orders & is T D h e n i r a a Lavano et al., Brain Disord Ther 2015, 4:3 p r y B Brain Disorders & Therapy DOI: 10.4172/2168-975X.1000168 ISSN: 2168-975X Review Article Open Access Deep Brain Stimulation for Treatment-Resistant Depression: Review of the Literature Angelo Lavano*, Attilio Della Torre, Giorgio Volpentesta, Giusy Guzzi, Marisa De Rose and Mary Romano Department of Neurosurgery, University “Magna Graecia” of Catanzaro, Italy Abstract Chronic Major depression is one of the most debilitating psychiatric disorders ; 8-13% of patients are treatment resistant. DBS has been applied to the following targets: Subcallosal cingulate gyrus (Brodmann 25a), Ventral Capsule and Ventral Striatum (VC/VS), Nucleus Accumbens (NA), Inferior thalamic Peduncle (ITP) Rostral Cingulate Cortex. In the contrary to neurological diseases, for major depression there is not a single pathological target structure; several brain structures presumably play different roles in the development as well as in the maintenance of symptoms; some targets are in close anatomical or functional relationship (neural networks) and an overlap of effect is plausible; different target might manipulate the pathological network at different nodes. This overview summarizes research on the mechanisms of brain networks with respect to psychiatric diseases and highlights the role of the reward system in DBS for patients with treatment-resistant depression. Keywords: Deep brain stimulation; Major depression; ventral approximately 1.5% of the general population at any one time and is a capsule; ventral striatum; Brodmann area 25; Subgenual cingulate; significant source of worldwide disability. It is defined as a state of extreme Nucleus accumbens sadness or melancholia that affects person’s activities in daily life as well as social functioning. Currently, antidepressants and/or psychotherapy Abbreviations: MAO: Monoamine Oxidase; TCA: Tricyclic are the mainstay of treatment, along with electroconvulsive therapy, Antidepressants; MD: Major Depression; DBS: Deep Brain Stimulation; which is reserved for treatment-resistant individuals. In fact 8-13% of OCD: Obsessive-Compulsive Disorder; TRD: Treatment-Resistant patients becomes refractory to these treatments at long-term follow-up Depression; SCG: Subcallosal Cingulate Gyrus; VC/VS: Ventral (treatment-resistant depression or TRD) [5]. Lately DBS has emerged Capsule and Ventral Striatum; NAcc: Nucleus Accumbens; ITP: as potential treatment for unremitting treatment-resistant depression [1,6]. Inferior Thalamic Peduncle; MFB: Medial Forebrain Bundle; slMFB: supero-lateral branch of the Medial Forebrain Bundle; HAMD-17: 17- Brain target selection for DBS in TRD has been guided tractography Item Hamilton Depression Rating Scale; HDRS: Hamilton Depression of older ablative techniques and by neuroimaging studies identifying Rating Scale; MADRS: Montgomery-Asberg Depression Rating Scale neuroanatomical structures within putatively dysfunctional neural circuits modulating different aspects of MD via connections to limbic, Introduction cortical and subcortical areas [7]. In the contrary to neurological Psychosurgery was first introduced in 1930s by Moniz with the diseases, there is not a single pathological structure in psychiatric prefrontal leucotomy, a surgical method that disrupted afferent/efferent illness; several brain structures presumably play different roles in the pathways of the frontal lobe and this method was further developed development as well as in the maintenance of symptoms, some targets in the transorbital frontal lobotomy by Freeman. Operation was crude, are in close anatomical or functional relationship (neural networks) and associated with high mortality and led to unacceptable adverse effects. an overlap of effect is plausible. At last different target might manipulate With discovery of psychotropic drugs (Lithium, Chlorpromazine, the pathological network at different nodes. The primary purpose of MAO e TCAs) in 1950s and their broad application, interest for surgery this article is to conduct a review concerning DBS in treatment of TRD declined rapidly. Improvement in knowledge of “neurophysiology with particular attention to the used targets and their clinical results. of emotion” and development of stereotactic methodology allowed to identify new targets for psychosurgery and to reach those targets Depression Neuroanatomy precisely with minimal lesions and minimal side effects. Several ablative Depression is not the result of dysfunction in a single brain region techniques were used for treatment of Major Depression (MD) such or of a single neurotransmitter system. The symptoms of depression are as anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy not simply the result of one or more of these pathways not functioning and limbic leucotomy [1,2]. appropriately, but also a failure of the other components of the system Chronic Deep Brain Stimulation (DBS) has been introduced in neurosurgical practice by Benabid for treatment of movement disorders; observation of induced psychiatric side effects in patients *Corresponding author: Angelo Lavano, Department of Neurosurgery, University “Magna Graecia” of Catanzaro, Italy, Tel: +39 0961 369 4079; E-mail: with DBS for movement disorders gave impulse to try DBS also for [email protected] psychiatric illness. Functional imaging has also played significant role Received May 07, 2015; Accepted May 26, 2015; Published June 03, 2015 in the diffusion of DBS. Another incentive was the fact that effective but Citation: Lavano A, Della Torre A, Volpentesta G, Guzzi G, De Rose M, et al. irreversible ablative interventions could be emulated using DBS with a (2015) Deep Brain Stimulation for Treatment-Resistant Depression: Review of the focused, fully reversible and treatable technique [3]. In 1999 there was Literature. Brain Disord Ther 4:168. doi:10.4172/2168-975X.1000168 the first report of use of DBS for a psychiatric disorder (anterior capsule Copyright: © 2015 Alonso F, et al. This is an open-access article distributed under DBS for OCD) [4]. the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and MD is a common and heterogeneous psychiatric disorder affecting source are credited.t Brain Disord Ther ISSN: 2168-975X BDT, an open access journal Volume 4 • Issue 3 • 1000168 Citation: Lavano A, Della Torre A, Volpentesta G, Guzzi G, DE Rose M, et al. (2015) Deep Brain Stimulation for Treatment-Resistant Depression: Review of the Literature. Brain Disord Ther 4:168. doi:10.4172/2168-975X.1000168 Page 2 of 5 to maintain homeostasis in times of increased stress to the organism. studies showed a decrease in limbic - striatal cerebral blood flow and Neurobiological correlates of depressive illness can be grouped into the increase in dorsal cortical after stimulation of area Cg25. At baseline following three main components: cortical, subcortical, and limbic FDG-PET showed elevated Cg25 metabolism (seen in responders and non-responders) and decreased PF9/46 metabolism; later FDG- The cortical component appears to give rise to the psychomotor and PET repeated at 3 and 6 months after DBS showed a decreased cognitive aspects of depressive symptoms and consists of the prefrontal Cg25 metabolism, increased PF9/46 metabolism (only responders), cortex, the dorsal portion of the anterior cingulate gyrus, and areas of decreased Hypothalamus, Anterior Insula, and PF10 metabolism (only the premotor cortex. This cortical component has access to the striatum responders) [10]. and then creates a feedback loop via the thalamus. Kennedy et al. successively published the data about the follow-up of The subcortical component involves the affective experiencing of these 20 patients after 3 to 6 years. The average response rates 1, 2, and 3 depressive symptoms, including anhedonia and sadness. This aspect years after DBS implantation were 62.5%, 46.2%, and 75%, respectively. of the neural circuit includes, among others, the subgenual anterior At the last follow-up visit (range = 3–6 years), the average response cingulate (Brodmann’s area 25), the orbitofrontal cortex, and limbic rate was 64.3%. Functional impairment in the areas of physical health structures in the brain involved with negative emotions, including the and social functioning progressively improved up to the last follow-up nucleus accumbens and amygdala. This component also interacts with visit. No significant adverse events were reported during this follow-up, the striatum and subsequently the thalamus to create a loop. although two patients died by suicide during depressive relapses [11]. The modulatory component seems to regulate the cortical and Holtzheimer et al. assessed the efficacy and safety of SCG DBS in subcortical circuits and includes the critical neuroendocrine aspects patients with TRD with both major depressive disorder (ten patients) of depressive symptoms. This “modulating pathway” involves the that bipolar II disorder (seven patients). Stimulation parameters were amygdala, pregenual anterior cingulate cortex, and the hypothalamic- frequency 130 Hz, amplitude 6.0 V, pulse width 91 microsec., contact pituitary-adrenal axis. It is hypothesized that it mediates the cortical monopolar. Patients received single-blind sham stimulation for 4 weeks and limbic circuits via inhibitory projections to these circuits [7,8]. followed by active stimulation for 24 weeks and then entered a single- Review