Neuroimaging in Psychiatric Pharmacogenetics Research: The Promise and Pitfalls

Abstract

The integration of research on neuroimaging and pharmacogenetics holds promise for improving treatment for neuropsychiatric conditions. Neuroimaging may provide a more sensitive early measure of treatment response in genetically defined patient groups, and could facilitate development of novel therapies based on an improved understanding of pathogenic mechanisms underlying pharmacogenetic associations. This review summarizes progress in efforts to incorporate neuroimaging into genetics and treatment research on major psychiatric disorders, such as schizophrenia, major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, and addiction. Methodological challenges include: performing genetic analyses in small study populations used in imaging studies; inclusion of patients with psychiatric comorbidities; and the extensive variability across studies in neuroimaging protocols, neurobehavioral task probes, and analytic strategies. Moreover, few studies use pharmacogenetic designs that permit testing of genotype  drug effects. As a result of these limitations, few findings have been fully replicated. Future studies that pre-screen participants for genetic variants selected a priori based on drug metabolism and targets have the greatest potential to advance the science and practice of psychiatric treatment.

Optimizing treatments for nicotine dependence by increasing cognitive performance during withdrawal

“…Furthermore, these techniques may also be used to examine individual differences in treatment response to identify those most likely to benefit from a particular treatment. Although a full review of the studies examining the neural substrates of cognitive function during nicotine withdrawal and in response to current treatments is beyond the scope of the present manuscript, for reviews see [134-136]. …”

Individual differences in the processing of smoking-cessation video messages: An imaging genetics study

“…Studies support a potential role for DRD2 and DRD4, but not COMT in attention processing (Barnett, Scoriels, & Munafo, 2008; Cheuk and Wong, 2006; Gizer et al, 2009; Sun, Yuan, Shen, Xiong, & Wu, 2014). Despite the known limitations of the single candidate gene approach, our findings set the stage for further research examining a more comprehensive set of candidate genes or genome-wide association (Tabor et al, 2002) that would provide a more complete picture of the neural and genetic effects of cessation videos on smoking (Falcone et al, 2013). Additionally, given the greater risk of Type I error with small sample sizes, our findings will need to be replicated in an independent cohort with a larger sample size.…”

Pathways to precision medicine in smoking cessation treatments

“…Rose, Uhl, and colleagues developed quit-success genotype score based on many variants arising from pooled GWAS results in smokers receiving nicotine replacement therapy [109, 110]. Different neuroimaging markers have also been examined [111]. For example, lower pre-treatment brain nAChR density has been shown as associated with a greater chance of quitting smoking with NRT or placebo [112].…”