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Chronic administration of antipsychotic drugs has been linked to structural brain changes observed in patients with schizophrenia. Recent MRI studies have shown rapid changes in regional brain volume following just a single dose of these drugs. However, it is not clear if these changes represent real volume changes or are artefacts ("apparent" volume changes) due to drug-induced physiological changes, such as increased cerebral blood flow (CBF). To address this, we examined the effects of a single, clinical dose of three commonly prescribed antipsychotics on quantitative measures of T1 and regional blood flow of the healthy human brain. Males (n = 42) were randomly assigned to one of two parallel groups in a double-blind, placebo-controlled, randomized, three-period cross-over study design. One group received a single oral dose of either 0.5 or 2 mg of risperidone or placebo during each visit. The other received olanzapine (7.5 mg), haloperidol (3 mg), or placebo. MR measures of quantitative T1, CBF, and T1-weighted images were acquired at the estimated peak plasma concentration of the drug. All three drugs caused localized increases in striatal blood flow, although drug and region specific effects were also apparent. In contrast, all assessments of T1 and brain volume remained stable across sessions, even in those areas experiencing large changes in CBF. This illustrates that a single clinically relevant oral dose of an antipsychotic has no detectable acute effect on T1 in healthy volunteers. We further provide a methodology for applying quantitative imaging methods to assess the acute effects of other compounds on structural MRI metrics. Hum Brain Mapp 39:319-331, 2018. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background and Purpose: Major depressive disorder (MDD) presents with extensive clinical heterogeneity. In particular, overlap with anxiety symptoms is common during depressive episodes and as a comorbid disorder. The aim of this study was to test for morphological brain differences between patients having a history of recurrent MDD with, and without, anxiety symptoms (MDD+A and MDD-A)., Methods: T1-weighted magnetic resonance images of age-, gender- and ethnically matched groups of MDD+A (n= 49) and MDD-A (n= 96) patients were available for voxel-based morphometry analysis of regional gray matter (GM) volume differences. Brain structural images were also contrasted with 183 age-, gender-, and ethnicity-matched healthy controls., Results: MDD+A patients had greater GM volume (P(FWE) = .002) than MDD-A patients in the right temporal cortex extending from the mid-posterior superior temporal gyrus into the posterior middle and inferior temporal gyrus. The MDD patients together showed lower GM volume than healthy controls in the superior parietal lobe., Conclusions: Regional volume differences in patients are consistent with altered neuronal or glial microstructure. The temporolateral cortical differences distinguishing the 2 MDD groups suggest neurobiological differences related to the expression of anxiety symptoms in depression and provide further rationale for considering these groups independently for therapeutic outcomes studies., (© 2010 by the American Society of Neuroimaging.)

The objective of this study was to characterize the performance of each recruitment center in multicenter clinical trials and to provide criteria to discriminate between informative and noninformative centers using the signal detection approach. Data were derived from the GlaxoSmithKline Clinical Trial database on paroxetine and bupropion, totaling 4,016 subjects with major depressive disorders (MDDs) across nine trials. The probability of observing clinically relevant difference of active treatment from placebo was estimated in each center as a function of the placebo Hamilton Depression Rating Scale (HAMD-17) scores at baseline and at week 8. The center's performance was defined using the posterior probability (PP) of detecting a signal of a treatment effect. Only 60% of the centers were classified as informative. In these centers, the signal of treatment effect increased by approximately 80%. The signal detection approach appears to be a useful methodology to rank the performance of recruitment centers and to classify each center as informative or not in respect of detection of clinically relevant signals of efficacy. A further analysis indicated that a minimal sample of four subjects is required in order to predict the typical placebo response in each center.