Introduction
Brain structural and functional alterations in neuronal circuits have been observed in both, bipolar disorder and major depressive disorder. While resting-state functional MRI (rs-fMRI) issues a measure of baseline brain activity and connectivity, amplitude of low frequency fluctuations acts as an indirect measure for spontaneous brain activity. Previously, amplitude of low frequency fluctuations has been found to be resourceful in identifying intrinsic brain activity in a number of brain diseases.
Objective
To evaluate the amplitude of low frequency fluctuation changes in bipolar disorder and major depressive disorder.
Study Design
A quantitative and voxel-based meta-analysis.
Methods
PubMed, Embase, Web of Science, SinoMed, Chinese National Knowledge Infrastructure (CNKI), and WanFang databases were searched and fifty studies on major depressive disorder and fifteen studies in bipolar disorder published until April 9, 2019 were included.
Results
- Differences in amplitude of low frequency fluctuation were reported between 1399 patients with major depressive disorder and 1332 healthy controls whereas in case of bipolar disorder, the amplitude of low frequency fluctuation differences were reported between 494 patients with bipolar disorder and 593 healthy controls.
- No variation was observed w.r.t. age or sex distribution in both the cases.
- While the mean score from the Hamilton depression rating scale (HAMD) was 23.1 in case of major depressive disorder patients, it was 16.4 in the patients with bipolar disorder.
- Amongst the bipolar disorder patients, 42.5% were depressed, 14.8% were euthymic, 11.7% were manic, 0.6% were mixed and 0.2% was hypomanic.
- 95 patients had type I bipolar disorder while 128 patients had type II bipolar disorder and the mean score from the Young mania rating scale (YMRS) was 9.6.
- While the duration of illness was found to be greater in bipolar disorder patients (36.8 months vs. 11.9 months, p < 0.05), the proportion of depressed patients was found to be greater in the major depressive disorder group (92% vs. 43%).
- Major depressive disorder patients demonstrated increased amplitude of low frequency fluctuation in the right superior frontal gyrus (SFG) [including the medial orbitofrontal cortex, medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC)], bilateral insula extending into the striatum, and left supramarginal gyrus.
- They also had decreased amplitude of low frequency fluctuation in the bilateral posterior lobes of cerebellum, bilateral precuneus and left occipital cortex as compared to the healthy controls.
- Based on the results of the jackknife sensitivity analysis in major depressive disorder patients, it was found that increases in amplitude of low frequency fluctuation in the right SFG, left insula, and left supramarginal gyrus and decreases in amplitude of low frequency fluctuation in the bilateral cerebellum and left precuneus.
- Bipolar disorder patients demonstrated increased amplitude of low frequency fluctuation in the bilateral inferior frontal gyrus (IFG) (including the orbital prefrontal cortex), bilateral insula extending into the striatum, right SFG (including the mPFC and dorsolateral prefrontal cortex), and right temporal pole, and decreased ALFF in the left posterior lobes of cerebellum (extending to the occipital cortex), bilateral precuneus, left ACC and left superior temporal gyrus (STG).
- The jackknife sensitivity analysis, showed increases in amplitude of low frequency fluctuation in the right IFG, left insula, right SFG (orbital prefrontal gyrus), and right occipital gyrus and decreases in amplitude of low frequency fluctuation in the left cerebellum, and right precuneus.
- Major depressive disorder patients showed an increased amplitude of low frequency fluctuation in the left lingual gyrus, left ACC, bilateral precuneus, and left STG, and decreased ALFF in the right insula, right mPFC, right fusiform gyrus, and bilateral striatum as opposed to the bipolar disorder patients.
- Thus, major depressive disorder and bipolar disorder, both had increased amplitude of low frequency fluctuation in bilateral insula and mPFC, and decreased amplitude of low frequency fluctuation in the left posterior lobe of cerebellum.
- A higher Hamilton depression rating scale (HAMD) score in major depressive disorder patients was associated with a greater increase in amplitude of low frequency fluctuation in the right ACC.
- In bipolar disorder patients, a higher HAMD score exhibited larger decreases in amplitude of low frequency fluctuation in the right precuneus/posterior cingulate cortex (PCC).
- A functionally similar brain was observed in major depressive disorder and bipolar disorder.
Conclusion
Major depressive disorder and bipolar disorder display a similar pattern of atypical regional intrinsic brain activity including the insula, mPFC and cerebellum along with marked alterations in the limbic system region.