Dataset Information

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.

SUBMITTER: Ray MT

PROVIDER: S-EPMC4035720 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Decreased BDNF and TrkB mRNA expression in multiple cortical areas of patients with schizophrenia and mood disorders.

Ray M T MT Shannon Weickert C C Webster M J MJ

Translational psychiatry 20140506

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 a ...[more]

PMID: 24802307

Similar Datasets

Project description:BackgroundBrain-derived neurotrophic factor (BDNF), tyrosine kinase receptor (trkB-TK+) and glutamic acid decarboxylase (GAD67) mRNA levels have previously been found to be reduced in the prefrontal cortex of patients with schizophrenia. To determine whether this reduction extends to other brain regions, we measured the expression levels of BDNF, trkB-TK+ and GAD67 mRNA in regions of the hippocampus, including the dentate gyrus (DG), cornu ammonis subfields (CA1-4), subiculum and entorhinal cortex (EC) of individuals with schizophrenia, bipolar disorder, major depression and unaffected controls.MethodsIn situ hybridization was performed on postmortem brain tissue obtained from the Stanley Foundation Consortium and analyzed using film-based quantification.ResultsAnalyses of covariance comparing the expression of mRNA among all groups revealed a significant decrease in BDNF mRNA in CA4 in the bipolar disorder group compared with controls (33%). We found trkB-TK+ mRNA levels to be significantly reduced in CA4 in the schizophrenia group (36%) and in layer II of the EC in the bipolar disorder and major depression groups (28%, 21%, respectively) compared with controls. In addition, GAD67 mRNA levels were reduced in patients with schizophrenia in both the DG (23%) and CA4 (60%) compared with controls. Individuals with major depression also expressed significantly less GAD67 mRNA (44%) compared with controls in CA4 of the hippocampus.LimitationsIt is necessary to account for factors that influence the molecular preservation in postmortem brain tissue, including pH, postmortem interval and tissue storage time. Moreover, there are limitations to the sensitivity of the film-based method of quantification.ConclusionOur findings show abnormal BDNF, trkB-TK+ and GAD67 mRNA expression in the hippocampus of individuals with schizophrenia and mood disorders, indicating that fundamental properties of hippocampal signalling transmission, plasticity and circuitry may be affected in individuals with these major mental illnesses.

Project description:The neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase TrkB serve important regulatory roles for multiple aspects of the biology of neurons including cell death, survival, growth, differentiation, and plasticity. Regulation of the local availability of BDNF/TrkB at distinct subcellular domains such as soma, dendrites, axons, growth cones, nerve terminals, and spines appears to contribute to their specific functions. In view of the variance in size and shape of neurons and their compartments, previous quantitative studies of the BDNF/TrkB protein and mRNA lacked a robust normalization procedure. To overcome this problem, we have established methods that use immunofluorescence detection of ?-tubulin as a normalization factor for the quantitative analysis of protein and mRNA in primary rat cortical and striatal neurons in culture. The efficacy of this approach is demonstrated by studying the dynamic distribution of proteins and mRNA at different growth stages or conditions. Treatment of cultured neurons with KCl resulted in increased levels of TrkB protein, reduced levels of BDNF mRNA (composite of multiple transcripts) and a slight reduction in BDNF protein levels in the dendrites from the cortex. The KCl treatment also lowered the percentage of BDNF and TrkB proteins in the soma indicative of protein transport. Finally, analysis of the rat cortical and striatal neurons demonstrated comparable or even higher levels of BDNF/TrkB protein and BDNF mRNA in the neurons from the striatum. Thus, in contrast to previous observations made in vivo, striatal neurons are capable of synthesizing BDNF mRNA when cultured in growth media in vitro. The analytical approach presented here provides a detailed understanding of BDNF/TrkB levels in response to a variety of neuronal activities. Our methods could be used broadly, including applications in cell and tissue cytometry, to yield accurate quantitative data of gene expression in cellular and subcellular contexts. © 2012 International Society for Advancement of Cytometry.

Project description:ImportanceChildren with strabismus have poorer functional vision and decreased quality of life than those without strabismus.ObjectiveTo evaluate the association between strabismus and mental illness among children.Design, setting, and participantsThis cross-sectional study analyzed claims data from the OptumLabs Data Warehouse, a longitudinal deidentified commercial insurance claims database, from 12 005 189 patients enrolled in the health plan between January 1, 2007, and December 31, 2017. Eligibility criteria included age younger than 19 years at the time of strabismus diagnosis, enrollment in the health plan between 2007 and 2018, and having at least 1 strabismus claim based on International Classification of Diseases, Ninth Revision, Clinical Modification and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification codes. Controls were children in the same database with no eye disease codes other than refractive error reported. Demographic characteristics and mental illness claims were compared. Statistical analysis was conducted from December 1, 2018, to July 31, 2021.Main outcomes and measuresPresence of mental illness claims.ResultsAmong the 12 005 189 patients (6 095 523 boys [50.8%]; mean [SD] age, 8.0 [5.9] years) in the study, adjusted odds ratios for the association of mental illnesses with strabismus were 2.01 (95% CI, 1.99-2.04) for anxiety disorder, 1.83 (95% CI, 1.76-1.90) for schizophrenia, 1.64 (95% CI, 1.59-1.70) for bipolar disorder, 1.61 (95% CI, 1.59-1.63) for depressive disorder, and 0.99 (95% CI, 0.97-1.02) for substance use disorder. There was a moderate association between each strabismus type (esotropia, exotropia, and hypertropia) and anxiety disorder, schizophrenia, bipolar disorder, and depressive disorder; odds ratios ranged from 1.23 (95% CI, 1.17-1.29) for the association between esotropia and bipolar disorder to 2.70 (95% CI, 2.66-2.74) for the association between exotropia and anxiety disorder.Conclusions and relevanceThis cross-sectional study suggests that there was a moderate association between strabismus and anxiety disorder, schizophrenia, bipolar disorder, and depressive disorder but not substance use disorder. Recognizing that these associations exist should encourage mental illness screening and treatment for patients with strabismus.

Dataset Information

Decreased BDNF and TrkB mRNA expression in multiple cortical areas of patients with schizophrenia and mood disorders.

Publications

Decreased BDNF and TrkB mRNA expression in multiple cortical areas of patients with schizophrenia and mood disorders.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets