological effects attributed to estrogen may be a consequence of estrogen-related changes in serotonin efficacy and receptor distribution. Here, we integrate data from endocrinology, molecular biology, neuroscience, and epidemiology to propose that serotonin may mediate the effects of estrogen. In the central nervous system, estrogen influences pain transmission, headache, dizziness, nausea, and depression, all of which are known to be a consequence of serotonergic signaling. Outside of the central nervous system, estrogen produces changes in bone density, vascular function, and immune cell self-recognition and activation that are consistent with serotonin's effects. For breast cancer risk, our hypothesis predicts heretofore unexplained observations of the opposing effects of obesity pre- and post-menopause and the increase following treatment with hormone replacement therapy using medroxyprogesterone. SUMMARY: Serotonergic mediation of estrogen has important clinical implications and warrants further evaluation

Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders

There is a long-standing paradox that N-methyl-D-aspartate receptors (NMDARs) can both promote neuronal health and kill neurons. Recent studies show that NMDAR-induced responses depend on the receptor location: stimulation of synaptic NMDARs, acting primarily through nuclear Ca(2+) signaling, leads to the build-up of a neuroprotective ‘shield’, whereas stimulation of extrasynaptic NMDARs promotes cell death. These differences result from the activation of distinct genomic programmes and opposing actions on intracellular signalling pathways. Perturbations in the balance between synaptic and extrasynaptic NMDAR activity contribute to neuronal dysfunction in acute ischaemia and Huntington’s disease and could be a common theme in the aetiology of neurodegenerative diseases. Neuroprotective therapies should aim to both enhance the effect of synaptic activity and disrupt extrasynaptic NMDAR-dependent death signalling