This Mentored Patient-Oriented Research Career Development Award will provide Dr. Arielle Stanford with the training and skills needed to become an independent investigator with expertise in the development of treatments targeting the negative symptoms of schizophrenia. Negative symptoms are among the strongest predictors of poor outcome and are not very responsive to treatment. Novel treatments are needed to alleviate these symptoms and improve functioning. Most treatment studies have not focused on the large between-patient variability in phenomenology and etiology that may contribute to reduced response rates. This project will evaluate the potential utility of repetitive transcranial magnetic stimulation (rTMS) as an intervention that may test etiological hypotheses linked to heterogeneity and treat negative symptoms. While it has been difficult to meaningfully separate schizophrenia disease variants, there are subgrouping strategies that could be explored with respect to negative symptoms, including the division of patients into Deficit Syndrome (DS) and nonDS groups, and data supporting Paternal Age Related Schizophrenia (PARS) as an independent variant. Studies suggest that different types of negative symptoms map to disparate neural circuits. Thus, noninvasive focal brain stimulation may have specific advantages over medications, which lack spatial resolution. rTMS can modulate neuronal activity and produce regionally specific excitatory or inhibitory effects through modulation of local physiology and chemistry. The efficacy of rTMS may be enhanced by site-specific application targeted to patient subgroups. None of the existing studies of rTMS in schizophrenia have entailed full characterization of patients, nor has DS been considered as a response mediator. Lastly, studies of negative symptoms have only targeted the DLPFC, omitting the potential role of other cortical regions.
The aims of this Mentored Patient-Oriented Research Career Development Award are to 1) to examine the efficacy and safety of rTMS as a treatment for the negative symptoms of schizophrenia and 2) to characterize responders vs. non-responders to rTMS with respect to etiological subgroup (DS vs. non-DS) and other baseline characteristics, including cognitive and demographic, using the focality of rTMS as a brain probe to test hypotheses regarding the neural underpinnings of negative symptoms. The candidate's career goal is to develop novel treatment strategies tailored to the symptom profile and schizophrenia subtype of the patient, i.e. to shape this novel intervention to the heterogeneity of schizophrenia. The career development plan will provide expertise in: 1) the neurocircuitry of negative symptoms, 2) the use of TMS as a neurobiological probe and as a treatment tool;and 3) clinical trial research design and statistical analysis. This training and research experience will position Dr. Stanford to become an independent investigator in the field of intervention development in the study and treatment of schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH076976-05
Application #
7992435
Study Section
Interventions Committee for Disorders Related to Schizophrenia, Late Life, or Personality (ITSP)
Program Officer
Wynne, Debra K
Project Start
2007-01-01
Project End
2011-06-30
Budget Start
2011-01-01
Budget End
2011-06-30
Support Year
5
Fiscal Year
2011
Total Cost
$59,852
Indirect Cost
Name
Columbia University (N.Y.)
Department
Psychiatry
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Chen, Chi-Ming A; Stanford, Arielle D; Mao, Xiangling et al. (2014) GABA level, gamma oscillation, and working memory performance in schizophrenia. Neuroimage Clin 4:531-9
Stanford, Arielle D; Luber, Bruce; Unger, Layla et al. (2013) Single pulse TMS differentially modulates reward behavior. Neuropsychologia 51:3041-7
Kegeles, Lawrence S; Mao, Xiangling; Stanford, Arielle D et al. (2012) Elevated prefrontal cortex ?-aminobutyric acid and glutamate-glutamine levels in schizophrenia measured in vivo with proton magnetic resonance spectroscopy. Arch Gen Psychiatry 69:449-59
Corcoran, C M; Kimhy, D; Parrilla-Escobar, M A et al. (2011) The relationship of social function to depressive and negative symptoms in individuals at clinical high risk for psychosis. Psychol Med 41:251-61
Stanford, Arielle D; Messinger, Julie; Malaspina, Dolores et al. (2011) Theory of Mind in patients at clinical high risk for psychosis. Schizophr Res 131:11-7
Stanford, Arielle D; Corcoran, Cheryl; Bulow, Peter et al. (2011) High-frequency prefrontal repetitive transcranial magnetic stimulation for the negative symptoms of schizophrenia: a case series. J ECT 27:11-7
Messinger, Julie W; Tremeau, Fabien; Antonius, Daniel et al. (2011) Avolition and expressive deficits capture negative symptom phenomenology: implications for DSM-5 and schizophrenia research. Clin Psychol Rev 31:161-8
Rosenfield, Paul J; Kleinhaus, Karine; Opler, Mark et al. (2010) Later paternal age and sex differences in schizophrenia symptoms. Schizophr Res 116:191-5
Lou, Hans C; Luber, Bruce; Stanford, Arielle et al. (2010) Self-specific processing in the default network: a single-pulse TMS study. Exp Brain Res 207:27-38
Anglin, Deidre; Stanford, Arielle D; Harkavy-Friedman, Jill M et al. (2009) Family history of affective illness in schizophrenia patients: symptoms and cognition. Schizophr Res 110:24-7

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