Abstract
Lithium and quetiapine are effective treatments for bipolar disorder, but their potential neuroprotective effects in humans remain unclear. A single blinded equivalence randomized controlled maintenance trial was conducted in a prospective cohort of first-episode mania (FEM) patients (n=26) to longitudinally compare the putative protective effects of lithium and quetapine on grey and white matter volume. A healthy control sample was also collected (n=20). Using structural MRI scans, voxel-wise grey and white matter volumes at baseline and changes over time in response to treatment were investigated. Patients were assessed at three time points (baseline, 3 and 12-month follow-up), whereas healthy controls were assessed at two time points (baseline and 12-month follow-up). Patients were randomized to lithium (serum level 0.6 mmol l−1, n=20) or quetiapine (flexibly dosed up to 800 mg per day, n=19) monotherapy. At baseline, compared with healthy control subjects, patients with FEM showed reduced grey matter in the orbitofrontal cortex, anterior cingulate, inferior frontal gyrus and cerebellum. In addition, patients had reduced internal capsule white matter volume bilaterally (t1,66>3.20, P<0.01). Longitudinally, there was a significant treatment × time effect only in the white matter of the left internal capsule (F2,112=8.54, P<0.01). Post hoc testing showed that, compared with baseline, lithium was more effective than quetiapine in slowing the progression of white matter volume reduction after 12 months (t1,24=3.76, P<0.01). Our data support the role of lithium but not quetiapine therapy in limiting white matter reduction early in the illness course after FEM.
Highlights
Many people with bipolar disorder (BD) manifest a progressive course
We found no group × time interaction effect for the lithium group when compared with healthy control subjects and only in the quetiapine group (F = 12.32, P o 0.01 corrected)
To the best of our knowledge, this is the first longitudinal structural neuroimaging study to characterize the neuroprotective effects of lithium and quetiapine in participants following a firstepisode mania (FEM)
Summary
Many people with bipolar disorder (BD) manifest a progressive course. This observation has been repeatedly verified[1,2] and is manifested by progressively shorter inter-episode intervals, increasing rates of functional impairment, comorbidity, suicide, hospitalisation and reduced treatment responsiveness.[3,4,5,6,7,8] there are replicated reports of changes over time in brain volume, suggesting that these neuroanatomical alterations might be more pronounced with repeated episodes. A larger number of episodes have been associated with decreased cortical and subcortical structures including prefrontal and temporal cortices, the hippocampus and the striatum[9,10,11,12] accompanied with an increase in lateral ventricular volume.[13,14,15] The timing of these serial changes in clinical and imaging variables remains uncertain. What is probable is that people at risk who later go on to develop BD do not, on aggregate, demonstrate marked deficits These appear with the onset of the disorder, and are evident in an established disease.[16] structural changes are inconsistent at a first episode, with some studies showing that individuals at a first episode manifest volumetric findings similar to controls,[17,18] whereas other studies suggest that changes are already evident.[19] Either way, the first episode appears to be the soonest pragmatic point to commence therapeutic strategies with neuroprotective potential
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
