Investigating the effect of repetitive transcranial magnetic stimulation applied to patients with bipolar disorder in the depressive phase on patients' serum NGF, GDNF, il-1ß levels, and cognitive functions

The aim of this study was to investigate the effect of rTMS on serum NGF, GDNF, IL-1ß levels and cognitive functions of patients with bipolar depression and the relationship between these parameters and the disease. The study included 59 patients with bipolar depression diagnosed according to DSM-5 and 30 healthy volunteers. Sociodemographic data form, HAM-D, YMDS, Trail Making Test A and B for cognitive functions, Stroop Test A,B,C and D, GZOT for theory of mind were applied to all participants. Blood samples were taken from healthy volunteers to compare with serum GDNF , NGF, IL-1ß levels of bipolar depression patients and cognitive tests were performed. Healthy volunteers were not included in TMS treatment. Among 59 participants with bipolar depression, 30 participants received active TMS and 29 participants received sham TMS. The TMS protocol consisted of 3000 pulses/session at high frequency (10 Hz) applied to the left dorsolateral prefrontal cortex (DLPFC) with a motor stimulation threshold (MT) of 120%. TMS sessions were performed once a day for a total of 10 sessions over a 2-week period. 59 patients with bipolar depression underwent cognitive testing before the first session and after the 10th session, and venous blood samples were collected between 08.00 and 10.00 in the morning and after an overnight fast. Participants continued TMS sessions to complement antidepressant treatment. The active group received 20 sessions of TMS treatment. The sham group completed the study after 10 sessions of sham treatment and started to receive active treatment. Venous blood samples were taken from all participants in the morning, between 08:00 and 10:00, after an overnight fast. Serum levels of GDNF, NGF, and IL-1ß in the participants were measured using the ELISA method at the Gaziantep University Biochemistry Laboratory. In our study, in the group of patients receiving active treatment, post-TMS GDNF and NGF values were significantly higher, while IL-1ß levels were significantly lower. When compared in terms of cognitive tests, a significant improvement in performance was observed in the Trail Making Test and Stroop Tests, as well as in the Eyes test in the active treatment group. The correlation analysis revealed a moderately positive relationship between changes in serum GDNF levels after TMS treatment and changes in Eyes Test performance. When the parameters of healthy controls were compared with those of bipolar patients, it was observed that GDNF and NGF levels were higher in healthy controls, IL-1ß levels were lower, and they exhibited better performance in all cognitive function tests. As far as we know, there is no study in the literature that investigates the relationship between GDNF and NGF levels and cognitive functions in bipolar depression patients after TMS application; however, there are a limited number of studies examining the relationship between TMS and IL-1ß in this condition. We believe that our study can contribute to understanding the mechanism of action of TMS and improving cognitive functions in bipolar depression patients. We believe that improving social cognition may be beneficial in correcting the impairment in psychosocial functioning in bipolar patients.