fMRI brain activation changes following treatment of a first bipolar manic episode

Abstract

Objectives: We tested the hypothesis that, with treatment, functional magnetic resonance imaging (fMRI) regional brain activation in first-episode mania would normalize - i.e., that differences from healthy subjects would diminish over time, and would be associated with clinical remission status, potentially identifying neuroanatomic treatment response markers.

Methods: Forty-two participants with bipolar I disorder were recruited during their first manic episode, pseudo-randomized to open-label lithium or quetiapine, and followed for 8 weeks. fMRI scans were obtained at baseline and then after 1 and 8 weeks of treatment, while participants performed a continuous performance task with emotional distracters. Healthy participants received fMRI scans at these same intervals. Specific region-of-interest (ROI) activations within prefrontal emotional networks were assessed as potential measures of treatment response.

Results: ROI data were reduced using exploratory factor analysis, which identified five factors that were organizationally consistent with functional anatomic models of human emotion modulation. Half of the participants with bipolar disorder achieved remission by Week 8 and were contrasted with the other half that did not. Analyses demonstrated that, in the bipolar disorder group in general, treatment led to decreases in activation across brain regions toward healthy subject values. However, differences in activation changes were observed between subjects with bipolar disorder who did or did not achieve remission in subcortical and amygdala factors.

Conclusions: These findings provide evidence for potential neuroanatomic treatment response markers in first-episode bipolar disorder.

Trial registration: ClinicalTrials.gov NCT00609193.

Keywords: amygdala; bipolar disorder; fMRI; first-episode; mania; prefrontal; treatment.

Conflict of interest statement

Disclosures

We do not believe that any of these relationships could influence the reported results, but we report them for transparency. SMS serves as DSMB chair for Sunovion and a consultant to Roche and Procter and Gamble. JRS receives research support through the University of Cincinnati from Eli Lilly & Co., Edgemont, Forest Research Laboratories, Lundbeck, Shire, and Assurex (material only); and is a consultant to Neuronetics. MPD receives research support through the University of Cincinnati from Eli Lilly & Co., Otsuka, GlaxoSmithKline, Merck, Martek, Novartis, Lundbeck, Shire, Purdue, Sunovion, and Pfizer; and is a consultant to Pfizer, Lundbeck, Sunovian, Otsuka, Supernus, Forest, Actavis, Jansen, and Neurostar. CMA has received research support through the University of Cincinnati from Johnson & Johnson, Merck, Forest, Otsuka, Purdue, Takeda, Pfizer, Shire, Sunovion, and SyneuRx; and is a consultant to Sunovion. DEF, JW, JCE, MN, MD, RAK, W-JC, WW, JAD, TJB, AS, CK, and J-HL declare no conflicts of interest.

© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Figures

Fig. 1

(A) Direct pathways of the ventrolateral and ventromedial prefrontal–subcortical circuits (B) Regions of an anterior-limbic network mask overlaid on a T1-weighted anatomic image. Colors represent twenty bilateral regions-of-interest (ROI) including amygdala (yellow), ventromedial prefrontal cortex (green), ventrolateral prefrontal cortex (PFC) (light green), subgenual anterior cingulate cortex (ACC) (yellow/green), dorsal anterior cingulate cortex (lime green), superior anterior cingulate cortex (light yellow), caudate (rust), putamen (orange), globus pallidus (dark orange), and thalamus (red). BA = Brodmann’s area.

Fig. 2

Mean functional magnetic resonance imaging (fMRI) factor scores as a function of Time and Group for the first four factors within the five-factor solution including: (A) subcortical structures, (B) anterior cingulate cortex, (C) prefrontal cortex, and (D), and amygdala.

Fig. 3

Mean functional magnetic resonance imaging (fMRI) signal change proportion as a function of Time and Group for (A) right ventrolateral prefrontal cortex and (B) left ventrolateral prefrontal cortex.

Fig. 4

Mean functional magnetic resonance imaging (fMRI) factor scores as a function of Time and Treatment Status for two factors within the five-factor solution including: (A) subcortical structures and (B) amygdala.