Author's response to reviews Title: Mood After Stroke: a case control study of biochemical, neuro-imaging and socio-economic risk factors for major depression in stroke survivors. Authors:

Background Though vascular factors may be important in the aetiology of late-life depression, it is not clear whether they have a major effect on the risk of depression after a stroke. We investigated the relationship between physiological, biochemical, neuro-imaging and socio-economic factors and late-phase post-stroke depression in a cross-sectional casecontrol study. Methods People living at home at least 9 months after a stroke were interviewed using a structured proforma. Depression was diagnosed according to DSM-IV criteria, together with a Montgomery Asberg (MADRS) score >17. Stroke survivors of similar age and functional status but without symptoms of, or recent treatment for, depression and with MADRS score <7, were recruited as controls. Results Stroke survivors with depression were more likely than controls to have been smokers, to have had hypertension or peripheral arterial disease, and to have had more than one stroke or multiple discrete brainscan lesions. In univariate analysis they had significantly higher blood pressure, lower Mini-Mental State (MMSE) scores, higher serum homocysteine and lower folate levels, as well as more extensive white matter and basal ganglia changes on brainscan. In logistic regression, previous hypertension (OR 3.4), peripheral vascular disease (OR 4.7), number of strokes (OR 2), MMSE score (OR 0.76) and basal ganglia changes (OR 2.2), were independently associated with depression. Conclusion These results suggest that patients with hypertension, hyperhomocysteinaemia and other factors associated with cerebral small vessel disease, may be more susceptible to poststroke depression. Future intervention trials should focus on such high risk groups.