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 preceding 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 waitlisted-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.

Public Health Relevance

The goal of this application 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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
5R33MH103231-05
Application #
9494689
Study Section
Special Emphasis Panel (ZMH1)
Program Officer
Wagner, Ann
Project Start
2016-07-28
Project End
2019-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
5
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
Bernard, Jessica A; Orr, Joseph M; Mittal, Vijay A (2017) Cerebello-thalamo-cortical networks predict positive symptom progression in individuals at ultra-high risk for psychosis. Neuroimage Clin 14:622-628
Osborne, K Juston; Bernard, Jessica A; Gupta, Tina et al. (2017) Beat gestures and postural control in youth at ultrahigh risk for psychosis. Schizophr Res 185:197-199
Bernard, Jessica A; Russell, Courtney E; Newberry, Raeana E et al. (2017) Patients with schizophrenia show aberrant patterns of basal ganglia activation: Evidence from ALE meta-analysis. Neuroimage Clin 14:450-463
Carol, Emily E; Spencer, Robert L; Mittal, Vijay A (2017) The relationship between cannabis use and cortisol levels in youth at ultra high-risk for psychosis. Psychoneuroendocrinology 83:58-64
Gupta, Tina; DeVylder, Jordan E; Auerbach, Randy P et al. (2017) Speech illusions and working memory performance in non-clinical psychosis. Schizophr Res :
Mittal, Vijay A; Wakschlag, Lauren S (2017) Research domain criteria (RDoC) grows up: Strengthening neurodevelopment investigation within the RDoC framework. J Affect Disord 216:30-35
Clark, Sarah V; Mittal, Vijay A; Bernard, Jessica A et al. (2017) Stronger default mode network connectivity is associated with poorer clinical insight in youth at ultra high-risk for psychotic disorders. Schizophr Res :
Lunsford-Avery, Jessica R; Gonçalves, Bruno da Silva Brandão; Brietzke, Elisa et al. (2017) Adolescents at clinical-high risk for psychosis: Circadian rhythm disturbances predict worsened prognosis at 1-year follow-up. Schizophr Res 189:37-42
Gupta, Tina; Hespos, Susan J; Horton, William S et al. (2017) Automated analysis of written narratives reveals abnormalities in referential cohesion in youth at ultra high risk for psychosis. Schizophr Res :
Mittal, Vijay A; Vargas, Teresa; Osborne, K Juston et al. (2017) Exercise Treatments for Psychosis: A Review. Curr Treat Options Psychiatry 4:152-166

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