Leveraging the utility of pharmacogenomics in psychiatry through clinical decision support: a focus group study.

BACKGROUND: Pharmacogenomics is starting to build momentum in clinical utility, perhaps the most in mental and behavioral healthcare. However, efficient delivery of this information to the point of prescribing remains a significant challenge. Clinical decision support has an opportunity to address this void by integrating pharmacogenomics into the clinician workflow. METHODS: To address the specific needs of mental health clinicians at the point of care, we conducted 3 focus groups with a total of 16 mental health clinicians. Each 1-h focus group was designed to identify the desired clinical decision support features, with a particular interest in pharmacogenomics, and potential negative or unintended consequences of clinical decision support integration at the point of care in a mental healthcare setting. We implemented an iterative design to expand upon knowledge generated in prior focus groups. The results from the guided discussion in the first focus group were used to develop a mental health clinical decision support prototype. This prototype was then presented during the next two focus groups to drive the discussion. RESULTS: This study has identified main themes related to the desired clinical decision support features of mental health clinicians, the use of pharmacogenomics in practice, and unintended and negative consequences of clinical decision support integration at the point of care. Clinicians desire a more complete picture of the medication history of patients and guidance to choose medications in relation to cost, insurance coverage, and pharmacogenetics interactions. Mental health clinicians agreed that pharmacogenetics is useful and impacts their prescribing decisions when the data are available. Several negative consequences of clinical decision support integration were identified including alert fatigue and frustration using the tool. Several points of contention were related to the integration of the clinical decision support with the electronic health record, including bidirectional flow of information, speed, location within workflow, and potential incompleteness of information. CONCLUSIONS: We have identified general and unique considerations of mental health clinicians with regard to clinical decision support. Clinical decision support that incorporates desired features while avoiding negative and unintended consequences will increase clinician usage and will have the potential to improve the care of patients.

Dopamine and the development of executive dysfunction in autism spectrum disorders.

Persons with autism regularly exhibit executive dysfunction (ED), including problems with deliberate goal-directed behavior, planning, and flexible responding in changing environments. Indeed, this array of deficits is sufficiently prominent to have prompted a theory that executive dysfunction is at the heart of these disorders. A more detailed examination of these behaviors reveals, however, that some aspects of executive function remain developmentaly appropriate. In particular, while people with autism often have difficulty with tasks requiring cognitive flexibility, their fundamental cognitive control capabilities, such as those involved in inhibiting an inappropriate but relatively automatic response, show no significant impairment on many tasks. In this article, an existing computational model of the prefrontal cortex and its role in executive control is shown to explain this dichotomous pattern of behavior by positing abnormalities in the dopamine-based modulation of frontal systems in individuals with autism. This model offers excellent qualitative and quantitative fits to performance on standard tests of cognitive control and cognitive flexibility in this clinical population. By simulating the development of the prefrontal cortex, the computational model also offers a potential explanation for an observed lack of executive dysfunction early in life.

Indirection and symbol-like processing in the prefrontal cortex and basal ganglia.

The ability to flexibly, rapidly, and accurately perform novel tasks is a hallmark of human behavior. In our everyday lives we are often faced with arbitrary instructions that we must understand and follow, and we are able to do so with remarkable ease. It has frequently been argued that this ability relies on symbol processing, which depends critically on the ability to represent variables and bind them to arbitrary values. Whereas symbol processing is a fundamental feature of all computer systems, it remains a mystery whether and how this ability is carried out by the brain. Here, we provide an example of how the structure and functioning of the prefrontal cortex/basal ganglia working memory system can support variable binding, through a form of indirection (akin to a pointer in computer science). We show how indirection enables the system to flexibly generalize its behavior substantially beyond its direct experience (i.e., systematicity). We argue that this provides a biologically plausible mechanism that approximates a key component of symbol processing, exhibiting both the flexibility, but also some of the limitations, that are associated with this ability in humans.

Strategic cognitive sequencing: a computational cognitive neuroscience approach.

We address strategic cognitive sequencing, the "outer loop" of human cognition: how the brain decides what cognitive process to apply at a given moment to solve complex, multistep cognitive tasks. We argue that this topic has been neglected relative to its importance for systematic reasons but that recent work on how individual brain systems accomplish their computations has set the stage for productively addressing how brain regions coordinate over time to accomplish our most impressive thinking. We present four preliminary neural network models. The first addresses how the prefrontal cortex (PFC) and basal ganglia (BG) cooperate to perform trial-and-error learning of short sequences; the next, how several areas of PFC learn to make predictions of likely reward, and how this contributes to the BG making decisions at the level of strategies. The third models address how PFC, BG, parietal cortex, and hippocampus can work together to memorize sequences of cognitive actions from instruction (or "self-instruction"). The last shows how a constraint satisfaction process can find useful plans. The PFC maintains current and goal states and associates from both of these to find a "bridging" state, an abstract plan. We discuss how these processes could work together to produce strategic cognitive sequencing and discuss future directions in this area.