Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia

Anatomical and molecular abnormalities of excitatory neurons in the dorsolateral prefrontal cortex (DLPFC) are found in schizophrenia. We hypothesized that brain-derived neurotrophic factor

(BDNF), a protein capable of increasing pyramidal neuron spine density and augmenting synaptic efficacy of glutamate, may be abnormally expressed in the DLPFC of patients with schizophrenia.

Using an RNase protection assay and Western blotting, we detected a significant reduction in BDNF mRNA (mean=23%) and protein (mean=40%) in the DLPFC of patients with schizophrenia compared

to normal individuals. At the cellular level, BDNF mRNA was expressed at varying intensities in pyramidal neurons throughout layers II, III, V, and VI of DLPFC. In patients with

schizophrenia; neuronal BDNF expression was decreased in layers III, V and VI. Our study demonstrates a reduction in BDNF production and availability in the DLPFC of schizophrenics, and

suggests that intrinsic cortical neurons, afferent neurons, and target neurons may receive less trophic support in this disorder.

We thank Dr David Kaplan for the generous donation of BDNF antibody. We thank our dedicated research assistants who contributed to this work: Robert Fatula, Nader Halim, Deborah Kittell,

Davinna Ligons, Benjamin McClintock, and Tara Romanczyk. We also thank those instrumental in the brain collection effort: Juraj Cervenak MD and Yeva Snitkovsky. This work was supported, in

part, by a NARSAD young investigator award to CSW.

Clinical Brain Disorders Branch, NIMH, IRP, NIH, Bethesda, MD, USA

C S Weickert, T M Hyde, B K Lipska, M M Herman, D R Weinberger & J E Kleinman

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