Roles of empathy in altruistic cooperation in adults with and without autism spectrum disorder.

Background: Altruistic cooperation (AC) is essential in human social interactions. Previous studies have investigated AC-related behavior in children with autism spectrum disorder (ASD), revealing that there is considerable individual variability in the behavior. However, this issue is still largely unexplored especially in the adult population. Aims: To investigate individual differences in AC-related behavior, we conducted the resource allocation task (RAT) and modified version of the ultimatum game (mUG) among adults with and without ASD. Methods and procedures: The study employed a cross-sectional design, involving 27 adults with ASD (mean age 29.1 ± 4.3 years; three females) and 27 adults with typical development (TD) (mean age 25.8 ± 6.7 years; two females), who completed the RAT and mUG tasks. Beyond clinical characteristics, we assessed three primary psychological metrics: the interpersonal reactivity index (IRI), Barratt impulsiveness scale, and the behavioral inhibition and activation systems. Outcomes and results: No significant differences were observed in the proportions of participants with high AC when assessed by RAT (p = 0.15) and mUG (p = 0.59) between the TD and ASD groups. Participants with high AC from the RAT demonstrated higher perspective-taking scores on the IRI than those with low AC within both the TD (p = 0.04) and ASD groups (p = 0.03). In the TD group, high AC individuals also scored higher on the IRI's fantasy subscale as per the mUG (p = 0.03); however, this trend was not present in the ASD group. Conclusions and implications: The present findings indicate that empathy plays an important role in individual differences in AC-related behavior among adults with and without ASD, although the role could be different depending on the types of AC-related behavior between TD and ASD populations.

Generalizable and transportable resting-state neural signatures characterized by functional networks, neurotransmitters, and clinical symptoms in autism.

Autism spectrum disorder (ASD) is a lifelong condition with elusive biological mechanisms. The complexity of factors, including inter-site and developmental differences, hinders the development of a generalizable neuroimaging classifier for ASD. Here, we developed a classifier for ASD using a large-scale, multisite resting-state fMRI dataset of 730 Japanese adults, aiming to capture neural signatures that reflect pathophysiology at the functional network level, neurotransmitters, and clinical symptoms of the autistic brain. Our adult ASD classifier was successfully generalized to adults in the United States, Belgium, and Japan. The classifier further demonstrated its successful transportability to children and adolescents. The classifier contained 141 functional connections (FCs) that were important for discriminating individuals with ASD from typically developing controls. These FCs and their terminal brain regions were associated with difficulties in social interaction and dopamine and serotonin, respectively. Finally, we mapped attention-deficit/hyperactivity disorder (ADHD), schizophrenia (SCZ), and major depressive disorder (MDD) onto the biological axis defined by the ASD classifier. ADHD and SCZ, but not MDD, were located proximate to ASD on the biological dimensions. Our results revealed functional signatures of the ASD brain, grounded in molecular characteristics and clinical symptoms, achieving generalizability and transportability applicable to the evaluation of the biological continuity of related diseases.

The status of MRI databases across the world focused on psychiatric and neurological disorders.

Neuroimaging databases for neuro-psychiatric disorders enable researchers to implement data-driven research approaches by providing access to rich data that can be used to study disease, build and validate machine learning models, and even redefine disease spectra. The importance of sharing large, multi-center, multi-disorder databases has gradually been recognized in order to truly translate brain imaging knowledge into real-world clinical practice. Here, we review MRI databases that share data globally to serve multiple psychiatric or neurological disorders. We found 42 datasets consisting of 23,293 samples from patients with psychiatry and neurological disorders and healthy controls; 1245 samples from mood disorders (major depressive disorder and bipolar disorder), 2015 samples from developmental disorders (autism spectrum disorder, attention-deficit hyperactivity disorder), 675 samples from schizophrenia, 1194 samples from Parkinson's disease, 5865 samples from dementia (including Alzheimer's disease), We recognize that large, multi-center databases should include governance processes that allow data to be shared across national boundaries. Addressing technical and regulatory issues of existing databases can lead to better design and implementation and improve data access for the research community. The current trend toward the development of shareable MRI databases will contribute to a better understanding of the pathophysiology, diagnosis and assessment, and development of early interventions for neuropsychiatric disorders.

Homogenization of word relationships in schizophrenia: Topological analysis of cortical semantic representations.

AIM: Patients with schizophrenia typically exhibit symptoms of disorganized thought and display concreteness and over-inclusion in verbal reports, depending on the level of abstraction. While concreteness and over-inclusion may appear contradictory, the underlying psychopathology that explains these symptoms remains unclear. In the current study, we used functional magnetic resonance imaging with an encoding modeling approach to examine how concepts of various words, represented as brain activity, are anomalously connected at different levels of abstraction in patients with schizophrenia. METHODS: Fourteen individuals diagnosed with schizophrenia and 17 healthy controls underwent functional magnetic resonance imaging to measure brain activity representing concepts of various words. We used a persistent homology (PH) method to analyze the topological structures of word representations in schizophrenia patients, healthy controls, and random data, across different levels of abstraction by varying dissimilarity scales in the representation space. RESULTS: The results revealed that patients with schizophrenia exhibited more homogeneous word relationships across different levels of abstraction compared with healthy controls. Additionally, topological structures exhibited a shift toward a random network structure in patients with schizophrenia compared with controls. The PH method successfully distinguished semantic representations of patients with schizophrenia from those of controls. CONCLUSIONS: The current results provide an explanation for the mechanisms underlying the deficits in abstraction ability observed in schizophrenia. The isotopic connection of individual concepts reflects both the reduction of contextual connections at a semantically fine-grained scale and the absence of clear boundaries between related concepts at a coarse scale, which lead to concreteness and over-inclusion, respectively.

Effectiveness of vortioxetine for winter depression in bipolar disorder: A case report.

Background: We present a case report on the efficacy of the short-term application of vortioxetine in managing winter depression in patients with seasonal bipolar disorder (BP). Standard treatment strategies for BP may not adequately address seasonal depressive symptoms during winter in patients with seasonal BP patterns. Depressive symptoms during winter may be linked to seasonal changes in serotonin transporter binding, such as a decrease in synaptic serotonin levels, necessitating alternative approaches. Although antidepressants, including vortioxetine, are effective in treating seasonal monopolar depression, their efficacy and safety in treating depression in patients with seasonal BP patterns remain unclear. Case Presentation: This case report focuses on a 44-year-old male patient diagnosed with seasonal BP who had recurrent depressive episodes, specifically during winter. Notably, the patient had a significant decrease in recurrent episodes after short-term seasonal vortioxetine use without inducing mania or rapid cycling. Conclusion: Our study highlights the potential effectiveness of a seasonal, short-term treatment strategy with antidepressants, including vortioxetine, for winter depression in individuals with BP.

Treatment readiness and prognosis for problematic smartphone use: Evaluation of the Stages of Change, Readiness, and Treatment Eagerness Scale (SOCRATES) and log data.

Aim: While moderate smartphone use contributes to information gathering and relationship building, excessive smartphone use, also referred to as problematic smartphone use (PSU), has raised concerns because of its addictive nature and associated health consequences. This study aimed to investigate the relationship between treatment readiness and prognosis in individuals with PSU and to assess the predictive ability of smartphone log data in evaluating treatment readiness. Methods: A sample of 47 patients with PSU participated in this study. Treatment readiness was assessed using the Stages of Change, Readiness, and Treatment Eagerness Scale (SOCRATES), and log data were collected using a smartphone log application. Results: The results showed a significant correlation between baseline SOCRATES scores and the difference in Global Assessment of Functioning scores between baseline and 6 months (Spearman's ρ = 0.640, P-value = .001), suggesting that treatment readiness may explain part of the treatment outcomes (Pearson's r 2 = 0.379, P-value = 0.032). In addition, baseline log data, including the log acquisition rate, showed a positive correlation with treatment readiness (Spearman's ρ = 0.328, P-value = 0.045). Conclusion: These findings provide valuable insights into the relationship between treatment readiness and clinical outcomes in patients with PSU, and suggest the potential of log data as objective indicators of treatment motivation.

Case report: Recurring and treatment-resistant depression in acquired hepatocerebral degeneration due to a congenital portosystemic shunt.

Introduction: Acquired hepatocerebral degeneration (AHD) is a neurological condition associated with cerebral manganese (Mn) accumulation caused by portosystemic shunts (PSS), usually because of advanced liver disease. AHD is diagnosed by the identification of T1-weighted brain magnetic resonance imaging (MRI) hyperintensities coupled with the presence of PSS and neurological symptoms. Clinical presentations primarily involve motor dysfunction and cognitive impairment. As a result of the frequently concurrent hepatic encephalopathy, the psychiatric symptoms of AHD alone remain unclear. This report is the first documentation of unique psychiatric symptoms of AHD due to a congenital PSS (CPSS) and suggests the efficacy of shunt embolization in achieving sustained remission of psychiatric symptoms in such cases. Methods: A 57-year-old Japanese woman presented with recurrent severe depression, pain, and somatosensory hallucinations, along with fluctuating motor dysfunction, including parkinsonism, and cognitive impairments. Psychiatric interventions, including antidepressants, antipsychotics or electroconvulsive therapy, had limited efficacy or did not prevent relapse. Results: T1-weighted MRI showed bilateral hyperintensity in the globus pallidus. No history of Mn exposure or metabolic abnormalities, including copper, was identified. Furthermore, no evidence of liver dysfunction or hyperammonemia was found. Eventually, a gastrorenal shunt was observed on contrast-enhanced abdominal computed tomography. The diagnosis of AHD due to CPSS was made based on the clinical manifestations and abnormal imaging findings. Shunt embolization was performed, which prevented the relapse of psychiatric symptoms and substantially reduced the T1-weighted MRI hyperintensities. Conclusions: This case highlights the potential involvement of AHD in adult-onset psychiatric symptoms, even in the absence of liver disease. Furthermore, this case underscores the efficacy of shunt embolization in treating the psychiatric symptoms of AHD due to CPSS.

Neural responses to gaming content on social media in young adults.

Excessive gaming can impair both mental and physical health, drawing widespread public and clinical attention, especially among young generations. People are now more exposed to gaming-related content on social media than before, and this exposure may have a significant impact on their behavior. However, the neural mechanisms underlying this effect remain unexplored. Using functional magnetic resonance imaging (fMRI), this study aimed to investigate the neural activity induced by gaming-related content on social media among young adults casually playing online games. While being assessed by fMRI, the participants watched gaming-related videos and neutral (nongaming) videos on social media. The gaming-related cues significantly activated several brain areas, including the medial prefrontal cortex, posterior cingulate cortex, hippocampus, thalamus, superior/middle temporal gyrus, precuneus and occipital regions, compared with the neutral cues. Additionally, the participants' gaming desire levels positively correlated with a gaming-related cue-induced activation in the left orbitofrontal cortex and the right superior temporal gyrus. These findings extend previous studies on gaming cues and provide useful information to elucidate the effects of gaming-related content on social media in young adults. Continued research using real-world gaming cues may help improve our understanding of promoting gaming habits and provide support to individuals vulnerable to gaming addiction.

Association of homocysteine with white matter dysconnectivity in schizophrenia.

Several studies have shown white matter (WM) dysconnectivity in people with schizophrenia (SZ). However, the underlying mechanism remains unclear. We investigated the relationship between plasma homocysteine (Hcy) levels and WM microstructure in people with SZ using diffusion tensor imaging (DTI). Fifty-three people with SZ and 83 healthy controls (HC) were included in this retrospective observational study. Tract-Based Spatial Statistics (TBSS) were used to evaluate group differences in WM microstructure. A significant negative correlation between plasma Hcy levels and WM microstructural disruption was noted in the SZ group (Spearman's ρ = -.330, P = 0.016) but not in the HC group (Spearman's ρ = .041, P = 0.712). These results suggest that increased Hcy may be associated with WM dysconnectivity in SZ, and the interaction between Hcy and WM dysconnectivity could be a potential mechanism of the pathophysiology of SZ. Further, longitudinal studies are required to investigate whether high Hcy levels subsequently cause WM microstructural disruption in people with SZ.

Temporal patterns of sleep latency in central hypersomnia and attention deficit hyperactivity disorder: a cluster analysis exploration using Multiple Sleep Latency Test.

Introduction: Excessive daytime sleepiness (EDS) is a crucial symptom that diminishes the quality of life. The primary causes of EDS are central hypersomnia, including narcolepsy type 1 (NT1), type 2 (NT2), and idiopathic hypersomnia (IH). EDS is often associated with other psychiatric disorders, particularly attention deficit hyperactivity disorder (ADHD). The Multiple Sleep Latency Test (MSLT) is the standard assessment tool for EDS. Although the MSLT yields numerous parameters, most are not employed in clinical practice. In this study, we leveraged novel MSLT parameters to discern central hypersomnia and ADHD presence. Our analysis focused on sleep latency variability and employed cluster analysis to identify unique temporal patterns. Methods: We examined the MSLT data from 333 patients; of these, 200 (aged 14-54, mean: 24.9 ± 8.1, years; 114 females) met the inclusion criteria comprising comprehensive data an Apnea-Hypopnea Index (AHI) below 5, and no prior diagnosis of sleep apnea syndrome. We employed a time-course cluster approach that specifically targeted sleep latency variability during the MSLT. Results: Considering both multiple clustering quality evaluations and the study's objectives, we identified 9 distinct clusters. Clusters 1 and 3 predominantly had MSLT-positive results; Cluster 2 was entirely MSLT-positive; Clusters 4, 5, 6, 8, and 9 were mainly MSLT-negative; and Cluster 7 had mixed results. The diagnosis of hypersomnia varied notably among Clusters 1, 2, 3, and 7, with Cluster 2 demonstrating a pronounced tendency towards NT1 and NT2 diagnoses (p < 0.005). However, no significant correlation was observed between ADHD diagnoses and specific sleep latency patterns in any cluster. Conclusions: Our study highlights the value of time-course clustering in understanding sleep latency patterns of patients with central hypersomnia.

Associations of conservatism and jumping to conclusions biases with aberrant salience and default mode network.

AIM: While conservatism bias refers to the human need for more evidence for decision-making than rational thinking expects, the jumping to conclusions (JTC) bias refers to the need for less evidence among individuals with schizophrenia/delusion compared to healthy people. Although the hippocampus-midbrain-striatal aberrant salience system and the salience, default mode (DMN), and frontoparietal networks ("triple networks") are implicated in delusion/schizophrenia pathophysiology, the associations between conservatism/JTC and these systems/networks are unclear. METHODS: Thirty-seven patients with schizophrenia and 33 healthy controls performed the beads task, with large and small numbers of bead draws to decision (DTD) indicating conservatism and JTC, respectively. We performed independent component analysis (ICA) of resting functional magnetic resonance imaging (fMRI) data. For systems/networks above, we investigated interactions between diagnosis and DTD, and main effects of DTD. We similarly applied ICA to structural and diffusion MRI to explore the associations between DTD and gray/white matter. RESULTS: We identified a significant main effect of DTD with functional connectivity between the striatum and DMN, which was negatively correlated with delusion severity in patients, indicating that the greater the anti-correlation between these networks, the stronger the JTC and delusion. We further observed the main effects of DTD on a gray matter network resembling the DMN, and a white matter network connecting the functional and gray matter networks (all P < 0.05, family-wise error [FWE] correction). Function and gray/white matter showed no significant interactions. CONCLUSION: Our results support the novel association of conservatism and JTC biases with aberrant salience and default brain mode.

Explicit and implicit effects of gaming content on social media on the behavior of young adults.

Excessive gameplay can have negative effects on both mental and physical health, especially among young people. Nowadays, social media platforms are bombarding users with gaming-related content daily. Understanding the effect of this content on people's behavior is essential to gain insight into problematic gaming habits. However, this issue is yet to be studied extensively. In this study, we examined how gaming-related content on social media affects young adults explicitly and implicitly. We studied 25 healthy young adults (average age 21.5 ± 2.2) who played online games casually and asked them to report their gaming desire. We also conducted an implicit association test (IAT) to measure their implicit attitudes toward gaming-related content. We also investigated the relationship between these measures and various psychological factors, such as personality traits, self-efficacy, impulsiveness, and cognitive flexibility. The results revealed that participants had a higher explicit gaming desire when exposed to gaming-related cues on social media than neutral cues. They also had a robust positive implicit attitude toward gaming-related content on social media. Explicit gaming desire was positively correlated with neuroticism levels. Furthermore, the IAT effect was negatively correlated with self-efficacy and cognitive flexibility levels. However, there were no significant correlations between explicit gaming desire/IAT effect and impulsiveness levels. These findings suggest that gaming-related content on social media can affect young adults' behavior both explicitly and implicitly, highlighting the need for further research to prevent gaming addiction in vulnerable individuals.

IMPDH2 forms spots at branching sites and distal ends of astrocyte stem processes.

Inosine monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme in the de novo GTP biosynthesis pathway. Recent studies suggest that IMPDH2, an isoform of IMPDH, can localize to specific subcellular compartments under certain conditions and regulate site-specific GTP availability and small GTPase activity in invasive cancer cells. However, it is unclear whether IMPDH2 plays a site-specific regulatory role in subcellular functions in healthy cells. In this study, we focused on brain cells and examined the localization pattern of IMPDH2. We discovered that IMPDH2 forms localized spots in the astrocytes of the adult mouse hippocampus. Further analysis of spot distribution in primary astrocyte cultures revealed that IMPDH2 spots are predominantly localized on branching sites and distal ends of astrocyte stem processes. Our findings suggest a potential unidentified role for IMPDH2 and GTP synthesis specifically at specialized nodes of astrocyte branches.

Hippocampal volume mediates the relationship of parental rejection in childhood with social cognition in healthy adults.

Childhood abuse reduces hippocampal and amygdala volumes and impairs social cognition, including the ability to recognize facial expressions. However, these associations have been studied primarily in individuals with a history of severe abuse and psychiatric symptoms; researchers have not determined whether these associations can also be observed in healthy adults. In the present study, we analyzed data from 400 healthy adults (208 men and 192 women) at Tamagawa University. Parental rejection reflecting childhood abuse was assessed using the short form of Egna Minnen Beträffande Uppfostran, while social cognition was assessed using the "Fake Smile Detection Task." Hippocampal and amygdala volumes were extracted from T1-weighted magnetic resonance imaging data using FreeSurfer. We found that greater parental rejection resulted in smaller hippocampal and amygdala volumes and poorer performance in the Fake Smile Detection Task. Structural equation modeling analysis supported the model that hippocampal volume mediates maternal rejection effect on performance on the Fake Smile Detection Task, with involvement of the amygdala. These findings are in line with the structural and functional connectivity found between the hippocampus and amygdala and their joint involvement in social cognition. Therefore, parental rejection may affect hippocampal and amygdala volumes and social cognitive function even in symptom-free adults.

The optimal dose of Ramelteon for the better treatment adherence of delayed sleep-wake phase disorder: a dropout rate study.

Background: Evidence regarding the effectiveness of melatonin receptor agonists in treating delayed sleep-wake phase disorder (DSWPD) remains limited. This study aimed to determine the optimal dose of ramelteon, a melatonin receptor agonist, for the better treatment adherence of DSWPD. Methods: The patients who were diagnosed definitely as having DSWPD by board-certified physicians specialized in sleep medicine and started to receive strategically timed ramelteon medications after the diagnosis were included. Data on the initial ramelteon dose and follow-up duration (up to 24 months) were collected retrospectively. Patients with treatment discontinuation, changes in ramelteon dose, or the addition of other sleep-related medications were considered dropouts. Kaplan-Meier estimates, log-rank tests, and Cox regression analyses were performed. Results: Overall, 373 patients were analyzed. The findings revealed that the 2 mg dose of ramelteon was associated with a lower dropout rate compared to the other doses (8 mg, 4 mg, and 1 mg). The dropout rate for the 2 mg group was estimated to have a hazard ratio (HR) of 0.5762 when compared with the 8 mg dose group. Sex did not reveal a significant HR, whereas older age exhibited a small but significant HR (0.9858). Conclusion: For achieving better adherence, a dosing regimen of strategically timed 2 mg ramelteon may be the best for the treatment of DSWPD. The therapeutic dose window for better adherence seems to center approximately 2 mg of ramelteon. Furthermore, caution should be exercised when treating younger patients to prevent dropouts.

Chronic kidney disease causes blood-brain barrier breakdown via urea-activated matrix metalloproteinase-2 and insolubility of tau protein.

Chronic kidney disease (CKD) causes cognitive impairment and contributes to the overall global burden of dementia. However, mechanisms through which the kidneys and brain communicate are not fully understood. We established a CKD mouse model through adenine-induced tubulointerstitial fibrosis. Novel object recognition tests indicated that CKD decreased recognition memory. Sarkosyl-insoluble-proteomic analyses of the CKD mouse hippocampus revealed an accumulation of insoluble MAPT (microtubule-associated protein tau) and RNA-binding proteins such as small nuclear ribonucleoprotein U1 subunit 70 (SNRNP70). Additionally, there was an accumulation of Immunoglobulin G (IgG), indicating blood-brain barrier (BBB) breakdown. We identified that expressions of essential tight-junction protein claudin-5 and adherens-junction protein platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) were decreased in the brain endothelial cells of CKD mice. We determined urea as a major uremic solute that dose dependently decreased both claudin-5 and PECAM-1 expression in the mouse brain endothelial cell line bEnd.3 cells. Gelatin zymography indicated that the serum of CKD mice activated matrix metalloproteinase-2 (MMP2), while marimastat ameliorated the reduction of claudin-5 expression by urea in bEnd.3 cells. This study established a brain proteomic signature of CKD indicating BBB breakdown and insolubility of tau protein, which are pathologically linked to Alzheimer's disease. Urea-mediated activation of MMP2 was partly responsible for BBB breakdown in CKD.

Seizure-related stress and arousal responses mediate a relationship between anxiety trait and state in epilepsy.

BACKGROUND: Epilepsy causes substantial psychological distress and anxiety, primarily due to seizures. However, the impact of stress responses and changes in arousal and their association with anxiety patterns in patients with epilepsy (PWE) remains unclear. This study aimed to investigate the relationships among seizures, stress and arousal characteristics, and trait and state anxiety characteristics in PWE. METHODS: Our sample consisted of 159 outpatients with epilepsy recruited from five institutions in Japan in 2020. Participants completed the State-Trait Anxiety Inventory-Form JYZ (STAI) and the Japanese-Stress Arousal Check List (J-SACL). We analyzed the correlations between inventory scores and clinical information. Using principal component analysis (PCA), we derived epilepsy-specific stress/arousal characteristics, which accounted for high arousal and low-stress levels, termed epilepsy-specific stress or arousal response (ESAR), from the J-SACL scores. We conducted a mediation analysis to assess the mediating role of ESAR in the relationship between traits and state anxiety. RESULTS: We found significant correlations between J-SACL stress and arousal factors (r = -0.845, p < 0.001), ESAR and seizure frequency (r = -0.29, p < 0.001), ESAR and trait anxiety scores on the STAI (r = -0.77, p < 0.0001), and ESAR and state anxiety scores on the STAI (r = -0.60, p < 0.0001). Mediation analysis supported by the Monte Carlo method revealed that ESAR significantly mediated the association between trait and state anxiety. CONCLUSIONS: These findings elucidate the epilepsy-specific stress and arousal characteristics and their roles in mediating traits and state anxiety. These results may reflect the long-term clinical course and unique emotion recognition tendencies in epilepsy.

Neural correlates of perceptual switching and their association with empathy and alexithymia in individuals with and without autism spectrum disorder.

Individuals with autism spectrum disorder (ASD) often show limited empathy (poor recognition of others' emotions) and high alexithymia (poor recognition of own emotions and external thinking), which can negatively impact their social functioning. Previous experimental studies suggest that alterations in cognitive flexibility play key roles in the development of these characteristics in ASD. However, the underlying neural mechanisms that link cognitive flexibility and empathy/alexithymia are still largely unknown. In this study, we examined the neural correlates of cognitive flexibility via functional magnetic resonance imaging during perceptual task-switching in typical development (TD) adults and adults with ASD. We also investigated associations between regional neural activity and psychometric empathy and alexithymia scores among these populations. In the TD group, stronger activation of the left middle frontal gyrus was associated with better perceptual switching and greater empathic concern. Among individuals with ASD, stronger activation of the left inferior frontal gyrus was associated with better perceptual switching, greater empathy, and lower alexithymia. These findings will contribute to develop a better understanding of social cognition, and could be informative for the development of new ASD therapies.

Increased glutamate and glutamine levels and their relationship to astrocytes and dopaminergic transmissions in the brains of adults with autism.

Increased excitatory neuronal tones have been implicated in autism, but its mechanism remains elusive. The amplified glutamate signals may arise from enhanced glutamatergic circuits, which can be affected by astrocyte activation and suppressive signaling of dopamine neurotransmission. We tested this hypothesis using magnetic resonance spectroscopy and positron emission tomography scan with 11C-SCH23390 for dopamine D1 receptors in the anterior cingulate cortex (ACC). We enrolled 18 male adults with high-functioning autism and 20 typically developed (TD) male subjects. The autism group showed elevated glutamate, glutamine, and myo-inositol (mI) levels compared with the TD group (p = 0.045, p = 0.044, p = 0.030, respectively) and a positive correlation between glutamine and mI levels in the ACC (r = 0.54, p = 0.020). In autism and TD groups, ACC D1 receptor radioligand binding was negatively correlated with ACC glutamine levels (r = - 0.55, p = 0.022; r = - 0.58, p = 0.008, respectively). The enhanced glutamate-glutamine metabolism might be due to astroglial activation and the consequent reinforcement of glutamine synthesis in autistic brains. Glutamine synthesis could underly the physiological inhibitory control of dopaminergic D1 receptor signals. Our findings suggest a high neuron excitation-inhibition ratio with astrocytic activation in the etiology of autism.