Lithium monotherapy associated clinical improvement effects on amygdala-ventromedial prefrontal cortex resting state connectivity in bipolar disorder

J Affect Disord. 2018 Jan 1:225:4-12. doi: 10.1016/j.jad.2017.06.047. Epub 2017 Jun 27.

Abstract

Background: This study, for the first time, investigated lithium monotherapy associated effects on amygdala- ventromedial prefrontal cortex (vMPFC) resting-state functional connectivity and correlation with clinical improvement in bipolar disorder (BP) METHODS: Thirty-six medication-free subjects - 24 BP (12 hypomanic BPM) and 12 depressed (BPD)) and 12 closely matched healthy controls (HC), were included. BP subjects were treated with lithium and scanned at baseline, after 2 weeks and 8 weeks. HC were scanned at same time points but were not treated. The effect of lithium was studied for the BP group as a whole using two way (group, time) ANOVA while regressing out effects of state. Next, correlation between changes in amygdala-vMPFC resting-state connectivity and clinical global impression (CGI) of severity and improvement scale scores for overall BP illness was calculated. An exploratory analysis was also conducted for the BPD and BPM subgroups separately.

Results: Group by time interaction revealed that lithium monotherapy in patients was associated with increase in amygdala-medial OFC connectivity after 8 weeks of treatment (p = 0.05 (cluster-wise corrected)) compared to repeat testing in healthy controls. Increased amygdala-vMPFC connectivity correlated with clinical improvement at week 2 and week 8 as measured with the CGI-I scale.

Limitations: The results pertain to open-label treatment and do not account for non-treatment related improvement effects. Only functional connectivity was measured which does not give information regarding one regions effect on the other.

Conclusions: Lithium monotherapy in BP is associated with modulation of amygdala-vMPFC connectivity which correlates with state-independent global clinical improvement.

MeSH terms

  • Adult
  • Amygdala / diagnostic imaging*
  • Amygdala / drug effects
  • Amygdala / physiopathology
  • Bipolar Disorder / diagnostic imaging
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / pathology
  • Case-Control Studies
  • Depression / physiopathology
  • Female
  • Humans
  • Lithium / therapeutic use*
  • Magnetic Resonance Imaging / methods
  • Male
  • Nerve Net / diagnostic imaging
  • Prefrontal Cortex / diagnostic imaging*
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiopathology

Substances

  • Lithium