In closing, we recognize that much knowledge has been buy Pictilisib gained over the past 15 to 20 years of neuroimaging research concerning frontolimbic dysfunction underlying fear and anxiety processing in anxiety disorders. However, more needs to be done to integrate these findings with that of animal studies, and to link more directly with anxiety disorder symptoms, behaviors, and treatment effects. Selected abbreviations and acronyms ACC anterior cingulate cortex GAD generalized anxiety disorder OFC orbitofrontal cortex PFC prefrontal cortex PTSD post-traumatic stress disorder SAD social anxiety

disorder
It is a daunting task to try to understand how genetic and environmental risk factors are translated into clinical symptoms, course Inhibitors,research,lifescience,medical of illness, and response to therapy of the complex disease, schizophrenia. Neuroimaging research has transformed the way we conceptualize schizophrenia. In this review, we are specifically concerned with the contribution of neuroimaging to understanding Inhibitors,research,lifescience,medical genetic risk. Since schizophrenia is a highly heritable disorder,1 understanding how genes act to confer risk for this devastating disease is an obvious

strategy in biological psychiatry. Clearly, genes can act on several levels, from the gene product itself through cellular, systemslevel, and behavioral levels of description, all the way to complex phenotypes such as therapeutic response or impaired social interactions. The impact of genes is not necessarily Inhibitors,research,lifescience,medical the same on each of these levels. A proposal that has found a sizeable following in psychiatry is to move away from disease entities such Inhibitors,research,lifescience,medical as schizophrenia to more biologically defined levels, such as cellular, systemslevel, or neurocognitive measures, in the hope that the effects of genes would be more prominent on these levels, and that the work of psychiatric

research, including the finding of new genetic variants conferring risk for the disorder, would be easier. This is the so-called “endophenotype” or intermediate phenotype concept.2,3 While there is evidence that this concept Inhibitors,research,lifescience,medical does not hold in general (in the sense that there are phenotypes, for example in the domain of cognition, that do not show higher genetic penetrance, at least for some genes that have been studied), the intermediate phenotype approach has had remarkable success when neuroimaging is used as the method of quantifying brain structure and function. Two meta-analyses now provide convergent support for the assertion that the penetrance of through genetic variations is high in neuroimaging.4,5 From these studies, estimates of effect sizes of 0.7 to 1.0 can be derived, corresponding to sample sizes to detect genetic effects at 80% power of around 80 participants, which is much less than would be necessary with clinical data. In this review, we will first discuss a paradigmatic example of a candidate genetic variant with clear impact on neural function related to dopamine: COMT rs4680 val/met.