Beyond monoamines: II. Novel applications for PET imaging in psychiatric disorders

Abstract

Early applications of positron emission tomography (PET) in psychiatry sought to identify derangements of cerebral blood flow and metabolism. The need for more specific neurochemical imaging probes was soon evident, and these probes initially targeted the sites of action of neuroleptic (dopamine D2 receptors) and psychoactive (serotonin receptors) drugs. For nearly 30 years, the centrality of monoamine dysfunction in psychiatric disorders drove the development of an armamentarium of monoaminergic PET radiopharmaceuticals and imaging methodologies. However, continued investments in monoamine‐enhancing drug development realized only modest gains in efficacy and tolerability. As patent protection for many widely prescribed and profitable psychiatric drugs lapsed, drug development pipelines shifted away from monoamines in search of novel targets with the promises of improved efficacy, or abandoned altogether. Over this period, PET radiopharmaceutical development activities closely parallelled drug development priorities, resulting in the development of new PET imaging agents for non‐monoamine targets. In part two of this review, we survey clinical research studies using the novel targets and radiotracers described in part one across major psychiatric application areas such as substance use disorders, anxiety disorders, eating disorders, personality disorders, mood disorders, and schizophrenia. Important limitations of the studies described are discussed, as well as key methodologic issues, challenges to the field, and the status of clinical trials seeking to exploit these targets for novel therapeutics.

Preclinical and clinical imaging techniques as pathophysiological biomarkers — A preface to the special issue “Brain Imaging”

“…Astrogliosis is not only an early neuroinflammatory event in several neurodegenerative conditions such as AD, but also represents a spectrum of molecular, morphological and functional changes characterized by a loss of normal protective function and a gain of toxic function as they respond to CNS insults (Kumar et al, 2021). Researchers at the University of Pittsburgh tackle the vast and complex issues related to the use of PET in psychiatric conditions (Lopresti et al, 2022; Royse et al, 2022). In the first part they recapitulate the history of PET in psychiatry with the study of dopamine and serotonin and then move beyond monoamines concentrating on novel probes for the assessment of synaptic neurotransmitters and receptors, enzymes as well as those tracers developed for assessing neuroinflammation (Lopresti et al, 2022).…”

“…In the first part they recapitulate the history of PET in psychiatry with the study of dopamine and serotonin and then move beyond monoamines concentrating on novel probes for the assessment of synaptic neurotransmitters and receptors, enzymes as well as those tracers developed for assessing neuroinflammation (Lopresti et al, 2022). In the second part, the group focuses on the application of these wide range of tracers across a wide range of major psychiatric conditions such as mood and schizoaffective conditions, anxiety, eating, and personality disorders as well as substance abuse (Royse et al, 2022).…”

“…Preclinical approaches allow the examination in real time of synaptic and intracellular signaling events in single and multiple neurons and their relationship to behavior, permitting a deeper mechanistic insight into brain function (Day-Cooney et al, 2022;Guo et al, 2022). Clinical applications using a wide variety of probes allow the assessment of proteinopathies (Hoenig & Drzezga, 2022), neuroinflammation (Kumar et al, 2021), the integrity of the nigrostriatal dopaminergic pathway (Nicastro et al, 2021), as well as the examination of neurotransmitter and neuroreceptor imaging in psychiatric disorders (Lopresti et al, 2022;Royse et al, 2022). complex issues related to the use of PET in psychiatric conditions (Lopresti et al, 2022;Royse et al, 2022).…”

“…Clinical applications using a wide variety of probes allow the assessment of proteinopathies (Hoenig & Drzezga, 2022), neuroinflammation (Kumar et al, 2021), the integrity of the nigrostriatal dopaminergic pathway (Nicastro et al, 2021), as well as the examination of neurotransmitter and neuroreceptor imaging in psychiatric disorders (Lopresti et al, 2022;Royse et al, 2022). complex issues related to the use of PET in psychiatric conditions (Lopresti et al, 2022;Royse et al, 2022). In the first part they recapitulate the history of PET in psychiatry with the study of dopamine and serotonin and then move beyond monoamines concentrating on novel probes for the assessment of synaptic neurotransmitters and receptors, enzymes as well as those tracers developed for assessing neuroinflammation (Lopresti et al, 2022).…”

“…In the second part, the group focuses on the application of these wide range of tracers across a wide range of major psychiatric conditions such as mood and schizoaffective conditions, anxiety, eating, and personality disorders as well as substance abuse (Royse et al, 2022).…”