Functional connectivity signatures of major depressive disorder: machine learning analysis of two multicenter neuroimaging studies.

The promise of machine learning has fueled the hope for developing diagnostic tools for psychiatry. Initial studies showed high accuracy for the identification of major depressive disorder (MDD) with resting-state connectivity, but progress has been hampered by the absence of large datasets. Here we used regular machine learning and advanced deep learning algorithms to differentiate patients with MDD from healthy controls and identify neurophysiological signatures of depression in two of the largest resting-state datasets for MDD.

Altered resting-state functional connectome in major depressive disorder: a mega-analysis from the PsyMRI consortium.

Major depressive disorder (MDD) is associated with abnormal neural circuitry. It can be measured by assessing functional connectivity (FC) at resting-state functional MRI, that may help identifying neural markers of MDD and provide further efficient diagnosis and monitor treatment outcomes. The main aim of the present study is to investigate, in an unbiased way, functional alterations in patients with MDD using a large multi-center dataset from the PsyMRI consortium including 1546 participants from 19 centers ( www.

On the relationship of first-episode psychosis to the amphetamine-sensitized state: a dopamine D receptor agonist radioligand study.

Schizophrenia is characterized by increased behavioral and neurochemical responses to dopamine-releasing drugs. This prompted the hypothesis of psychosis as a state of "endogenous" sensitization of the dopamine system although the exact basis of dopaminergic disturbances and the possible role of prefrontal cortical regulation have remained uncertain. To show that patients with first-episode psychosis release more dopamine upon amphetamine-stimulation than healthy volunteers, and to reveal for the first time that prospective sensitization induced by repeated amphetamine exposure increases dopamine-release in stimulant-naïve healthy volunteers to levels observed in patients, we collected data on amphetamine-induced dopamine release using the dopamine D receptor agonist radioligand [C]-(+)-PHNO and positron emission tomography.

Prefrontal networks dynamically related to recovery from major depressive disorder: a longitudinal pharmacological fMRI study.

Due to lacking predictors of depression recovery, successful treatment of major depressive disorder (MDD) is frequently only achieved after therapeutic optimization leading to a prolonged suffering of patients. This study aimed to determine neural prognostic predictors identifying non-remitters prior or early after treatment initiation. Moreover, it intended to detect time-sensitive neural mediators indicating depression recovery.

Midday and nadir salivary cortisol appear superior to cortisol awakening response in burnout assessment and monitoring.

Burnout and work-related stress symptoms of anxiety disorder and depression cause prolonged work absenteeism and early retirement. Hence, reliable identification of patients under risk and monitoring of treatment success is highly warranted. We aimed to evaluate stress-specific biomarkers in a population-based, "real-world" cohort (burnouts: n = 40, healthy controls: n = 26), recruited at a preventive care ward, at baseline and after a four-month follow up, during which patients received medical and psychological treatment.

rs6295 [C]-Allele Protects Against Depressive Mood in Elderly Endurance Athletes.

A single nucleotide variant within the promoter of the 5-hydroxytryptamine1A (5HT1A) receptor, rs6295, is part of a binding site for the transcription factor. We aimed to ascertain whether the rs6295 mediates the effect of exercise on depressive mood in elderly endurance athletes. We prospectively enrolled 55 elderly athletes (marathon runners/bicyclists) and 58 controls.

Physical exercise counteracts genetic susceptibility to depression.

Background/aims: Depression is a highly prevalent disorder in elderly individuals. A genetic variant (rs6265) of the brain-derived neurotrophic factor (BDNF) impacting on emotion processing is known to increase the risk for depression. We aim to investigate whether intensive endurance sports might attenuate this genetic susceptibility in a cohort of elderly marathon athletes.

fMRI measurements of amygdala activation are confounded by stimulus correlated signal fluctuation in nearby veins draining distant brain regions.

Imaging the amygdala with functional MRI is confounded by multiple averse factors, notably signal dropouts due to magnetic inhomogeneity and low signal-to-noise ratio, making it difficult to obtain consistent activation patterns in this region. However, even when consistent signal changes are identified, they are likely to be due to nearby vessels, most notably the basal vein of rosenthal (BVR). Using an accelerated fMRI sequence with a high temporal resolution (TR = 333 ms) combined with susceptibility-weighted imaging, we show how signal changes in the amygdala region can be related to a venous origin.

Reduced default mode network suppression during a working memory task in remitted major depression.

Insufficient default mode network (DMN) suppression was linked to increased rumination in symptomatic Major Depressive Disorder (MDD). Since rumination is known to predict relapse and a more severe course of MDD, we hypothesized that similar DMN alterations might also exist during full remission of MDD (rMDD), a condition known to be associated with increased relapse rates specifically in patients with adolescent onset. Within a cross-sectional functional magnetic resonance imaging study activation and functional connectivity (FC) were investigated in 120 adults comprising 78 drug-free rMDD patients with adolescent- (n = 42) and adult-onset (n = 36) as well as 42 healthy controls (HC), while performing the n-back task.

Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults.

Prefrontal dopamine levels are relatively increased in adolescence compared to adulthood. Genetic variation of COMT (COMT Val158Met) results in lower enzymatic activity and higher dopamine availability in Met carriers. Given the dramatic changes of synaptic dopamine during adolescence, it has been suggested that effects of COMT Val158Met genotypes might have oppositional effects in adolescents and adults.

A multivariate approach linking reported side effects of clinical antidepressant and antipsychotic trials to in vitro binding affinities.

The vast majority of approved antidepressants and antipsychotics exhibit a complex pharmacology. The mechanistic understanding of how these psychotropic medications are related to adverse drug reactions (ADRs) is crucial for the development of novel drug candidates and patient adherence. This study aims to associate in vitro assessed binding affinity profiles (39 compounds, 24 molecular drug targets) and ADRs (n=22) reported in clinical trials of antidepressants and antipsychotics (n>59.

The spectral diversity of resting-state fluctuations in the human brain.

In order to assess whole-brain resting-state fluctuations at a wide range of frequencies, resting-state fMRI data of 20 healthy subjects were acquired using a multiband EPI sequence with a low TR (354 ms) and compared to 20 resting-state datasets from standard, high-TR (1800 ms) EPI scans. The spatial distribution of fluctuations in various frequency ranges are analyzed along with the spectra of the time-series in voxels from different regions of interest. Functional connectivity specific to different frequency ranges (<0.

Platelet serotonin transporter function predicts default-mode network activity.

Background: The serotonin transporter (5-HTT) is abundantly expressed in humans by the serotonin transporter gene SLC6A4 and removes serotonin (5-HT) from extracellular space. A blood-brain relationship between platelet and synaptosomal 5-HT reuptake has been suggested, but it is unknown today, if platelet 5-HT uptake can predict neural activation of human brain networks that are known to be under serotonergic influence.

Methods: A functional magnetic resonance study was performed in 48 healthy subjects and maximal 5-HT uptake velocity (Vmax) was assessed in blood platelets.

Affective and inflammatory responses among orchestra musicians in performance situation.

A number of studies have shown that mental challenge under controlled experimental conditions is associated with elevations in inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP). However, relatively little work has been done on the effects of 'naturalistic' stressors on acute changes in inflammatory markers. The present study examined whether perceived arousal, valence and dominance in musicians are associated with pro-inflammatory and oxidative responses to a concert situation.

Neuroplasticity and memory formation in major depressive disorder: an imaging genetics perspective on serotonin and BDNF.

A vast number of imaging studies have demonstrated the impact of serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) on emotion and memory-related networks in the context of Major Depressive Disorder (MDD). Underlying molecular mechanisms that affect the functionality of these networks have been examined in detail in animals and corroborate imaging findings. The crucial role of 5-HT and BDNF signaling in the context of MDD is reflected in the etiologic models of MDD such as the monoamine or neuroplasticity hypothesis as well as in pharmacological models of antidepressant response.

Fully exploratory network independent component analysis of the 1000 functional connectomes database.

The 1000 Functional Connectomes Project is a collection of resting-state fMRI datasets from more than 1000 subjects acquired in more than 30 independent studies from around the globe. This large, heterogeneous sample of resting-state data offers the unique opportunity to study the consistencies of resting-state networks at both subject and study level. In extension to the seminal paper by Biswal et al.

A highly parallelized framework for computationally intensive MR data analysis.

Object: The goal of this study was to develop a comprehensive magnetic resonance (MR) data analysis framework for handling very large datasets with user-friendly tools for parallelization and to provide an example implementation.

Materials And Methods: Commonly used software packages (AFNI, FSL, SPM) were connected via a framework based on the free software environment R, with the possibility of using Nvidia CUDA GPU processing integrated for high-speed linear algebra operations in R. Three hundred single-subject datasets from the 1,000 Functional Connectomes project were used to demonstrate the capabilities of the framework.

The genetic blueprint of major depressive disorder: contributions of imaging genetics studies.

Objectives: To review neuroimaging intermediate phenotypes of MDD and their relation to genetic risk variants.

Methods: A systematic literature search of peer-reviewed English language articels using PubMed ( www.pubmed.

Is there a personalized medicine for mood disorders?

Major Depressive Disorder (MDD) and antidepressant therapy response are largely based on behavioral criteria, which are known to correlate at best modestly with biological measures. Therefore, it is not surprising that the search for peripheral biological markers (biomarkers) being assessed in distant biological systems such as body fluids has not yet resulted in clinically convincing measures for MDD diagnostics or treatment evaluation. Imaging genetics studies, however, have been successful in the search for intermediate imaging phenotypes of MDD and treatment response that are directly related to the neurobiological underpinnings of MDD, but are not suitable for a broad clinical use today.