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Decreased expression of Freud-1/CC2D1A, a transcriptional repressor of the 5-HT1A receptor, in the prefrontal cortex of subjects with major depression

  • Bernadeta Szewczyk (a1) (a2), Paul R. Albert (a3), Anastasia Rogaeva (a3), Heidi Fitzgibbon (a1), Warren L. May (a4), Grazyna Rajkowska (a1), Jose J. Miguel-Hidalgo (a1), Craig A. Stockmeier (a1) (a5), William L. Woolverton (a1), Patrick B. Kyle (a6), Zhixia Wang (a1) and Mark C. Austin (a1)
  • DOI:
  • Published online: 15 April 2010

Serotonin1A (5-HT1A) receptors are reported altered in the brain of subjects with major depressive disorder (MDD). Recent studies have identified transcriptional regulators of the 5-HT1A receptor and have documented gender-specific alterations in 5-HT1A transcription factor and 5-HT1A receptors in female MDD subjects. The 5′ repressor element under dual repression binding protein-1 (Freud-1) is a calcium-regulated repressor that negatively regulates the 5-HT1A receptor gene. This study documented the cellular expression of Freud-1 in the human prefrontal cortex (PFC) and quantified Freud-1 protein in the PFC of MDD and control subjects as well as in the PFC of rhesus monkeys chronically treated with fluoxetine. Freud-1 immunoreactivity was present in neurons and glia and was co-localized with 5-HT1A receptors. Freud-1 protein level was significantly decreased in the PFC of male MDD subjects (37%, p=0.02) relative to gender-matched control subjects. Freud-1 protein was also reduced in the PFC of female MDD subjects (36%, p=0.18) but was not statistically significant. When the data was combined across genders and analysed by age, the decrease in Freud-1 protein level was greater in the younger MDD subjects (48%, p=0.01) relative to age-matched controls as opposed to older depressed subjects. Similarly, 5-HT1A receptor protein was significantly reduced in the PFC of the younger MDD subjects (48%, p=0.01) relative to age-matched controls. Adult male rhesus monkeys administered fluoxetine daily for 39 wk revealed no significant change in cortical Freud-1 or 5-HT1A receptor proteins compared to vehicle-treated control monkeys. Reduced protein expression of Freud-1 in MDD subjects may reflect dysregulation of this transcription factor, which may contribute to the altered regulation of 5-HT1A receptors observed in subjects with MDD. These data may also suggest that reductions in Freud-1 protein expression in the PFC may be associated with early onset of MDD.

Corresponding author
Address for correspondence: M. C. Austin, Ph.D., Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 North St. Street, Jackson, MS39216-4505, USA. Tel.: 601-984-5742Fax: 601-984-5899Email:
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