Major Depressive Disorder Clinical Trial
Official title:
Exercise Promotes Neuroplasticity in Depressed and Healthy Brains: An fMRI Pilot Study
To investigate the impact of a structured eight week exercise intervention as an add-on therapy in treating Major Depressive Disorder. Using behavioural techniques and neuroimaging to measure changes in brain function following an exercise intervention in people with clinical depression. By correlating changes in the hippocampus with changes in HPA axis hormones, inflammatory cytokines and growth factors it is possible to determine which of the biochemical markers is most predictive of improved neural function.
Memory impairment is the most frequently reported cognitive symptom in people with
depression. However, research in this area has presented mixed findings in terms of the
type, severity and specificity of memory deficits. One finding that has been well
established is the impairment in episodic memory (memory for a specific past experience in
one's life) with a sparing of semantic memory (present knowledge of universal truths such as
"the sky is blue"), and short-term memory. Behavioural and neuroimaging studies
investigating the stage of the memory deficit in people with depression have found that both
the encoding and retrieval processes are impaired. Although the neural underpinnings of
impaired memory in MDD are not completely understood, the majority of evidence implicates
abnormal activity in the hippocampal region critical for normal memory formation.
Exercise for depression has been a common research theme for the past several years however
its mechanism of action remains unknown. Many studies have reported higher levels of
cardiorespiratory fitness and increased habitual physical activity being associated with
lower depressive symptomatology and greater emotional well-being, while lower levels of
cardiorespiratory fitness being associated with increased risk of developing depressive
illness. Exercise alone or in combination with other treatment options, such as
pharmacotherapy or cognitive behavioural therapy have all been effective in treating
depression with response rates for exercise being comparable to these mainstream therapies.
Exercise protects against the development of neurodegenerative diseases delays the negative
effects of aging and improves sleep quality. Exercise also reduces inflammation, normalizes
cortisol secretion, increases hippocampal neurogenesis, increases cerebrovascular perfusion,
improves the structure and function of the hippocampus, facilitates neurocognitive recovery
from traumatic brain injury reverses brain volume loss in elderly and schizophrenic
individuals and improves learning and memory. These findings suggest that the relationship
between fitness and cognition is partly mediated by processes that involve cerebral
circulation. These positive effects of exercise on neuroanatomy and vascularization can be
partly explained by the interactive cascade of growth factor signalling associated with
exercise that increases the ability of cerebral blood vessels to respond to demand. Habitual
exercise is an effective way to improve endothelial function by increasing arterial
compliance and decreasing arterial stiffness, oxidative stress, and vascular inflammation.
The overall goal of this research study is to investigate the effects of a well-defined,
structured, supervised exercise program on brain function in healthy and clinically
depressed individuals. This research aims to fill the gaps in the literature by elucidating
the anti-depressant mechanisms which exercise targets and if these effects parallel young
healthy sedentary individuals.
To investigate the effects of a moderate-intensity structured, supervised 8 week exercise
program in people with MDD when combined with a Mental Health Day Treatment (MHDT) program,
as compared to the MHDT on its own. All outcome measures will be assessed at baseline and 8
weeks. A non-depressed exercise control group will be used to compare the effects of
exercise in depressed and non-depressed individuals:
i. depressive symptoms ii. anxiety iii. sleep quality iv. plasma IL-1β, IL-1ra, IL-6, IFN-γ,
TNF-α and IL-10, BDNF v. salivary cortisol vi. performance on an associative memory task and
concomitant fMRI hippocampal activation.
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