The investigation of cerebral metabolic rate of glucose (CMRGlu) at baseline and during specific tasks previously required separate scans with the drawback of high intrasubject variability. We aimed to validate a novel approach to assessing baseline glucose metabolism and task-specific changes in a single measurement with a constant infusion of 18 F-FDG. Methods: Fifteen healthy subjects underwent two PET measurements with arterial blood sampling. As a reference, baseline CMRGlu was quantified from a 60-min scan after 18 F-FDG bolus application using the Patlak plot (eyes closed). For the other scan, a constant radioligand infusion was applied for 95 min, during which the subjects opened their eyes at 10-20 min and 60-70 min and tapped their right thumb to their fingers at 35-45 min and 85-95 min. The constant-infusion scan was quantified in two steps. First, the general linear model was used to fit regional time-activity curves with regressors for baseline metabolism, task-specific changes for the eyes-open and finger-tapping conditions, and movement parameters. Second, the Patlak plot was used for quantification of CMRGlu. Multiplication of the baseline regressor by β-values from the general linear model yielded regionally specific time-activity curves for baseline metabolism. Further, taskspecific changes in metabolism are directly proportional to changes in the slope of the time-activity curve and hence to changes in CMRGlu. Results: Baseline CMRGlu from the constant-infusion scan matched that from the bolus application (test-retest variability, 1.1% ± 24.7%), which was not the case for a previously suggested approach (variability, −39.9% ± 25.2%, P , 0.001). Task-specific CMRGlu increased in the primary visual and motor cortices for eyes open and finger tapping, respectively (P , 0.05, familywise errorcorrected), with absolute changes of up to 2.1 μmol/100 g/min and 6.3% relative to baseline. For eyes open, a decreased CMRGlu was observed in default-mode regions (P , 0.05, familywise errorcorrected). CMRGlu quantified with venous blood samples (n 5 6) showed excellent agreement with results obtained from arterial samples (r . 0.99). Conclusion: Baseline glucose metabolism and taskspecific changes can be quantified in a single measurement with constant infusion of 18 F-FDG and venous blood sampling. The high sensitivity and regional specificity of the approach offer novel possibilities for functional and multimodal brain imaging.
Objectives Clinical variables were investigated in the ‘treatment resistant depression ( TRD )‐ III ’ sample to replicate earlier findings by the European research consortium ‘Group for the Study of Resistant Depression’ ( GSRD ) and enable cross‐sample prediction of treatment outcome in TRD . Experimental procedures TRD was defined by a Montgomery and Åsberg Depression Rating Scale ( MADRS ) score ≥22 after at least two antidepressive trials. Response was defined by a decline in MADRS score by ≥50% and below a threshold of 22. Logistic regression was applied to replicate predictors for TRD among 16 clinical variables in 916 patients. Elastic net regression was applied for prediction of treatment outcome. Results Symptom severity (odds ratio ( OR ) = 3.31), psychotic symptoms ( OR = 2.52), suicidal risk ( OR = 1.74), generalized anxiety disorder ( OR = 1.68), inpatient status ( OR = 1.65), higher number of antidepressants administered previously ( OR = 1.23), and lifetime depressive episodes ( OR = 1.15) as well as longer duration of the current episode ( OR = 1.022) increased the risk of TRD . Prediction of TRD reached an accuracy of 0.86 in the independent validation set, TRD ‐I. Conclusion Symptom severity, suicidal risk, higher number of lifetime depressive episodes, and comorbid anxiety disorder were replicated as the most prominent risk factors for TRD . Significant predictors in TRD ‐ III enabled robust prediction of treatment outcome in TRD ‐I.
BackgroundElectroconvulsive therapy (ECT) is the treatment of choice for severe mental illness including treatment-resistant depression (TRD). Increases in volume of the hippocampus and amygdala following ECT have consistently been reported.AimsTo investigate neuroplastic changes after ECT in specific hippocampal subfields and amygdala nuclei using high-resolution structural magnetic resonance imaging (MRI) (trial registration: clinicaltrials.gov – NCT02379767).MethodMRI scans were carried out in 14 patients (11 women, 46.9 years (s.d. = 8.1)) with unipolar TRD twice before and once after a series of right unilateral ECT in a pre–post study design. Volumes of subcortical structures, including subfields of the hippocampus and amygdala, and cortical thickness were extracted using FreeSurfer. The effect of ECT was tested using repeated-measures ANOVA. Correlations of imaging and clinical parameters were explored.ResultsIncreases in volume of the right hippocampus by 139.4 mm3 (s.d. = 34.9), right amygdala by 82.3 mm3 (s.d. = 43.9) and right putamen by 73.9 mm3 (s.d. = 77.0) were observed. These changes were localised in the basal and lateral nuclei, and the corticoamygdaloid transition area of the amygdala, the hippocampal–amygdaloid transition area and the granule cell and molecular layer of the dentate gyrus. Cortical thickness increased in the temporal, parietal and insular cortices of the right hemisphere.ConclusionsFollowing ECT structural changes were observed in hippocampal subfields and amygdala nuclei that are specifically implicated in the pathophysiology of depression and stress-related disorders and retain a high potential for neuroplasticity in adulthood.Declaration of interestS.K. has received grants/research support, consulting fees and/or honoraria within the past 3 years from Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Celegne GmbH, Eli Lilly, Janssen-Cilag Pharma GmbH, KRKA-Pharma, Lundbeck A/S, Neuraxpharm, Pfizer, Pierre Fabre, Schwabe and Servier. R.L. received travel grants and/or conference speaker honoraria from Shire, AstraZeneca, Lundbeck A/S, Dr. Willmar Schwabe GmbH, Orphan Pharmaceuticals AG, Janssen-Cilag Pharma GmbH, and Roche Austria GmbH.
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