Biological psychiatry
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Biological psychiatry · Sep 2009
Randomized Controlled TrialInflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity.
Inflammatory cytokines are implicated in the pathophysiology of depression. In rodents, systemically administered inflammatory cytokines induce depression-like behavior. Similarly in humans, therapeutic interferon-alpha induces clinical depression in a third of patients. Conversely, patients with depression also show elevated pro-inflammatory cytokines. ⋯ Inflammation-associated mood deterioration is reflected in changes in sACC activity and functional connectivity during evoked responses to emotional stimuli. Peripheral cytokines modulate this mood-dependent sACC connectivity, suggesting a common pathophysiological basis for major depressive disorder and sickness-associated mood change and depression.
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Biological psychiatry · Jul 2009
Decreased neurokinin-1 (substance P) receptor binding in patients with panic disorder: positron emission tomographic study with [18F]SPA-RQ.
Positron emission tomography (PET) can localize and quantify neurokinin-1 (NK(1)) receptors in brain using the nonpeptide antagonist radioligand, [(18)F]SPA-RQ. We sought to determine if patients with panic disorder have altered density of NK(1) receptors in brain because of their history of recurrent panic attacks. We also sought to determine if a drug-induced panic attack releases substance P in brain, as measured by decreased binding of [(18)F]SPA-RQ. ⋯ Although induction of a panic attack has no significant effect on [(18)F]SPA-RQ binding to NK(1) receptors, patients with panic disorder have widespread reduction of NK(1) receptor binding in brain.
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Biological psychiatry · Jun 2009
Co-administration of a D-amino acid oxidase inhibitor potentiates the efficacy of D-serine in attenuating prepulse inhibition deficits after administration of dizocilpine.
D-Serine, an endogenous agonist of the N-methyl-D-aspartate (NMDA) receptors, is effective in the treatment of schizophrenia. However, orally administered D-serine is metabolized substantially by D-amino acid oxidase (DAAO), diminishing its oral bioavailability. In this study, we examined the effects of oral D-serine administration with or without a DAAO inhibitor, 5-chloro-benzo[d]isoxazol-3-ol (CBIO), on the prepulse inhibition (PPI) deficits after administration of the NMDA receptor antagonist dizocilpine. ⋯ These findings suggest that coadministration of CBIO significantly enhanced the efficacy of D-serine in attenuating PPI deficits by administration of dizocilpine. Therefore, coadministration of D-serine and a DAAO inhibitor has therapeutic potential for the treatment of schizophrenia.
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Biological psychiatry · Jun 2009
Blood-based microcirculation markers in Alzheimer's disease-diagnostic value of midregional pro-atrial natriuretic peptide/C-terminal endothelin-1 precursor fragment ratio.
There is evidence that vascular factors contribute substantially to Alzheimer's disease (AD). We have developed assays to reliably detect the circulation and microcirculation regulating factors C-terminal endothelin-1 precursor fragment (CT-proET-1), midregional pro-adrenomedullin (MR-proADM), and midregional pro-atrial natriuretic peptide (MR-proANP). We hypothesized that this set of blood-based (micro)circulation parameters is altered in AD. ⋯ This indicates altered expression of microcirculation parameters and supports the hypothesis of a disturbed microvascular homeostasis in AD. We generated the hypothesis that the vasodilator/vasoconstrictor ratios hold promise as a diagnostic marker of AD. The best diagnostic accuracy was achieved for the MR-proANP/CT-proET-1 ratio.
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Biological psychiatry · May 2009
Pattern of intake and drug craving predict the development of cocaine addiction-like behavior in rats.
Clinical observations suggest that cocaine addiction often emerges with new patterns of use. Whether these changes are a cause of addiction or its consequence is unknown. We investigated whether the development of an addiction-like behavior in the rat is associated with the pattern of cocaine intake and with cocaine craving, a major feature of cocaine addiction. ⋯ Our results identify key predictors of cocaine addiction-intensified pattern of drug use and high drug-induced craving-that may help in the identification of subjects at risk for subsequent development of severe cocaine addiction.