Simvastatin add-on to escitalopram in patients with comorbid obesity and major depression (SIMCODE): study protocol of a multicentre, randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Major depressive disorder (MDD) and obesity are both common disorders associated with significant burden of disease worldwide. Importantly, MDD and obesity often co-occur, with each disorder increasing the risk for developing the other by about 50%-60%. Statins are among the most prescribed medications with well-established safety and efficacy. Statins are recommended in primary prevention of cardiovascular disease, which has been linked to both MDD and obesity. Moreover, statins are promising candidates to treat MDD because a meta-analysis of pilot randomised controlled trials has found antidepressive effects of statins as adjunct therapy to antidepressants. However, no study so far has tested the antidepressive potential of statins in patients with MDD and comorbid obesity. Importantly, this is a difficult-to-treat population that often exhibits a chronic course of MDD and is more likely to be treatment resistant. Thus, in this confirmatory randomised controlled trial, we will determine whether add-on simvastatin to standard antidepressant medication with escitalopram is more efficacious than add-on placebo over 12 weeks in 160 patients with MDD and comorbid obesity. METHODS AND ANALYSIS: This is a protocol for a randomised, placebo-controlled, double-blind multicentre trial with parallel-group design (phase II). One hundred and sixty patients with MDD and comorbid obesity will be randomised 1:1 to simvastatin or placebo as add-on to standard antidepressant medication with escitalopram. The primary outcome is change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 12. Secondary outcomes include MADRS response (defined as 50% MADRS score reduction from baseline), MADRS remission (defined as MADRS score <10), mean change in patients' self-reported Beck Depression Inventory (BDI-II) and mean change in high-density lipoprotein, low-density lipoprotein and total cholesterol from baseline to week 12. ETHICS AND DISSEMINATION: This protocol has been approved by the ethics committee of the federal state of Berlin (Ethik-Kommission des Landes Berlin, reference: 19/0226-EK 11) and by the relevant federal authority (Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), reference: 4043387). Study findings will be published in peer-reviewed journals and will be presented at (inter)national conferences. TRIAL REGISTRATION NUMBERS: NCT04301271, DRKS00021119, EudraCT 2018-002947-27.

Resting-state connectivity in the prodromal phase of schizophrenia: insights from EEG microstates.

INTRODUCTION: Resting-state EEG microstates are thought to reflect the momentary local states and interactions of distributed neural networks in the brain. Several changes in resting-state EEG microstates have been described in acutely ill patients with schizophrenia, but it is not known whether these represent trait or state abnormalities. The present study aimed to investigate this issue by assessing EEG microstate characteristics in high-risk individuals (HR) and clinically stable first-episode patients with schizophrenia (SZ) with low symptom levels, compared to each other and healthy controls (HC). METHOD: Participants were 18 HR, 18 SZ, and 22 HC subjects. 64-channel resting-state EEG recordings were used for microstate analyses. Microstates were clustered into four classes (A-D) according to their topography. Temporal parameters and topographies of microstates were compared among groups. RESULTS: Microstate class A displayed higher coverage and occurrence in HR than SZ and HC, while microstate class B covered significantly more time in SZ compared to both HR and HC. Microstate class B displayed an aberrant spatial configuration in SZ, and to a lesser extent also in HR, compared to HC, with patients exhibiting significantly higher activity in the vicinity of the left posterior cingulate. DISCUSSION: Microstate abnormalities observed in HR were similar to those previously reported in acutely ill patients with schizophrenia. Moreover, there was evidence that HR and SZ might share specific disturbances in brain functional connectivity. These findings raise the possibility that certain abnormalities in resting-state EEG microstates might be associated with an increased risk for psychosis.