Imaging Habenula Volume in Schizophrenia and Bipolar Disorder

Abstract

The habenula (Hb), a bilateral nucleus located next to the dorsomedial thalamus, is of particular relevance to psychiatric disorders based on preclinical evidence linking the Hb to depressive and amotivational states. However, studies in clinical samples are scant because segmentation of the Hb in neuroimaging data is challenging due to its small size and low contrast from the surrounding tissues. Negative affective states dominate the clinical course of schizophrenia and bipolar disorder and represent a major cause of disability. Diagnosis-related alterations in the volume of Hb in these disorders have therefore been hypothesized but remain largely untested. To probe this question, we used a recently developed objective and reliable semi-automated Hb segmentation method based on myelin-sensitive magnetic resonance imaging (MRI) data. We ascertained case-control differences in Hb volume from high resolution structural MRI data obtained from patients with schizophrenia (n = 95), bipolar disorder (n = 44) and demographically matched healthy individuals (n = 52). Following strict quality control of the MRI data, the final sample comprised 68 patients with schizophrenia, 32 with bipolar disorder and 40 healthy individuals. Regardless of diagnosis, age, sex, and IQ were not correlated with Hb volume. This was also the case for age of illness onset and medication (i.e., antipsychotic dose and lithium-treatment status). Case-control differences in Hb volume did not reach statistical significance; their effect size (Cohen's d) was negligible on the left (schizophrenia: 0.14; bipolar disorder: −0.03) and small on the right (schizophrenia: 0.34; bipolar disorder: 0.26). Nevertheless, variability in the volume of the right Hb was associated with suicidality in the entire patient sample (ρ = 0.29, p = 0.004) as well as in each patient group (bipolar disorder: ρ = 0.34, p = 0.04; schizophrenia: ρ = 0.25, p = 0.04). These findings warrant replication in larger samples and longitudinal designs and encourage more comprehensive characterization of Hb connectivity and function in clinical populations.

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

“…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).…”

Design, challenges, and the potential of transcriptomics to understand social behavior

“…2018 ; Drobisz and Damborská 2019 ), schizophrenia ( Zhang et al. 2017 ; Schafer et al. 2018 ), and panic disorders ( Pobbe and Zangrossi 2008 ; Mathuru and Jesuthasan 2013 ; Mathis and Kenny 2018 ; Ma et al.…”

The Habenula in the Link Between ADHD and Mood Disorder

“…In addition to ADHD and MDD, habenular deficits have been implicated in other psychiatric disorders. As is the case with MDD, although a relatively large number of animal model studies have provided support for habenular deficits in schizophrenia ( Lecourtier and Kelly, 2005 ; Heldt and Ressler, 2006 ; Lecourtier et al, 2006 ; Boulos et al, 2017 ; Fakhoury, 2017 ; Li et al, 2019 ; Hu et al, 2020 ) and drug addiction ( Velasquez et al, 2014 ; Boulos et al, 2017 ; Fakhoury, 2017 ; Mathuru, 2018 ; Mathis and Kenny, 2019 ; Hu et al, 2020 ), there has been little or inconsistent evidence regarding habenular deficits in human patients with these disorders ( Shepard et al, 2006 ; Ranft et al, 2010 ; Boulos et al, 2017 ; Fakhoury, 2017 ; Zhang et al, 2017 ; Schafer et al, 2018 ; Germann et al, 2020 ; Hu et al, 2020 ).…”