Effects of Aerobic Exercise Intensity on Clinical & Neural Outcomes in Depressed Youth
Effects of Aerobic Exercise Intensity on Clinical & Neural Outcomes in Depressed Youth
This study will assess the effects of moderate vs. high intensity aerobic exercise, performed
 3 times a week for 12 weeks under supervised conditions, on symptoms of depression, cognitive
 functioning and brain function in transitional aged youth (TAY: aged 16-24 years).
Rationale: Major depressive disorder (MDD) is a debilitating disorder characterized by
 persistent negative mood and a broad range of cognitive, and functional impairments. MDD is
 estimated to affect 4.4% of the global population, or over 300 million individuals,
 representing the single largest contributor to non-fatal health loss worldwide. Current
 treatment options are associated with sub-optimal rates of remission, with only 30-35% of MDD
 sufferers attaining remission with antidepressant drug monotherapy. One group for whom
 treatment selection is a particular challenge is transitional aged youth (TAY), encompassing
 the late teenage years into the early twenties. Although MDD onset typically occurs during
 this period - as high as 8.2% in Canadian TAY - the psychiatric community has only recently
 begun to recognize TAY as a unique psychiatric cohort in need of directed treatment. For
 example, although the use selective serotonin reuptake inhibitors (SSRIs) is the first-line
 treatment for MDD in adults, their utility in TAY is hampered by the possibility of increased
 suicidal ideation within this cohort. The need for alternative and tailored treatment options
 for TAY with MDD is therefore of paramount importance. Aerobic exercise (AE) has recently
 been recognized as one such intervention, with some reports showing outcomes comparable to
 pharmacological and psychotherapeutic approaches in adult populations. Few studies however,
 have investigated to what extent these findings extend to TAY. Further, there is little
 consensus as to which intensity level, or "dose", of AE offers the most benefit, which neural
 features underlie the putative benefits of AE in depressed TAY, and the impact on both
 psychosocial and cognitive processes.

 Objectives: The primary objectives of this study are: 1) to determine the effects of moderate
 vs. high intensity AE on clinically-rated and subjective symptoms of MDD in TAY; and 2) to
 examine the psychosocial, cognitive, and neuromodulatory effects of these interventions.

 Methods: This two-arm, randomized trial will recruit 40 TAY (16-24 yrs) with MDD/persistent
 depressive disorder (PDD) into one of two AE intensity groups: medium or high. Intensity is
 defined as a percentage of heart rate reserve (HRR) achieved during exercise, as outlined in
 the American College of Sports Medicine (ACSM) guidelines (moderate: 50-55% of HRR; N=20;
 high: 80-85% HRR; N=20). All participants will undergo supervised and guided AE intervention
 sessions (~30min), three times per week, for twelve consecutive weeks. Pertinent clinical and
 psychosocial scores, as well as cardiac function (as assessed by maximal oxygen consumption
 [VO2max]), will be recorded pre-intervention (Week 0), mid-intervention (Week 6), and
 post-intervention (Week 12). Additionally, participants will undergo electroencephalographic
 (EEG) and functional magnetic resonance neuroimaging (fMRI) before and after the completion
 of AE intervention. Specifically, neural dynamics will be recorded at rest and during
 cognitive tasks engaging working memory (N-Back task) and response inhibition (Flanker task)
 - cognitive abilities, which have been shown to be impaired in MDD in TAY. Both
 clinical/psychosocial and neuroimaging outcomes will be compared using time as the
 within-group, and intervention type as between-group factors.

 Hypotheses: The investigators expect a significant reduction in depression symptoms post (vs.
 pre) intervention and, based on preliminary evidence in adults, a greater reduction may
 emerge in those participating in the high (vs. moderate) intensity AE. Further, the
 investigators expect changes in fMRI profiles from pre- to post-intervention (showing
 normalization of brain activity and connectivity profiles); the same is true of
 EEG/event-related potential (ERP) features. They also expect a positive relation between
 VO2max and brain-based changes.

 Significance: Findings from this project will help guide future large-scale investigations of
 AE as a potential treatment for TAY by clarifying the relation between changes to physical
 indices, depressive symptoms and neural profiles. Importantly, identifying the brain features
 modulated by AE will broaden our understanding of the neurobiological markers underlying
 depressive states, allowing for targeted therapeutic approaches and better outcomes for TAY
 suffering from MDD.
Inclusion Criteria:

 -  Currently experiencing depression (MDD or PDD);

 -  Free of pharmacotherapy (ie. antidepressant medication) for >5 weeks;

 -  Not currently engaging in regular moderate or vigorous intensity exercise;

 -  Able to read/understand English;

 -  Body mass index [BMI] < 40;

 -  Medically cleared to engage in aerobic exercise.

 Exclusion Criteria:

 -  Currently engaged in another exercise trial;

 -  Another Axis I/II DSM-5 disorder, apart from co-morbid anxiety disorder(s);

 -  Current or lifetime history of serious medical or neurological conditions;

 -  Currently taking psychoactive drugs (occasional use of anti-anxiety medication
 permitted);

 -  Regular user of nicotine products;

 -  Unstable medical conditions, especially those that prevent exercise;

 -  Exhibiting significant suicide risk;

 -  MRI contraindications;

 -  Currently pregnant or breastfeeding.