Francine Benes, M.D., Ph.D.

Professor of Psychiatry (Neuroscience)

McLean Hospital
115 Mill St
Belmont, MA 02478
Telephone: 617 855-2401
Fax: (617) 855-3199
Email: benesf@mclean.harvard.edu

Dr. Benes pioneered the application of rigorous quantitative approaches to characterize anomalies in the circuitry involving anterior cingulated (ACCx), hippocampus (HIPP) and basolateral amygdale (BLa). Her research program uses a two-pronged approach in which postmortem studies of limbic lobe structures are conducted in parallel with a rodent model for the neural circuitry changes observed in the anterior cingulated cortex and hippocampus of schizophrenic and bipolar subjects. Usina a broad array of microscopic (double and single in situ hybridization), molecular (laser capture microdissection (LCM), microarray-based gene expression profiling (GEP), quantitative RT-PCR) in postmortem and rodent studies, her lab has been systematically delineating how GABA cell dysfunction in amygdalo-hippocampal circuitry contributes to the pathophysiology of psychotic disorders. Additionall, patch clamping approaches are also used to assess the electrophysiological properties of GABA cells following amygdalae activation in awake, freely moving rats. Specifically, excessive glutmatergic activity from the BLa seems to induce dysfunction of GABA cells in layer II of the ACCx and sectors CA3/2 of the hippocampus, two sites that receive a rich innervation from this nucleus. During postnatal development, results in changes in GABA cells that remarkably dimilar to those seen in SZs and BDs. Gaba cell dysfunction seems to be further exacerbated by the ingrowth of amygdalar and dopamine afferents during the postnatal period as they form functional interactions with GABAergic interneurons. It is believed that these developmental changes may help “trigger” the onset of schizophrenia during late adolescence and early adulthood. Dr. Benes’ laboratory is currently defining the cellular endophenotypes for SZ and BD using LCM, GEP and sophisticated network association analyses of functional genetic pathways.

Selected References:

• Woo W, Walsh J, Benes F, Heckers S. (2004) Decreased expression of the NR2A subunit in GABAergic neurons in anterior cingulated cortex of schizophrenics and bipolars. Archives of General Psychiatry: 61:649-57.
• Benes FM, Burke RE, Berretta S, Walsh J, Matzilevich D, Konradi C, Minns M. (2004) Acute Amygdalar activation induces an upregulation of multi monamine G-coupled protein receptors in rat hippocampus. Molecular Psychiatry; 9:32-45.
• Gisabella B, Bolshakov VY, Benes FM, Regulation of synaptic plasticity in a schizophrenia model. (2005) Proceedings of National Academy Sciences, USA; 102:13301-13306.
• Burke RE, Walsh JP, Matzilevich DA, Benes FM. (2005) Mapping of hippocampal gene clusters regulated by the amygdale to non-linkage sites for schizophrenia. Molecular Psychiatry, 1-14.
• Benes FM, Matzilevich D, Burke R, Walsh JP. (2005) The expression of pro-apoptosis genes is increased in bipolar disorder, but not in schizophrenia. Molecular Psychiatry; 1-11.

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