Association of Lesion Location and Depressive Symptoms Poststroke

Julian Klingbeil, MD; Max-Lennart Brandt; Max Wawrzyniak, MD; Anika Stockert, MD; Hans R. Schneider; Petra Baum, MD; Karl-Titus Hoffmann, MD; Dorothee Saur, MD


Stroke. 2021;52(3):830-837. 

In This Article

Abstract and Introduction


Background and Purpose: Poststroke depression is a common stroke sequel, yet its neurobiological substrates are still unclear. We sought to determine whether specific lesion locations are associated with depressive symptoms after stroke.

Methods: In a prospective study, 270 patients with first ever stroke were repeatedly tested with the depression subscale of the Hospital Anxiety and Depression Scale within the first 4 weeks and 6 months after stroke. Voxel-based lesion behavior mapping based on clinical imaging was performed to test for associations between symptoms of depression and lesion locations.

Results: Frequency of poststroke depression (Hospital Anxiety and Depression Scale-D score >7) after 6 months was 19.6%. Higher Hospital Anxiety and Depression Scale-D scores for depression within the first 4 weeks were the only independent predictor for poststroke depression after 6 months in a multiple logistic regression also including age, sex, lesion volume, stroke severity, Barthel-Index, and the anxiety subscale of the Hospital Anxiety and Depression Scale. Nonparametric permutation-test based voxel-based lesion behavior mapping identified a cluster of voxels mostly within the left ventrolateral prefrontal cortex where lesions were significantly associated with more depressive symptoms after 6 months. No such association was observed within the right hemisphere despite better lesion coverage.

Conclusions: Lesions in the left ventrolateral prefrontal cortex increase the risk of depressive symptoms 6 months poststroke. Lesions within the right hemisphere are unrelated to depressive symptoms. Recognition of left frontal lesions as a risk factor should help in the early diagnosis of poststroke depression through better risk stratification. The results are in line with evidence from functional imaging and noninvasive brain stimulation in patients without focal brain damage indicating that dysfunction in the left lateral prefrontal cortex contributes to depressive disorders.


Poststroke depression (PSD) is a common sequelae of stroke affecting around 30% of all stroke survivors.[1] It is an independent predictor of worse functional status and increased mortality.[2] Known risk factors for PSD include disability,[3] cognitive impairment,[4] and previous depression,[3,5] but these account for only one-third of the variance.[6] Depression may not solely be explained as a psychological reaction to disability because it is far more common in patients with stroke than after orthopedic injuries with comparable disability[7] and also occurs in patients with anosognosia.[8] Lesion location has been considered as one possible biological factor in a biopsychosocial model of PSD, and left frontal regions were first reported to be associated with PSD.[9] However, despite over 80 lesion studies in the last decades, no consistent association has been identified.[10] One major reason is the use of different techniques with rather low anatomic precision for inference of structure-function relationships in these studies.[11] Meanwhile, voxel-based lesion behavior mapping (VLBM) has become the standard approach for lesion analyses.[12] A recent VLBM study in a small sample restricted to left hemisphere strokes suggested that lesions in the dorsolateral prefrontal cortex (DLPFC) may be associated with symptoms of depression.[13] Contrarily, neither a VLBM analyses in a larger population[14] nor a pooled analysis of several previous studies[15] was able to confirm any lesion behavior association for PSD. To elucidate the question whether lesion location is a biological factor for PSD, in our prospective study, we tested for depressive symptoms within 4 weeks and 6 months after stroke and performed VLBM in a large sample of patients with strokes covering both hemispheres.