Molecular imaging in neuropsychiatry

This volume, entitled ‘Molecular Imaging in Neuropsychiatry’, focuses on state of the art molecular imaging methods, as applied to the most challenging diagnostic and therapeutic issues in psychology and neurology, and demonstrates the critical role of molecular brain imaging in understanding neurobiological mechanisms and in potentially informing the development of more effective treatments. The topics range from neurodevelopmental to mood disorders, addictions, to the non-motor symptoms of movement disorders. The past two decades have witnessed remarkable advances in radiotracer chemistry for positron emission tomography (PET), as well as methodological advances for magnetic resonance spectroscopy (MRS) that provides complementary information to PET imaging. Radiotracer development has made possible the investigation of enzymes, neurotransmitter synthesis/metabolism, transporters, and receptors for a variety of neurotransmitters and neuromodulators (including second messengers and neuropeptides) in the living brain. A major focus over the past decade has been in vivo imaging of neurodegenerative disease mechanisms that previously could be studied only at post-mortem examination, including inflammation, betaamyloid, and Tau proteins (Hammoud, 2016; Mathis, Lopresti, Ikonomovic, & Klunk, 2017). MRS provides a unique opportunity to study amino acid neurotransmitters (GABA, glutamate), and measures of neuronal metabolism and oxidative stress. Recent advances include edited MRS, which has resulted in more precise quantification of neurotransmitters and metabolites at lower field strength that can be performed even in multi-site studies, as well as high field strength MRS imaging (Godlewska, Clare, Cowen, & Emir, 2017; Mikkelsen et al., 2017). In parallel to advances in PET radiotracer chemistry, developments in instrumentation have substantially improved the spatial resolution of PET. The highresolution research tomograph is a dedicated human brain PET scanner with a resolution of 2.3–3.4mm (de Jong et al., 2007; Wienhard et al., 2002). The development of dual modality imaging has been another major innovation in instrumentation, including PET/ computed tomography scanners and PET/magnetic resonance imaging (MRI) scanners. Sequential imaging of structure and function (PET/CT, PET/MRI) and, more recently, simultaneous acquisition of structure/circuitry and function (PET/MRI; Bailey et al., 2017). Simultaneous PET/MRI is an important opportunity to study pharmacologic and/or behaviour induced changes in neural circuitry and specific neurobiological mechanisms. The review by Hwang, Mohamed, and Brasic (2017) describes the complementary contributions of PET and MRS to the understanding of the pathophysiology of autism spectrum disorders (ASD), where molecular imaging studies are critical to inform the development of treatments for cognitive dysfunction and neuropsychiatric symptoms. The authors discuss the challenges of conducting neuroimaging research in ASD. They present the major MRS and PET neuroimaging findings, including their own important contributions. MRS studies of GABA and glutamate and PET studies of dopamine, serotonin, glucose metabolism, and cerebral blood flow are reviewed. The results presented underscore the need to understand the neurobiology of ASD across the lifespan, as well as to relate the molecular imaging findings to symptomatology in larger patient samples. While chronic schizophrenia has been a major focus of the molecular imaging research, the study of individuals at clinical high risk for schizophrenia has been more limited. Schifani et al. (2017) have performed innovative molecular imaging studies of early psychosis, including studying individuals at clinical high risk for schizophrenia and first episode psychosis. This challenging area of research is critical to identify molecular targets that may alter the early course of psychosis and may have implications for understanding the co-morbidity between psychosis and substance use that may have a negative impact on psychosis risk and course. In their review, the authors focus on imaging of extra-striatal dopamine, neuroinflammation, glutamate, GABA, and endocannabinoids. Importantly, they discuss future applications to study novel mechanisms such as other endocannabinoid targets, synaptic density, and nociceptin receptors, based on recent advances in radiotracer chemistry. The role of the hypothalamic-pituitary-adrenocortical (HPA) axis is well established in post-traumatic stress disorder (PTSD), and has been appreciated recently in substance use disorders and their co-morbidity with PTSD. As PET radiotracer development for the HPA axis has been challenging, human studies have focused