ORIGINAL ARTICLE Microstructural abnormality in white matter, regulatory T lymphocytes, and depressive symptoms after stroke Fumihiko YASUNO, 1,2 Akihiko TAGUCHI, 3,4 Akihide YAMAMOTO, 2 Katsufumi KAJIMOTO, 3 Hiroaki KAZUI, 5 Takashi KUDO, 5 Akie KIKUCHI-TAURA, 6 Atsuo SEKIYAMA, 7 Toshifumi KISHIMOTO, 1 Hidehiro IIDA 3 and Kazuyuki NAGATSUKA 3 1 Department of Neuropsychiatry, Nara Medical University, Kashihara, Departments of 2 Investigative Radiology and 3 Neurology, National Cerebral and Cardiovascular Center, 4 Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, Kobe, 5 Department of Neuropsychiatry, Osaka University Medical School, Suita, 6 Department of Clinical Research, National Hospital Organization, Osaka Minami Medical Center, Kawachinagano, and 7 Department of Brain Science, Osaka City University Graduate School of Medicine, Osaka, Japan Correspondence: Dr Fumihiko Yasuno MD PhD, Department of Psychiatry, Nara Medical University, 840 Shijocho, Kashihara, Nara, 634-8522, Japan. Email: ejm86rp@yahoo.co.jp Received 12 September 2013; revision received 30 April 2014; accepted 4 June 2014. Abstract Background: The purpose of the present study was to investigate the existence of microstructure abnormalities in the white matter circuit in stroke patients and its relationship to depressive episodes. To target the prevention of depression, we also investigated the relationship between lymphocyte subsets and cerebral abnormalities in patients. Methods: Participants included 18 patients with acute ischemic stroke and 22 healthy control subjects. Diffusion tensor imaging was performed. Whole- brain voxel-based analysis was used to compare fractional anisotropy (FA) between groups. Blood samples were obtained, and the lymphocyte subsets were evaluated using flow cytometry. Follow-up examinations were con- ducted on 12 patients at 6 months. Results: FA was decreased in the bilateral anterior limb of the internal capsule in stroke patients. At the 6-month follow-up examination, there was a significant increase in FA, which was associated with a lower depression scale score. Patients showed a decreased percentage of circulated regula- tory T lymphocytes, and the degree of reduction was related to the decrease in the FA value in the internal capsule. Conclusions: FA reductions in the anterior limb of the internal capsule cause abnormality in the frontal-subcortical circuits and confer a biological vulnerability, which in combination with environmental stressors results in the onset of depression. Our findings also demonstrated the possibility of preventing post-stroke depression by targeting the role of regulatory T lym- phocytes in brain tissue repair and regeneration after stroke. Key words: diffusion tensor imaging, fractional anisotropy (FA), magnetic resonance imaging (MRI), post-stroke depression, regulatory T lymphocytes (T reg), stroke. INTRODUCTION Stroke is the third leading cause of death and the most frequent cause of permanent disability in adults worldwide. 1 Depression is common and serious emo- tional symptom following stroke and is associated with excess disability, cognitive impairment, and mor- tality. 2 Despite considerable advances in understand- ing the pathophysiology of cerebral ischemia, therapeutic options for stroke and its related emo- tional symptoms are still limited. Inflammatory mecha- nisms activated after brain ischemia represent a key target of current translational cerebrovascular research. Stroke induces profound local inflammatory response involving various types of immune cells that transmigrate across the activated blood–brain barrier to invade the brain. 3 In attempts to target the prevention of cerebral damage due to stroke, several factors related to inflammation have received considerable attention. 4–6 T lymphocytes are especially central to the develop- ment of a sustained inflammatory response in brain injury after a stroke. T cells are sources of pro- inflammatory cytokines and cytotoxic substances, such as reactive oxygen species, in the brain after a stroke; these likely contribute to neuronal death and poor outcomes. However, recent evidence has doi:10.1111/psyg.12084 PSYCHOGERIATRICS 2014; 14: 213–221 213 © 2014 The Authors Psychogeriatrics © 2014 Japanese Psychogeriatric Society