Deficits in attention and working memory, the abilities that allow individuals to selectively attend to and mentally maintain and manipulate information to guide behavior, are considered to be central components to the cognitive dysfunction in schizophrenia. While advances in antipsychotic pharmacotherapy have resulted in important gains for treating symptoms of hallucinations and delusions, cognitive deficits have been far less responsive to standard treatments. Developing novel pharmacological agents to target these persistent cognitive deficits is an important goal of ongoing schizophrenia treatment research. This is a broad and multidimensional problem involving drug development and translational animal models. In the end, success will depend on the ability of trained investigators who have the expertise and tools to evaluate drug effects on neurocognitive systems in the clinic.
The aim of this proposed career development program is to facilitate the candidate's efforts to become a successful independent clinical investigator in this area. Primary objectives of this career development program are to provide the candidate with advanced training in three main areas: (1) functional brain imaging;(2) cognitive neuroscience and neuropharmacological models of working memory;and (3) clinical trial design and methodology. Research activities will focus on designing and conducting behavioral and event-related functional neuroimaging studies of working memory and attention using paradigms translated from animal models to examine antipsychotic treatment effects on these core cognitive deficits in schizophrenia. These activities will prepare the candidate for an independent program of research examining disturbances in functional brain systems that underlie cognitive impairments in schizophrenia and how these are impacted by antipsychotic treatments. The knowledge and skills gained from proposed training and research activities will be important for the Pi's career objective to use integrative approaches to investigate the effectiveness of pharmacological treatments developed to reduce cognitive impairments in schizophrenia.
Schizophrenia is a debilitating psychiatric disorder. With a prevalence of 1% of the population and billions of dollars expended annually in direct costs and lost productivity, it is a major public health concern. Cognitive symptoms, which are not adequately treated, account for much of the long-term functional disability, and the need to understand the brain basis of these deficits is imperative to advance treatments for this disorder.
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|Rubin, Leah H; Yao, Li; Keedy, Sarah K et al. (2017) Sex differences in associations of arginine vasopressin and oxytocin with resting-state functional brain connectivity. J Neurosci Res 95:576-586|
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|Rubin, Leah H; Connelly, Jessica J; Reilly, James L et al. (2016) Sex and diagnosis specific associations between DNA methylation of the oxytocin receptor gene with emotion processing and temporal-limbic and prefrontal brain volumes in psychotic disorders. Biol Psychiatry Cogn Neurosci Neuroimaging 1:141-151|
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|Lencer, Rebekka; Bishop, Jeffrey R; Harris, Margret S H et al. (2014) Association of variants in DRD2 and GRM3 with motor and cognitive function in first-episode psychosis. Eur Arch Psychiatry Clin Neurosci 264:345-55|
|Reilly, James L; Frankovich, Kyle; Hill, Scot et al. (2014) Elevated antisaccade error rate as an intermediate phenotype for psychosis across diagnostic categories. Schizophr Bull 40:1011-21|
|Keedy, Sarah K; Bishop, Jeffrey R; Weiden, Peter J et al. (2014) Disease and drug effects on internally-generated and externally-elicited responses in first episode schizophrenia and psychotic bipolar disorder. Schizophr Res 159:101-6|
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