Fluoxetine increases relative metabolic rate in prefrontal cortex in impulsive aggression.
ABSTRACT Impulsive aggressive personality disordered patients have been shown to have decreased relative glucose metabolism in orbito-frontal cortex and anterior cingulate gyrus compared with normal subjects. In addition, patients with impulsive aggression have an attenuation of symptoms with selective serotonin reuptake inhibitor (SSRI) treatment.
The goals of the present study were to attempt to replicate the finding of improvement in impulsive aggression in borderline personality disorder with SSRIs and to investigate the specific cortical areas modified by medication, which might underlie the observed clinical improvement using (18)FDG-PET.
Ten impulsive aggressive patients with borderline personality disorder were imaged with (18)F-deoxyglucose positron emission tomography at baseline and after receiving fluoxetine at 20 mg/day for 12 weeks. Anatomical MRIs were coregistered to PET and relative metabolic rates were obtained in 39 Brodmann areas.
Brodmann areas 11 and 12 in the orbito-frontal cortex showed significant increases in relative metabolic rate. Significant clinical improvement was also observed as assessed by the Overt Aggression Scale-Modified.
These changes are consistent with a normalizing effect of fluoxetine on prefrontal cortex metabolism in impulsive aggressive disorder.
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ABSTRACT: Criminal behaviour and violence are increasingly viewed as worldwide public health problems. A growing body of knowledge shows that criminal behaviour has a neurobiological basis, and this has intensified judicial interest in the potential application of neuroscience to criminal law. It also gives rise to important questions. What are the implications of such application for predicting future criminal behaviour and protecting society? Can it be used to prevent violence? And what are the implications for the way offenders are punished?Nature Reviews Neuroscience 12/2013; · 31.38 Impact Factor
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ABSTRACT: Summary form only given, as follows. Pulsed power driven flash radiographic sources have been used for over thirty years to interrogate the interior mass distribution evolution in dynamic objects. A wide variety of drivers and electron beam diodes have been developed for this purpose, providing a spectrum of test capabilities in voltage (penetration capability), dose (detected signal level), and spot size (spatial resolution) in sub-hundred-nanosecond pulses (motion freeze). Recent efforts by a multiorganizational team have been directed toward understanding the underlying physical mechanisms governing the performance of radiographic sources. Industrial tapered anode, paraxial gas transport, rod-pinch, and magnetically immersed diodes have been studied. Modern numerical simulation codes (Fluid/Particle-in-Cell/Monte Carlo) have been developed and are being compared to experimental data from these different radiographic diodes on a variety of pulsed power drivers. This coupled experimental-theoretical approach is providing insight into the fundamental limits of different source architectures and gives confidence in the design of future radiographic systems. For example, led by these new insights the radiographic performance (dose/spot size) of an existing accelerator was increased by a factor of seven. Future pulsed power driven radiographic system options are also discussedIEEE International Conference on Plasma Science 01/2000;
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ABSTRACT: The termination of serotonin (5-hydroxytryptamine, 5-HT) neurotransmission is regulated by its uptake by the 5-HT transporter (5-HTT), as well as its degradation by monoamine oxidase (MAO)-A. MAO-A deficiency results in a wide set of behavioral alterations, including perseverative behaviors and social deficits. These anomalies are likely related to 5-HTergic homeostatic imbalances; however, the role of 5-HTT in these abnormalities remains unclear. To ascertain the role of 5-HTT in the behavioral anomalies associated to MAO-A deficiency, we tested the behavioral effects of its blocker fluoxetine on perseverative, social and aggressive behaviors in transgenic animals with hypomorphic or null-allele MAO-A mutations. Acute treatment with the 5-HTT blocker fluoxetine (10 mg/kg, i.p.) reduced aggressive behavior in MAO-A knockout (KO) mice and social deficits in hypomorphic MAO-A(Neo) mice. Furthermore, this treatment also reduced perseverative responses (including marble burying and water mist-induced grooming) in both MAO-A mutant genotypes. Both MAO-A mutant lines displayed significant reductions in 5-HTT expression across the prefrontal cortex, amygdala and striatum, as quantified by immunohistochemical detection; however, the down-regulation of 5-HTT in MAO-A(Neo) mice was more pervasive and widespread than in their KO counterparts, possibly indicating a greater ability of the hypomorphic line to enact compensatory mechanisms with respect to 5-HT homeostasis. Collectively, these findings suggest that the behavioral deficits associated with low MAO-A activity may reflect developmental alterations of 5-HTT within 5-HTergic neurons. Furthermore, the translational implications of our results highlight 5-HT reuptake inhibition as an interesting approach for the control of aggressive outbursts in MAO-A deficient individuals.Journal of Psychiatric Research 05/2014; · 4.09 Impact Factor