Pharmacogenetic Approaches to Cognitive Enhancement in Schizophrenia

Abstract

Research in the area of pharmacogenetics in psychiatry is aimed at identifying clinically relevant genetic variations that can predict treatment response. Ultimately, the goal is to individualize treatment in order to optimize outcome in disorders in which incomplete treatment response is common. Positive symptoms in patients with schizophrenia appear to be the most amenable to the currently available agents; however, negative symptoms and cognitive deficits frequently persist even when frank psychosis is well controlled. Given the relationship between these persistent traits and functional disability in schizophrenia, efforts are under way to directly target cognitive impairment and negative symptoms pharmacologically in order to improve quality of life. To date, most pharmacogenetic studies of schizophrenia have been focused on predicting clinical efficacy and side effects. In this review, we discuss the potential use of cognition as a primary outcome measure of interest in future pharmacogenetic trials of schizophrenia.

Meta-analysis of the association between dopamine transporter genotype and response to methylphenidate treatment in ADHD

“…It has the potential to explain some of the variability not only in clinical or cognitive response to pharmacological compounds but also in side-effect severity on the basis of quantitative, neurobiologically determined predictors. [28][29][30][31] In case of methylphenidate, the pronounced action of this drug at the dopamine transporter has led to numerous pharmacogenetic studies involving the dopamine transporter gene (SLC6A3). The dopamine transporter plays an important role in the regulation of dopamine neurotransmission through reuptake of dopamine from the synaptic cleft into the presynaptic neuron.…”

The nicotinic α7 receptor agonist GTS-21 improves cognitive performance in ketamine impaired rhesus monkeys

“…Schizophrenia affects approximately seven individuals per 1000 (McGrath et al, 2008), and although the diagnostic criteria include a variety of symptoms, cognitive deficits impacting attention, executive function, and memory have become increasingly recognized as key components of the disorder (Elvevag and Goldberg, 2000;van Os and Kapur, 2009;Burdick et al, 2011;Goff et al, 2011). The importance of cognitive impairment has led to highly collaborative scientific movements such as the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and the subsequent Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS), to guide research and therapeutic development, including an increased focus on improving the predictability of preclinical models (Marder et al, 2004;Buchanan et al, 2005;Carter et al, 2008).…”

Potential therapeutic avenues to tackle social cognition problems in schizophrenia

“…Consequently, future treatments for improving or enhancing social functioning are likely to become more 'neurocentric', with treatments aimed at improving brain function in measurable ways through cognitive training strategies and neurobiological interventions. In addition to this, we are likely to see more work invested in exploring the potential for psychopharmaceutical cognitive enhancers to improve both neurocognitive and social cognitive deficits [112,117].…”