Environmental factors linked to depression vulnerability are associated with altered cerebellar resting-state synchronization.

Aldo Córdova-Palomera,Nuria Bargalló,Paolo Brambilla,Benedicto Crespo-Facorro,Cristian Tornador,Gustavo Deco,Carles Falcón,Lourdes Fañanás

doi:10.1038/srep37384

Abstract

Hosting nearly eighty percent of all human neurons, the cerebellum is functionally connected to large regions of the brain. Accumulating data suggest that some cerebellar resting-state alterations may constitute a key candidate mechanism for depressive psychopathology. While there is some evidence linking cerebellar function and depression, two topics remain largely unexplored. First, the genetic or environmental roots of this putative association have not been elicited. Secondly, while different mathematical representations of resting-state fMRI patterns can embed diverse information of relevance for health and disease, many of them have not been studied in detail regarding the cerebellum and depression. Here, high-resolution fMRI scans were examined to estimate functional connectivity patterns across twenty-six cerebellar regions in a sample of 48 identical twins (24 pairs) informative for depression liability. A network-based statistic approach was employed to analyze cerebellar functional networks built using three methods: the conventional approach of filtered BOLD fMRI time-series, and two analytic components of this oscillatory activity (amplitude envelope and instantaneous phase). The findings indicate that some environmental factors may lead to depression vulnerability through alterations of the neural oscillatory activity of the cerebellum during resting-state. These effects may be observed particularly when exploring the amplitude envelope of fMRI oscillations.

Highlights

Activity disruptions observed across several psychiatric disorders[3,4,5,6,7,8]
A genetically-informative design was implemented here to evaluate the putative relationship between depression liability and different cerebellar resting-state synchronization patterns, as measured by fMRI
Three different coupling types among the distinct anatomical subdivisions of the cerebellum were analyzed in relation to both familial and unique environmental factors underlying depression liability

Summary

Introduction

Activity disruptions observed across several psychiatric disorders[3,4,5,6,7,8]. Notably, recent research findings have consistently suggested cerebellar resting-state connectivity changes in depression, making it one of the best candidate mechanisms to elicit the neural alterations of the depressed brain[9,10,11,12]. While the presence of resting-state fMRI alterations at cerebral regions –i.e., the default mode network– is broadly acknowledged in depressive disorders, the contribution of cerebellar function to those clinical phenotypes has recently been gaining attention[9] This is a relevant point since data on healthy twins and families shows significant quantitative genetic components of whole-brain resting-state fMRI activity at cerebellar regions[13,14], but their putative modulation of depression vulnerability remains only scarcely explored. In this context, it is worth mentioning that some specific genetic and environmental factors can induce neurobiological changes that lead to depressive psychopathology. In terms of large-scale neuronal networks, the brain disturbances reported in the literature of depression would indicate modifications of the information processing performance through the cerebellum

Methods

Results

Conclusion