Physical Activity Reduces Clinical Symptoms and Restores Neuroplasticity in Major Depression

Abstract

Major depressive disorder (MDD) is the most common mental disorder and deficits in neuroplasticity are discussed as one pathophysiological mechanism. Physical activity (PA) enhances neuroplasticity in healthy subjects and improves clinical symptoms of MDD. However, it is unclear whether this clinical effect of PA is due to restoring deficient neuroplasticity in MDD. We investigated the effect of a 3-week PA program applied on clinical symptoms, motor excitability and plasticity, and on cognition in patients with MDD (N = 23), in comparison to a control intervention (CI; N = 18). Before and after the interventions, the clinical symptom severity was tested using self- (BDI-II) and investigator- (HAMD-17) rated scales, transcranial magnetic stimulation (TMS) protocols were used to test motor excitability and paired-associative stimulation (PAS) to test long-term-potentiation (LTP)-like plasticity. Additionally, cognitive functions such as attention, working memory and executive functions were tested. After the interventions, the BDI-II and HAMD-17 decreased significantly in both groups, but the decrease in HAMD-17 was significantly stronger in the PA group. Cognition did not change notably in either group. Motor excitability did not differ between the groups and remained unchanged by either intervention. Baseline levels of LTP-like plasticity in the motor cortex were low in both groups (PA: 113.40 ± 2.55%; CI: 116.83 ± 3.70%) and increased significantly after PA (155.06 ± 10.48%) but not after CI (122.01 ± 4.1%). Higher baseline BDI-II scores were correlated with lower levels of neuroplasticity. Importantly, the more the BDI-II score decreased during the interventions, the stronger did neuroplasticity increase. The latter effect was particularly strong after PA (r = -0.835; p < 0.001). The level of neuroplasticity related specifically to the psychological/affective items, which are tested predominantly in the BDI-II. However, the significant clinical difference in the intervention effects was shown in the HAMD-17 which focuses more on somatic/neurovegetative items known to improve earlier in the course of MDD. In summary, PA improved symptoms of MDD and restored the deficient neuroplasticity. Importantly, both changes were strongly related on the individual patients' level, highlighting the key role of neuroplasticity in the pathophysiology and the clinical relevance of neuroplasticity-enhancing interventions for the treatment of MDD.

Keywords: major depression; neuroplasticity and exercise; paired associative stimulation; physical activity; transcranial magnetic stimulation.

Figure 1

Experimental design.

Figure 2

HAMD-17 (A) and BDI-II (B) scores with subscales. The mean scores of all items (total) as well as subscores for psychological/affective and somatic/neurovegetative items are given (mean ± SEM; t-test: **p < 0.001; *p < 0.01). Below the score change (after – before intervention) is given for each single item of the questionnaire (t-test; ^#p < 0.05).

Figure 3

IOcurves and SICI. (A,B) displays the IOcurves measured in PA (A) and CI (B) groups before and after the intervention, with the IOslope given in the inserted diagram (mean ± SEM). IOcurves and IOslopes were not changed by the interventions within the groups, and there were no between-group differences. (C,D) displays the SICI results for PA (C) and CI (D) groups, again there were no differences within the groups (before/after intervention) nor between the groups.

Figure 4

PASeffect and correlations. (A) Displays the PASeffects measured before (clear bars) and after (hatched bars) the interventions in PA (red bars) and CI (gray bars) groups. The PASeffect increased significantly after the intervention in the PA group, but not in the CI group (t-test results are given). (B,C) display the correlation between the PASeffects measured before and after the intervention in PA (B) and CI (C) groups; (D,E) display the correlation between the PASeffect measured before the intervention and PASchange for each group [PA: (D) and CI: (E)]. The results of Pearson's correlation are given.

Figure 5

Correlations between BDI-II and PAS. The correlations of BDI-II and PAS are given for PA (A,C,E,G) and CI (B,D,F,H) groups. Pearson's r and p-values are given in each figure. BDI-II and PASeffect measured before the intervention (M1) were negatively correlated in each group (A,B): the higher the BDI-II score, the smaller was the PASeffect. Similarly, the change of BDI-II and PASeffects by the intervention were negatively correlated in each group (E,F). The BDI-II at baseline did not predict the amount of PASchange that could be induced by the interventions (C,D), neither did the PASeffect at baseline (M1) predict the amount of BDI-II change (G,H).