Molecular imaging of autism spectrum disorder.

Autism spectrum disorder (ASD) is a condition with onset in early childhood characterized by marked deficits in interpersonal interactions and communication and by a restricted and repetitive range of interests and activities. This review points out key recent findings utilizing molecular imaging including magnetic resonance spectroscopy (MRS) and nuclear neuroimaging techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). MRS indicates an excitatory/inhibitory imbalance in high-functioning autism. Dysfunction of neurotransmitter and glucose metabolism has been demonstrated by PET and SPECT. Levels of serotonin synthesis in typically developing children are approximately twice those of adults; after the age of 5 years, levels decrease to those of adults. In contrast, levels of serotonin synthesis of children with ASD increase between ages 2 and 15 to 1.5-times adult values. The dopamine transporter is increased in the orbitofrontal cortex of men with ASD. The serotonin transporter is reduced in the brains of children, adolescents, and adults with ASD. Reduced serotonin receptors in the thalamus of adults with ASD are associated with communication difficulties. Glucose metabolism is reduced in the brains of people with ASD. Molecular imaging will provide the preliminary data for promising therapeutic interventions.

An evaluation of lumateperone tosylate for the treatment of schizophrenia.

Introduction: Schizophrenia, a devastating disorder with onset in adolescence or young adulthood, afflicts 1% of the population leading to severe social, educational, and occupational impairments. Lumateperone is a first-in-class investigational drug under development for the treatment of multiple neuropsychiatric and neurodegenerative disorders including schizophrenia. Its unique receptor affinity profile together with synergistic modulation of serotonergic, glutamatergic, and dopaminergic pathways imparts efficacy over a broad-spectrum of symptoms associated with schizophrenia.Areas covered: This narrative drug evaluation includes a review of lumateperone tosylate (lumateperone, ITI-007, ITI-722, Intra-Cellular Therapies, Inc.) for patients with schizophrenia. This review describes the receptor affinity profile, pharmacodynamics, pharmacokinetics, distribution, metabolism, and clinical trials that address how lumateperone could potentially emerge as an important therapeutic option for schizophrenia patients.Expert opinion: The unique pharmacological properties of lumateperone may provide the key to dramatically ameliorate the symptoms of schizophrenia as indicated by some clinical trials. Future clinical trials may be enhanced by the administration of more comprehensive long-term behavioral measures and utilization of molecular imaging to confirm the target engagement of the many possible sites of action. The results of ongoing and future studies will provide the evidence to determine if lumateperone will revolutionize the therapy of schizophrenia.