Schizophrenia is a common and costly disorder currently defined by descriptive criteria. This type of diagnostic nosology suggests that schizophrenia is most likely a syndrome caused by a variety of different pathophysiological mechanisms rather than a single disease. If schizophrenia is a heterogeneous syndrome, then the equivocal findings of most large etiopathophysiologic studies and the less than robust results of most treatment trials are understandable. The investigators believe that it is imperative to develop reliable and reproducible methods to categorize patients with schizophrenia into biologically relevant subtypes. This application investigates one biological finding, the association between increased serum soluble interleukin-2 receptors (SIL-2Rs) and schizophrenia. This research is an extension of the PI and others' work which has led us to hypothesize that increased serum SIL-2r in schizophrenia are caused by TH1 T-cell activation. TH1 cells are a subset of activated CD4+ helper T-cells which modulate macrophage activation and T-cell mediated immunity. TH1 cells preferentially release the cytokines interleukin-2 (IL-2) and interferon-gamma (INF-g), and IL-2 has been found to stimulate central nervous system dopamine release in animal models. The specific objectives of this application are: 1) to determine whether immune activation seen in a subgroup of schizophrenic patients is due to TH1 cell activation and to investigate the reproducibility of this finding in African-American and Hispanic-American patients; 2) to explore the relationship between this subgroups of patients, clinical measures of psychopathology, and the deficit syndrome model; 3) to determine if there are two forms of immune activation in schizophrenia - one being TH1 cell activation which occurs in a small group of patients and is relatively fixed, and the second, a general nonspecific activation which decreases with the resolution of the psychosis; and 4) to determine whether patients with TH1 activation are more likely to develop spontaneous dyskinesia. These findings would be important because they would allow us to biologically subtype a group of schizophrenic patients.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
First Independent Research Support & Transition (FIRST) Awards (R29)
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Psychobiological, Biological, and Neurosciences Subcommittee (MHAI)
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Veterans Medical Research Fdn/San Diego
San Diego
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Rapaport, Mark H; Bresee, Catherine (2010) Serial mitogen-stimulated cytokine production from continuously ill patients with schizophrenia. Neuropsychopharmacology 35:428-34
Bresee, Catherine; Rapaport, Mark H (2009) Persistently increased serum soluble interleukin-2 receptors in continuously ill patients with schizophrenia. Int J Neuropsychopharmacol 12:861-5
Mendlowicz, Mauro V; Akiskal, Hagop S; Kelsoe, John R et al. (2005) Temperament in the clinical differentiation of depressed bipolar and unipolar major depressive patients. J Affect Disord 84:219-23
Akiskal, Hagop S; Mendlowicz, Mauro V; Jean-Louis, Girardin et al. (2005) TEMPS-A: validation of a short version of a self-rated instrument designed to measure variations in temperament. J Affect Disord 85:45-52
Mendlowicz, Mauro V; Jean-Louis, Girardin; Kelsoe, John R et al. (2005) A comparison of recovered bipolar patients, healthy relatives of bipolar probands, and normal controls using the short TEMPS-A. J Affect Disord 85:147-51
Wang, Xiao-Fen; Wang, Dunrui; Zhu, Weiguo et al. (2003) Studies characterizing 60 kda autoantibodies in subjects with schizophrenia. Biol Psychiatry 53:361-75
Rapaport, Mark Hyman; Judd, Lewis L; Schettler, Pamela J et al. (2002) A descriptive analysis of minor depression. Am J Psychiatry 159:637-43
Gladsjo, J A; Rapaport, M H; McKinney, R et al. (2001) Absence of neuropsychologic deficits in patients receiving long-term treatment with alprazolam-XR for panic disorder. J Clin Psychopharmacol 21:131-8
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Mendlowicz, M V; Jean-Louis, G; Gekker, M et al. (1999) Neonaticide in the city of Rio de Janeiro: forensic and psycholegal perspectives. J Forensic Sci 44:741-5

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