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Cited by 161Schizophrenia research and treatmentNerve injury and regenerationTreatment of Major Depression

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

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Ray, M T, Shannon Weickert, C, Webster, M J·2014·Translational Psychiatry
DOI 10.1038/tp.2014.26PMC PMC4035720
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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.

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  • Patients with depression and related mental illnesses have lower BDNF and/or TRKB mRNA levels, reduced cortical neuron size, lower synaptic protein levels, decreased mTOR signaling, and fewer dendritic spines/synapses in the PFC.

    “Postmortem studies have demonstrated that patients with depression and related mental illnesses have lower BDNF and/or TRKB mRNA levels (75–77), reduced cortical neuron size (75, 78, 79), lower synaptic protein levels (80), decreased mTOR signaling (81), and fewer dendritic spines/synapses (82, 83) in the PFC.”

    From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [76]

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Cited by

Sorted by citations

Authors
Ray, M. T., Shannon Weickert, C., & Webster, M. J.
Affiliations
  • Trinity Washington University (US)
  • Stanley Medical Research Institute (US)
Corresponding author
Webster, M J
ORCID
Webster, M J
Venue
Translational Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2014-05-06
Volume
4
Issue
5
Pages
e389-e389
ISSN
2158-3188 (ISSN-L)
DOI
10.1038/tp.2014.26
PMC
PMC4035720
OpenAlex
W1980841278
Cited by
161
References
9
Citations by year
2026: 9 · 2025: 15 · 2024: 13 · 2023: 10 · 2022: 14 · 2021: 20 · 2020: 11 · 2019: 6 · 2018: 12 · 2017: 8 · 2016: 18 · 2015: 14 · 2014: 11
FWCI
12.98
Type
journal article
Language
en
Open access
Licence
Locations
  • Translational Psychiatry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
Funders
  • Stanley Medical Research Institute
  • Neuroscience Research Australia
  • University of New South Wales
  • NSW Ministry of Health
  • Macquarie Group Foundation
  • Medical Research Council
  • National Health and Medical Research Council (1021970)
  • National Institute on Alcohol Abuse and Alcoholism (R28AA012725)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
brain-derived neurotrophic factor, TrkB receptor, BDNF mRNA expression, schizophrenia, bipolar disorder, major depressive disorder, mood disorders, cortical layers, prefrontal cortex, anterior cingulate cortex, inferior temporal gyrus, superior temporal gyrus, orbitofrontal cortex, neurotrophin signaling, cortical plasticity
MeSH terms
Adult, Bipolar Disorder, Major Depressive Disorder, Depressive Disorder, Major, Female, Frontal Lobe, Gyrus Cinguli, Humans, Male, Membrane Glycoproteins, Middle Aged, Protein-Tyrosine Kinases, RNA, Messenger, Schizophrenia, Temporal Lobe, Brain-Derived Neurotrophic Factor, Receptor, trkB

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