Biological psychiatry
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Biological psychiatry · Mar 2011
Fear extinction in traumatized civilians with posttraumatic stress disorder: relation to symptom severity.
The symptoms of posttraumatic stress disorder (PTSD) can be explained, at least in part, as an inability to inhibit learned fear during conditions of safety. Our group has shown that fear inhibition is impaired in both combat and civilian PTSD populations. On the basis of our earlier findings, we employed an established fear extinction paradigm to further explore fear dysregulation in a civilian traumatized population. ⋯ These results suggest that PTSD is associated with enhanced fear learning and a greater "fear load" to extinguish after conditioned fear is acquired.
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Biological psychiatry · Mar 2011
Elevated functional connectivity along a corticostriatal loop and the mechanism of auditory/verbal hallucinations in patients with schizophrenia.
Higher levels of inter-region functional coordination can facilitate emergence of neural activity as conscious percepts. We consequently tested the hypothesis that auditory/verbal hallucinations (AVHs) arise from elevated functional coordination within a speech processing network. ⋯ These findings suggest that higher levels of functional coordination intrinsic to a corticostriatal loop comprise a causal factor leading to AVHs in schizophrenia.
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Biological psychiatry · Feb 2011
Cocaine-insensitive dopamine transporters with intact substrate transport produced by self-administration.
Psychomotor stimulant drugs such as cocaine and amphetamine activate brain dopamine (DA) neurotransmission and support self-administration in humans and laboratory animals. Cocaine amplifies DA signaling by blocking the DA transporter (DAT), and this has been described as the most important mechanism underlying cocaine's reinforcing effects. Amphetamine has the added mechanism of reverse transport of intracellular DA through the DAT. ⋯ Here, we, for the first time, demonstrate an in vivo, pharmacologically induced alteration in the sensitivity of the DAT to cocaine that is specific to cocaine, spares DAT and substrate/releaser interactions, and is independent of maximal rate of DA uptake (V(max)).
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Biological psychiatry · Feb 2011
Sigma receptor agonists: receptor binding and effects on mesolimbic dopamine neurotransmission assessed by microdialysis.
Subtypes of sigma (σ) receptors, σ₁ and σ₂, can be pharmacologically distinguished, and each may be involved in substance-abuse disorders. σ-Receptor antagonists block cocaine place conditioning and σ-receptor agonists are self-administered in rats that previously self-administered cocaine. Self-administration of abused drugs has been related to increased dopamine (DA) neurotransmission, however, σ-receptor agonist effects on mesolimbic DA are not fully characterized. ⋯ σ-Receptor agonists stimulated DA in a brain area critical for reinforcing effects of cocaine. DTG effects on DA appear to be mediated by σ₂-receptors rather than σ₁-receptors. However, DA stimulation by cocaine or PRE-084 does not likely involve σ-receptors. The relatively low potency on DA transmission of the selective σ₁-receptor agonist, PRE-084, and its previously reported potent reinforcing effects, suggest a dopamine-independent reinforcing pathway that may contribute to substance-abuse disorders.
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Biological psychiatry · Jan 2011
ReviewNovel approaches to the study of postmortem brain in psychiatric illness: old limitations and new challenges.
Biological psychiatry has made significant advances through the development of postmortem studies, animal models, and studies with living humans. Although these approaches each have advantages and disadvantages, the postmortem field is undergoing a significant shift toward more complex and informative methodologies. ⋯ In the second part of the article, we discuss the innovative approaches being used for postmortem studies, including laser capture microdissection and subcellular fractionization. These techniques will permit scientists working in the postmortem field to ask and answer the largest possible questions, providing new targets for drug discovery and improved treatments for severe mental illness.