Remission of Major Depression Under Deep Brain Stimulation of the Lateral Habenula in a Therapy-Refractory Patient

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, J5, D-68159 Mannheim, Germany.
Biological psychiatry (Impact Factor: 10.26). 10/2009; 67(2):e9-e11. DOI: 10.1016/j.biopsych.2009.08.027
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Available from: Andreas Meyer-Lindenberg, Nov 10, 2015
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    • "The LHb controls monoaminergic systems in the midbrain, and may act as a center for the etiology of psychiatric disorders. The LHb has been implicated in depression: in vivo activation of LHb neurons induces depressive-like behaviors (Han et al., 2015), while inactivation can correct depression symptoms (Addolorato et al., 2012; Fowler and Kenny, 2014; Sachs et al., 2015; Sartorius et al., 2010; Winter et al., 2011; Yang et al., 2008). Based on our in vitro study, we propose that 5-HT excites LHb neurons via the binding to the 5-HT 2/3 Rs, and the activation of TRP channels. "
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    ABSTRACT: There is growing interest on the role of the lateral habenula (LHb) in depression, because it closely and bilaterally connects with the serotoninergic raphe nuclei. The LHb sends glutamate efferents to the raphe nuclei, while it receives serotoninergic afferents, and expresses a high density of serotonin (5-HT) receptors. Recent studies suggest that 5-HT receptors exist both in the presynaptic and postsynaptic sites of LHb neurons, and activation of these receptors may have different effects on the activity of LHb neurons. The current study focused on the effect of 5-HT on the postsynaptic membrane. We found that 5-HT initiated a depolarizing inward current (I(5-HTi)) and accelerated spontaneous firing in ∼80% of LHb neurons in rat brain slices. I(5-HTi) was also induced by the 5-HT uptake blocker citalopram, indicating activity of endogenous 5-HT. I(5-HTi) was diminished by 5-HT2/3 receptor antagonists (ritanserin, SB-200646 or ondansetron), and activated by the selective 5-HT2/3 agonists 1-(3-Chlorophenyl) piperazine hydrochloride or 1-(3-Chlorophenyl) biguanide hydrochloride. Furthermore, I(5-HTi) was attenuated by 2-Aminoethyl diphenylborinate, a blocker of transient receptor potential channels, and an IP3 receptor inhibitor, indicating the involvement of transient receptor potential channels. These results demonstrate that the reciprocal connection between the LHb and the 5-HT system highlights a key role for 5-HT stimulation of LHb neurons that may be important in the pathogenesis of depression.
    Full-text · Article · Oct 2015 · Neuropharmacology
    • "In humans, patients with recurrent MDD showed increased habenular activity after tryptophan depletion (Morris et al., 1999; Roiser et al., 2009). Moreover, a patient who underwent deep brain stimulation of Hb for treatment-resistant depression presented a full recovery, presumably as the result of suppressing the habenular functional hyperactivity (Sartorius et al., 2010). A recent functional neuroimaging study revealed a differential pattern of habenular activation during aversive conditioning in non-medicated patients with MDD, with no differences in baseline blood flow or Hb volume compared to healthy subjects (Lawson et al., 2014). "
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    ABSTRACT: The habenula (Hb) can play an important role in major depressive disorder (MDD) as it is a key node between fronto-limbic areas and midbrain monoaminergic structures. In vivo neuroimaging studies have shown reductions in Hb volume in a post-mortem sample of patients with affective disorders but findings in unipolar MDD are not consistent. The current study aimed to investigate whether the Hb volume differed between patients with different stages of unipolar MDD and healthy subjects. We also explored differences in grey (GM) and white matter (WM) volumes and potential age and gender effects. High-resolution images were acquired using a 3T-scanner from 95 participants (21 with first-episode MDD; 20 with remitted-recurrent MDD; 20 with treatment-resistant/chronic MDD; and 34 healthy controls).Two researchers blinded to clinical data manually delineated habenular nuclei, with excellent inter-rater agreement. Multivariate analysis of covariance revealed a significant group-by-gender interaction (F9,258=2.22; p=0.02). Univariate effects emerged for Hb-WM volumes (F3,86=3.12; p=0.03) but not for total Hb volumes (F3,86=0.59; p=0.62) or Hb-GM volumes (F3,86=2.01; p=0.12). Women with a first-episode MDD had greater Hb-WM volumes than healthy controls and patients with treatment-resistant/chronic MDD (p<0.01). These findings remained unaltered when controlled for total intracranial volume or medication load. Our results do not support decreased total Hb volumes in unipolar MDD, in patients with first-episode or in patients with long-lasting recurrent or chronic depression. However, the increased Hb-WM volume we observed in women with a first-episode suggests involvement of Hb and its projections in early stages of the recovery process and in the course of MDD.
    No preview · Article · Sep 2015 · European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology
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    • "Increased activity in the lateral habenula (induced e.g., by stress) can lead to an increase in the salience of aversive stimuli and a decrease in the saliency of appetitive stimuli, and as such offers a plausible neurobiological substrate for the negative information-processing bias seen in e.g., depressed patients (Disner et al., 2011; Willner et al., 2013). Dysfunctions of this limbic-striatal relay nucleus have been implicated in depression and schizophrenia (Hikosaka et al., 2008), and recently beneficial effects were reported in a treatment-resistant depressed patient receiving deep brain stimulation in this target (Sartorius et al., 2010). Overall, more studies are needed before we can make conclusive statements regarding the role of wanting, liking, and learning processes in anhedonia in psychiatric disorders. "
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    ABSTRACT: Anhedonia, the lack of pleasure, has been shown to be a critical feature of a range of psychiatric disorders. Yet, it is currently measured primarily through subjective self-reports and as such has been difficult to submit to rigorous scientific analysis. New insights from affective neuroscience hold considerable promise in improving our understanding of anhedonia and for providing useful objective behavioral measures to complement traditional self-report measures, potentially leading to better diagnoses and novel treatments. Here, we review the state-of-the-art of hedonia research and specifically the established mechanisms of wanting, liking, and learning. Based on this framework we propose to conceptualize anhedonia as impairments in some or all of these processes, thereby departing from the longstanding view of anhedonia as solely reduced subjective experience of pleasure. We discuss how deficits in each of the reward components can lead to different expressions, or subtypes, of anhedonia affording novel ways of measurement. Specifically, we review evidence suggesting that patients suffering from depression and schizophrenia show impairments in wanting and learning, while some aspects of conscious liking seem surprisingly intact. Furthermore, the evidence suggests that anhedonia is heterogeneous across psychiatric disorders, depending on which parts of the pleasure networks are most affected. This in turn has implications for diagnosis and treatment of anhedonia.
    Full-text · Article · Mar 2015 · Frontiers in Behavioral Neuroscience
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