title: Gray and white matter trajectories in patients with bipolar disorder.
abstract: OBJECTIVE
  Findings on brain structural abnormalities in patients with bipolar disorder (BP) are inconsistent and little is known about age-related evolution of these changes. We employed a cross-sectional, case-control study to compare structural age-related brain trajectories in patients with BP and healthy control subjects (HC) over a period of approximately 50 years. The primary aim was to understand whether white (WM) and gray matter (GM) abnormalities are present from the beginning of the illness and how they change over time.
  
  
  METHODS
  Seventy-eight patients with BP and 78 HC matched for age, gender, and educational level underwent a high-resolution structural magnetic resonance imaging protocol. A voxel-based morphometry (VBM) analysis was used to capture GM and WM differences between subjects with BP and HC. Factorial analysis of covariance was used to compare brain volume alterations at different ages between the groups.
  
  
  RESULTS
  We found an age-related atrophy in GM and WM volumes both in patients with BP and HC. 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 BP throughout the entire age range under investigation.
  
  
  CONCLUSIONS
  Brain alterations in patients with BP 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 BP.
authors.affiliation: Neurosciences, Mental Health, and Sensory Organs Department (NESMOS), Sapienza University, Rome, School of Medicine and Psychology, Sant' Andrea Hospital, Italy.|Centro Lucio Bini, Rome, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Sani
authors.affiliation: Neuropsychiatry Laboratory, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.|Department of Medicine of Systems, Tor Vergata University, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Chiapponi
authors.affiliation: Neuropsychiatry Laboratory, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.|Enrico Fermi Center for Study and Research, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Piras
authors.affiliation: Neurosciences, Mental Health, and Sensory Organs Department (NESMOS), Sapienza University, Rome, School of Medicine and Psychology, Sant' Andrea Hospital, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Ambrosi
authors.affiliation: Neurosciences, Mental Health, and Sensory Organs Department (NESMOS), Sapienza University, Rome, School of Medicine and Psychology, Sant' Andrea Hospital, Italy.|Centro Lucio Bini, Rome, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Simonetti
authors.affiliation: Neurosciences, Mental Health, and Sensory Organs Department (NESMOS), Sapienza University, Rome, School of Medicine and Psychology, Sant' Andrea Hospital, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Danese
authors.affiliation: Neurosciences, Mental Health, and Sensory Organs Department (NESMOS), Sapienza University, Rome, School of Medicine and Psychology, Sant' Andrea Hospital, Italy.|Centro Lucio Bini, Rome, Italy.
authors.forename: Delfina
authors.initials: D
authors.lastname: Janiri
authors.affiliation: Neurosciences, Mental Health, and Sensory Organs Department (NESMOS), Sapienza University, Rome, School of Medicine and Psychology, Sant' Andrea Hospital, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Brugnoli
authors.affiliation: Villa Von Siebenthal, Genzano, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: De Filippis
authors.affiliation: Neuropsychiatry Laboratory, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.|Department of Medicine of Systems, Tor Vergata University, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.affiliation: Neurosciences, Mental Health, and Sensory Organs Department (NESMOS), Sapienza University, Rome, School of Medicine and Psychology, Sant' Andrea Hospital, Italy.|Centro Lucio Bini, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Girardi
authors.affiliation: Neuropsychiatry Laboratory, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.|Division of Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Spalletta
mesh_terms: D000328:Adult; D000367:Age Factors; D001284:Atrophy; D001714:Bipolar Disorder / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D002531:Cerebellum / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D066128:Gray Matter / Q000473:pathology*; D006179:Gyrus Cinguli / Q000473:pathology; D006801:Humans; D020772:Internal Capsule / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D013788:Thalamus / Q000473:pathology; D066127:White Matter / Q000473:pathology*
keywords: bipolar disorder; brain alterations; cerebellum; posterior cingulate cortex; posterior limb of the internal capsule; thalamus; voxel-based morphometry