RT conference output
T1 Early antidepressant response of deep brain stimulation for depression treatment: a translational study.
A1 Perez-Caballero, Laura
A1 Pérez- Egea, R.
A1 Puigdemont, D.
A1 Molet, J.
A1 Micó Segura, Juan Antonio
A1 Pérez, V
A1 Berrocoso Domínguez, Esther María
A2 Psicología
K1 Deep Brain Stimulation (DBS)
K1 depressive disorder
AB Background: Deep Brain Stimulation (DBS) in the subgenualcingulated (Cg25) has revealed as a new and promising innovativetechnique that may be able to provide sustained remission inresistant major depressive disorder. However and strikingly, thefirst clinical series have reported an initial large effect followedby a decay in the first month of treatment [1][2]. This unexpectedphenomenon, attributed to a possible placebo or to an organiccause, remains to be resolved.Methods: To address this question the current study will focusin the early phase of DBS treatment in a translational study. Tothis end, we characterized the effect of electrode implantationin the infralimbic cortex (the rodent Cg25 correlate), without orwith electrical stimulation (i.e. DBS), in experimental animalsthat are devoid of any placebo effect by using the forced swimmingtest (mFST), an animal model of antidepressant activity.Furthermore, the effect of analgesic/antiinflammatory drugs thatare usually prescribed postoperatively in patients will be evaluated.Additionally, these results will be compared with the earlyoutcome of a controlled clinical trial of DBS procedure in theCg25 in patients diagnosed with treatment-resistant depression.Results were analyzed by a one- or two-way ANOVA followed byBonferroni test. p<0.05 were considered to be significant.Results: The preclinical results demonstrated that animals justwith electrode implantation showed a similar antidepressant-likeeffect than those which in addition received electrical brain stimulation.This effect was of similar magnitude than animals treatedwith imipramine and was not related with a general increase inlocomotor activity. This “electrode effect” was via a main actionon 5-HT transmission because the decrease of the immobilitywas accompanied by an increase of swimming behaviour andthe antidepressant-like effect was blocked by the pre-treatmentwith pCPA, inhibitor of serotonin synthesis. On the other hand,this effect was specific to this area because similar procedurein the subthalamic nucleus did not produce any modification.Furthermore, the “electrode effect” could be caused by a regionalneuroinflammation because the antidepressant-like effectwas self-limiting over the time and correlated with an increase ofGFAP inmunoreactivity. In agreement, this effect was preventedby indomethacin or acetaminophen treatment. Accordingly, westudied restrospectively the patients evolution. Thus, we saw thatalthough all patients received bilateral DBS, there was a differentevolution over the first month if the patients were treated withanalgesic/anti-inflammatory treatment or not. Indeed, non-treatedpatients showed a dramatic reduction in HDRS score in the firstweek after intervention and this state was pretty conserved over the month. In contrast, the group that was under analgesic/antiinflammatorytreatment reached the response criterion in the firstweek after intervention but there was a deterioration of depressivesymptomatology over the following weeks.Conclusions: Our study shows that electrode implantation issufficient to produces an early antidepressant-like effect of similarmagnitude to those who are receiving DBS too. Moreover, wepropose that the use of antiinflamatory drugs may oppose to theearly response in DBS-treated patients.
PB Elsevier
SN 0924-977X
YR 2011
FD 2011
LK http://hdl.handle.net/10498/38918
UL http://hdl.handle.net/10498/38918
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 21-sep-2026