Neurostimulatory and ablative treatment options in major depressive disorder: a systematic review

Introduction Major depressive disorder is one of the most disabling and common diagnoses amongst psychiatric disorders, with a current worldwide prevalence of 5-10% of the general population and up to 20-25% for the lifetime period. Historical perspective Nowadays, conventional treatment includes psychotherapy and pharmacotherapy; however, more than 60% of the treated patients respond unsatisfactorily, and almost one fifth becomes refractory to these therapies at long-term follow-up. Nonpharmacological techniques Growing social incapacity and economic burdens make the medical community strive for better therapies, with fewer complications. Various nonpharmacological techniques like electroconvulsive therapy, vagus nerve stimulation, transcranial magnetic stimulation, lesion surgery, and deep brain stimulation have been developed for this purpose. Discussion We reviewed the literature from the beginning of the twentieth century until July 2009 and described the early clinical effects and main reported complications of these methods. © The Author(s) 2010.Link_to_subscribed_fulltex

Deep Brain Stimulation of Medial Dorsal and Ventral Anterior Nucleus of the Thalamus in OCD: A Retrospective Case Series

The current notion that cortico-striato-thalamo-cortical circuits are involved in the pathophysiology of obsessive-compulsive disorder (OCD) has instigated the search for the most suitable target for deep brain stimulation (DBS). However, despite extensive research, uncertainty about the ideal target remains with many structures being underexplored. The aim of this report is to address a new target for DBS, the medial dorsal (MD) and the ventral anterior (VA) nucleus of the thalamus, which has thus far received little attention in the treatment of OCD.In this retrospective trial, four patients (three female, one male) aged 31-48 years, suffering from therapy-refractory OCD underwent high-frequency DBS of the MD and VA. In two patients (de novo group) the thalamus was chosen as a primary target for DBS, whereas in two patients (rescue DBS group) lead implantation was performed in a rescue DBS attempt following unsuccessful primary stimulation.Continuous thalamic stimulation yielded no significant improvement in OCD symptom severity. Over the course of thalamic DBS symptoms improved in only one patient who showed "partial response" on the Yale-Brown Obsessive Compulsive (Y-BOCS) Scale. Beck Depression Inventory scores dropped by around 46% in the de novo group; anxiety symptoms improved by up to 34%. In the de novo DBS group no effect of DBS on anxiety and mood was observable.MD/VA-DBS yielded no adequate alleviation of therapy-refractory OCD, the overall strategy in targeting MD/VA as described in this paper can thus not be recommended in DBS for OCD. The magnocellular portion of MD (MDMC), however, might prove a promising target in the treatment of mood related and anxiety disorders

Tractographic Analysis of Historical Lesion Surgery for Depression

Various surgical brain ablation procedures for the treatment of refractory depression were developed in the twentieth century. Most notably, key target sites were (i) the anterior cingulum, (ii) the anterior limb of the internal capsule, and (iii) the subcaudate white matter, which were regarded as effective targets. Long-term symptom remissions were better following lesions of the anterior internal capsule and subcaudate white matter than of the cingulum. It is possible that the observed clinical improvements of these various surgical procedures may reflect shared influences on presently unspecified brain affect-regulating networks. Such possibilities can now be analyzed using modern brain connectivity procedures such as diffusion tensor imaging (DTI) tractography. We determined whether the shared connectivities of the above lesion sites in healthy volunteers might explain the therapeutic effects of the various surgical approaches. Accordingly, modestly sized historical lesions, especially of the anatomical overlap areas, were ‘implanted' in brain-MRI scans of 53 healthy subjects. These were entered as seed regions for probabilistic DTI connectivity reconstructions. We analyzed for the shared connectivities of bilateral anterior capsulotomy, anterior cingulotomy, subcaudate tractotomy, and stereotactic limbic leucotomy (a combination of the last two lesion sites). Shared connectivities between the four surgical approaches mapped onto the most mediobasal aspects of bilateral frontal lobe fibers, including the forceps minor and the anterior thalamic radiations that contacted subgenual cingulate regions. Anatomically, convergence of these shared connectivities may derive from the superolateral branch of the medial forebrain bundle (MFB), a structure that connects these frontal areas to the origin of the mesolimbic dopaminergic ‘reward' system in the midbrain ventral tegmental area. Thus, all four surgical anti-depressant approaches may be promoting positive affect by converging influences onto the MFB