Thomas E Schlaepfer

• Professor of Psychiatry
• Head of Faculty at University of Freiburg

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when “at least two blinded...

Deep brain stimulation (DBS) in psychiatric illnesses has been clinically tested over the past 20 years. The clinical application of DBS to the superolateral branch of the medial forebrain bundle in treatment‐resistant depressed patients—one of several targets under investigation—has shown to be promising in a number of uncontrolled open label tria...

Background: Growing interest exists for superolateral medial forebrain bundle (slMFB) deep brain stimulation (DBS) in psychiatric disorders. The surgical approach warrants tractographic rendition. Commercial stereotactic planning systems use deterministic tractography which suffers from inherent limitations, is dependent on manual interaction (ROI...

Short- and long-term antidepressant effects of deep brain stimulation (DBS) in treatment-resistant depression (TRD) have been demonstrated for several brain targets in open-label studies. For two stimulation targets, pivotal randomized trials have been conducted; both failed a futility analysis. We assessed efficacy and safety of DBS of the supero-...

The clinical use of deep brain stimulation (DBS) is among the most important advances in the clinical neurosciences in the past two decades. As a surgical tool, DBS can directly measure pathological brain activity and can deliver adjustable stimulation for therapeutic effect in neurological and psychiatric disorders correlated with dysfunctional ci...

Background: Deep brain stimulation (DBS) of the superolateral branch of the medial forebrain bundle (slMFB) emerges as a - yet experimental - treatment for major depressive disorder (MDD) and other treatment refractory psychiatric diseases. First experiences have been reported from two open label pilot trials in major depression (MDD) and long-ter...

Tractography-assisted deep brain stimulation of the superolateral branch of the medial forebrain bundle (slMFB DBS) in major depression. The medial forebrain bundle is an important structure of reward and motivation. The slMFB emerges as a potential region for the treatment of major depression (and other psychiatric diseases) with DBS. So far it...

Objectives: Magnetic seizure therapy (MST) is a novel convulsive brain stimulation method in clinical testing, which is used as an alternative for electroconvulsive therapy in patients with treatment-resistant depression (TRD). Preliminary studies have suggested that MST leads to fewer cognitive adverse effects than electroconvulsive therapy but h...

Background Reports of changes in patients’ social behavior during deep brain stimulation (DBS) raised the question whether DBS induces changes in personality. This study explored if (1) DBS is associated with changes in personality in patients suffering from treatment-resistant depression (TRD), (2) how personality dimensions and depression are ass...

Introduction: Despite their importance in reward, motivation, and learning there is only sparse anatomical knowledge about the human medial forebrain bundle (MFB) and the connectivity of the ventral tegmental area (VTA). A thorough anatomical and microstructural description of the reward related PFC/OFC regions and their connection to the VTA - the...

Nach einer kurzen Einführung zur tiefen Hirnstimulation (THS) zur möglichen Behandlung von therapieresistenten Depressionen werden Therapiebausteine zur praktischen Durchführung der THS – die zurzeit nur in Form von klinischen Studien erfolgt – dargestellt. Die einzelnen Therapiebausteine umfassen hierbei die Patientenauswahl, die Operation sowie d...

Objectives: Anesthesia is required for both magnetic seizure therapy (MST) and electroconvulsive therapy (ECT), although it has anticonvulsant properties. In this case, bispectral index (BIS) monitoring, a specific electroencephalogram-derived monitoring, can be used to find the optimal seizure induction time during anesthesia to elicit adequate s...

According to the World Health Organization, depression is one of the most common and most disabling psychiatric disorders, affecting at any given time approximately 325 million people worldwide. As there is strong evidence that depressive disorders are associated with a dynamic dysregulation of neural circuits involved in emotional processing, rece...

Background: Deep brain stimulation (DBS) of the supero-lateral branch of the medial forebrain bundle (slMFB) in treatment-resistant depression (TRD) is associated with acute antidepressant effects. Objective: Long-term clinical effects including changes in quality of life, side effects and cognition as well as long-term data covering four years...

Background Acute effects of deep brain stimulation (DBS) have not been assessed systematically lacking valid instruments. In this study, a clinical tool for the assessment of acute antidepressant effects was developed and the predictive value of acute effects for long-term outcome was evaluated. Methods Acute effects were assessed with the depress...

As part of the efforts of a multi-disciplinary, international working group focused on ethical issues in neuromodulation for neuro-psychiatric disorders, we propose a novel; strategy for study design which iteratively applies new knowledge to on-going and future trials. Under current practice, device studies may be closed or categorized as “failure...

Reduced motor activity is associated with depression. Lewinsohn's cognitive behavioural model of depression assumes a lack of positive experience due to a reduced level of activity as a key aspect of depression. The acute relationship between motor activity and mood as well as between motor activity and incentive drive (the motivation to engage in...

Deep brain stimulation (DBS) is a promising putative modality for the treatment of refractory psychiatric disorders such as major depression and obsessive-compulsive disorder (OCD). Several targets have been posited; however, a clear consensus on differential efficacy and possible modes of action remain unclear. DBS to the supero-lateral branch of...

We report on a Parkinson patient with motor fluctuations and dyskinesias in whom deep brain stimulation (DBS) of the subthalamic nucleus (STN) not only improved motor symptoms but also pre-existing arachnophobia. Arachnophobia had been unchanged by the course of Parkinson’s disease but rapidly improved with STN-DBS. Both, motor effects and the impr...

Research on deep brain stimulation (DBS) for treatment-resistant psychiatric disorders has established preliminary efficacy signals for treatment-resistant depression. There are only few studies on DBS that included patients suffering from bipolar disorder. This article gives an overview of these studies concerning DBS targets, antidepressant effic...

About 30% of patients suffering from a major depressive disorder do not respond sufficiently to established pharmacological, psychotherapeutic, or somatic treatments. Advances in technology and emerging knowledge about the dysfunctional brain circuits underlying depression have led to the development of different neuromodulation techniques. The aim...

Die tiefe Hirnstimulation (THS) ist in der Therapie des schweren Morbus Parkinson längst etabliert. Seit einigen Jahren steht sie auch auf dem Prüfstand bei psychiatrischen Erkrankungen, allen voran der Depression. Weltweit wurde die THS bislang bei etwa 120 Patienten mit therapieresistenter Depression eingesetzt. Doch die Methode ist nicht unumstr...

Deep brain stimulation (DBS) is the chronic electrical stimulation of selected target sites in the brain through stereotactically implanted electrodes. More than 150 000 patients around the world have been treated to date with DBS for medically intractable conditions. The indications for DBS include movement disorders, epilepsy, and some types of m...

Due to its position in cortico-subthalamic and cortico-striatal pathways, the subthalamic nucleus (STN) is considered to play a crucial role not only in motor, but also in cognitive and motivational functions. In the present study we aimed to characterize how different aspects of reward processing are affected by disease and deep brain stimulation...

From an evolutionary perspective the startle eye-blink response forms an integral part of the human avoidance behavioral repertoire and is typically diminished by pleasant emotional states. In major depressive disorder (MDD) appetitive motivation is impaired, evident in a reduced interference of positive emotion with the startle response. Given the...

Major depressive disorder (MDD) is a prevalent and disabling condition, and many patients do not respond to available treatments. Deep transcranial magnetic stimulation (dTMS) is a new technology allowing non-surgical stimulation of relatively deep brain areas. This is the first double-blind randomized controlled multicenter study evaluating the ef...

Current perspectives on the molecular underpinnings of major depressive disorder (MDD) posit a mechanistic role of epigenetic DNA modifications in mediating the interaction between environmental risk factors and a genetic predisposition. However, conclusive evidence for differential methylation signatures in the brain’s epigenome of MDD patients as...

Magnetic seizure therapy (MST), despite being in an early phase of clinical research, has been demonstrated to be associated with antidepressant efficacy. However, safety, tolerability and efficacy data in connection with functional brain activity from larger samples are lacking. The aim of this study was to determine clinical and cognitive effects...

Background: Current neurocircuitry models of anxiety disorders posit a lack of inhibitory tone in the amygdala during acquisition of Pavlovian fear responses and deficient encoding of extinction responses in amygdala-medial prefrontal cortex circuits. Competition between these two responses often results in a return of fear, limiting control over...

Current perspectives on the evolutionary roots of human morality suggest it arose to incentivize social cooperation by promoting feelings of disgust toward selfish behavior, although the underlying neural mechanisms remain unclear. To investigate whether the ancient mammalian neuropeptide oxytocin (OXT) influences self-referential processing in the...

We investigated the moderating influence of apathy, depression and transient mood changes on executive functions under best medical treatment and under postoperative stimulation-on and -off conditions in a sample of 33 patients with Parkinson's disease (PD) after deep brain stimulation of the subthalamic nucleus (STN), 33 PD patients with pharmacol...

Ein Drittel der an einer Depression erkrankten Patienten leidet nach der Behandlung mit etablierten Therapieverfahren wie Pharmakotherapie und Psychotherapie weiterhin an erheblichen Restsymptomen. Diese therapieresistente Depression (TRD) verursacht oft grose Einschrankungen in allen Lebensbereichen und in der Lebensqualitat. Neue Hirnstimulations...

Mammalian brains contain seven primary-process affective substrates for primal emotional feelings and behaviors. Scientific labels for these interactive systems are SEEKING, RAGE, FEAR, LUST, CARE, PANIC, and PLAY. Understanding these brain substrates could lead to new treatments of emotional disturbances that accompany mental illnesses. We summari...

Objectives: Electroconvulsive therapy (ECT) is currently the most effective treatment for severe depression. However, it is frequently associated with negative cognitive side effects. Magnetic seizure therapy (MST) depicts an alternative, although experimental, convulsive treatment for major depression. Initial results suggest comparable antidepre...

Social communication through touch and mutual grooming can convey highly salient socio-emotional signals and has been shown to involve the neuropeptide oxytocin (OXT) in several species. Less is known about the modulatory influence of OXT on the neural and emotional responses to human interpersonal touch. The present randomized placebo (PLC)-contro...

Deep brain stimulation (DBS) as a putative approach for treatment resistant depression (TRD) has now been researched for about a decade. Several uncontrolled studies-all in relatively small patient populations and different target regions-have shown clinically relevant antidepressant effects in about half of the patients and very recently, DBS to a...

Es gibt in der modernen klinischen Medizin kaum etwas, über das so viele Missverständnisse existieren und das so viel Angst macht, wie die Methode der tiefen Hirnstimulation (THS), besonders in ihrer Anwendung bei neuropsychiatrischen Erkrankungen. Dieser Beitrag will am Beispiel der Depressionsbehandlung über THS informieren, um Vorurteile abzubau...

There are many fearful prejudices and misunderstandings on the method of deep brain stimulation (DBS), especially in its application to neuropsychiatric diseases. Using the example of the treatment of resistant depression this article will discuss the current state of DBS in an attempt to overcome some of the prejudices and to elaborate on its pote...

For patients with psychiatric illnesses remaining refractory to 'standard' therapies, neurosurgical procedures may be considered. Guidelines for safe and ethical conduct of such procedures have previously and independently been proposed by various local and regional expert groups. To expand on these earlier documents, representative members of cont...

Epidemiological surveys and treatment studies have clearly established that both detection and treatment rates in depression and in anxiety disorders revolve only around 50%. This figure appears to be stable, over a number of decades, despite significant educational and policy efforts to change this pattern. Since depression is a leading cause of d...

/st>Electroconvulsive therapy (ECT) is a highly effective and established treatment for depression. Magnetic seizure therapy (MST) has recently been developed and seems equally effective while associated with fewer side-effects. Both require general anaesthesia, which could be quantified using the bispectral index (BIS). We compared ECT and MST wit...

A third of patients suffering from major depression cannot be helped by conventional treatment methods. These patients face reduced quality of life, high risk of suicide, and little hope of recovery. Deep brain stimulation (DBS) is under scientific evaluation as a new treatment option for these treatment-resistant patients. First clinical studies w...

Research of Deep Brain Stimulation as a putative treatment for resistant psychiatric disorders might very well lead to the most significant development in clinical psychiatry of the last 40 years-possibly offering a rise of hope for patients to whom medicine had hitherto little to offer. Furthermore, translational research on neuromodulation will a...

Hippocampal learning is thought to induce metaplasticity that can facilitate subsequent learning. Administered at single low doses, the N-methyl-D-aspartate-type glutamate receptor (NMDAR) antagonist memantine predominantly blocks α7 nicotinic acetylcholine receptors (α7 nAChRs). We hypothesized that if α7 nAChRs contribute to learning-induced meta...

Electroconvulsive therapy (ECT) is highly effective for treatment-resistant depression (TRD); however, its use for less severe forms of depression is somewhat limited by a lack of control over current spreading to medial temporal lobe memory structures, resulting in various cognitive side effects. In contrast, magnetic seizure therapy (MST), which...

Verschiedene Neuromodulationsmethoden werden in der Therapie schwerer psychiatrischer Erkrankungen eingesetzt oder im Rahmen von klinischen Studien erforscht. Die Elektrokrampftherapie (EKT), die transkranielle Magnetstimulation (TMS), die Magnetkrampftherapie (MKT), die Vagusnervstimulation (VNS) und die tiefe Hirnstimulation (THS) werden in Bezug...

Background: Treatment-resistant major depressive disorder is a prevalent and debilitating condition. Deep brain stimulation to different targets has been proposed as a putative treatment. Methods: In this pilot study, we assessed safety and efficacy of deep brain stimulation to the supero-lateral branch of the medial forebrain bundle in seven pa...

Hippocampal learning is thought to induce metaplasticity, which can facilitate subsequent learning. Administered at single low doses, the N-methyl-d-aspartate-type glutamate receptor antagonist memantine predominantly blocks α7 nicotinic acetylcholine receptors (α7 nAChRs). Placebo-controlled administration of a single low dose of memantine in a ph...

Conceptualizations of the underlying neurobiology of major depression have changed their focus from dysfunctions of neurotransmission to dysfunctions of neurogenesis and neuroprotection. The “neurogenesis hypothesis of depression” posits that changes in the rate of neurogenesis are the underlying mechanism in the pathology and treatment of major de...

In approximately 50% of patients suffering from major depressive disorder (MDD), first-line antidepressant treatment is ineffective, and in about 30% of MDD patients, even four treatment steps yield insufficient antidepressant response. Stimulation of the human cerebral cortex with electrical currents was first described in 1874. In 1938, electroco...

Electroconvulsive therapy (ECT) is highly effective for treatment-resistant depression (TRD); however, its use for less severe forms of depression is somewhat limited by a lack of control over current spreading to medial temporal lobe memory structures, resulting in various cognitive side effects. In contrast, magnetic seizure therapy (MST), which...

Anhedonie – definiert als der Verlust der Fähigkeit, Freude zu empfinden, in Situationen, die früher Freude bereitet haben – ist ein wesentliches diagnostisches Merkmal der depressiven Störung. So stellt dieses Symptom gemäß den Kriterien der ICD-10 und des DSM-IV eines der drei Hauptsymptome der Erkrankung dar und ist somit für die Diagnose der de...

Patienten, bei denen die Durchführung einer Elektrokonvulsionstherapie indiziert ist, leiden meistens an einer schweren therapieresistenten psychiatrischen Erkrankung. Jedoch sollte wie bei anderen Therapieformen eine detaillierte Nutzen-Risiko-Analyse individuell für jeden Patienten durchgeführt werden. Eine umfassende Aufklärung des Patienten, vo...

ECT is a well-established, effective, and safe treatment for many neuropsychiatric conditions, especially major depression. However, ECT is also associated with a high relapse rate, notable side-effects, and significant social stigma. Additionally, ECT is ineffective in a sizable minority of patients. Based on this, several other brain stimulation...

Diffusion tensor imaging (DTI) is more than just a useful adjunct to invasive techniques like optogenetics which recently have tremendously influenced our understanding of the mechanisms of deep brain stimulation (DBS). In combination with other technologies, DTI helps us to understand which parts of the brain tissue are connected to others and whi...

The phenomenon of anhedonia, the inability to experience pleasure, is one of the essential elements for the diagnosis of depressive disorders. According to the criteria of both the ICD-10 and the DSM-IV, the presence of this symptom is crucial for the diagnosis of depressive disorders. In recent years scientific approaches using animal studies and...

Several brain structures play a germane role in the development and maintenance of symptoms in depression. Current studies in treatment-resistant depression (TRD) are targeting the nucleus accumbens (NAc), the medial forebrain bundle, the anterior cingulate cortex (Cg25), and the anterior limb of the internal capsule. The NAc has been studied as a...

Depression is a major complication during treatment of chronic hepatitis C virus (HCV) infection with interferon-α (IFN-α). It is unclear whether antidepressants can prevent IFN-induced depression in patients without psychiatric risk factors. To examine whether preemptive antidepressant treatment with escitalopram can decrease the incidence or seve...

Cigarette smoking, a major, yet avoidable, cause of disability and premature death, is the most prevalent form of nicotine addiction. An emerging theme in the neurobiology of nicotine addiction is the integrity of the amygdala. Using functional MRI, amygdala responses during a face perception task were compared between 28 chronic smokers [14 female...

Background / Purpose: This research looks at treatment resistant depressive patients, and the possibility of employing different brain stimulation methods, e.g. DBS, ECT and MST. Main conclusion: New brain stimulation methods may be a viable treatment option in patients with severe depression.

Deep brain stimulation (DBS) to the nucleus accumbens (NAcc-DBS) was associated with antidepressant, anxiolytic, and procognitive effects in a small sample of patients suffering from treatment-resistant depression (TRD), followed over 1 year. Results of long-term follow-up of up to 4 years of NAcc-DBS are described in a group of 11 patients. Clinic...

Treatment-resistant depression (TRD) presents many challenges for both patients and physicians. This review aims to evaluate the current status of the field of TRD and reflects the main findings of a consensus meeting held in September 2009. Literature searches were also conducted using PubMed and EMBASE. Abstracts of the retrieved articles were re...