17 research outputs found
Peripheral blood and neuropsychological markers for the onset of action of antidepressant drugs in patients with Major Depressive Disorder
<p>Abstract</p> <p>Background</p> <p>In Major Depressive Disorder (MDD), treatment outcomes with currently available strategies are often disappointing. Therefore, it is sensible to develop new strategies to increase remission rates in acutely depressed patients. Many studies reported that true drug response can be observed within 14 days (early improvement) of antidepressant treatment. The identical time course of symptom amelioration after early improvement in patients treated with antidepressants of all classes or with placebo strongly suggests a common biological mechanism, which is not specific for a particular antidepressant medication. However, the biology underlying early improvement and final treatment response is not understood and there is no established biological marker as yet, which can predict treatment response for the individual patient before initiation or during the course of antidepressant treatment. Peripheral blood markers and executive functions are particularly promising candidates as markers for the onset of action and thus the prediction of final treatment outcome in MDD.</p> <p>Methods/Design</p> <p>The present paper presents the rationales, objectives and methods of a multi-centre study applying close-meshed repetitive measurements of peripheral blood and neuropsychological parameters in patients with MDD and healthy controls during a study period of eight weeks for the identification of biomarkers for the onset of antidepressants' action in patients with MDD. Peripheral blood parameters and depression severity are assessed in weekly intervals from baseline to week 8, executive performance in bi-weekly intervals. Patients are participating in a randomized controlled multi-level clinical trial, healthy controls are matched according to mean age, sex and general intelligence.</p> <p>Discussion</p> <p>This investigation will help to identify a biomarker or a set of biomarkers with decision-making quality in the treatment of MDD in order to increase the currently disappointing remission rates of antidepressant treatment.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00974155">NCT00974155</a></p
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Cerebral blood flow patterns underlying the differential impairment in category vs letter fluency in Alzheimer's disease
Verbal ¯uency tasks are used to assess language functioning in Alzheimer's disease (AD), and performance typically declines as the disease progresses. However, several studies have shown that Category Fluency performance (produce words from a category) declines faster than Letter Fluency performance (produce words beginning with a certain letter), which is not the case for other dementias. The purpose of this study was to determine if each of these two types of ¯uency tasks was associated with di€erent patterns of cerebral blood ¯ow abnormality in AD. A resting, Xenon-inhalation regional cerebral blood ¯ow measurement (133Xe rCBF) and neuropsychological evaluation was administered to 25 patients with probable AD and 24 healthy elderly controls. Stepwise regression using rCBF measures as predictor variables was used to predict Category and Letter Fluency performance, in both a combined group of patients and controls, and in the patient group alone. Correlations were also computed between rCBF variables and the di€erence between normatively corrected scores on each task for each subject, which characterized the extent of the discrepancy between them. In full sample regressions, both Category and Letter Fluency were predicted by education and the decline in left inferior parietal ¯ow, a focal AD-related de®cit. Additional variance in Category ¯uency, however, was predicted by global mean ¯ow, while additional variance in Letter Fluency was predicted by frontal ¯ow. Within the patient sample, in turn, the primary predictor of Category Fluency was mean ¯ow; the primary predictor of Letter Fluency was left-sided frontal ¯ow. Analysis of the ¯uency di€erence score revealed that relatively greater impairment of Category Fluency was associated with more typical, AD-related de®cits in posterior temporal and parietal perfusion. When the two were equivalently impaired, typical AD-related de®cits were accompanied by marked de®cits in frontal perfusion. These ®ndings are consistent with the underlying neuropsychology of these tasks, and suggest that Category Fluency's stronger association to the most typical CBF de®cits of AD account for its greater sensitivity to this disease. Letter Fluency de®cits, on the other hand, carry signi®cant information about the degree to which perfusion de®cits have spread to frontal cortex. # 1999 Elsevier Science Ltd. All rights reserved