2019 BHI/CCNP Pilot Grants have been awarded

The investigator teams that were funded included-

(1) Anna Konova (RBHS-RWJMS) and Matthew Lee (RU-NB-SAS) (funded by Office of the VCRI, RU-NB)

Testing latent decision processes associated with distal versus proximal risk for alcohol use
There is recognized need for identifying novel mechanisms of distal (etiological) and more proximal (disease-maintenance) risk for substance use and addiction. Such knowledge could help guide prevention efforts to where they are needed most, as well as inform development of more targeted approaches. Our recent work suggests two behavioral markers of risky decision-making may have differential utility in this regard. These markers capture latent decision processes in situations where the precise odds of an outcome are known (known-risk tolerance) versus when these odds are not fully known and cannot be estimated (ambiguity tolerance). We previously found evidence that increased known- risk tolerance is a stable and specific feature of addiction, while increased ambiguity tolerance uniquely tracked (more proximal) risk for continued use. However, it remains unknown whether either parameter reflects premorbid etiologic risk (which if so, could inform primary prevention) or a less clinically-actionable illness effect, and whether indeed there is differential specificity to disease-maintenance risk (which if so, could inform secondary/tertiary prevention). To answer these questions, here we will study individuals at-risk for alcohol use disorder (AUD, based on family history), with and without AUD (2×2 design). This design will allow us to determine whether known-risk tolerance is a distal etiologic risk factor for AUD, as opposed to a consequence of AUD, and whether ambiguity tolerance is a proximal risk factor in AUD, independent of etiologic risk for AUD. This project will facilitate the growth of addiction research at the CCNP, expand the PIs’ existing research programs, provide pilot results for larger NIAAA/NIDA funding, and ultimately help inform real-world addiction prevention/intervention.

(2) Pernille Hemmer (RU-NB-SAS) and Julien Musolino (RU-NB-SAS) (funded by Office of the VCRI, RU-NB)

Evaluating the influence of prior expectations on episodic memory in patients with schizophrenia
This project concerns a fundamental aspect of our mental lives, namely the prior expectations that we bring to bear on our understanding of the regularities of our environment. Prior expectations shape our understanding of the world, and thus exert an important influence on our thinking and behavior, ranging from perception to memory, judgment, and decision making. In certain clinical populations, however, like patients suffering from Schizophrenia use of prior expectations been shown to be compromised (e.g., Dima et al., 2009). This effect has been demonstrated in perception using hollow mask illusions, which are thought to be influenced by familiarity and prior expectations for objects. The goal of this project is to bring together two lines of research bearing on the assessment of prior expectations. The first line seeks to determine whether this failure in patients suffering from Schizophrenia to employ prior expectations in perception extends to the domain of memory. In typical populations prior expectations are known to influence episodic memory, and might account for as much as 80% of episodic recall. To our knowledge this is the first assessment of the influence of prior expectations om memory in patients suffering from Schizophrenia. The second line of work stems from Bayesian models of cognition showing that using prior knowledge in memory is an optimal strategy. We seek to implement a computational framework for assessing individual differences in subjective mental representations. Characterizing the parameter space for an individual patient has the potential to be used as a diagnostic and predictive tool.

(3) Bonnie L. Firestein (RU-NB-SAS), Steve Silverstein (RBHS-RWJMS) and Michael Gara (RBHS-RWJMS) (funded by BHI)

Proteins associated with schizophrenia in epithelial cheek cells and relationship to cognitive symptoms
Schizophrenia is a debilitating psychiatric illness that disrupts affected individuals’ thoughts and behavior and can significantly diminish quality of life. There is thus an urgent need for new methods and discoveries in the psychopharmacology of schizophrenia. One critical task is the identification of state-sensitive markers that can be used to predict treatment response. We have been studying the role of Nitric Oxide Synthase 1 Adaptor Protein (NOS1AP) in neuronal function. NOS1AP negatively regulates NMDA receptor signaling and has been implicated in susceptibility for schizophrenia. We have shown that NOS1AP mRNA and protein are increased in postmortem dorsolateral prefrontal cortex of subjects with schizophrenia, and this overexpression is thought to result in NMDA receptor hypofunction. Moreover, our preliminary data show that 1) NOS1AP protein can be detected in buccal cells from humans; 2) may be elevated in buccal cells of a subset of patients with schizophrenia; and 3) buccal cell NOS1AP expression may correlate to SNPs in NOS1AP in patients with schizophrenia. Therefore, we now propose to correlate an individual’s genotype (presence of SNPs) and cognitive function to their protein expression levels of NOS1AP. We will collect buccal cells from a total of 50 healthy subjects and a total of 50 patients with schizophrenia to assess NOS1AP expression, genotype, and cognitive function, following our IRB-approved protocols. This information will help determine if NOS1AP may serve as an easy-to-acquire biomarker for schizophrenia..

(4) Anthony Deo (RBHS-RWJMS) (funded by BHI)

Improving the reliability of the diagnosis of psychosis in children
Individuals with psychosis experience distressing symptoms which include hallucinations. The presence of psychosis greatly increases the risk of suicide. Psychosis symptoms are common both transiently in childhood (13-17% of children with symptoms resolving in most) and in children with mental illness (8%). Providers are hesitant to diagnose psychosis in children as children often has difficulty describing their inner experience making it challenging to know if they are truly experiencing symptoms of psychosis. Reliable diagnosis of psychosis in children is critical. Unfortunately, there are no truly objective measures to diagnose psychosis or predict who will develop a serious mental illness with psychosis in children. Adults with psychosis tend to misattribute internal and external stimuli. This misattribution bias can be measured quantitatively, though this has not been tested in children. Additionally, visual hallucinations are more common in children with psychosis as compared to adults, though the features of visual hallucinations that are specific to children with or who will develop psychosis are unknown. This project will use a quantitative cognitive task to determine if there is an auditory misattribution bias in children with psychosis. We will use a new tablet app to have children safely render their visual illusions/hallucinations to identify features of visual disturbances that distinguish those with or at risk for psychosis. The ultimate goal is to determine if both a quantitative measure of auditory misattribution bias and an app-based rendering of visual illusions/hallucinations can be used to reliably diagnose psychosis in children and predict who will develop psychosis.