Did Children in Single-Parent Households Have a Higher Probability of Emotional Instability during the COVID-19 Pandemic? A Nationwide Cross-Sectional Study in Japan

The influence of public health measures against COVID-19 in Japan on child mental health by household type is unknown. This study aimed to investigate whether COVID-19 and the declaration of a state of emergency in Japan affected children’s mental health between single-parent and two-parent households disproportionately. A large cross-sectional online survey was conducted from August to September 2020. The study included 3365 parents with children aged 0–14 years old who reported their children’s mental status during the declared state of emergency. Emotional instability was reported dichotomously by parents. As the primary result, the probability of emotional instability was higher in single-parent households compared with that in two-parent households after adjustments for potential covariates; the adjusted prevalence ratio (95% CI) was 1.26 (1.07–1.49). Our findings suggest a disproportionate impact on children’s mental health due to the pandemic

Regional differences in occupancy of dopamine D2 receptors by second-generation antipsychotics in humans measured using PET

Effects of antipsychotic drug have widely been considered to be mediated by blockade of dopamine D2 receptors. This hypothesis has been supported by positron emission tomography (PET) studies to determine occupancy of dopamine D2 receptors in patients with schizophrenia treated by antipsychotics [1]. The concept of limbic and cortical selectivity of second-generation antipsychotics, that is higher occupancy of dopamine D2 receptors in the cerebral cortices than in the striatum, has been suggested to explain those clinical efficacy with few extrapyramidal side effects [2]. In the present study, to elucidate the limbic and cortical selectivity of second-generation antipsychotics, regional distribution of occupancy of dopamine D2 receptors by risperidone was determined.Neuroreceptor Mapping 200

Effects of the antipsychotic risperidone on dopamine synthesis in human brain measured by positron emission tomography with L-[beta-11C]DOPA: a stabilizing effect for dopaminergic neurotransmission?

Effects of antipsychotic drugs have widely been considered to be mediated by blockade of dopamine D2 receptors. Effects of antipsychotics on presynaptic functions of dopaminergic neurotransmission might also be related to therapeutic effects of antipsychotics. To investigate the effects of antipsychotics on presynaptic functions of dopaminergic neurotransmission in relation with occupancy of dopamine D2 receptors, changes in dopamine synthesis rate by antipsychotics and occupancy of dopamine D2 receptors were measured by positron emission tomography (PET) in healthy men. PET studies using [11C]raclopride and L-[beta-11C]DOPA were performed under resting condition and oral administration of single dose of the antipsychotic drug risperidone on separate days. While occupancy of dopamine D2 receptors corresponding dose of risperidone was observed, the changes in dopamine synthesis rate by the administration of risperidone were not significant, nor was the relation between the occupancy of dopamine D2 receptors and these changes. A significant negative correlation was observed between the baseline dopamine synthesis rate and the changes in dopamine synthesis rate by risperidone, indicating that this antipsychotic can be assumed to stabilize the dopamine synthesis rate. The therapeutic effects of risperidone in schizophrenia might be related to such stabilizing effects on dopaminergic neurotransmission responsivity

EFFECTS OF SECOND-GENERATION ANTIPSYCHOTIC DRUG ON DOPAMINE SYNTHESIS IN HUMAN BRAIN MEASURED BY PET WITH L-[C-11]DOPA

Objectives: Effects of antipsychotic drugs have widely been considered to be mediated by blockade of dopamine D2 receptors. Effects of antipsychotics on presynaptic functions of dopaminergic neurotransmission might also be related to therapeutic effects of antipsychotics. In the present study, changes in dopamine synthesis rate by administration of single dose of second-generation antipsychotics in relation with occupancy of dopamine D2 receptors were measured by positron emission tomography (PET) in healthy human subjects. Methods: PET studies were performed on 12 healthy men (21-29 years of age) under resting condition (baseline study) and oral administration of single dose of antipsychotic drug, risperidone of 0.5-2.0 mg, (drug challenge study) on separate days. In each study, both PET scans with [C-11]raclopride and L-[C-11]DOPA were performed sequentially to measure dopamine D2 receptor binding and dopamine synthesis rate, respectively. For [C-11]raclopride PET, the binding potential (BP) in the striatum was calculated by the reference tissue model method with use of the cerebellum as a reference region. The occupancy of dopamine D2 receptors by risperidone was calculated from BP values in baseline and drug challenge studies. The uptake rate constant, Ki, for L-[C-11]DOPA in the striatum indicating the dopamine synthesis rate was estimated by the graphical analysis with use of the occipital cortex as a reference region [1]. The percentage change in Ki by risperidone was calculated from Ki values in baseline and drug challenge studies. Results: The occupancies of dopamine D2 receptors ranged from 39% to 75% in the putamen. The dopamine synthesis rate Ki values were 0.0136 +- 0.0017 (1/min) and 0.0142 +- 0.0010 (1/min) (mean +- SD) in the putamen for the baseline and drug challenge studies, respectively. While occupancy of dopamine D2 receptors corresponding dose of risperidone was observed, no significant change in dopamine synthesis rate by risperidone was observed. No significant correlation between the occupancy of dopamine D2 receptors and the change in dopamine synthesis rate by risperidone was also observed. On the other hand, a significant negative correlation was observed between the baseline dopamine synthesis rate and the change in dopamine synthesis rate by risperidone (r = -0.87, P < 0.001). Conclusions: The negative correlation between the baseline dopamine synthesis rate and the change in dopamine synthesis rate by risperidone, and smaller coefficient of variation of dopamine synthesis rate Ki in drug challenge studies than in baseline studies indicate that second-generation antipsychotic, risperidone, can be considered to stabilize the level of dopamine synthesis rate. The concept of phasic and tonic dopamine release with relation to the modulation of dopaminergic neurotransmission has been proposed, and abnormal responsivity in both the phasic and tonic dopamine release in schizophrenia have been considered [2]. Therapeutic effects of risperidone might be related to stabilizing effects on such dopaminergic neurotransmission responsivity. References: [1] Patlak CS, Blasberg RG. J Cereb Blood Flow Metab 1985; 5: 584-590. [2] Grace AA. Neuroscience 1991; 41: 1-24.Brain \u2709 & Brain PET \u270

Correlation between Intraindividual Serotonin Transporter and Serotonin 1A Receptor in Normal Male Subjects: A Positron Emission Tomography Study

Background and aims: The central serotonergic (5-HT) system is closely involved in regulating various mental functions associated with mood, anxiety, impulsive behavior etc. To date, several reports have addressed the comparison between pre- and postsynaptic functions of 5-HT (1, 2); however, these studies are limited in their applicability because of their small sample size. The aim of this study was to investigate the intraindividual relationship between 5-HTT and 5-HT1A receptors using PET in a relatively large group of normal male subjects.Methods: Dynamic PET scans were performed on 23 young, healthy males with both [C-11]DASB and [C-11]WAY-100635 to measure the binding of 5-HTT and 5-HT1A receptors, respectively. A 2-parameter multilinear reference tissue model and a reference tissue model were used to calculate the binding potential (BPND) of [C-11]DASB and [C-11]WAY-100635, respectively, on a voxel-by-voxel basis, with the cerebellum as the reference region. All PET images were anatomically standardized to the template magnetic resonance image and smoothed with an 8-mm Gaussian filter using SPM2. Furthermore, the volumes-of-interest (VOIs), namely, the raphe nucleus, thalamus, striatum, parahippocampal gyrus, insula, temporal cortex, base of the frontal cortex, and the convexity of the frontal cortex were manually traced on the standardized and smoothed BPND images. Pearson\u27s coefficient correlation was used to compare the bindings of both the tracers in the same VOIs; corrections for multiple comparisons among VOIs were not performed.Results: The BPND values of each VOI are presented in Table (mean +/- SD).[tab_01] Pearson\u27s correlation coefficient indicated significant inverse correlations between BPND of [C-11]DASB and that of [C-11]WAY-100635 in the insula (r = -0.46, p = 0.028), base side of the frontal cortex (r = -0.47, p = 0.023), and the convex side of the frontal cortex (r = -0.46, p = 0.029). No significant correlation was observed in other regions.Conclusions: The distribution of 5-HTT and 5-HT1A receptors in the brain was consistent with the findings of post-mortem studies. In addition, we found inverse correlations between BPND values of 5-HTT and 5-HT1A in the insula and frontal cortex. These relationships might indicate a complementary nature between 5-HTT and 5-HT1A functions in such regions. Further investigations are required to elucidate the relationship between the activity of the pre- and postsynaptic serotonergic system in relation to mental functions.Reference:1) Lundberg et al. Psychopharmacology, 195, 425-433, 20072) Frey et al. Neuroimage, 42, 850-857, 2008Brain \u2709 & Brain PET \u270

Serotonergic neurotransmission in the living human brain: A positron emission tomography study using [11C]DASB and [11C]WAY100635 in young healthy men

The central serotonergic (5-HT) system is closely involved in regulating various mental functions such as mood and emotion. In this system, the serotonin transporter (5-HTT) and the 5-HT1A receptor play important roles in the pathophysiology and treatment of mood and anxiety disorders. However, only a few integrated databases have considered the intraindividual relationship between pre-and postsynaptic serotonergic transmission. In the present study, we constructed a database of 5-HTT and 5-HT1A receptors using positron emission tomography (PET) with [C-11]DASB and [C-11]WAY100635, respectively. Seventeen healthy young men participated in this study. After anatomic standardization of original images, BPND was calculated on a voxel-byvoxel basis using reference tissue methods. The highest binding to 5-HTT was observed in the dorsal raphe nucleus, striatum, and thalamus; moderate binding, in the insula and cingulate cortex; and very low binding, in the cerebral neocortex. In contrast, the highest binding to 5-HT1A receptors was seen in the hippocampal regions, insula, neocortical regions, and dorsal raphe nucleus, and very low binding was found in the thalamus and basal ganglia. These distribution patterns were in agreement with those reported in human postmortem studies and previous PET investigations. In addition, exploratory analysis indicated significant negative correlations between the BPND values with both radiotracers in certain regions of the brain, such as the cingulate, insula, and frontal, temporal and parietal cortices (Pearson\u27s correlation, P < 0.05). These databases facilitate the understanding of the regional distribution of serotonergic neurotransmission function in the living human brain and the pathophysiology of various neuropsychiatric disorders

No regional difference in dopamine D2 receptor occupancy by the second-generation antipsychotic drug risperidone in humans: a positron emission tomography study

The effects of antipsychotic drugs have generally been considered to be mediated by blockade of dopamine D2 receptors. The concept of limbic and cortical selectivity of second-generation antipsychotics, i.e. higher dopamine D2 receptor occupancy in the cerebral cortices than in the striatum, has been suggested to explain their clinical efficacy with lower incidence of extrapyramidal side-effects. In this study, regional distribution of dopamine D2 receptor occupancy by risperidone was determined in order to elucidate the limbic and cortical selectivity of second-generation antipsychotics. Striatal and extrastriatal dopamine D2 receptor binding at baseline and after oral administration of 2 mg risperidone were measured in ten healthy men by positron emission tomography (PET) using different tracers with different affinity for the receptors, [11C]raclopride and [11C]FLB 457, respectively. Striatal and extrastriatal occupancies of dopamine D2 receptors were calculated for each brain region. Occupancies of dopamine D2 receptors were about 70% and 60% in the striatum and extrastriatum, respectively. A simulation study showed that non-negligible specific binding in the reference region (cerebellum), could cause systemic underestimation of occupancy in [11C]FLB 457 PET studies, indicating that occupancies in both the striatum and extrastriatum may not have differed. Among the extrastriatal regions including limbic and neocortical regions, no significant regional differences in dopamine D2 receptor occupancy were observed. Thus, limbic and cortical selectivity was not observed by one of the second-generation antipsychotics, risperidone

EFFECT OF RISPERIDONE ON HIGH-AFFINITY STATE OF DOPAMINE D2 RECEPTOR; A PET STUDY WITH [C-11]MNPA

Objectives: Early in vitro studies have revealed that dopamine D2 receptors (D2 receptors) have two interconvertible affinity states for endogenous dopamine, referred to as high- and low-affinity state [1]. [C-11]-(R)-2-CH3O-N-n-propylnorapomorphine ([C-11]MNPA), a newly developed D2 receptor agonist ligand, is more sensitive to displacement by endogenous dopamine than [C-11]raclopride in the primate brain[2]. For this reason, [C-11]MNPA represents a promising radioligand for positron emission tomography (PET) imaging of the high-affinity state of the dopamine D2 receptor. Risperidone, which is well known as a serotonin-dopamine antagonist and a commonly prescribed antipsychotic to alleviate positive symptoms of schizophrenia, acts as a full antagonist against dopamine D2 receptors. While the occupancy of dopamine D2 receptors by risperidone has been measured by PET with conventional D2 receptor antagonist ligands such as [C-11]raclopride and [C-11]FLB457, little is known about its pharmacological behavior against the high-affinity state of D2 receptor because those conventional D2 receptor antagonist ligands have affinity to both the high- and low-affinity state of D2 receptor. Here, we measured D2 receptor occupancy of [C-11]MNPA and [C-11]raclopride after oral administration of risperidone to evaluate its pharmacological action against the high-affinity state of D2 receptor.\nMethods: PET studies were performed on eleven healthy men (21-39 years) under resting condition and oral administration of a single dose of risperidone (0.5-2.0 mg) on separate days. In each condition, PET scans using [C-11]raclopride and [C-11]MNPA were performed sequentially. For each PET study, the binding potentials (BPs) in the striatum were calculated by reference tissue model method with use of the cerebellum as reference region. The occupancy of dopamine D2 receptors was then calculated from the BP values of resting and drug challenge conditions. Relations between dopamine D2 receptor occupancy and the administered dose of risperidone were analyzed for each radioligand.\nResults: The occupancies of dopamine D2 receptors in [C-11]raclopride and [C-11]MNPA studies ranged from 24% to 70% and from 22% to 66% in the striatum, respectively. The occupancy of [C-11]raclopride was positively correlated with that of [C-11]MNPA (r = 0.72, P = 0.012). The relation between dopamine D2 receptor occupancy and the dose of risperidone (dose-occupancy curve) with [C-11]raclopride and [C-11]MNPA was positive and logarithmically fitted (r = 0.85 for [C-11]raclopride, r = 0.69 for [C-11]MNPA). ED50 values calculated from the dose-occupancy curves with [C-11]raclopride and [C-11]MNPA were 0.98 mg and 1.03 mg, respectively.\nConclusions: The positive correlation of occupancies between both [C-11]raclopride and [C-11]MNPA studies and similar ED50 values of both studies indicate that risperidone blocks both high- and low-affinity state of dopamine D2 receptors in a similar dose-dependent manner.\nReferences:[1] Sibley DR, De Lean A. J Biol Chem 1982; 257(11): 6351-6361.[2] Seneca N, Finnema SJ. Synapse 2006; 59(5): 260-269.Brain \u2709 & Brain PET \u270