title: Antidepressant effects after short-term and chronic stimulation of the subgenual cingulate gyrus in treatment-resistant depression.
abstract: BACKGROUND
  Deep brain stimulation (DBS) of the subcallosal cingulate gyrus (SCG) is an experimental approach in treatment-resistant depression (TRD). Apart from its potential long-term antidepressant effects acute stimulation effects have been described. We investigated putative neuroanatomical clusters in which such acute effects accumulate and followed patients over the long-term.
  
  
  METHODS
  We assessed safety and efficacy of DBS in six patients with TRD receiving bilateral DBS with electrodes implanted in the SCG. First, high intensity 130 Hz stimulation was applied on five consecutive days after surgery for 24 h comprising a sham condition in a double-blind, randomized design. Acute stimulation was conducted at all four homologous electrode contacts on both sides. Afterwards, chronic stimulation was initiated and the clinical effect was evaluated at 24-36 weeks compared to baseline (50% reduction in HAMD scores). The primary outcome criterion was depression severity as assessed with the Hamilton Depression Rating Scale (HAMD-24); secondary outcome parameters were the Montgomery-Åsberg Rating-Scale and Beck Depression Inventory following DBS. The clinical effect over the three scores was compared to sham stimulation and was correlated to the anatomical localization of active contacts by stereotactically delimiting the cluster of most effective contacts in responding patients.
  
  
  RESULTS
  Acute 24 h of stimulation showed only moderate reductions in mean HAMD-24, MADRS and BDI scores. At the last observation (24-36 weeks), two patients were remitters (HAMD-24 < 10) and the four other patients were non-responders.
  
  
  CONCLUSIONS
  Our results confirm that stimulation of the SCG is capable of exerting moderate acute and chronic antidepressant effects. The predictive value of these findings needs to be addressed in future studies.
authors.affiliation: Department of Psychiatry, Charité - Universitätsmedizin, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany; Dahlem Institute for Neuroimaging of Emotion, Freie Universität Berlin, Habelschwerdter Allee 45, 14195 Berlin, Germany; Department of Neurology, Charité - Universitätsmedizin, Campus Virchow, Augustenburger Platz 1, 13353 Berlin, Germany. Electronic address: angela.merkl@charite.de.
authors.forename: Angela
authors.initials: A
authors.lastname: Merkl
authors.forename: Gerd-Helge
authors.initials: GH
authors.lastname: Schneider
authors.forename: Thomas
authors.initials: T
authors.lastname: Schönecker
authors.forename: Sabine
authors.initials: S
authors.lastname: Aust
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Kühl
authors.forename: Andreas
authors.initials: A
authors.lastname: Kupsch
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Kühn
authors.forename: Malek
authors.initials: M
authors.lastname: Bajbouj
mesh_terms: D000328:Adult; D046690:Deep Brain Stimulation / Q000379:methods*; D003865:Major Depressive Disorder / Q000523:psychology* / Q000628:therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000523:psychology* / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006179:Gyrus Cinguli / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D013997:Time Factors; D016896:Treatment Outcome
keywords: Affective disorders; Anterior subgenual cingulate gyrus; Cg25; Deep brain stimulation; Depression; Treatment-resistant