Neuronal connectivity in major depressive disorder: a systematic review

Abstract

BackgroundThe causes of major depressive disorder (MDD), as one of the most common psychiatric disorders, still remain unclear. Neuroimaging has substantially contributed to understanding the putative neuronal mechanisms underlying depressed mood and motivational as well as cognitive impairments in depressed individuals. In particular, analyses addressing changes in interregional connectivity seem to be a promising approach to capture the effects of MDD at a systems level. However, a plethora of different, sometimes contradicting results have been published so far, making general conclusions difficult. Here we provide a systematic overview about connectivity studies published in the field over the last decade considering different methodological as well as clinical issues.MethodsA systematic review was conducted extracting neuronal connectivity results from studies published between 2002 and 2015. The findings were summarized in tables and were graphically visualized.ResultsThe review supports and summarizes the notion of an altered frontolimbic mood regulation circuitry in MDD patients, but also stresses the heterogeneity of the findings. The brain regions that are most consistently affected across studies are the orbitomedial prefrontal cortex, anterior cingulate cortex, amygdala, hippocampus, cerebellum and the basal ganglia.ConclusionThe results on connectivity in MDD are very heterogeneous, partly due to different methods and study designs, but also due to the temporal dynamics of connectivity. While connectivity research is an important step toward a complex systems approach to brain functioning, future research should focus on the dynamics of functional and effective connectivity.

Antidepressant mechanism of classical herbal formula lily bulb and Rehmannia decoction: insights from gene expression profile of medial prefrontal cortex of mice with stress‐induced depression‐like behavior

“…The mechanisms underlying the pathophysiology and treatment of depression remain unclear, although studies in rodent models and patients with depression have shown promising results. These studies have shown that chronic stress exposure causes structural atrophy of neurons as well as functional alterations in cortical and limbic brain regions . According to recent evidence, mPFC neurons play a role in mediating mood .…”

“…The sustained stress to individuals with genetic susceptibility leads to hypothalamus‐pituitary‐adrenal axis deficits, monoamine/cytokine imbalance, decreased neurogenesis and altered dynamics of connectivity in the reward and motivational circuitry . These mechanisms reduce neuroplasticity and impair the functional integrity of neurocircuitry regulation in depressed patients …”

Predicting Antidepressant Citalopram Treatment Response via Changes in Brain Functional Connectivity After Acute Intravenous Challenge

“…Sikora et al ( 2016 ) found a relationship of similar strength ( r = 0.41) between predicted and real responses to placebo but not antidepressant medication based on connectivity within the SN [included in the VA network of the Yeo atlas (Yeo et al, 2011 )], especially the rostral anterior cingulate cortex. Figures 3 , 4 show that connections within and including subregions of the anterior cingulate, which is known for being affected by MDD (Chen et al, 2018 ; Helm et al, 2018 ) as well as SSRIs (Arnone et al, 2018 ; Schrantee et al, 2018 ) contribute highly to the HAM-D predictors. A much stronger correlation between predicted and true absolute HAM-D scores of healthy and MDD subjects of r = 0.91 was reported by Qin et al ( 2015 ).…”

Time heals all wounds? A 2-year longitudinal diffusion tensor imaging study in major depressive disorder

“…[7][8][9] In MDD, recent studies have implicated alterations in certain structural and functional subnetworks with specific depression symptom dimensions. 10,11 Diffusion tensor imaging (DTI) techniques such as tract-based spatial statistics (TBSS) allow for the investigation of diffusion in the brain, which is employed to derive information about white matter integrity. 12 Studies using DTI have repeatedly shown impaired white matter, 7,13,14 especially in frontal tracts such as the genu of the corpus callosum, as well as longitudinal tracts; some studies have shown that increasing age, longer illness duration and early age of onset might be associated with lower fractional anisotropy (FA).…”