Psychotic disorders (e.g., schizophrenia, schizoaffective disorder, depression and bipolar disorder with psychotic features) are devastating for patients and their families as they involve the onset of symptoms and significant impairment during late adolescence- a critical developmental period when youth are only just starting to make a transition into independence. These disorders are highly prevalent, and once diagnosed, involve a chronic course and bleak prognosis. However, an emerging research field suggests that we can now effectively identify those who are at imminently high-risk for psychosis, several years before onset. These ultra high-risk (UHR) adolescents exhibit attenuated psychosis symptoms (e.g., experiencing unusual thoughts, seeing brief shadows, hearing strange sounds). Those who meet criteria for a UHR syndrome have a significant chance of developing schizophrenia or an affective disorder with psychotic features within a two-year period. This serves as a foundation for a line of research that suggests that if we can identify high-risk adolescents and provide early intervention, the course of illness will be improved or perhaps prevented entirely. In a neural diathesis-stress conceptualization of psychosis, individuals with an early biological susceptibility exhibit subtle signs of impairment in childhood. Later in development these vulnerabilities interact with maturational factors and environmental stressors, ultimately contributing to the onset of psychosis. My research involves developing and applying this model to work with adolescents and young adults exhibiting high-risk syndromes as well as those who have recently developed psychotic disorders. Specifically, I conduct prospective studies that follow a range of characteristics that may be used to enhance identification of these individuals, predict who among them may eventually transition to psychosis, and concurrently, refine understanding of pathophysiology. Additionally, I utilize the information from these longitudinal studies to develop novel targeted treatments and remediations. The website below describes one such recent treatment focusing on aerobic exercise and neurogenesis that I am currently in the process of testing in the context of a randomized clinical trial.
Mittal, V. A., & Walker, E. F. (2007). Movement abnormalities predict conversion to Axis I psychosis among prodromal adolescents. Journal of Abnormal Psychology, 116(4), 796-803.
Mittal, V. A., Neumann, C., Saczawa, M., & Walker, E. F. (2008). The longitudinal progression of movement abnormalities and psychotic symptoms in adolescents at high-risk for psychosis. Archives of General Psychiatry, 65(2), 165-170.
Mittal, V. A., Ellman, L. M. & Cannon, T. D. (2008). Gene-environment interaction and covariation in schizophrenia: The role of obstetric complications. Schizophrenia Bulletin 34, 1083-1094.
Mittal, V. A. Walker, E. F., Walder, D., Trottman, H., Bearden, C. E., Daley, M. Simone, A. & Cannon, T. D. (2010). Markers of basal ganglia dysfunction and conversion to psychosis: Neurocognitive deficits and dyskinesias in the prodromal period. Biological Psychiatry, 68, 93-99.
Mittal, V.A., Dean, D.J., Bernard, J.A., Orr, JM., Pelletier, A., Carol, E., Gupta, T., Turner, J., Leopold, D., Robustelli, B., Millman, Z. (2014) Neurological Signs predict cerebellar-thalamic tract development and negative symptoms in adolescents at high risk for psychosis: a longitudinal perspective. Schizophrenia Bulletin, 40(6) 1204-1215 doi:10.1093/schbul/sbt199
Carol, E., Mittal, V.A. (2015). Resting cortisol level, self-concept, and putative familial environment in adolescents at ultra high-risk for psychotic disorders. Psychoneuroendocrinology, 57, 26-36. doi:10.1016/j.psyneuen.2015.03.018, PMC4437835
Bernard, J., Mittal, V.A. (2015) Updating the research domain criteria: the utility of a motor dimension. Psychological Medicine, 45(13):2685-9. doi: 10.1017/S0033291715000872. PMC4565742
Mittal, V.A., *Dean, D., Mittal, J., Saks, E. (2015). Ethical, legal, and clinical considerations when disclosing a high-risk syndrome for psychosis. Bioethics, 29, 543-56. doi: 10.1111/bioe.12155
Mittal, V.A.M., Wakschlag, L.S., (2017). RDoC Grows Up: Strengthening neurodevelopmental investigation within the RDoC Framework. Journal of Affective Disorders. 216, 30-35.
Dean, DJ, Bryan, A, *Gupta, T., *Carol, E, *Pelletier-Baldelli, A., *Newberry, R., Mittal, VA. (2017) A supervised exercise intervention for youth at risk for psychosis: An open-label pilot study, Journal of Clinical Psychiatry, 78(9) e1167-e1173, doi: 10.4088/JCP.16m11365.
van Harten, P. Walther, S., Kent, J, Sponheim, S., Mittal, V.A, The clinical and prognostic value of motor abnormalities in psychosis, and the importance of instrumental assessment (2017). Neuroscience and Biobehavioral Reviews, 80, 476-487.
Mittal, V.A., Bernard, J.A., Northoff, G. (2017). What can different motor circuits tell us about psychosis? An RDoC perspective. Schizophrenia Bulletin, 43 (5), 949-955.
Walther S., Mittal, V.A. (2017) Motor system pathology in psychosis. Current Psychiatry Reports, 19:97.
Vargas, T., Dean, D., Osborne, K., Gupta, T., Ristanovic, I, Ozturk, S., Turner, J, van Erp, T., Mittal, V. (2018) Hippocampal subregions and psychosis spectrum. Schizophrenia Bulletin, 44(5), 1091-1099.
Gupta, T, Dean, D, Kelley, N, Bernard, J, Ristanovic, I, Mittal, V (2018). Cerebellar transcranial direct current stimulation (tDCS) improves procedural learning in non-clinical psychosis: a double-blind crossover study. Schizophrenia Bulletin, 44(6) 1373-1380.
Dean, D., Walther, S., Bernard, J., Mittal, V.A. (2018). Motor clusters reveal differences in risk for psychosis, cognitive functioning, and thalamocortical connectivity: evidence for vulnerability subtypes. Clinical Psychological Science. 6(5) 721-734. doi: 10.1177/2167702618773759
Gupta, T., Haase, C., Strauss, G., Cohen, A., Mittal, V.A. (in press) Alterations in facial affect in youth at clinical high-risk for psychosis. Journal of Abnorml Psychology, doi: 10.1037/abn0000413
Schiffman, J., Ellman, L., Mittal., VA (2019). Individual differences and psychosis-risk screening: Practical suggestions to improve the scope and quality of Early identification. Frontiers in Psychiatry: Special issue Identifying individuals at clinical high risk for psychosis in different cultures and countries. 10(6) doi: 10.3389/fpsyt.2019.00006
Mittal, V.A., Walker, EF Advances in the neurobiology of stress and psychosis. Schizophrenia Research. 2019 Nov;213:1-5. doi: 10.1016/j.schres.2019.08.030
Osborne, J., Damme, K., Gupta, T., Dean, D.J., Bernard, J., Mittal, V.A. Timing dysfunction and cerebellar resting state functional connectivity abnormalities in youth at clinical high-risk for psychosis. Psychol Med. 2020 3:1-10. doi: 10.1017/S003329171900416
Osborne, KJ, Kraus, Lam, P, Vargas, T. Mittal, VA. Contingent Negative Variation Blunting and Psychomotor Dysfunction in Schizophrenia: A Systematic Review. Schizophrenia Bulletin 2020 pii: sbaa043. doi: 10.1093/schbul/sbaa043.
Damme, K, Ristanovic, I., Vargas, T., Mittal, V.A. (2020). Timing of Menarche and Abnormal Hippocampal Connectivity in Youth at Clinical-High Risk for Psychosis. Psychoneuroendocrinology. https://doi.org/10.1016/j.psyneuen.2020.104672
Strauss G.P., Pelletier-Baldelli, A., Frost-Visser, K., Walker, E. Mittal, V.A. A review of negative symptom assessment strategies in youth at clinical high-risk for psychosis. (in press) Schizophrenia Research.
Dean, D., Bernard, J., Damme, K, O’Reilly, R., Orr, J., Mittal, V.A., (2020) Longitudinal assessment and functional neuroimaging of movement variability
reveals novel insights into motor dysfunction in clinical high-risk for psychosis. Schizophrenia Bulletin https://doi.org/10.1093/schbul/sbaa072
Vargas, T., Damme, K, Ellman, L., Ered, A, Capizzi, R., Mittal, V.A. Neuroimaging markers of resiliency in Clinical High Rick (CHR) for psychosis youth: a qualitative review. Biological Psychiatry CNNI, 27 2020
Gold, J., Corlette, P.R., Strauss, G., Schiffman, J., Ellman, L.M., Walker, E.F., Powers, A.R., Woods, S.W., Waltz, J., Silverstein, S.M., Mittal, V.A. (in press) Enhancing psychosis risk prediction through computational cognitive neuroscience. Schizophrenia Bulletin.
Vargas, T., Damme, K., Mittal, V.A. Neighborhood deprivation, prefrontal morphology and neurocognition in late childhood to early adolescence. Neuroimage 2020 117086
Hitczenko, K., Mittal, V.A., Goldrick. (in press) Understanding language abnormalities and associated clinical markers in psychosis: The promise of computational methods. Schizophrenia Bulletin.
Damme, K., Schiffman, J., Ellman, L.E., Mittal, V.A. (in press), Sensorimotor and Activity Psychosis-Risk (SMAP-R) Scale. Schizophrenia Bulletin.
Mittal, V.A, Bernard, J., Walther, S. (in press). Cerebellar-thalamic circuits play a crtical role in psychomotor function. Molecular Psychiatry
Corcoran, C., Mittal, V.A.,Woods, S. APS should be in the DSM5 TR. JAMA-Psychiatry.