A significant risk factor for poststroke depression: the depression-related subnetwork

Abstract

IntroductionPoststroke depression (PSD) is one of the most common emotional disorders afflicting those who experience stroke. A meta-analysis has indicated that the prevalence of major or mild depression is approximately 18% (range 8%-46%), 1 with the presence of PSD being associated with increased mortality.2 Converging evidence has implicated particular neural networks in the pathophysiology of mood disorders.3 However, despite being one of the direct causes of depression, whether stroke-induced neuroanatomical deterioration actually plays an important role in the onset of PSD is still controversial. Previous neuroimaging studies have focused mainly on regional differences and severity of local brain lesions. 4 In addition, an often-cited meta-analysis that reported no clear association between PSD and any specific lesion location or hemisphere 4 has fueled intense debate. Recently, although statistical parametric mapping linked affective depression to lesions centred in the left basal ganglia and left frontal cortex, the conclusions remain in doubt because results were not corrected for multiple comparisons. 5,6 Diffusion tensor imaging (DTI) is a noninvasive technique that assesses white matter connectivity, particularly fibre density and myelination. In addition, structural brain network interactions can be quantified using brain graphs 7,8 in which neuroanatomical regions are defined as a set of nodes and DTI-derived white matter connections act as interconnecting edges.7 Using this approach, a disruption of neural topology has been shown in several brain diseases, 9-11 including those occurring in chronic stroke patients. 12 Here, we evaluated 3 markers of brain-damage severity: lesion index, fractional anisotropy (FA) reduction and brain structural networks. We hypothesized that a specific brain subnetwork is associated with PSD and that the damage to it might serve as a predictor of poststroke major depression. We constructed a depression-related subnetwork based on Background: Despite being one of the direct causes of depression, whether stroke-induced neuroanatomical deterioration actually plays an important role in the onset of poststroke depression (PSD) is controversial. We assessed the structural basis of PSD, particularly with regard to white matter connectivity. Methods: We evaluated lesion index, fractional anisotropy (FA) reduction and brain structural networks and then analyzed whole brain voxel-based lesions and FA maps. To understand brain damage in the context of brain connectivity, we used a graph theoretical approach. We selected nodes whose degree correlated with the Hamilton Rating Scale for Depression score (p < 0.05, false discovery rate-corrected), after controlling for age, sex, years of education, lesion size, Mini Mental State Examination score and National Institutes of Health Stroke Scale score. We used Poisson regression with robust standard errors to assess the contribution of the identified network toward poststroke major depression. Results: We included 116 stroke patients ...

Persistent post-stroke depression in mice following unilateral medial prefrontal cortical stroke

“…Although strokes restricted to the mPFC are rare in humans, we targeted this region to determine the outcome of an ischemic lesion in the mPFC, given that this region has been implicated in PSD. 61 , 62 , 63 , 64 , 65 We also decided to use mice to generate a model that could exploit the large variety of conditional and inducible gene knockout mouse strains for future studies to further investigate the role of cellular remodeling and circuitry changes in PSD. Our results suggest that unilateral lesion of the PFC is sufficient to induce a robust anxiety and depression phenotype, in the absence of infarct in other cortical and subcortical gray and white matter.…”

Depression Symptoms in Chronic Left Hemisphere Stroke Are Related to Dorsolateral Prefrontal Cortex Damage

“…One of these recent studies used graph theory analysis of diffusion tensor imaging data to demonstrate that damage within a broad "depressionrelated network" was associated with increased rates of PSD. 34 The other recent notable study used a univariate voxel-wise approach with T1-weighted images, and failed to find a relationship between lesion location and PSD in a cohort of 55 subacute stroke survivors with left, right, or bilateral strokes. 35 The authors attribute the negative results to methodological limitations, primarily an overly diverse group of participants who did not have sufficient overlap in lesion locations to provide adequate power for lesionsymptom mapping.…”

Chronic Fluoxetine Induces Activity Changes in Recovery From Poststroke Anxiety, Depression, and Cognitive Impairment

“…Evidence from human imaging studies suggests that alterations in the activity of the mPFC-DR limbic circuitry are associated with anxiety disorders and major depression [22,29,30]. Therefore, we targeted mPFC as a central node of the mPFC-subcortical limbic circuitry [31] to model PSD phenotypes [32,33]. While lesion of the mPFC from anterior cerebral artery stroke is rare, much more common large ischemic or white-matter strokes appear to disrupt multiple nodes and connections within the anxiety-depression circuitry, resulting in PSD [34,35].…”