The purpose of this study is to examine the role of serum brain-derived neurotrophic factor (BDNF) as a potential biomarker for the response to neuroplasticity-based cognitive remediation in patients with schizophrenia. We are requesting a modest amount of supplemental funding to our original RO1 grant, Cognitive Remediation in Schizophrenia (grant period 2004-2009). The requested supplement grant will be used to obtain and process a series of blood samples for serum BDNF levels from schizophrenia subjects enrolled in a randomized trial of intensive, computerized, neuroplasticity-based cognitive training exercises, as well as healthy comparison subjects matched on age, gender, and IQ. Supplemental funds will be used to analyze BDNF levels in stored serum samples from all current subjects as well as to gather additional samples form these and future incoming subjects. The serum BDNF results will be analyzed with respect to longitudinal clinical and neurocognitive data being obtained in the parent study. ? ? We study is supported by pilot data from our first cohort of schizophrenia subjects who have completed 50 hours of intensive neuroplasticity-based cognitive training exercises. Serum BDNF levels were increased by 30% in 15 subjects who underwent 12 weeks of the training, but not in 11 subjects who underwent the active computer games control condition (change measures significantly different between the two groups, p<0.05). Statistically significant associations were present between changes in serum BDNF levels and measures of working memory and learning after the cognitive training, consistent with a trophic response in hippocampal and cortical neurons as a result of the intensive training.
The specific aims of this study are thus: 1) To obtain measures of serum BDNF levels on each subject at 5 time points at study entry, and then after 2, 10, and 20 weeks of intervention, as well as at 6-month follow- up; 2) To examine the relationship of baseline serum BDNF levels to baseline neurocognitive function in schizophrenia subjects and in healthy comparison subjects; 3) To examine the relationship of change in serum BDNF levels to change in neurocognitive function in the two groups of schizophrenia subjects, those undergoing neuroplasticity-based targeted cognitive training (N = 40) as compared to those undergoing a computer games control condition (N = 40).

Public Health Relevance

This purpose of this study is to investigate the relationship between serum levels of brain-derived neurotrophic factor (BDNF) and response to neuroscience-guided cognitive remediation in patients with schizophrenia. BDNF is a factor that promotes the health and functioning of neurons, plays a key role in learning, and enhances the brain's resiliency to stress. We will investigate whether measures of serum BDNF can serve as a biomarker for observed improvements in cognitive functioning in schizophrenia subjects who are undergoing an intensive computerized cognitive remediation program. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
3R01MH068725-05S1
Application #
7467654
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Kozak, Michael J
Project Start
2003-07-01
Project End
2010-02-28
Budget Start
2008-07-15
Budget End
2010-02-28
Support Year
5
Fiscal Year
2008
Total Cost
$91,147
Indirect Cost
Name
Northern California Institute Research & Education
Department
Type
DUNS #
613338789
City
San Francisco
State
CA
Country
United States
Zip Code
94121
Subramaniam, Karuna; Gill, Jeevit; Fisher, Melissa et al. (2018) White matter microstructure predicts cognitive training-induced improvements in attention and executive functioning in schizophrenia. Schizophr Res 193:276-283
Kantrowitz, Joshua T; Swerdlow, Neal R; Dunn, Walter et al. (2018) Auditory System Target Engagement During Plasticity-Based Interventions in Schizophrenia: A Focus on Modulation of N-Methyl-D-Aspartate-Type Glutamate Receptor Function. Biol Psychiatry Cogn Neurosci Neuroimaging 3:581-590
Subramaniam, Karuna; Ranasinghe, Kamalini G; Mathalon, Daniel et al. (2017) Neural mechanisms of mood-induced modulation of reality monitoring in schizophrenia. Cortex 91:271-286
Dale, Corby L; Brown, Ethan G; Fisher, Melissa et al. (2016) Auditory Cortical Plasticity Drives Training-Induced Cognitive Changes in Schizophrenia. Schizophr Bull 42:220-8
Biagianti, Bruno; Fisher, Melissa; Neilands, Torsten B et al. (2016) Engagement with the auditory processing system during targeted auditory cognitive training mediates changes in cognitive outcomes in individuals with schizophrenia. Neuropsychology 30:998-1008
Vinogradov, Sophia; Herman, Alexander (2016) Psychiatric Illnesses as Oscillatory Connectomopathies. Neuropsychopharmacology 41:387-8
Subramaniam, Karuna; Gill, Jeevit; Slattery, Patrick et al. (2016) Neural Mechanisms of Positive Mood Induced Modulation of Reality Monitoring. Front Hum Neurosci 10:581
Fisher, Melissa; Mellon, Synthia H; Wolkowitz, Owen et al. (2016) Neuroscience-informed Auditory Training in Schizophrenia: A Final Report of the Effects on Cognition and Serum Brain-Derived Neurotrophic Factor. Schizophr Res Cogn 3:1-7
Woolley, J D; Chuang, B; Lam, O et al. (2014) Oxytocin administration enhances controlled social cognition in patients with schizophrenia. Psychoneuroendocrinology 47:116-25
Subramaniam, Karuna; Luks, Tracy L; Garrett, Coleman et al. (2014) Intensive cognitive training in schizophrenia enhances working memory and associated prefrontal cortical efficiency in a manner that drives long-term functional gains. Neuroimage 99:281-92

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