Biological psychiatry
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Biological psychiatry · Jun 2006
ReviewAttrition in randomized controlled clinical trials: methodological issues in psychopharmacology.
Attrition is a ubiquitous problem in randomized controlled clinical trials (RCT) of psychotropic agents that can cause biased estimates of the treatment effect, reduce statistical power, and restrict the generalizability of results. The extent of the problem of attrition in central nervous system (CNS) trials is considered here and its consequences are examined. The taxonomy of missingness mechanisms is then briefly reviewed in order to introduce issues underlying the choice of data analytic strategies appropriate for RCTs with various forms of incomplete data. ⋯ Mixed-effects models often provide a useful data analytic strategy for attrition as do the pattern-mixture and propensity adjustments. Finally, investigators are encouraged to consider asking participants, at each assessment session, the likelihood of attendance at the subsequent assessment session. This information can be used to eliminate some of the very obstacles that lead to attrition, and can be incorporated in data analyses to reduce bias, but it will not eliminate all attrition bias.
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Biological psychiatry · May 2006
Comparative StudyTNFalpha signaling in depression and anxiety: behavioral consequences of individual receptor targeting.
Increased serum levels of TNFalpha and other pro-inflammatory cytokines have been found in patients with major depression and several other psychiatric conditions. In rodents, these cytokines produce symptoms commonly referred to as "sickness behavior." Some of these, including reduced feeding and decreased social and exploratory behavior, are reminiscent of those seen in depressed patients. Interpretation of these effects is complicated by the malaise caused by acute injections of pro-inflammatory cytokines, however. Thus, it is unclear whether cytokines are involved in the etiology of depressive symptoms. ⋯ These results are consistent with the hypothesis that TNFalpha can induce depression-like symptoms even in the absence of malaise and demonstrate that both receptor subtypes can be involved in this response.
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Biological psychiatry · Mar 2006
Evidence for impaired cortical inhibition in patients with unipolar major depression.
Several lines of evidence suggest that central cortical inhibitory mechanisms, especially associated with gamma-aminobutyric acid (GABA) neurotransmission, may play a role in the pathophysiology of major depression. Transcranial magnetic stimulation is a useful tool for investigating central cortical inhibitory mechanisms associated with GABAergic neurotransmission in psychiatric and neurological disorders. ⋯ This study provides evidence of reduced GABAergic tone and motor threshold asymmetry in patients with major depression.
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Biological psychiatry · Jan 2006
Comparative StudyERK phosphorylation and FosB expression are associated with L-DOPA-induced dyskinesia in hemiparkinsonian mice.
The dopamine precursor 3,4-dihydroxyphenyl-L-alanine (L-DOPA) is currently the most efficacious noninvasive therapy for Parkinson's disease. A major complication of this therapy, however, is the appearance of the abnormal involuntary movements known as dyskinesias. We have developed a model of L-DOPA-induced dyskinesias in mice that reproduces the main clinical features of dyskinesia in humans. ⋯ This model provides a system in which genetic manipulation of individual genes can be used to elucidate the molecular mechanisms responsible for the development and expression of dyskinesia.
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Biological psychiatry · Nov 2005
Reduced anterior cingulate glutamate in pediatric major depression: a magnetic resonance spectroscopy study.
Anterior cingulate cortex has been implicated in the pathogenesis of major depressive disorder (MDD). With single voxel proton magnetic resonance spectroscopy, we reported reductions in anterior cingulate glutamatergic concentrations (grouped value of glutamate and glutamine) in 14 pediatric MDD patients versus 14 case-matched healthy control subjects. These changes might reflect a change in glutamate, glutamine, or their combination. ⋯ These findings provide confirmatory evidence of anterior cingulate glutamate alterations in pediatric MDD.