Consider Role of Glutamatergic Habenula-projecting Globus Pallidus in OCD

Loonen, Anton J. M.; Ivanova, Svetlana A.

doi:10.1055/a-0835-6447

Cited by 4 publications

(3 citation statements)

References 10 publications

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“…For example, DBS of LHb in rats reduced sucrose seeking and cocaine seeking behavior (51, 52) consistent with the putative role of Hb in addiction (17,34,53,54). Furthermore, studies have demonstrated that the Hb plays a role in the pathophysiology of a number of neuropsychiatric disorders beyond depression and addiction such as schizophrenia (15,55,56), bipolar disorder (BD) (15,33,(57)(58)(59), obsessive-compulsive disorder (OCD) (60,61) and autism (62).…”

Section: Introductionmentioning

confidence: 75%

Deep Brain Stimulation of the Habenula: Systematic Review of the Literature and Clinical Trial Registries

et al. 2021

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The habenula is a small bilateral epithalamic structure that plays a key role in the regulation of the main monoaminergic systems. It is implicated in many aspects of behavior such as reward processing, motivational behavior, behavioral adaptation, and sensory integration. A role of the habenula has been indicated in the pathophysiology of a number of neuropsychiatric disorders such as depression, addiction, obsessive-compulsive disorder, and bipolar disorder. Neuromodulation of the habenula using deep brain stimulation (DBS) as potential treatment has been proposed and a first successful case of habenula DBS was reported a decade ago. To provide an overview of the current state of habenula DBS in human subjects for the treatment of neuropsychiatric disorders we conducted a systematic review of both the published literature using PUBMED and current and past registered clinical trials using ClinicalTrials.gov as well as the International Clinical Trials Registry Platform. Using PRISMA guidelines five articles and five registered clinical trials were identified. The published articles detailed the results of habenula DBS for the treatment of schizophrenia, depression, obsessive-compulsive disorder, and bipolar disorder. Four are single case studies; one reports findings in two patients and positive clinical outcome is described in five of the six patients. Of the five registered clinical trials identified, four investigate habenula DBS for the treatment of depression and one for obsessive-compulsive disorder. One trial is listed as terminated, one is recruiting, two are not yet recruiting and the status of the fifth is unknown. The planned enrollment varies between 2 to 13 subjects and four of the five are open label trials. While the published studies suggest a potential role of habenula DBS for a number of indications, future trials and studies are necessary. The outcomes of the ongoing clinical trials will provide further valuable insights. Establishing habenula DBS, however, will depend on successful randomized clinical trials to confirm application and clinical benefit of this promising intervention.

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Section: Introductionmentioning

confidence: 75%

Deep Brain Stimulation of the Habenula: Systematic Review of the Literature and Clinical Trial Registries

et al. 2021

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“…However, the distinct connections of the (more than 15) different habenula subnuclei are organised in far too complex a way to allow fruitful analysis of the underlying mechanisms to explain these findings. In addition, major depressive disorder (Loonen & Ivanova, 2016b;Duman et al, 2019), obsessive-compulsive disorder (Vlček et al, 2018;Loonen & Ivanova, 2019b) and schizophrenia (Owen et al, 2016;Guan et al, 2021) are composite disorders which are likely to be simultaneously caused by multiple neurobiological disturbances to a mutually variable extent. The role of the habenula in the symptoms of neuropsychiatric disorders based on non-congenital brain damage has been little investigated.…”

Section: Putative Involvement Of Habenular Physiology In (Neuro) Psyc...mentioning

confidence: 99%

Circuits regulating pleasure and happiness – focus on potential biomarkers for circuitry including the habenuloid complex

Loonen

Ivanova

2022

Acta Neuropsychiatr.

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Introduction The multiplicity and complexity of the neuronal connections in the central nervous system make it difficult to disentangle circuits that play an essential role in the development or treatment of (neuro)psychiatric disorders. By choosing the evolutionary development of the forebrain as a starting point, a certain order in the connections can be created. The dorsal diencephalic connection (DDC) system can be applied for the development of biomarkers that can predict treatment response. Materials and methods After providing a brief introduction to the theory, we examined neuroanatomical publications on the connectivity of the DDC system. We then searched for neurochemical components that are specific for the habenula. Results and discussion The best strategy to find biomarkers which reflect the function of the habenular connection is to use genetic variants of receptors, transporters or enzymes specific to this complex. By activating these with probes and measuring the response in people with different functional genotypes, the usefulness of biomarkers can be assessed. Conclusion The most promising biomarkers in this respect are those linked to activation or inhibition of the nicotine receptor, dopamine D4 receptor, μ-opioid receptor and also those of the functioning of habenular glia cells (astrocytes and microglia).

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“…It is, furthermore, a key region for reward processing and critically involved in a number of depressive behaviours 1 , 6 , 31 , 32 . In addition, studies have implicated the habenula in bipolar disorder (BD) 33 – 35 , obsessive–compulsive disorder (OCD) 36 , 37 as well as schizophrenia 38 , 39 and altered habenula volume has been reported in subjects diagnosed with BD and schizophrenia 40 , 41 . Previous studies have reported altered amygdala volume in subjects with ASD compared to age matched controls 25 , 42 .…”

Section: Introductionmentioning

confidence: 99%

Involvement of the habenula in the pathophysiology of autism spectrum disorder

Germann

Gouveia

Brentani

et al. 2021

Sci Rep

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The habenula is a small epithalamic structure with widespread connections to multiple cortical, subcortical and brainstem regions. It has been identified as the central structure modulating the reward value of social interactions, behavioral adaptation, sensory integration and circadian rhythm. Autism spectrum disorder (ASD) is characterized by social communication deficits, restricted interests, repetitive behaviors, and is frequently associated with altered sensory perception and mood and sleep disorders. The habenula is implicated in all these behaviors and results of preclinical studies suggest a possible involvement of the habenula in the pathophysiology of this disorder. Using anatomical magnetic resonance imaging and automated segmentation we show that the habenula is significantly enlarged in ASD subjects compared to controls across the entire age range studied (6–30 years). No differences were observed between sexes. Furthermore, support-vector machine modeling classified ASD with 85% accuracy (model using habenula volume, age and sex) and 64% accuracy in cross validation. The Social Responsiveness Scale (SRS) significantly differed between groups, however, it was not related to individual habenula volume. The present study is the first to provide evidence in human subjects of an involvement of the habenula in the pathophysiology of ASD.

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Consider Role of Glutamatergic Habenula-projecting Globus Pallidus in OCD

Cited by 4 publications

References 10 publications

Deep Brain Stimulation of the Habenula: Systematic Review of the Literature and Clinical Trial Registries

Deep Brain Stimulation of the Habenula: Systematic Review of the Literature and Clinical Trial Registries

Circuits regulating pleasure and happiness – focus on potential biomarkers for circuitry including the habenuloid complex

Involvement of the habenula in the pathophysiology of autism spectrum disorder

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