Can molecular imaging techniques identify biomarkers for neuropsychiatric disorders?

Podem as técnicas de imagem molecular identificar biomarcadores nos distúrbios neuropsiquiátricos? The phenomenological paradigm used for neuropsychiatric diagnosis is still hegemonic in the currently adopted classifications. This paradigm, however, has the particular caveat of not including any information from biological or pathophysiological mechanisms. With recent advances in the methods for clinical neurosciences investigations, promising new approaches to investigate the pathophysiology of neuropsychiatric disorders (NPD) have become available and are now leading to studies that attempt to unravel the neurobiological underpinnings of these diseases. Advances in molecular imaging techniques, such as positron emission tomography (PET) and single photon emission computerized tomography (SPECT), have made important contributions to the understanding of the pathophysiology of NPD. These techniques use radiolabeled tracers, which allow direct investigation of neuroreceptors in vivo at any stage of the NPD. More sensitive than neuroanatomical imaging techniques, molecular imaging approaches are able to identify subtle cerebral pathophysiological changes before neurostructural abnormalities take place. One of the major goals of molecular imaging research has been the identification of biomarkers, which are defined as the characteristics that are objectively measured and can differentiate normal biologic processes from pathogenic processes. These approaches are at a privileged condition to potentially provide accurate and early NPD recognition, evaluate disease progression, and monitor treatment efficacy. In recent years, attention has been turned to individuals at risk of developing NPD aiming to prevent the progression of these disorders. Biomarkers, as indicators of underlying biological processes, offer the potential to identify asymptomatic individuals who will develop the NPD in the following years. An example of the use of PET and SPECT to identify biomarkers of NPD are the dopamine transporter (DAT) radiotracers that evaluate dopamine neuronal loss in Parkinson’s disease (PD). The DAT are located in the axon terminals of nigrostriatal dopamine neurons located in the striatum and are expected to decrease with the dopaminergic neurodegeneration observed in PD. Several receptor-imaging studies have shown that PD patients have decreased DAT when compared to matched controls (for review see Ravina et al., 2005). We have recently performed a study with similar results in Brazil. The studies have consistently shown a negative correlation between DAT density and PD progression. Figure 1 shows several SPECT brain images of PD patients at the level of the striatum (higher color intensity means higher DAT density). The images were acquired from patients with increasing PD severity as measured with Hoehn & Yahr scale. The decrease in DAT density with the progression of PD is evident in these scans. Current diagnosis of PD still relies on subjective clinical criteria, which include bradykinesia, and at least one of other three core symptoms (resting tremor, postural instability, and rigidity). This Editorial