Exercise and Markers of Medial Temporal Health in Youth At-risk for Psychosis
| Status: | Recruiting |
|---|---|
| Conditions: | Psychiatric, Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 16 - 24 |
| Updated: | 5/4/2018 |
| Start Date: | July 2014 |
| End Date: | June 2019 |
| Contact: | Vijay A Mittal, Ph.D. |
| Email: | vijay.mittal@colorado.edu |
| Phone: | (303) 492-3303 |
Exercise and Markers of Medial Temporal Health in Youth at Ultra High-risk for Psychosis
The goal of this proposal is to test the feasibility and effectiveness of cardiovascular
exercise in promoting brain health and improving related symptoms (e.g., hearing sounds that
are not there, feeling emotionally detached from self and others), cognitive difficulties
(troubles with memory and learning), and every day social-occupational functioning in youth
at imminent risk for developing a psychotic disorder such as schizophrenia. Understanding how
exercise may protect or improve the health of a brain area that is implicated as a major
contributing factor to the onset of psychosis may lead to a path-breaking new intervention
that does not suffer from many of the side effects, costs, and other barriers that
characterize treatments that are currently available for this group. Because a significant
portion of high-risk youth go on to develop a psychotic disorder in a short period,
intervening at this stage may help to improve the clinical course and ultimately prevent the
onset of a devastating and prevalent mental illness.
exercise in promoting brain health and improving related symptoms (e.g., hearing sounds that
are not there, feeling emotionally detached from self and others), cognitive difficulties
(troubles with memory and learning), and every day social-occupational functioning in youth
at imminent risk for developing a psychotic disorder such as schizophrenia. Understanding how
exercise may protect or improve the health of a brain area that is implicated as a major
contributing factor to the onset of psychosis may lead to a path-breaking new intervention
that does not suffer from many of the side effects, costs, and other barriers that
characterize treatments that are currently available for this group. Because a significant
portion of high-risk youth go on to develop a psychotic disorder in a short period,
intervening at this stage may help to improve the clinical course and ultimately prevent the
onset of a devastating and prevalent mental illness.
Accumulating evidence from the animal literature, healthy populations, and schizophrenia
studies suggests that regular exercise positively affects integral functions such as
neurogenesis, synaptic plasticity and cognition. Likewise, preliminary evidence suggests that
aerobic activity has been associated with improved quality of life and a lower level of
symptoms in patients with schizophrenia. Because exercise has been found to stimulate human
medial temporal neurogenesis, and related abnormalities have been widely observed in studies
of schizophrenia, physical activity may be in an important intervention. During the psychosis
prodrome, a period immediately proceeding formal onset of psychotic disorders, adolescents
experience subtle attenuated symptoms coupled with cognitive deterioration and a global
decline in socio-occupational functioning and anywhere between 10-35% go on to transition to
a psychotic disorder such as schizophrenia in a two-year period. Despite the promise of
exercise interventions, and the critical role medial temporal lobe abnormalities play in
etiological models of psychosis, there have been no experimental studies of aerobic exercise
in ultra-high risk youth (UHR). Understanding the potential benefits of aerobic exercise in
UHR youth is integral as the prodrome is a viable period of intervention in which
considerable brain development is still occurring. Further, as there have been challenges
associated with many of the available interventions, and an increasing level of potential
found in neuroplasticity-based interventions, understanding the effect of exercise on
respective brain-behavior holds considerable promise. Experimental research is sorely needed
to determine if prescribed aerobic exercise can stimulate medial-temporal neurogenesis and
ameliorate cognition and symptoms/functioning in this vital group. In the proposed study, an
expert team of experienced prodromal and exercise investigators will follow a group of 15 UHR
adolescent and young adults (ages 16-24) through a 12 week exercise trial to determine which
level of exercise intensity/frequency is tolerable for participants and optimal for improving
aerobic fitness (65% of VO2max and 2 sessions per week versus 85% intensity and 3 sessions
per peek) and if improvements in aerobic fitness (i.e., VO2max, VO2peak, ventilatory
threshold) are associated with increases in medial temporal structure volume (hippocampus and
parahippocampal gyrus) and accompanying improvements in cognitive function (i.e., including
tasks known to recruit heavily on medial temporal structures) as well as symptomatology and
social/role functioning. If the benchmarks are met, this data will be used to streamline a
three-year rater-blind controlled trial (15 UHR-exercise, 15 UHR waitlist-control) to
determine the efficacy of the intervention in promoting medial temporal health as well as
accompanying cognitive, clinical, and socio-occupational function improvement. Participants
will be followed up to 24-months to determine if the intervention has an affect on clinical
course and transition to psychosis. Taken together, this study is important for understanding
the lessons necessary for planning a future large-scale trial, and has the potential to shed
light on a promising new treatment for UHR youth.
studies suggests that regular exercise positively affects integral functions such as
neurogenesis, synaptic plasticity and cognition. Likewise, preliminary evidence suggests that
aerobic activity has been associated with improved quality of life and a lower level of
symptoms in patients with schizophrenia. Because exercise has been found to stimulate human
medial temporal neurogenesis, and related abnormalities have been widely observed in studies
of schizophrenia, physical activity may be in an important intervention. During the psychosis
prodrome, a period immediately proceeding formal onset of psychotic disorders, adolescents
experience subtle attenuated symptoms coupled with cognitive deterioration and a global
decline in socio-occupational functioning and anywhere between 10-35% go on to transition to
a psychotic disorder such as schizophrenia in a two-year period. Despite the promise of
exercise interventions, and the critical role medial temporal lobe abnormalities play in
etiological models of psychosis, there have been no experimental studies of aerobic exercise
in ultra-high risk youth (UHR). Understanding the potential benefits of aerobic exercise in
UHR youth is integral as the prodrome is a viable period of intervention in which
considerable brain development is still occurring. Further, as there have been challenges
associated with many of the available interventions, and an increasing level of potential
found in neuroplasticity-based interventions, understanding the effect of exercise on
respective brain-behavior holds considerable promise. Experimental research is sorely needed
to determine if prescribed aerobic exercise can stimulate medial-temporal neurogenesis and
ameliorate cognition and symptoms/functioning in this vital group. In the proposed study, an
expert team of experienced prodromal and exercise investigators will follow a group of 15 UHR
adolescent and young adults (ages 16-24) through a 12 week exercise trial to determine which
level of exercise intensity/frequency is tolerable for participants and optimal for improving
aerobic fitness (65% of VO2max and 2 sessions per week versus 85% intensity and 3 sessions
per peek) and if improvements in aerobic fitness (i.e., VO2max, VO2peak, ventilatory
threshold) are associated with increases in medial temporal structure volume (hippocampus and
parahippocampal gyrus) and accompanying improvements in cognitive function (i.e., including
tasks known to recruit heavily on medial temporal structures) as well as symptomatology and
social/role functioning. If the benchmarks are met, this data will be used to streamline a
three-year rater-blind controlled trial (15 UHR-exercise, 15 UHR waitlist-control) to
determine the efficacy of the intervention in promoting medial temporal health as well as
accompanying cognitive, clinical, and socio-occupational function improvement. Participants
will be followed up to 24-months to determine if the intervention has an affect on clinical
course and transition to psychosis. Taken together, this study is important for understanding
the lessons necessary for planning a future large-scale trial, and has the potential to shed
light on a promising new treatment for UHR youth.
Inclusion Criteria:
- age 16-24
- no history of brain injury or neurological disease
- no contraindications to exercise training (as assessed by a Clinical Translational
Research Center CTRC physician)
- no history or current treatment with antipsychotics
- no contraindications for being in an magnetic resonance imaging scanner.
- meet criteria for a prodromal syndrome based upon the Structure Interview for
Prodromal Syndromes (SIPS) interview.
Exclusion Criteria:
- people who are extremely claustrophobic
- have a history of significant head injury
- other physical disorder that could affect brain functioning
- mental retardation
- history of substance use disorder within 6 months of screening interview
- have a psychotic disorder (at study entry) and/or have exhibited serious self-harm
behaviors
- pregnant females
- people who have contraindications to magnetic resonance (MR) scanning including
intracranial, intraorbital or intraspinal metal, pacemakers, cochlear implants or
other non-MR-compatible devices
- inability of the subject or their parent/guardian to understand the informed consent
document
- meeting criteria for an Axis I psychotic disorder
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