title: Brain-derived Neurotrophic Factor (BDNF) and gray matter volume in bipolar disorder.
abstract: Bipolar Disorder (BD) is a severe psychiatric condition characterized by grey matter (GM) volumes reduction. Neurotrophic factors have been suggested to play a role in the neuroprogressive changes during the illness course. In particular peripheral brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker related to disease activity and neuroprogression in BD. The aim of our study was to investigate if serum levels of BDNF are associated with GM volumes in BD patients and healthy controls (HC).
  
  
  
  We studied 36 inpatients affected by a major depressive episode in course of BD type I and 17 HC. Analysis of variance was performed to investigate the effect of diagnosis on GM volumes in the whole brain. Threshold for significance was P<0.05, Family Wise Error (FWE) corrected for multiple comparisons. All the analyses were controlled for the effect of nuisance covariates known to influence GM volumes, such as age, gender and lithium treatment.
  
  
  
  BD patients showed significantly higher serum BDNF levels compared with HC. Reduced GM volumes in BD patients compared to HC were observed in several brain areas, encompassing the caudate head, superior temporal gyrus, insula, fusiform gyrus, parahippocampal gyrus, and anterior cingulate cortex. The interaction analysis between BDNF levels and diagnosis showed a significant effect in the middle frontal gyrus. HC reported higher BDNF levels associated with higher GM volumes, whereas no association between BDNF and GM volumes was observed in BD.
  
  
  
  Our study seems to suggest that although the production of BDNF is increased in BD possibly to prevent and repair neural damage, its effects could be hampered by underlying neuroinflammatory processes interfering with the neurodevelopmental role of BDNF.
authors.affiliation: Department of clinical neurosciences, CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), scientific institute, university Vita-Salute San Raffaele, Milan, Italy; Department of immunology, Erasmus university medical centre, Rotterdam, The Netherlands. Electronic address: poletti.sara@hsr.it.
authors.forename: S
authors.initials: S
authors.lastname: Poletti
authors.affiliation: Department of clinical neurosciences, CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), scientific institute, university Vita-Salute San Raffaele, Milan, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Aggio
authors.affiliation: Department of immunology, Erasmus university medical centre, Rotterdam, The Netherlands.
authors.forename: T A
authors.initials: TA
authors.lastname: Hoogenboezem
authors.affiliation: Department of psychiatry, university of Münster, Münster, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Ambrée
authors.affiliation: Department of immunology, Erasmus university medical centre, Rotterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: de Wit
authors.affiliation: Department of immunology, Erasmus university medical centre, Rotterdam, The Netherlands.
authors.forename: A J M
authors.initials: AJ
authors.lastname: Wijkhuijs
authors.affiliation: Department of clinical neurosciences, CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), scientific institute, university Vita-Salute San Raffaele, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Locatelli
authors.affiliation: Department of clinical neurosciences, CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), scientific institute, university Vita-Salute San Raffaele, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Colombo
authors.affiliation: Department of psychiatry, university of Münster, Münster, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Arolt
authors.affiliation: Department of immunology, Erasmus university medical centre, Rotterdam, The Netherlands.
authors.forename: H A
authors.initials: HA
authors.lastname: Drexhage
authors.affiliation: Department of clinical neurosciences, CERMAC (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), scientific institute, university Vita-Salute San Raffaele, Milan, Italy; Department of immunology, Erasmus university medical centre, Rotterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Benedetti
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000187:drug effects; D003865:Major Depressive Disorder / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D066128:Gray Matter / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D008094:Lithium / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human; D008094:Lithium
keywords: BDNF; Bipolar disorder; Gray matter; Neuroinflammation