Abstract Aim Significant, positive correlations between internet gaming disorder (IGD) and autism spectrum disorder (ASD) are known. Individuals with ASD are prone to problematic internet use due to addiction or restricted interests. Here, we examined cortical neural activity in individuals with IGD comorbid with ASD during a gaming‐related cue reactivity task, using magnetoencephalography (MEG). Methods MEG was used to record neural activity in right‐handed male participants aged 11–20 years (11 IGD–ASD, 13 healthy controls; intelligence quotient [IQ] ≥ 80). IGD and ASD were diagnosed per DSM‐5‐TR criteria. During MEG recording, participants viewed gaming cues and neutral base stimuli in a cue reactivity task. Source‐level cortical activity was estimated using minimum norm estimation (MNE), and statistical comparisons were performed using two‐tailed nonparametric permutation tests with false discovery rate (FDR) correction. Results In the IGD–ASD group, neural activity was significantly elevated at 137 ms in the right fusiform gyrus during gaming cues compared with the base condition (p = 0.000039). Between‐group comparisons under cue conditions (200–270 ms) showed higher right frontal activation (p = 0.0028) and lower activation in left lateral occipital (p = 0.000092), fusiform (p = 0.00025), lingual (p = 0.0017), and parahippocampal regions (p = 0.000049) in the IGD–ASD group compared with controls. Conclusion The IGD–ASD group showed increased right frontal activity and decreased left occipital, fusiform, lingual, and parahippocampal activity during exposure to the gaming cue, suggesting atypical visual and cognitive processing mechanisms in this comorbid group. Further studies comparing individuals with ASD and those with IGD–ASD, as well as by examining the neurophysiological characteristics of individuals with ASD who develop or recover from IGD, might clarify the pathology of these populations.

BackgroundSchool bullying is a major public health concern and is associated with adolescent mental health status. Although validated instruments exist to assess bullying victimization and witnessing in Japan, the psychometric validity of perpetration measures remains unclear. This study aimed to evaluate the psychometric validity of the revised Olweus Bully/Victim Questionnaire (OBVQ-R), focusing particularly on its perpetration subscale.MethodsData from a cross-sectional online self-report survey were collected from 339 students in Grades 4–9 from four private schools in Niigata Prefecture, Japan. Participants completed the Japanese versions of the OBVQ-R, the Japan Ijime Scale (JaIS), and the Strengths and Difficulties Questionnaire (SDQ). We conducted reliability analysis, confirmatory factor analysis, and structural equation modeling.ResultsFrom the original 39-item OBVQ-R, all 10 victimization items were retained, whereas 6 perpetration items were included after excluding 4 items due to insufficient variability and low variance. The 16-item OBVQ-R total scale demonstrated acceptable internal consistency overall, with satisfactory reliability for the victimization subscale but lower reliability for the perpetration subscale. Despite this, the two-factor OBVQ model showed excellent fit [comparative fit index (CFI) = 0.995, root mean square error of approximation (RMSEA) = 0.018]. The JaIS model also demonstrated excellent fit (CFI = 0.973, RMSEA = 0.038). OBVQ-R perpetration was strongly associated with JaIS perpetration (β = 0.70) and significantly associated with conduct problems, hyperactivity, and peer problems, as well as lower prosocial behavior.ConclusionAlthough the OBVQ-R victimization subscale demonstrated satisfactory reliability, the perpetration subscale showed limited internal consistency despite clear construct relevance and meaningful associations with psychosocial difficulties. These findings highlight the importance of assessing perpetration alongside victimization and witnessing, and the need for culturally sensitive adaptation of perpetration subscales to reduce reporting reluctance in the Japanese context and thus inform bullying prevention and intervention strategies.

Exclusive breastfeeding is essential for the health and well-being of both mothers and infants, but various factors may influence whether mothers are able to sustain exclusive breastfeeding during the early postpartum period. In this study, we explored the relationship of obstetric characteristics, the timing of delivery during the COVID-19 pandemic, and the season of birth with exclusive breastfeeding among Japanese mothers. Data included self-report survey and medical records of 5719 Japanese mothers at 1 month postpartum. We conducted path analysis on parity, maternal age, type of delivery, type of birth, pandemic-related delivery, birth season, and feeding method. The findings of a good-fit model suggested that being a first-time mother, older maternal age, having twins, giving birth during the pandemic, and delivering in winter were all associated with lower rates of exclusive breastfeeding (all P = 0.001). Mothers who were younger, had previous childbirth experience, delivered a singleton, gave birth before the pandemic, and delivered in summer, spring, or autumn were more likely to breastfeed exclusively. These findings support the need for targeted breastfeeding interventions that address obstetric, seasonal, and pandemic-related risk factors.

Objectives:Attention deficit hyperactivity disorder (ADHD) can significantly impact multiple life conditions across the lifespan. Reliable clinical practice guidelines (CPGs) are crucial for the clinical decision-making for the diagnosis and management of ADHD. This study aimed to assess the quality of current CPGs for the diagnosis and management of ADHD. Methods:We conducted a systematic literature search within Pubmed, Google Scholar, the Agency for Healthcare Research and Quality, Dynamed, the National Institute for Health and Care Excellence (NICE), the National Health and Medical Research Council (NHMRC), and other local and online databases started January 19, 2022. We assessed the guideline quality using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. All of the included guidelines were critically appraised by five independent reviewers. We also evaluated the interrater reliability of each AGREE II domain and the overall domain score by calculating the intraclass correlation coefficient (ICC) using IBM SPSS Statistics version 28. Results:A total of 11 CPGs were included in the study. The majority of the CPGs achieved the highest score in domain 4 "Clarity of Presentation" (mean ± standard deviation, 73.73% ± 12.5%). The domains that achieved the lowest scores were domains 5 "Applicability" (mean ± standard deviation, 45.18% ± 16.4%) and 3 "Rigor of Development" (mean ± standard deviation, 51.09% ± 24.1%). The American Academy of Pediatrics (AAP), NICE, and the Malaysian Health Technology Assessment Section (MAHTAS) CPGs were identified as the strongly recommended guidelines. All AGREE II domains yielded varied interrater reliability results; the full domain ICC ranged from 0.265 (95% confidence interval, -0.470 to 0.665) to 0.758 (95% confidence interval, 0.515 to 0.889). Conclusions:Our appraisal indicated that the quality of current ADHD guidelines is varied, and three CPGs were classified as strongly recommended. Our findings offer relevant healthcare providers valuable insight into the appropriate selection of ADHD guidelines in clinical practice. Systematic review registration:https://inplasy.com/inplasy-2022-8-0001/, identifier INPLASY202280001.

Next-generation sequencing has identified risk genes with large effect sizes for autism spectrum disorders (ASD). Although functional analysis of individual risk genes has progressed, the overall picture of ASD pathogenesis is unclear. Therefore, there is a need for morphological profiling of variants in these genes to fully comprehend their pathomechanism in cultured cells. High-content analysis (HCA) is a powerful approach to thoroughly analyze cellular alterations following genetic modifications in many disorders, including ASD. We begin this review with the latest phenotypic descriptions of ASD risk variants and different ASD cell models, which provide a basis to select features for extraction in image-based analysis to best capture ASD mechanisms. We then describe recent genetic and pharmacological screening campaigns for ASD using HCA systems. Generally, HCA enables imaging of ASD-derived cell models using measurements such as cell proliferation, differentiation, process growth, synapse numbers, and other morphological changes to neurons, astrocytes, and microglia. Advances in machine learning are reducing bias in feature identification and extraction. These data can be transformed for downstream analyses and visualization, such as clustering using heatmaps for morphological profiling. This provides image-based profiling data that can be used to determine the mechanisms of action of genetic modifications. Additionally, comprehensive methods, such as mixture-based and common structure ranking approaches, which can systematically examine the effects of millions of compounds, could identify compounds that might ameliorate the effects of ASD risk gene mutations using morphological profiling.

BACKGROUND:Few studies have investigated relationships among adult attachment style, depression, anxiety, and prenatal mother-to-fetus/postnatal mother-to-infant bonding in perinatal women, with varied findings. We examined the direct effects of adult attachment style on bonding as well as indirect effects via depression and anxiety. METHODS:In this prospective observational, longitudinal cohort study, 1897 Japanese perinatal women were recruited from 34 obstetric institutions in Niigata Prefecture. Adult attachment was assessed at T1 (early pregnancy), with depression/anxiety and bonding assessed at T1, T2 (late pregnancy), and T3 (postpartum). We used parallel process latent growth curve modeling to examine direct effects of the T1 adult attachment style on bonding across the perinatal period, as well as the mediating roles of depression and anxiety over three time points. RESULTS:No significant direct effects of adult attachment on bonding trajectories were observed. However, significant indirect effects were found, suggesting that adult attachment style influenced both the initial levels and change in bonding via its impact on the developmental trajectories of both depression and anxiety, with distinct roles for each mediator. The model fit was good to acceptable. LIMITATIONS:This study was limited by reliance on self-report measures, geographically restricted samples, and the absence of long-term follow-up. CONCLUSION:We found that the impact of adult attachment style on bonding was mediated by depression and anxiety across the perinatal period. Early screening and intervention for depressive and anxiety symptoms related to the mother's attachment toward her romantic partner is essential to prevent bonding difficulties.

Abstract Background Attention deficit hyperactivity disorder (ADHD) is a common mental disorder that co-occurs with pain disorders.1 In comorbidity of ADHD and chronic pain, many patients may first present to the clinic with only pain complaints. Treatment that merely focuses on eliminating pain may obscure the diagnosis of ADHD. In addition, untreated ADHD can lead to worsened symptoms, including chronic pain.2 Aims We present a well-documented case of an adult patient with chronic pain and a late diagnosis of ADHD that was effectively managed with methylphenidate (MPH). We discuss whether the effectiveness of MPH in treating pain regardless of ADHD comorbidity was likely coincidental or a potentially consistent phenomenon. Method A case report and literature review. Result A 43-year-old Japanese male patient with 15 years of chronic idiopathic pain symptoms did not adequately respond to standard pain management. Pain also persisted after treatments with antidepressants, an epidural block, and modified electroconvulsive therapy. After a thorough assessment, we confirmed a diagnosis of adult ADHD with a predominantly inattentive type. Considering this newly established diagnosis, we prescribed osmotic-release oral system (OROS) methylphenidate. Within 1 month of treatment at a dose of 18 mg/day of OROS-MPH, the patient’ s chronic pain unexpectedly improved dramatically. The dosage of OROS-MPH was titrated monthly, reaching 72 mg/day as a maintenance dose, and ADHD symptoms improved after 4 months of treatment (Figure 1). The patient was followed up regularly for 7 years during OROS-MPH treatment. He was stable overall and functioned well in his daily activities. Discussion & Conclusion Although MPH use as an analgesic for pain treatment remains uncommon and off-label, several studies have investigated its antinociceptive effect.3,4,5 This case report suggests that MPH may be potentially effective in treating chronic pain. Further studies are needed to confirm whether MPH improved chronic pain simultaneously with or separately from the improvement in ADHD. Moreover, elucidating the anatomical sites and molecular pharmacological mechanisms related to the action of MPH in pain modulation and perception is essential, including descending dopaminergic pain pathways and higher cortical areas. Furthering our understanding will reinforce the justification of MPH in treating chronic pain. References 1.Stickley, A, Koyanagi, A, Takahashi, H, and Kamio, Y. ADHD symptoms and pain among adults in England. Psychiatry Res. (2016) 246:326–31. 2.Siddall, PJ, and Cousins, MJ. Persistent pain as a disease entity: Implications for clinical management. Anesth Analg. (2004) 99:510–20. 3.Pud, D, Broitman, E, Hameed, O, Suzan, E, Aviram, J, Haddad, M, et al. Methylphenidate attenuates the response to cold pain but not to aversive auditory stimuli in healthy human: a double-blind randomized controlled study. Pain Rep. (2017) 2:e593. 4.Johansson, B, Wentzel, AP, André ll, P, Odenstedt, J, Mannheimer, C, and Rö nnbä ck, L. Evaluation of dosage, safety and effects of methylphenidate on post-traumatic brain injury symptoms with a focus on mental fatigue and pain. Brain Inj. (2014) 28:304–10. 5.Yamamotová, A, Fricová, J, Rokyta, R, and Š lamberová, R. The effect of combined treatment of opioids with methylphenidate on nociception in rats and pain in human. Physiol Res. (2016) 65:S567–75.

ABSTRACT Background Contactin‐5 (CNTN5), a neural adhesion molecule involved in synaptogenesis and synaptic maturation in the auditory pathway, has been associated with the pathophysiology of autism spectrum disorder (ASD), particularly hyperacusis. To investigate the role of rare CNTN5 variants in ASD susceptibility, we performed resequencing and association analysis in a Japanese population. Methods We resequenced the CNTN5 coding regions in 302 patients with ASD and prioritized rare putatively damaging variants. The prioritized variants were then genotyped in 313 patients with ASD and 1065 controls. Subsequently, we conducted an association study of selected variants with ASD in 614 patients with ASD and 61 057 controls. Clinical data were reviewed for patients carrying prioritized variants. Results Through resequencing, we prioritized three rare putatively damaging missense variants (W69G, I227L, and L1000S) in patients with ASD. Although we found a nominally significant association between the I227L variant and ASD, it did not remain significant after post hoc correction. Hyperacusis was found in three out of nine patients carrying prioritized variants. Conclusion This study does not provide evidence for the contribution of rare CNTN5 variants to the genetic etiology of ASD in the Japanese population.

BackgroundIndividuals with autism spectrum disorder (ASD) exhibit persistent deficits in social interaction and communication in adulthood. Pioneering studies have suggested that these difficulties arise from a lack of immediate, spontaneous mentalizing (i.e., theory of mind: ToM), specifically, an ability to attribute false beliefs to others, which should be usually acquired during neurotypical development. However, this view has been challenged by recent reports of nonreplications of spontaneous mentalizing, even in neurotypical adults.ObjectivesWe aimed to evaluate (1) whether measurements of spontaneous ToM in two representative paradigms, gaze bias in the anticipatory looking (AL) test and reaction time bias in the object detection (OD) test, are correlated in neurotypical adults and (2) whether these two measurements are altered in individuals with ASD.MethodsWe developed a novel hybridized spontaneous false belief test combining the AL and OD paradigms to enable within-subject comparison of different spontaneous ToM measurements.ResultsThe results obtained with our hybridized test replicated the earlier positive evidence for spontaneous ToM in both AL and OD paradigms. Our results also revealed a correlation between the participants’ spontaneous gaze bias in the AL paradigm and reaction time bias in the OD paradigm, indicating that the participants who had spontaneously anticipated other’s false belief driven actions more quickly detected the object. We further found that spontaneous gaze and reaction time biases were altered in individuals with ASD. Finally, we ascertained those inclusions of these biases as diagnostic variables in a regression model improved the accuracy of diagnosing ASD. ASD diagnosis was best predicted by the model when variables obtained from both AL and OD methods were included in the model.Conclusions/implicationsOur hybridized paradigm not only replicated spontaneous gaze bias in early AL studies and reaction time bias in the OD paradigms, but indicated significant correlation between them, suggesting that different implicit tasks tap the same spontaneous ToM in neurotypical adults. Group differences of these indices between ASD and neurotypical adult groups indicated that our task could help diagnose ASD, which is essential for evaluating the social difficulties that individuals with ASD face in adulthood.

Animacy perception, the ability to discern living from non-living entities, is crucial for survival and social interaction, as it includes recognizing abstract concepts such as movement, purpose, and intentions. This process involves interpreting cues that may suggest the intentions or actions of others. It engages the temporal cortex (TC), particularly the superior temporal sulcus (STS) and the adjacent region of the inferior temporal cortex (ITC), as well as the dorsomedial prefrontal cortex (dmPFC). However, it remains unclear how animacy is dynamically encoded over time in these brain areas and whether its processing is distributed or localized. In this study, we addressed these questions by employing a symbolic categorization task involving animate and inanimate objects using natural movie stimuli. Simultaneously, electrocorticography were conducted in both the TC and dmPFC. Time-frequency analysis revealed region-specific frequency representations throughout the observation of the movies. Spatial searchlight decoding analysis demonstrated that animacy processing is represented in a distributed manner. Regions encoding animacy information were found to be dispersed across the fundus and lip of the STS, as well as in the ITC. Next, we examined whether these dispersed regions form functional networks. Independent component analysis revealed that the spatial distribution of the component with the most significant animacy information corresponded with the dispersed regions identified by the spatial decoding analysis. Furthermore, Granger causality analysis indicated that these regions exhibit frequency-specific directional functional connectivity, with a general trend of causal influence from the ITC to STS across multiple frequency bands. Notably, a prominent feedback flow in the alpha band from the ITC to both the ventral bank and fundus of the STS was identified. These findings suggest a distributed and functionally interconnected neural substrate for animacy processing across the STS and ITC.

Background In the Diagnostic and Statistical Manual and Mental Disorders, Fifth Edition (DSM-5), autism spectrum disorder (ASD) and social (pragmatic) communication disorder (SCD) were described as a new category of psychiatry nosography. SCD involves impairments in social communication and social interaction but not restricted, repetitive patterns of behavior, interests, or activities. The autism spectrum quotient (AQ) was developed to screen for autism tendencies in adults with normal intelligence. However, AQ cutoff scores for screening ASD and SCD in the DSM-5 have not been established. This study examined whether the Japanese version of the AQ (AQ-J) total scores could discriminate between an ASD group, an SCD group, and a neurotypical (NT) group. Methods Participants were 127 ASD patients, 52 SCD patients, and 49 NT individuals. Receiver operating characteristic (ROC) analyses were used to examine AQ-J total score cutoff values to distinguish between ASD and NT groups, SCD and NT groups, and ASD and SCD groups. Results In the ROC analysis for the ASD and NT groups, the area under the curve (AUC) was 0.96, and the optimum cutoff value was 23 points (sensitivity 92.9%, specificity 85.7%). The AUC for the SCD and NT groups was 0.89, and the optimum cutoff value was 22 points (sensitivity 84.6%, specificity 85.7%). The AUC for the ASD and SCD groups was 0.75; the optimum cutoff value was 32 points (sensitivity 67.7%, specificity 71.2%). Conclusion Our findings suggest the usefulness of the AQ-J in screening for ASD and SCD.

BackgroundThere is a rising interest in perinatal mental health studies, and proper psychometric tools to assess autistic traits among this population in Japan are vital.ObjectiveThis study aimed to clarify the optimal factor structure of the AQ as part of a perinatal mental health research project.MethodsWe used the Japanese version of the AQ (AQ-J) to measure autistic-like traits in pregnant women. Participants were 4,287 Japanese women who were pregnant or who had given birth within the last month. We performed exploratory factor analysis (EFA) using the first sample group (n = 2,154) to obtain factor structures for the final item selections. We performed confirmatory factor analysis (CFA) using the second sample group (n = 2,133) to obtain a model with good fit, then compared the model to all previously proposed models to determine the best-fitting model.ResultsThe EFA analysis identified a model consisting of 25 items distributed across three factors. Cronbach’s alpha for the total 25-item AQ-J, 9-item “Social interaction” factor, 11-item “Non-verbal communication” factor, and 5-item “Restricted interest” factor was 0.829, 0.829, 0.755, and 0.576, respectively. McDonald’s omega and its 95% confidence interval were 0.826 (0.821–0.836), 0.835 (0.821–0.837), 0.755 (0.744–0.766), and 0.603 (0.556–0.596), respectively. CFA confirmed that the three-factor structure had an acceptable fit (goodness of fit index: 0.900, comparative fit index: 0.860, root mean square error of approximation: 0.066). These findings indicated that the three-factor model was better than the 13 existing models.ConclusionThe findings are discussed in relation to the adequacy of the AQ-J for assessing autistic traits in perinatal women. We recommend the use of this 25-item, three-factor AQ-J model for this population owing to its superiority to all previous models.

Background Although several studies have found significant relationships between autistic traits and depression/anxiety, the relationships between autistic traits and postpartum depression/anxiety remain unclear. Moreover, few studies have examined the relationships between autistic traits and mother–infant bonding while considering depression or anxiety. Methods This study used a cross-sectional data analysis design. Participants were 2692 women who completed the Autism-Spectrum Quotient (AQ), Hospital Anxiety and Depression Scale (HADS), and Mother-to-Infant Bonding Scale (MIBS) at 1 month postpartum. We performed path analysis that included parity, the five AQ subscales (social skills, attention switching, attention to detail, communication, and imagination), both HADS subscales (anxiety and depression), and the two MIBS subscales (lack of affection and anger and rejection). Results Our path analysis revealed that higher scores for social skills, attention switching, communication, and imagination were associated with higher scores for depression. Higher scores for social skills, attention switching, attention to detail, and communication were associated with higher scores for anxiety. Moreover, difficulties in social skills and imagination were associated with failure of maternal–infant bonding. However, more attention to detail was associated with better maternal–infant bonding. Conclusions This study suggests that maternal autistic traits are related to anxiety and depression to a certain degree, but only slightly related to maternal–infant bonding at 1 month postpartum. To improve autistic women’s quality of life and that of their newborns, perinatal mental health issues such as anxiety, depression, and maternal–fetal bonding difficulties should be appropriately addressed.

Abstract This study aimed to determine how paternal and maternal parenting before adolescence affects adult attachment to a partner during the perinatal period, using three different models of attachment. We used the Parental Bonding Instrument (PBI) and the Relationship Questionnaire (RQ) to examine perceived parenting practices and adult attachment styles, respectively. The participants included 4586 Japanese women who were pregnant and who had given birth, up until one month after childbirth. We performed structural equation modeling analysis between PBI and RQ scores with three different category models, including the four-category model (secure, fearful, preoccupied, and dismissing attachment) as Model 1, the two-category model (model of the self and others) as Model 2, and the single-category model (total attachment style) as Model 3. Models 1 and 2 showed a good fit. Both path models showed a significant association between adult attachment style and perceived paternal and maternal parenting before adolescence, where high care and low overprotection from both paternal and maternal parents predicted adult attachment. Our findings indicate that attachment styles are best described using the four-category and two-category models, suggesting that both paternal and maternal overprotection and care are important in forming adult attachment with a partner during the perinatal period.

Spasm of near reflex (SNR) involves intermittent spasm of one or more of the three near reflex components. Psychiatric disorders are one cause of SNR. We describe a patient with SNR diagnosed with autism spectrum disorder (ASD). A 36-year-old male with esotropia since childhood was referred due to headache and dizziness. The alternate prism cover test showed 30 prism diopters at both near and distant fixation. Four months after his first visit, he was diagnosed with ASD. Twenty-nine months after his first visit, he underwent strabismus surgery to treat concomitant esotropia. Postoperatively, the angle of strabismus improved but remained variable. Because the angle of strabismus varied, we suspected SNR; the diagnosis was performed after evaluating the patient’s microfluctuations in accommodation with Speedy-K. However, it was difficult to distinguish convergence spasm from concomitant esotropia in this patient because he has had a history of esotropia since childhood. In a patient with concomitant esotropia, if the symptoms are not exclusively due to strabismus, SNR should be suspected. Although the relationship between SNR and the pathology of ASD is unknown, it is possible that patients with ASD are more likely to develop SNR.

This study aimed to determine how paternal and maternal parenting before adolescence affects adult attachment to a partner during the perinatal period, using three different models of attachment. We used the Parental Bonding Instrument (PBI) and the Relationship Questionnaire (RQ) to examine perceived parenting practices and adult attachment styles, respectively. The participants included 4586 Japanese women who were pregnant or who had given birth, up until one month after childbirth. We performed structural equation modeling analysis between PBI and RQ scores with three different category models, including the four-category model (secure, fearful, preoccupied, and dismissive attachment) as Model 1, the two-category model (model of the self and others) as Model 2, and the single-category model (total attachment style) as Model 3. Models 1 and 2 showed a good fit. Both path models showed a significant association between adult attachment style and perceived paternal and maternal parenting before adolescence, where high care and low overprotection from both paternal and maternal parents predicted adult attachment. Our findings indicate that attachment styles are best described using the four-category and two-category models, and suggest that both paternal and maternal overprotection and care influence adult attachment with a partner during the perinatal period.

Introduction Chronic pain remains a health problem that is difficult to treat adequately. Its unknown cause and complex comorbidity with other illnesses, including mental disorders, amplify the severity of symptoms, which consequently decreases the quality of life of patients long term. In our clinical practice, we coincidentally found evidence that methylphenidate (MPH) effectively managed chronic pain in an adult patient with attention deficit hyperactivity disorder (ADHD). The effectiveness of MPH in the treatment of ADHD is well-established; however, its utility in treating pain remains unclear. Case presentation We present a rare case of a 43-year-old male patient with 15 years of chronic idiopathic pain symptoms that did not adequately respond to standard pain management, such as acetaminophen, non-opioid analgesics, and muscle relaxers. Pain also persisted after treatments with antidepressants and an epidural block. Furthermore, symptoms worsened following several sessions of modified electroconvulsive therapy. After a thorough assessment at our child and adolescent psychiatric outpatient clinic, we confirmed a diagnosis of adult ADHD with a predominantly inattentive type. Considering this newly established diagnosis, we prescribed osmotic-release oral system (OROS) methylphenidate. Within 1 month of treatment at a dose of 18 mg/day of OROS-MPH, the patient’s chronic pain unexpectedly improved dramatically, and the patient no longer experienced pain symptoms. The dosage of OROS-MPH was titrated monthly, reaching 72 mg/day as a maintenance dose, and ADHD symptoms improved after 4 months of treatment. The patient was followed up regularly for 7 years during his OROS-MPH treatment. No adverse effects were reported, including stimulant addiction. He was stable overall and functioned well in his daily activities. His pain never recurred. Conclusion This case report suggests that MPH may be potentially effective in treating chronic pain. Further studies are needed to confirm whether MPH improved chronic pain simultaneously with or separately from the improvement in ADHD. Moreover, elucidating the anatomical sites and molecular pharmacological mechanisms related to the action of MPH in pain modulation and perception is essential. Such sites include the descending dopaminergic pain pathway and higher cortical areas. Furthering our understanding may reinforce the justification for treating chronic pain using MPH.

AIM:The present study aimed to examine the association between copy number variations (CNVs) in parkin (PRKN) and schizophrenia (SCZ) and autism spectrum disorder (ASD) in a large case-control sample. METHOD:Array comparative genomic hybridization was performed on 3111 cases with SCZ, 1236 cases with ASD, and 2713 controls. We systematically prioritized likely pathogenic CNVs (LP-CNVs) in PRKN and examined their association with SCZ and ASD. RESULTS:In total, 3014 SCZ cases (96.9%), 1205 ASD cases (97.5%), and 2671 controls (98.5%) passed quality control. We found that monoallelic carriers of LP-CNVs in PRKN were common (70/6890, 1.02%) and were not at higher risk of SCZ (p = 0.29) or ASD (p = 0.72). We observed that the distribution pattern of LP-CNVs in the Japanese population was consistent with those in other populations. We also identified a patient diagnosed with SCZ and early-onset Parkinson's disease carrying biallelic pathogenic CNVs in PRKN. The absence of Parkinson's symptoms in 10 other monoallelic carriers of the same pathogenic CNV further reflects the lack of effect of monoallelic pathogenic variants in PRKN in the absence of a second hit. CONCLUSION:The present findings suggest that monoallelic CNVs in PRKN do not confer a significant risk for SCZ or ASD. However, further studies to investigate the association between biallelic CNVs in PRKN and SCZ and ASD are warranted.

Protein kinases are responsible for protein phosphorylation and are involved in important intracellular signal transduction pathways in various cells, including neurons; however, a considerable number of poorly characterized kinases may be involved in neuronal development. Here, we considered mitogen-activated protein kinase kinase kinase kinases (MAP4Ks), related to as candidate regulators of neurite outgrowth and synaptogenesis, by examining the effects of a selective MAP4K inhibitor PF06260933. PF06260933 treatments of the cultured neurons reduced neurite lengths, not the number of synapses, and phosphorylation of GAP43 and JNK, relative to the control. These results suggest that MAP4Ks are physiologically involved in normal neuronal development and that the resultant impaired neurite outgrowth by diminished MAP4Ks’ activity, is related to psychiatric disorders.