Research report Activation of a ΔFOSB dependent gene expression pattern in the dorsolateral prefrontal cortex of patients with major depressive disorder Jean-Raymond Teyssier a, b, c, ⁎, Sylviane Ragot a , Jean-Christophe Chauvet-Gélinier b, c , Benoit Trojak b, c , Bernard Bonin b, c a Department of Genetics, University Hospital, PTB, 2 rue Angélique Ducoudray, BP 37013, 21070 Dijon, France b Psychiatry Unit, Department of Neurosciences, University Hospital, 3 rue du Faubourg Raines, BP 1519, 21033 Dijon, France c Laboratory of Clinical Psychology and Psychopathology (IFR 100), University of Burgundy, France article info abstract Article history: Received 25 November 2010 Received in revised form 24 March 2011 Accepted 21 April 2011 Available online 25 May 2011 Background: A ΔFOSB mediated transcriptional response in the nucleus accumbens (NAc) is induced by chronic social stress in rodent and a 50% down-regulation of ΔFOSB has been also reported in the NAc of eight depressed subjects. To evaluate the role of ΔFOSB in the prefrontal cortex which is critically involved in negative cognitive bias associated with major depressive disorder (MDD) we have quantified the mRNA levels of ΔFOSB and of five of its major target genes in the Brodmann area 46 from 24 patients with MDD (11 with psychotic symptoms) and 12 controls. Method: Expression of the six genes has been quantified by a real-time quantitative PCR method: ΔFOSB, GRIA2 (encoding the GluR2 subunit of the AMPA receptor), SPARCL1 (encoding hevin), SG3 (encoding the secretogranin III), PCP4 (encoding the Purkinje cell protein 4), ATP6V0C (encoding a subunit of the lysosomal ATPase). Results: Expression of ΔFOSB and GRIA2 was significantly up-regulated (≈1.60) in the BA 46 of MDD patients. Overexpression of SCG3 and PCP4 was restricted to psychotic subjects. The mRNA levels of GRIA2, SCG3 and PCP4 were strongly correlated in the depressed group. Limitations: All the patients were treated by antidepressants and the number of subjects in each subgroup was rather small. Conclusions: Induction of a ΔFOSB mediated transcriptional pattern in the prefrontal cortex is opposite to the down-regulation observed in the NAc. The major consequence might be a shift in the excitability of the glutamatergic synapses which depends on GluR2 (high in the NAc and low in the BA 46). © 2011 Elsevier B.V. All rights reserved. Keywords: Major depressive disorder (MDD) Prefrontal cortex Postmortem Gene expression DELTAFOSB GRIA2 1. Introduction Major depressive disorder (MDD) is a complex and heterogeneous clinical entity shaped by pervasive morbid negativity bias, which interfere with the basic dimensions of experience including mood, cognition and memory. A compre- hensive neurobiological model is still lacking, but structural and functional cerebral imaging studies have identified brain regions and neuronal circuits implicated in the regulation of emotions, executive functions, and more recently reward and resilience (Krishnan and Nestler, 2008; Ressler and Mayberg, 2007). This rather crude “localization of functions” approach suggests that a dysregulation of the limbic-cortical circuitry, involved in the emotion–cognition control, may play a crucial role in the pathophysiology of MDD (Mayberg et al., 1999). According to this hypothesis overactivity of the emotional module (which comprises the amygdala, the nucleus accumbens, and the ventromedial prefrontal cortex) and hypoactivity of the dorsolateral prefrontal cortex (DLPFC: Journal of Affective Disorders 133 (2011) 174–178 ⁎ Corresponding author at: Department of Genetics, University Hospital, PTB, 2 rue Angélique Ducoudray, BP 37013, 21070 Dijon, France. Tel.: +33 38029572; fax: + 33 380293566. E-mail address: teyssier@u-bourgogne.fr (J.-R. Teyssier). 0165-0327/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.jad.2011.04.021 Contents lists available at ScienceDirect Journal of Affective Disorders journal homepage: www.elsevier.com/locate/jad