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.
Highlights
Schizophrenia (SCZ) and bipolar disorder (BD) consistently rank among the leading causes of disability worldwide [1]
Patients fulfilled diagnostic criteria of either BD, type I or SCZ based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) [54] while healthy individuals were included if they had no lifetime personal history of mental disorders and no family history of SCZ or BD
Medication type and dose was recorded in all patients and the daily antipsychotic dose was converted to chlorpromazine equivalents (CPZE) [60]
Summary
Schizophrenia (SCZ) and bipolar disorder (BD) consistently rank among the leading causes of disability worldwide [1] These disorders show similarities across multiple levels, including shared genetic risk factors [2, 3], overlapping brain structural [4,5,6,7] and cognitive deficits [8, 9] and common abnormalities in reality testing and affect regulation [10, 11]. A similar overlap is noted for amotivational states as patients with either SCZ or BD seem to report similar rates of anhedonia, avolition and asociality [15, 16] Both disorders are associated with increased suicidality in recent onset and in chronic patients [17,18,19,20]
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