An increasing emphasis in the development of treatments for psychotic illness, especially in early stages, has been in the area of cognitive enhancement, neuroprotection and cognitive remediation. Individuals at Clinical High Risk (CHR) develop a psychotic illness at rates between 20-40% over a 1-2 year period but the majority have neurocognitive and functional deficits whether they develop psychosis or not. Neurocognitive deficits predict a later psychotic illness and also poor functional status at follow up. By intervening early in the course of psychosis to target neurocognitive deficits, it might be possible to affect the functional outcome of this devastating disease. The proposed R34 Application, in response to RFA-MH-14-212 - Research to Improve the Care of Persons at Clinical High Risk for Psychotic Disorders, will assess Compensatory Cognitive Training (CCT) versus Recreational Training (RT) in Latino Clinical High Risk (CHR) subjects in the US and Mexico. Although CCT has been studied extensively in chronic psychotic illness, demonstrating moderate to large effect sizes on neurocognitive domains and functional capacity, it has never been studied in CHR subjects. In a 12 week randomized clinical trial design, 120 CHR Latino subjects will be randomized by groups into CCT or RT. Subjects will be assessed 4 times, at the beginning and end of the study, and at intermediary monthly intervals.
The Specific Aims are to 1) Compare CCT augmentation versus RT on Primary Neurocognitive (Global Cognitive Index) and Functional Capacity (UCSD Performance-based Skill Assessment - UPSA) measures and Secondary Self-Rated Functioning (Specific Level of Functioning) and Clinical Symptom (Scale of Prodromal Syndromes - SOPS) measures;2) Explore predictors (moderators) of treatment response (eg, age, baseline symptoms, neurocognition) and 3) explore mediators of treatment response (change in neurocognition and functioning). Also unique to this proposal will be the focus on Latino subjects at CHR for psychosis. The Latino community is underserved yet represents 55% of school children in San Diego county. The inclusion of a Mexico City site will enable an accelerated recruitment, given their access to large numbers of early psychosis subjects, increase sample diversity and minority representation by including large numbers of Latino subjects and assist in the implementation of a Spanish version of CCT. The laboratories of Kristin Cadenhead, MD, at University of California San Diego (UCSD) and Camilo de la Fuente MD, PhD, from the Laboratorio de Psiquiatr?a Experimental, Instituto Nacional de Neurolog?a y Neurocirug?a (INNN), Mexico City, have an existing collaborative relationship, funded by grants through the University of California Institute for Mexico and the United States (UC MEXUS), that allowed establishment of comparability of early psychosis populations across sites and implementation of reliability and quality control methodology in preparation for the proposed study.

Public Health Relevance

The evaluation of a novel treatment such as Compensatory Cognitive Training in clinical high risk youth will provide empirical support for a lower risk; brod spectrum treatment; that could have important implications for public health if it improves neurocognition and functioning. Additionally; this collaboration between the University of California; San Diego (UCSD) and the Instituto Nacional de Neurolog?a y Neurocirug?a (INNN); Mexico City will enable increased sample diversity and minority representation by including Latino subjects.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Planning Grant (R34)
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Special Emphasis Panel (ZMH1-ERB-D (05))
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Goldstein, Amy B
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University of California San Diego
Schools of Medicine
La Jolla
United States
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Minichino, Amedeo; Cadenhead, Kristin (2017) Mirror Neurons in Psychiatric Disorders: from Neuroception to Bio-behavioral System Dysregulation. Neuropsychopharmacology 42:366
Cadenhead, Kristin S; Mirzakhanian, Heline (2016) A Case of Attenuated Psychosis Syndrome: A Broad Differential Diagnosis Requires Broad-Spectrum Treatment. Am J Psychiatry 173:321-9