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Context: The need for improved treatment options for patients with major depressive disorder (MDD) is critical. Faster-acting antidepressants and biomarkers that predict clinical response will facilitate treatment. Scopolamine produces rapid antidepressant effects and thus offers the opportunity to characterize potential biomarkers of treatment response within short periods. Objective: To determine if baseline brain activity when processing emotional information can predict treatment response to scopolamine in MDD. Design: A double-blind, placebo-controlled, crossover study together with repeated functional magnetic resonance imaging, acquired as participants performed faceidentity and face-emotion working memory tasks. Setting: National Institute of Mental Health Division of Intramural Research Programs. Participants: Fifteen currently depressed outpatients meeting DSM-IV criteria for recurrent MDD and 21 healthy participants, between 18 and 55 years of age. Main Outcome Measure: The magnitude of treatment response to scopolamine (percentage of change in the Montgomery-Asberg Depression Rating Scale score between study end and baseline) was correlated with blood oxygen level-dependent (BOLD) signal associated with each working memory component (encode, maintenance, and test) for both identity and emotion tasks. Treatment response also was correlated with change in BOLD response (scopolamine vs baseline). Baseline activity was compared between healthy and MDD groups. Results: Baseline BOLD response in the bilateral middle occipital cortex, selectivelyduring the stimulus - processing components of the emotion working memory task (no correlation during the identity task), correlated with treatment response magnitude. Change in BOLD response following scopolamine administration in overlapping areas in the middle occipital cortex while performing the same task conditions also correlated with clinical response. Healthy controls showed higher activity in the same visual regions than patients with MDD during baseline. Conclusion: These results implicate cholinergic and visual processing dysfunction in the pathophysiology of MDD and suggest that neural response in the visual cortex, selectively to emotional stimuli, may provide a useful biomarker for identifying patients who will respond favorably to scopolamine. Trial Registration: clinicaltrials.gov Identifier: NCT00055575 [ABSTRACT FROM AUTHOR]

: BackgroundThe changes in brain activity produced by repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex (PFC) remain unclear. We examined intensity-related changes in brain activity with positron emission tomography (PET) in normal volunteers during rTMS delivered to the left PFC.: MethodsIn 10 healthy volunteers, we delivered 1-Hz rTMS at randomized intensities over left PFC with a figure-eight coil. Intensities were 80, 90, 100, 110, and 120% of the right-hand muscle twitch threshold. Regional cerebral blood flow (rCBF) scans were acquired with H215O PET during rTMS at each intensity.: ResultsRepetitive transcranial magnetic stimulation intensity was inversely correlated with rCBF in the stimulated and contralateral PFC, ipsilateral medial temporal lobe, both parahippocampi, and posterior middle temporal gyri. Positive correlations of rCBF with intensity occurred in ipsilateral anterior cingulate, cerebellum, contralateral insula, primary auditory cortex, and somatosensory face area.: ConclusionsThe intensity-related inverse relationship between 1-Hz rTMS and prefrontal activity appears opposite to that seen with rTMS over the motor cortex in a companion study. Intensity-dependent increases in rCBF were seen in a number of distant cortical and subcortical areas with PFC rTMS, suggesting activation of left anterior cingulate, claustrum, and cerebellum. The regional differences in direction of rTMS effects and the greater activation of distant structures at higher intensities sug-gest the potential importance of higher-intensity prefrontal rTMS for therapeutic applications in neuropsychiatric patients. [Copyright &y& Elsevier]

: BackgroundRepetitive transcranial magnetic stimulation (rTMS) affects the excitability of the motor cortex and is thought to influence activity in other brain areas as well. We combined the administration of varying intensities of 1-Hz rTMS of the motor cortex with simultaneous positron emission tomography (PET) to delineate local and distant effects on brain activity.: MethodsTen healthy subjects received 1-Hz rTMS to the optimal position over motor cortex (M1) for producing a twitch in the right hand at 80, 90, 100, 110, and 120% of the twitch threshold, while regional cerebral blood flow (rCBF) was measured using H215O and PET. Repetitive transcranial magnetic stimulation (rTMS) was delivered in 75-pulse trains at each intensity every 10 min through a figure-eight coil. The regional relationship of stimulation intensity to normalized rCBF was assessed statistically.: ResultsIntensity-dependent rCBF increases were produced under the M1 stimulation site in ipsilateral primary auditory cortex, contralateral cerebellum, and bilateral putamen, insula, and red nucleus. Intensity-dependent reductions in rCBF occurred in contralateral frontal and parietal cortices and bilateral anterior cingulate gyrus and occipital cortex.: ConclusionsThis study demonstrates that 1-Hz rTMS delivered to the primary motor cortex (M1) produces intensity-dependent increases in brain activity locally and has associated effects in distant sites with known connections to M1. [Copyright &y& Elsevier]

Background: The objective of the current study was to examine possible clinical predictors of positive response to lamotrigine or gabapentin monotherapy in treatment-refractory affectively ill patients.Methods: Forty-five patients with treatment refractory bipolar (n = 35) or unipolar (n = 10) affective disorder participated in a clinical study evaluating six weeks of treatment with lamotrigine, gabapentin, or placebo monotherapy given in a double-blind, randomized fashion with two subsequent cross-overs to the other agents. Patients received daily mood ratings and weekly cross-sectional scales. Much or very much improved on the Clinical Global Impression scale modified for bipolar illness was considered a positive response. Degree of response was correlated with a number of baseline demographic and course of illness variables in a univariate analysis and then by linear regression.Results: Response rates to lamotrigine (51%) exceeded those to gabapentin (28%) and placebo (21%). A positive response to lamotrigine monotherapy was associated with a bipolar diagnosis; fewer hospitalizations; fewer prior medication trials; and male gender (of which the latter two variables survived logistic regression). For gabapentin, degree of response correlated with shorter duration of illness; younger age; and lower baseline weight (with the latter two surviving linear regression).Conclusions: In this highly treatment-refractory population, lamotrigine appeared most effective for male patients with fewer prior medication trials. Gabapentin monotherapy, although not better than placebo, appeared most effective in those with younger age and lower baseline weight. These preliminary data in a treatment refractory subgroup may help in the further definition of the range of clinical utility of these widely used anticonvulsants. [ABSTRACT FROM AUTHOR]