A Longitudinal Study on the Neurobiological Basis of Antidepressant Efficacy in Bipolar II Disorder

Abstract

Background: Bipolar II disorder is a chronic and disabling psychiatric disorder, with subjects spending up to half of their time depressed. Current guidelines recommend the proof of concept agent lithium as a valuable treatment for acute bipolar II depression. However, little is known about the neurobiological basis of the antidepressant efficacy in bipolar II disorder. Methods: Fourteen drug-free individuals with a DSM-IV diagnosis of bipolar II disorder (BD-II) during a depressive episode (HAM-D≥18) were followed-up in a 6-week open-label trial with lithium monotherapy. All subjects had less than three lifetime mood episodes. 1H-MRS was performed at baseline and after 6 weeks (with additional 7Li-MRS at endpoint) Results: Lithium monotherapy showed a significant antidepressant efficacy in bipolar II depression. Post-treatment with lithium induced a significant increase in glutamate levels in the anterior cingulate cortex (ACC) compared to baseline levels, which was associated with brain lithium levels and clinical improvement of depressive symptoms. Conclusions: Our findings support a key role for ACC glutamate levels in the pathophysiology and therapeutics of Bipolar II disorder. These findings have important clinical and theoretical implications, also suggesting a potential role for glutamate as a valuable therapeutic target in Bipolar II depression. Keyword(s): bipolar disorder, depression, lithium, imaging, biomarker