Abstract
The pathogenesis of schizophrenia (SCH) is associated with the dysfunction of monoamine neurotransmitters, the synthesis and release of which are mainly regulated by a key structure, the habenular (Hb) nucleus. However, little is known regarding whether SCH is associated with structural or functional alterations in the Hb. In this study, we combined structural and resting-state functional magnetic resonance imaging to investigate the changes in volume and functional connectivity of the Hb in 15 patients with SCH vs. 16 age- and gender-matched healthy controls (HCs). Morphologically, the absolute volume of the bilateral Hb was significantly lower in the SCH patients than in the HCs. Functionally, the bilateral Hb showed significantly enhanced functional connectivity with the left medial prefrontal cortex (mPFC) in the SCH patients. Additionally, the SCH patients exhibited increased functional connectivity of the left Hb with the left lingual gyrus and right inferior frontal gyrus (IFG). A further exploratory analysis revealed that the SCH patients showed increased functional connectivity between the right Hb and several subcortical regions related to dopaminergic pathways, including the left ventral striatum, caudate and putamen. Finally, the increased functional connectivity of the right Hb with the mPFC was positively correlated with the Brief Psychiatric Rating Scale (BPRS) scores in the patients. Together, these results suggest that the altered volume and functional connectivity of the Hb may be involved in the pathogenesis of SCH and thus that the Hb may serve as a potential target in developing new therapeutic strategies in SCH.
Highlights
Schizophrenia (SCH) is a complicated mental disorder characterized by severe dysfunctions of thought, affect and behavior (Andreasen, 1999)
The Hb is reported to show a higher incidence of calcification in patients with SCH (Sandyk, 1992). All these findings suggest a critical role for the Hb in the pathogenesis of SCH
SCH was diagnosed by an experienced clinical psychiatrist and a trained interviewer according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria and excluded the presence of Axis I conditions in control participants (Mai et al, 2008)
Summary
Schizophrenia (SCH) is a complicated mental disorder characterized by severe dysfunctions of thought, affect and behavior (Andreasen, 1999). The habenula (Hb) is an epithalamic structure located in the dorsal diencephalic conduction system It includes the medial habenula and lateral habenula (LHb) and provides an important link between the limbic forebrain and the midbrain regions (Sutherland, 1982; Andres et al, 1999). The regions included the bilateral SN/VTA, caudate, putamen and ventral striatum which were related to SCH (Guillin et al, 2007; Ellison-Wright et al, 2008; Yoon et al, 2013), and be important downstream targets of the Hb. Given the important role of the Hb in regulating the DA system, the dysfunction of which is closely related to the pathogenesis of SCH, we characterized the SCH-related alterations of Hb in both brain structure and function to assess its potential as an imaging biomarker
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