Recent findings from epidemiological studies suggest that that there may be a link between the experience of early traumatic events and later development of psychotic symptoms. Animal studies provide a model of "stress sensitization" whereby early stressful events contribute to dopamine dysregulation and a sensitivity to psychosocial stress in young adulthood. "Prodrome" studies provide a unique opportunity to assess stress responsivity prospectively, prior to the onset of full psychosis, by identifying youth with an "ultra-high-risk" syndrome that confers approximately 35 percent risk for conversion to a full psychotic disorder within 2.5 years. In Study 1, we test the hypotheses that 1) UHR participants age 16-25 report a greater number of traumatic life events than healthy controls matched on age, gender and SES;and, 2) UHR participants show dysregulated stress-responsivity compared to healthy controls as exhibited by higher baseline salivary Cortisol levels, a slower return to baseline levels after a laboratory social stressor task, and higher Cortisol levels 16 hours after administration of dexamethasone, which triggers the negative feedback response of the hypothalamic- pituitary-adrenal axis. We will also collect pilot data to demonstrate the feasibility of a longitudinal follow-up to Study 1 by repeating clinical and stress-responsivity assessments with the UHR group 6- and 12-months later. We hypothesize that a greater number of traumatic events and dysregulated stress responsivity in the UHR group will predict later positive symptoms, poor functioning and risk for conversion to full psychosis. Identifying the mechanisms linking early trauma and later psychosis will allow us to identify potential targets for prevention and early intervention in psychosis, while future studies should examine possible gene- environment interactions between early trauma and candidate schizophrenia genes.

Public Health Relevance

Schizophrenia is a chronic and debilitating disorder that affects approximately 1 percent of the population and costs society more than depression, dementia and medical illnesses across most of the lifespan. Examining the role of early adverse life events and stress-responsivity in young people at ultra-high-risk for psychosis will help to identify risk factors for the development of schizophrenia and potential targets for prevention and early intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH086618-05
Application #
8464788
Study Section
Social Psychology, Personality and Interpersonal Processes Study Section (SPIP)
Program Officer
Friedman-Hill, Stacia
Project Start
2009-09-22
Project End
2014-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
5
Fiscal Year
2013
Total Cost
$167,941
Indirect Cost
$12,292
Name
University of California San Francisco
Department
Psychiatry
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Fulford, Daniel; Pearson, Rahel; Stuart, Barbara K et al. (2014) Symptom assessment in early psychosis: the use of well-established rating scales in clinical high-risk and recent-onset populations. Psychiatry Res 220:1077-83
Loewy, Rachel L; Therman, Sebastian; Manninen, Marko et al. (2012) Prodromal psychosis screening in adolescent psychiatry clinics. Early Interv Psychiatry 6:69-75
Loewy, Rachel L; Pearson, Rahel; Vinogradov, Sophia et al. (2011) Psychosis risk screening with the Prodromal Questionnaire--brief version (PQ-B). Schizophr Res 129:42-6