Biological psychiatry
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Biological psychiatry · Jul 2012
Increasing histone acetylation in the hippocampus-infralimbic network enhances fear extinction.
A key finding from recent studies of epigenetic mechanisms of memory is that increasing histone acetylation after a learning experience enhances memory consolidation. This has been demonstrated in several preparations, but little is known about whether excitatory and inhibitory memories are equally sensitive to drugs that promote histone acetylation and how transcriptional changes in the hippocampal-medial prefrontal cortex network contribute to these drug effects. ⋯ These studies show that the memory modulating ability of drugs that enhance acetylation is sensitive to a variety of behavioral and molecular conditions. We further identify transcriptional changes in the hippocampal-infralimbic circuit associated with extinction enhancements induced by the histone deacetylase inhibitor NaB.
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Biological psychiatry · Jun 2012
Randomized Controlled TrialReplication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial.
Currently, no pharmacological treatments for bipolar depression exist that exert rapid (within hours) antidepressant or antisuicidal effects. We previously reported that intravenous administration of the N-methyl-D-aspartate antagonist ketamine produced rapid antidepressant effects in patients with treatment-resistant bipolar depression. The present study sought to replicate this finding in an independent sample. ⋯ This study replicated our previous finding that patients with bipolar depression who received a single ketamine infusion experienced a rapid and robust antidepressant response. In addition, we found that ketamine rapidly improved suicidal ideation in these patients.
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Biological psychiatry · May 2012
Depressive symptoms in mild cognitive impairment predict greater atrophy in Alzheimer's disease-related regions.
Depression has been associated with higher conversion rates from mild cognitive impairment (MCI) to Alzheimer's disease (AD) and may be a marker of prodromal AD that can be used to identify individuals with MCI who are most likely to progress to AD. Thus, we examined the neuroanatomical changes associated with depressive symptoms in MCI. ⋯ Depressive symptoms were associated with greater atrophy in AD-affected regions, increased cognitive decline, and higher rates of conversion to AD. Depression in individuals with MCI may be associated with underlying neuropathological changes, including prodromal AD, and may be a potentially useful clinical marker in identifying MCI patients who are most likely to progress to AD.
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Biological psychiatry · May 2012
Regional expansion of hypometabolism in Alzheimer's disease follows amyloid deposition with temporal delay.
Cross-sectional imaging studies suggest that patterns of hypometabolism (measured by [(18)F] fluorodeoxyglucose positron emission tomography [FDG-PET]) and amyloid deposition (measured by [(11)C] Pittsburgh Compound B [PiB]- PET) in Alzheimer's disease (AD) show some overlap with each other. This indicates that neuronal dysfunction might spread within the anatomical pattern of amyloid deposition. The aim of this study was to examine longitudinal regional patterns of amyloid deposition and hypometabolism in the same population of mild AD subjects and to establish their regional relationship to each other. ⋯ Longitudinal regional expansion of cerebral hypometabolism, as a measure of neuronal dysfunction in AD, seems to follow the anatomical pattern of amyloid deposition with temporal delay. This indicates that amyloid-based disruption of neuronal integrity might contribute to the regional expansion of neuronal dysfunction.
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Biological psychiatry · Apr 2012
β-arrestin2 regulates cannabinoid CB1 receptor signaling and adaptation in a central nervous system region-dependent manner.
Cannabinoid CB(1) receptors (CB(1)Rs) mediate the effects of ▵(9)-tetrahydrocannabinol (THC), the psychoactive component in marijuana. Repeated THC administration produces tolerance and dependence, which limit therapeutic development. Moreover, THC produces motor and psychoactive side effects. β-arrestin2 mediates receptor desensitization, internalization, and signaling, but its role in these CB(1)R effects and receptor regulation is unclear. ⋯ β-arrestin2 regulation of CB(1)R signaling following acute and repeated THC administration was region-specific, and results suggest that multiple, overlapping mechanisms regulate CB(1)Rs. The observations that βarr2-KO mice display enhanced antinociceptive responses to acute THC and decreased tolerance to the antinociceptive effects of the drug, yet enhanced tolerance to catalepsy, suggest that development of cannabinoid drugs that minimize CB(1)R interactions with β-arrestin2 might produce improved cannabinoid analgesics with reduced motor suppression.