Molecular imaging with positron emission tomography (PET) and single photon emission computed tomography (SPECT) is a well-established and important in vivo technique to evaluate fundamental biological processes and unravel the role of neurotransmitter receptors in various neuropsychiatric disorders. Specific ligands are available for PET/SPECT studies of dopamine, serotonin, and opiate receptors, but corresponding development of radiotracers for receptors of glutamate, the main excitatory neurotransmitter in mammalian brain, has lagged behind. This state of affairs has persisted despite the central importance of glutamate neurotransmission in brain physiology and in disorders such as stroke, epilepsy, schizophrenia, and neurodegenerative diseases. Recent years have seen extensive efforts to develop useful ligands for molecular imaging of subtypes of the ionotropic (N-methyl-D-aspartate (NMDA), kainate, and AMPA/quisqualate receptors) and metabotropic glutamate receptors (types I, II, and III mGluRs). We now review the state of development of radioligands for glutamate receptor imaging, placing main emphasis on the suitability of available ligands for reliable in vivo applications. We give a brief account of the radiosynthetic approach for selected molecules. In general, with the exception of ligands for the GluN2B subunit of NMDA receptors, there has been little success in developing radiotracers for imaging ionotropic glutamate receptors; failure of ligands for the PCP/MK801 binding site in vivo doubtless relates their dependence on the open, unblocked state of the ion channel. Many AMPA and kainite receptor ligands with good binding properties in vitro have failed to give measurable specific binding in the living brain. This may reflect the challenge of developing brain-penetrating ligands for amino acid receptors, compounded by conformational differences in vivo. The situation is better with respect to mGluR imaging, particularly for the mGluR5 subtype. Several successful PET ligands serve for investigations of mGluRs in conditions such as schizophrenia, depression, substance abuse and aging. Considering the centrality and diversity of glutamatergic signaling in brain function, we have relatively few selective and sensitive tools for molecular imaging of ionotropic and metabotropic glutamate receptors. Further radiopharmaceutical research targeting specific subtypes and subunits of the glutamate receptors may yet open up new investigational vistas with broad applications in basic and clinical research.

A positron emission tomography (PET)–magnetic resonance imaging (MRI) hybrid system has been developed to improve the accuracy of molecular imaging with structural imaging. However, the mismatch in spatial resolution between the two systems hinders the use of the hybrid system. As the magnetic field of the MRI increased up to 7.0 tesla in the commercial system, the performance of the MRI system largely improved. Several technical attempts in terms of the detector and the software used with the PET were made to improve the performance. As a result, the high resolution of the PET–MRI fusion system enables quantitation of metabolism and molecular information in the small substructures of the brainstem, hippocampus, and thalamus. Many studies on psychiatric disorders, which are difficult to diagnose with medical imaging, have been accomplished using various radioligands, but only a few studies have been conducted using the PET–MRI fusion system. To increase the clinical usefulness of medical imaging in psychiatric disorders, a high-resolution PET–MRI fusion system can play a key role by providing important information on both molecular and structural aspects in the fine structures of the brain. The development of high-resolution PET–MR systems and their potential roles in clinical studies of psychiatric disorders were reviewed as prospective views in future diagnostics.

To elucidate the potential roles of serotonergic activity in human character traits (i.e., self-directedness, cooperativeness, and self-transcendence), we investigated the relationship between these character traits and serotonin transporter (5-HTT) in healthy subjects. Twenty-four participants underwent High-Resolution Research Tomograph–positron emission tomography scans with [11C]DASB. To quantify 5-HTT availability, binding potential (BPND) of [11C]DASB was obtained using the simplified reference tissue model. The Temperament and Character Inventory was used to assess subjects’ levels of three character traits. There were no significant correlations between the three character traits. Self-directedness was significantly positively correlated with [11C]DASB BPND in the left hippocampus, left middle occipital gyrus, bilateral superior parietal gyrus, left inferior parietal gyrus, left middle temporal gyrus (MTG), and left inferior temporal gyrus (ITG). Cooperativeness was significantly negatively correlated with [11C]DASB BPND in the median raphe nucleus. Self-transcendence was significantly negatively correlated with [11C]DASB BPND in the right MTG and right ITG. Our results show significant correlations between the three character traits and 5-HTT availability in specific brain regions. In particular, self-directedness was significantly positively correlated with 5-HTT availability, suggesting that a goal-oriented, self-confident, and resourceful character may be related to higher serotonergic neurotransmission.

Many individuals are suffering from depression, and various improvements are being proposed. This study was conducted on young people diagnosed with depression and aimed to assess the effects of flavonoid-rich orange juice on the major depressive disorder (MDD) using a randomized controlled trial. In all, 40 young men and women with MDD aged 18–29 years were randomly assigned to a flavonoid-rich orange juice group (FR group) and a flavonoid-low orange cordial group (FL group). The subjects drank the corresponding juice three times a day (190 mL per bottle) for 8 weeks. The blood BDNF, zonulin, and claudin-5 levels significantly increased (p < 0.0001, p < 0.01, and p < 0.05, respectively) in the FR group, and the fatty acid binding protein 2 (FABP2) level was significantly decreased (p < 0.0001) in the FR group after the juice intervention. The FABP2, LPS, and valeric acid levels were negatively correlated with the abundance of Butyricicoccus pullicaecorum, which was higher in the FR group. Orange juice intake improved depressive symptoms in young adults with MDD in the FR group. This B. pullicaecorum can be a potential biomarker for clinical improvement in young adults with MDD patients.

Background Previous research has shown that metabotropic glutamate receptor-5 (mGluR5) signaling is significantly involved in social avoidance. We investigated the relationship between levels of social avoidance and mGluR5 availability in drug-naïve young patients with major depressive disorder (MDD). Methods Twenty non-smoking patients and eighteen matched non-smoking healthy controls underwent [ 11 C]ABP688 positron emission tomography (PET) and magnetic resonance imaging scans. The binding potential (BP ND ) of [ 11 C]ABP688 was obtained using the simplified reference tissue model. Patients’ level of social avoidance was assessed using the Social Avoidance and Distress Scale (SADS). For [ 11 C]ABP688 BP ND , the region-of-interest (ROI)-based between-group comparisons and correlations with SADS scores were investigated. The frontal cortices were chosen as a priori ROIs based on previous PET investigations in MDD, and on literature underscoring the importance of the frontal cortex in social avoidance. Results Independent samples t -tests revealed no significant differences in [ 11 C]ABP688 BP ND in the frontal cortices between the MDD patient group as a whole and healthy controls. One-way analysis of variance with post-hoc tests revealed significantly lower BP ND in the bilateral superior frontal cortex (SFC) and left middle frontal cortex (MFC) in MDD patients with low levels of social avoidance (L-SADS) than in healthy controls. The L-SADS patients also had significantly lower BP ND in the medial part of the right SFC than both MDD patients with high levels of social avoidance (H-SADS) and healthy controls. The L-SADS patients also showed significantly lower BP ND in the orbital parts of the SFC, MFC, and inferior frontal cortex than H-SADS patients. No significant group differences were found between H-SADS patients and healthy controls. The ROI-based correlation analysis revealed significant positive correlations between social avoidance levels and frontal [ 11 C]ABP688 BP ND in the entire patients. Conclusion Our exploratory study shows significant differences in frontal mGluR5 availability depending on the level of social avoidance in drug-naïve non-smoking MDD patients, suggesting that social avoidance should be considered as one of the clinical factors involved in mGluR5 signaling changes in depression.