Abstracts

Rationale: Depression is common in individuals with epilepsy, and there is a bidirectional relationship between the two conditions. However, the pathophysiological mechanisms underlying the effects of depressive symptoms on seizure frequency are largely unknown. We hypothesized that altered functional connectivity (FC) might be implicated in the mechanisms that worsen seizure activity in epilepsy patients with depression. The purpose of this study was to identify the independent effect of depression on seizure frequency and to explore the role of depression-related altered FC in increasing seizure frequency.


Methods: A total of 99 epilepsy patients who completed scales for evaluating depression, anxiety, and autonomic dysfunction were included in this study. Based on the Beck Depression Inventory-II (BDI-II) with a cut-off of 14 points, patients were categorized into those with depression (n = 33) and those without depression (n = 66).

MRI examinations were performed using a 3 Tesla scanner. The structural images were obtained using high-resolution 3D MPRAGE sequence. The fMRI sequence used single-shot echo planar imaging. Resting-state FC analysis, with the medial prefrontal cortex (MPFC) as the seed region, was performed using the CONN toolbox v.21.a.

Preprocessing included realignment, coregistration, normalization, and smoothing with an 8-mm kernel. Band-pass filtering (0.008–0.9 Hz) was applied. First-level correlation maps were converted to z scores using Fisher’s transformation. Group comparisons of FC maps were assessed using a two-sample t-test, with statistical significance set at uncorrected p < 0.05.


Results: Compared to epilepsy patients without depression, those with depression showed no significant differences in age, gender, years of education, or body mass index (Table 1). However, they exhibited significantly higher seizure frequency, BDI-II scores, anxiety scale scores, and autonomic dysfunction scale scores (all p < 0.001). Multiple regression analysis identified BDI-II as the only significant contributor to seizure frequency (β = 0.44, p = 0.003).

Resting-state fMRI results with the MPFC as the seed region revealed FC with the anterior cingulate cortex ACC and PCC in both groups, but a weakened FC intensity in the group with comorbid depression (Figure 1). Mediation analysis using the Sobel test confirmed that depressive symptoms led to changes in MPFC-based FC, which ultimately affected the increase in seizure frequency (z = 4.438, p < 0.001).


Conclusions: Our findings suggest that epilepsy patients with depressive symptoms have increased impairment in the DMN and suggest that active interventions to alleviate depressive symptoms may reduce seizure frequency by mitigating further DMN impairment.


Funding: This study was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea under Grant: HI22C0946.