title: Decreased BDNF and TrkB mRNA expression in multiple cortical areas of patients with schizophrenia and mood disorders.
abstract: Abnormalities in brain-derived neurotrophic factor (BDNF)/trkB signaling have been implicated in the etiology of schizophrenia and mood disorders. Patients with schizophrenia, bipolar disorder (BPD) and major depression (MDD) have reduced levels of neurotrophins in their brains when compared with normal unaffected individuals; however, only a few brain areas have been examined to date. Owing to the broad range of symptoms manifested in these disorders, we hypothesized that multiple associative areas of the neocortex may be implicated and that the degree of change in BDNF and trkB-TK+ mRNA expression and the cortical region or layers involved may vary according to Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis. We compared BDNF and trkB-TK+ mRNA levels across all layers of the prefrontal cortex (dorsolateral prefrontal cortex, DLPFC), orbital frontal cortex (OFC), anterior cingulate cortex (ACC), inferior temporal gyrus (ITG) and superior temporal gyrus (STG) in four groups: schizophrenia, BPD, MDD and unaffected controls (n=60). BDNF mRNA levels were significantly decreased in layers IV and V of DLPFC in schizophrenia patients, in layer VI of ACC in schizophrenia and MDD and in layer VI of ITG in schizophrenia, BPD and MDD. BDNF mRNA levels were also significantly decreased in layer V and/or VI of STG in schizophrenia, BPD and MDD. TrkB-TK+ mRNA levels were only significantly decreased in the cortical layer VI of OFC in BPD. The shared and distinct patterns of neurotrophin transcript reductions, with some specific to each group, may compromise the function and plasticity of distinct cortical areas to various degrees in the different groups and contribute to the range and overlap of symptoms manifested across the diagnoses.
authors.affiliation: 1] Stanley Medical Research Institute, Laboratory of Brain Research, Rockville, MD, USA [2] Trinity Washington University, NE Washington, DC, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Ray
authors.affiliation: 1] Schizophrenia Research Institute, Sydney, NSW, Australia [2] Neuroscience Research Australia, Randwick, NSW, Australia [3] School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Shannon Weickert
authors.affiliation: Stanley Medical Research Institute, Laboratory of Brain Research, Rockville, MD, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Webster
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D006179:Gyrus Cinguli / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020813:Receptor, trkB; D012559:Schizophrenia / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; C000591259:tropomyosin-related kinase-B, human