1718

Enhanced striatum connectivity is irrelevant to baseline perfusion in major depressive disorder following sertraline treatment
Changwei W. Wu1,2, Zi-Xuan Chang3, I-Ling Chung4, Chien-Yuan Lin5, Ching-Po Lin6, Chi-Bin Yeh7, and Hong-Wen Kao4

1Graduate Institute of Humanities in Medicine, Taipei Medical University, Taipei, Taiwan, 2Brain and Consciousness Research Center, Taipei Medical University, Taipei, Taiwan, 3Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, Taiwan, 4Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, 5GE Healthcare, Taipei, Taiwan, 6Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan, 7Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

Synopsis

We revisited the sertraline treatment effect on RSFC in drug-naïve MDD patients and evaluated the association between RSFC, ALFF and baseline CBF level. Twenty-four unmedicated MDD subjects were recruited and treated with sertraline for 6 weeks. Results showed negative correlation between HAM-D scores and striatum-MPFC RSFC. However, the therapeutic effect on RSFC was irrelevant to the CBF or ALFF levels, implying better temporal synchronizations from the neural basis.

INTRODUCTION

Sertraline, an effective antidepressant for major depressive disorder (MDD), is shown to enhance amygdala and striatum connectivity in MDD patients1,2. However, the sertraline effect on brain connectivity remains elusive, which could be either from perfusion or from neuronal connections. To this point, we revisited sertraline treatment effect and acquired both resting-state fMRI (RS-fMRI) and arterial spin labeling (ASL) in MDD patients for clarifying its underlying mechanism.

METHODS

We recruited 24 unmedicated MDD subjects (age: 42.3±11.3, 6 males) and 33 healthy control subjects (HC, age: 41.5±10.3, 10 males) and collected their Hamilton depression rating scale (HAM-D). FMRI scans were carried out on a 3T MR scanner (GE MR750) using 8-channel coil (RS-fMRI settings: GE-EPI with matrix size=64x64, 200 measurements, TR/TE=2500/30 ms, flip angle of 90; ASL in the same settings with TI=2025 ms). After the baseline scan (Pre), the patient started sertraline treatment and then received the second scan after six weeks (Post). The fMRI data underwent the standard preprocessing using SPM8, whereas functional connectivity and amplitude of low-frequency fluctuations (ALFF) were performed using REST for striatum, amygdala and default-mode network (DMN). Group comparisons were conducted by paired t-test (Post vs. Pre) or two-sample t-test (HC vs. Pre) on Z-map, ALFF and CBF (uncorrected p<0.001).

RESULTS

After the 6-week sertraline treatment, the drug-naïve MDD patients expressed significant reduction on HAM-D scale (p<0.05). Compared with HC, the MDD patients showed declined RSFC between the striatum and the medial prefrontal cortex (MPFC, BA 10). After the treatment, the RSFC of striatum-MPFC was enhanced and returned back to the normal level, and the striatum connectivity to MPFC correlated with HAM-D score in MDD patients. However, the therapeutic effect was not observed in the perfusion levels, neither was ALFF. At last, we did not observe therapeutic effects on amygdala and DMN.

DISCUSSION

Sertraline treatment in MDD patients showed network specificity on the resting-state functional connectivity, but the therapeutic effect is not associated with changes of CBF and ALFF. In other words, the therapeutic effect on RSFC was not contributed from the alterations of baseline blood flow level or from the fluctuation strength. Since sertraline serves as the serotonin reuptake inhibitor and increases serotonin levels, the unchanged fluctuation and perfusion levels suggested that enhanced striatum-MPFC RSFC was resulted from a better temporal synchronization without time delays.

CONCLUSION

We revisited the sertraline treatment effect on RSFC in drug-naïve MDD patients and evaluated the association between RSFC, ALFF and baseline CBF level. The therapeutic effect on RSFC was irrelevant to the CBF or ALFF levels, implying better neural synchronizations between target regions.

Acknowledgements

No acknowledgement found.

References

1. Anand A, Li Y, Wang Y, et al. Antidepressant Effect on Connectivity of the Mood-Regulating Circuit: An fMRI Study. Neuropsychopharmacology 2005;30(7):1334-44.

2. Anand A, Li Y, Wang Y, et al. Reciprocal Effects of Antidepressant Treatment on Activity and Connectivity of the Mood Regulating Circuit: An fMRI Study. J Neuropsychiatry Clin Neurosci, 2007;19(3):274-82

Figures

Sertraline treatment in depression patients showed network specificity on the functional connectivity, but the therapeutic effect is not associated with changes of CBF and ALFF.

Proc. Intl. Soc. Mag. Reson. Med. 25 (2017)
1718