title: Differentiating unipolar and bipolar depression by alterations in large-scale brain networks.
abstract: BACKGROUND
  Misdiagnosing bipolar depression can lead to very deleterious consequences of mistreatment. Although depressive symptoms may be similarly expressed in unipolar and bipolar disorder, changes in specific brain networks could be very distinct, being therefore informative markers for the differential diagnosis. We aimed to characterize specific alterations in candidate large-scale networks (frontoparietal, cingulo-opercular, and default mode) in symptomatic unipolar and bipolar patients using resting state fMRI, a cognitively low demanding paradigm ideal to investigate patients.
  
  
  METHODS
  Networks were selected after independent component analysis, compared across 40 patients acutely depressed (20 unipolar, 20 bipolar), and 20 controls well-matched for age, gender, and education levels, and alterations were correlated to clinical parameters.
  
  
  RESULTS
  Despite comparable symptoms, patient groups were robustly differentiated by large-scale network alterations. Differences were driven in bipolar patients by increased functional connectivity in the frontoparietal network, a central executive and externally-oriented network. Conversely, unipolar patients presented increased functional connectivity in the default mode network, an introspective and self-referential network, as much as reduced connectivity of the cingulo-opercular network to default mode regions, a network involved in detecting the need to switch between internally and externally oriented demands. These findings were mostly unaffected by current medication, comorbidity, and structural changes. Moreover, network alterations in unipolar patients were significantly correlated to the number of depressive episodes.
  
  
  CONCLUSIONS
  Unipolar and bipolar groups displaying similar symptomatology could be clearly distinguished by characteristic changes in large-scale networks, encouraging further investigation of network fingerprints for clinical use. Hum Brain Mapp 37:808-818, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Psychiatry and Psychotherapy, Center for Translational Research in Systems Neuroscience and Psychiatry, University Medical Center, Georg-August-University, Goettingen, Germany.
authors.forename: Roberto
authors.initials: R
authors.lastname: Goya-Maldonado
authors.affiliation: Department of Psychiatry and Psychotherapy, Center for Translational Research in Systems Neuroscience and Psychiatry, University Medical Center, Georg-August-University, Goettingen, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Brodmann
authors.affiliation: Department of Psychiatry and Psychotherapy, Center for Translational Research in Systems Neuroscience and Psychiatry, University Medical Center, Georg-August-University, Goettingen, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Keil
authors.affiliation: Department of Psychiatry and Psychotherapy, Center for Translational Research in Systems Neuroscience and Psychiatry, University Medical Center, Georg-August-University, Goettingen, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Trost
authors.affiliation: Department of Cognitive Neurology, Research Group 'MR-Research in Neurology and Psychiatry', University Medical Center, Georg-August-University, Goettingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Dechent
authors.affiliation: Department of Psychiatry and Psychotherapy, Center for Translational Research in Systems Neuroscience and Psychiatry, University Medical Center, Georg-August-University, Goettingen, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gruber
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods; D003866:Depressive Disorder / Q000175:diagnosis* / Q000503:physiopathology*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D011594:Psychometrics; D012146:Rest
keywords: cingulo-opercular; default mode; depression; frontoparietal; functional connectivity; large-scale networks; mood disorders