Differential relationships between apathy and depression with white matter microstructural changes and functional outcomes
Barrick, Thomas R
Morris, Robin G
Oxford University Press
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Hollocks, M., Lawrence, A., Brookes, R., Barrick, T. R., Morris, R. G., Husain, M., & Markus, H. (2015). Differential relationships between apathy and depression with white matter microstructural changes and functional outcomes. Brain, 138 3803-3815. https://doi.org/10.1093/brain/awv304
Small vessel disease is a stroke sub-type characterised by pathology of the small perforating arteries, which supply the sub-cortical structures of the brain. Small vessel disease is associated with high-rates of apathy and depression, thought to be caused by a disruption of white matter cortical-subcortical pathways important for emotion regulation. It provides an important biological model to investigate mechanisms underlying these key neuropsychiatric disorders. This study investigated whether apathy and depression can be distinguished in small vessel disease both in terms of their relative relationship with white matter microstructure, and secondly whether they can independently predict functional outcomes. 118 participants with small vessel disease (mean age 68.9 years; Male 65%) defined as a clinical and MRI confirmed lacunar stroke with radiological leukoaraiosis were recruited and completed cognitive testing, measures of apathy, depression, quality of life and diffusion tensor imaging. 398 healthy controls (mean age 64.3 years; Male 52%) were also studied in order to interpret the degree of apathy and depression found within the small vessel disease group. Firstly, a multilevel structural equation modelling approach was used to identify, 1) the relationships between median fractional anisotropy and apathy, depression and cognitive impairment and 2) if apathy and depression make independent contributions to quality of life in patients with small vessel disease. Secondly, we applied a whole brain voxel based analysis to investigate which regions of white matter were associated with apathy and depression, controlling for age, gender and cognitive functioning. Structural equation modelling results indicated both apathy (r = - 0.23, p ≤ 0.001) and depression (r = - 0.41, p ≤ 0.001) were independent predictors of quality of life. A reduced median fractional anisotropy was significantly associated with apathy (r = - 0.38, p ≤ 0.001), but not depression (r = - 0.16, p = .09). On voxel based analysis apathy was associated with widespread reduction in white matter integrity, with the strongest effects in limbic association tracts such as the anterior cingulum, fornix, and uncinate fasciculus. In contrast when controlling for apathy we found no significant relationship between our white matter parameters and symptoms of depression. In conclusion, white matter microstructural changes in small vessel disease are associated with apathy but not directly with depressive symptoms. These results suggest that apathy, but not depression, in small vessel disease is related to damage to cortical-subcortical networks associated with emotion regulation, reward and goaldirected behaviour.
Diffusion-Tensor Imaging, Emotion, Lacunar Stroke, Motivation, Vascular Dementia
The SCANS study was supported by a Wellcome Trust grant (081589). Recruitment to the SCANS study was supported by the English National Institute of Health Research Clinical Stroke Research Network. Matthew Hollocks is supported by a Stroke Association/British Heart Foundation Project Grant (TSA/BHF Prog 2010/01). Andrew Lawrence is supported by an Alzheimer’s Research UK project grant (ARUKPG2013-2). Masud Husain is supported by a Wellcome Trust Principal Research Fellowship. Hugh Markus is supported by an NIHR Senior Investigator award and by the Cambridge University Hospitals Department of Health’s NIHR Comprehensive Biomedical Research Centre.
British Heart Foundation (PG/13/30/30005)
External DOI: https://doi.org/10.1093/brain/awv304
This record's URL: https://www.repository.cam.ac.uk/handle/1810/250581
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/Attribution 2.0 UK: England & Wales