Investigating rTMS Interventions in an Adolescent Model of Mood Disorders (22004)
Major depressive disorder is one of the most prevelant mental health disorders affecting adolescents.Unfortunately, approximately 50% of individuals do not respond to conventional antidepressant treatments, highlighting the need for alternative interventions. Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive brain stimulation widely used as an intervention for adults with treatment resistant depression. However, rTMS use in younger populations is underdeveloped and outcomes such as efficacy and the underlying neurobiological mechanisms remain poorly characterised.
To address these concerns, we investigated the neurobiological and behavioural outcomes of rTMS in a mouse model of adolescent mood disorders. Time-mated mice underwent daily restraint stress until birth to induce anxiety and depression-like behaviours in offspring. When offspring reached adolescence (4 weeks post-birth), rTMS (10Hz, 140mT) was administered for 3 minutes a day, 5 days a week for 4 weeks. Anxiety and depression-like behaviours were assessed before and after rTMS with multiple behavioural tests including the light/dark emergence test and markers of neuroplasticity (e.g. hippocampal neurogenesis) were assessed in post-mortem brain sections.
Experiments are currently ongoing but preliminary evidence suggests that rTMS increased exploratory behaviour in prenatally stressed animals compared to sham (p<0.05). Immunofluorescent imaging suggests that rTMS increased neurogenesis in the dentate gyrus of the hippocampus in stressed animals (p<0.05) and was accompanied with changes in brain derived neurotrophic factor protein levels. Our results provide important insight into the mechanisms of rTMS in adolescents and may help to expand the therapeutic reach of rTMS in this population.