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We employed a cross\u2010sectional, case\u2013control study to compare structural age\u2010related brain trajectories in patients with <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content> and healthy control subjects (<jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>) over a period of approximately 50 years. The primary aim was to understand whether white (<jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content>) and gray matter (<jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content>) abnormalities are present from the beginning of the illness and how they change over time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seventy\u2010eight patients with <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content> and 78 <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content> matched for age, gender, and educational level underwent a high\u2010resolution structural magnetic resonance imaging protocol. A voxel\u2010based morphometry (<jats:styled-content style=\"fixed-case\">VBM<\/jats:styled-content>) analysis was used to capture <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content> differences between subjects with <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>. Factorial analysis of covariance was used to compare brain volume alterations at different ages between the groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found an age\u2010related atrophy in <jats:styled-content style=\"fixed-case\">GM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content> volumes both in patients with <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">HC<\/jats:styled-content>. A main effect of diagnosis emerged in the posterior cingulate cortex bilaterally, in the right thalamus, in the cerebellum bilaterally, and in the left posterior limb of the internal capsule. No interaction between diagnosis and age emerged, indicating that the volumes of these areas were permanently reduced in subjects with <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content> throughout the entire age range under investigation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Brain alterations in patients with <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content> are present from the beginning of the illness and remain stable over time. All the affected areas are involved in mood and psychomotor control process. This suggests a possible neurodevelopmental involvement in the mechanism of <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.12359","type":"journal-article","created":{"date-parts":[[2016,1,19]],"date-time":"2016-01-19T06:21:20Z","timestamp":1453184480000},"page":"52-62","source":"Crossref","is-referenced-by-count":40,"title":["Gray and white matter trajectories in patients with bipolar disorder"],"prefix":"10.1111","volume":"18","author":[{"given":"Gabriele","family":"Sani","sequence":"first","affiliation":[{"name":"Neurosciences, Mental Health, and Sensory Organs Department (NESMOS) Sapienza University, Rome School of Medicine and Psychology Sant' Andrea Hospital Italy"},{"name":"Centro Lucio Bini Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Chiapponi","sequence":"additional","affiliation":[{"name":"Neuropsychiatry Laboratory Department of Clinical and Behavioral Neurology 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