Anxiety and depression symptoms disrupt resting state connectivity in patients with genetic generalized epilepsies

Abstract

Objective: To analyze the lifetime trajectories in genetic generalized epilepsies (GGEs) and investigate the impact of symptoms of anxiety and depression on resting state functional connectivity (FC).

Methods: Seventy-four GGE patients were classified according to the pharmacological response as seizure-free (12 patients), pharmacoresistant (PhR; 14 patients), and fluctuating (FL; 48 patients). Fifty-four subjects completed both the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), and 38 also underwent 3-T resting state functional magnetic resonance imaging. These 38 patients were subdivided into a positive group (13 patients with concurrent symptoms of depression and anxiety) and a negative group (21 asymptomatic patients and four with mild anxiety or depression symptoms). For FC analysis of resting state networks, we matched 38 healthy asymptomatic volunteers and used the UF2C toolbox running on MATLAB2017/SPM12.

Results: The PhR group presented shorter duration of epilepsy (P = 0.016) and follow-up (P < 0.001) compared to the FL group. The PhR group showed higher levels (median = 20) on the BAI and BDI. Myoclonic seizures were the most difficult to control, as 50% of subjects persisted with them at last appointment, compared to generalized tonic-clonic seizures and absence seizures (<40%). Patients with concurrent anxiety and depression symptoms were 7.7 times more likely to exhibit pharmacoresistant seizures, although an increase of 1 year of epilepsy duration was associated with a decrease in the odds of presenting pharmacoresistance by a factor of 0.9. Overall, FC was altered between default mode network (DMN) and visuospatial/dorsal attention. However, only the positive group displayed abnormal FC between DMN and left executive control network, and between salience and visuospatial/dorsal attention.

Significance: Our findings may help clinicians to have a better understanding of GGE clinical course and increase attention to the potential relationship of psychopathologies and brain connectivity.

Keywords: default mode network; executive control network; pharmacological response; psychopathologies; salience network; seizure control.