Polygenic risk score analysis revealed shared genetic background in attention deficit hyperactivity disorder and narcolepsy.

Attention deficit hyperactive disorder (ADHD) is a highly heritable neurodevelopmental disorder, and excessive daytime sleepiness is frequently observed in ADHD patients. Excessive daytime sleepiness is also a core symptom of narcolepsy and essential hypersomnia (EHS), which are also heritable conditions. Psychostimulants are effective for the symptomatic control of ADHD (primary recommended intervention) and the two sleep disorders (frequent off-label use). However, the common biological mechanism for these disorders has not been well understood. Using a previously collected genome-wide association study of narcolepsy and EHS, we calculated polygenic risk scores (PRS) for each individual. We investigated a possible genetic association between ADHD and narcolepsy traits in the Hamamatsu Birth Cohort for mothers and children (HBC study) (n = 876). Gene-set enrichment analyses were used to identify common pathways underlying these disorders. Narcolepsy PRS were significantly associated with ADHD traits both in the hyperactivity domain (e.g., P-value threshold < 0.05, ß [SE], 5.815 [1.774]; P = 0.002) and inattention domain (e.g., P-value threshold < 0.05, ß [SE], 5.734 [1.761]; P = 0.004). However, EHS PRS was not significantly associated with either domain of ADHD traits. Gene-set enrichment analyses revealed that pathways related to dopaminergic signaling, immune systems, iron metabolism, and glial cell function involved in both ADHD and narcolepsy. Findings indicate that ADHD and narcolepsy are genetically related, and there are possible common underlying biological mechanisms for this relationship. Future studies replicating these findings would be warranted to elucidate the genetic vulnerability for daytime sleepiness in individuals with ADHD.

Developmental changes in attention to social information from childhood to adolescence in autism spectrum disorders: a comparative study.

BACKGROUND: Elucidating developmental changes in the symptoms of autism spectrum disorder (ASD) is important to support individuals with ASD. However, no report has clarified the developmental changes in attention to social information for a broad age range. The aim of this study was to investigate the developmental changes in attention to social information from early childhood to adolescence in individuals with ASD and typically developed (TD) children. METHODS: We recruited children with ASD (n = 83) and TD participants (n = 307) between 2 and 18 years of age. Using the all-in-one-eye-tracking system, Gazefinder, we measured the percentage fixation time allocated to areas of interest (AoIs) depicted in movies (the eyes and mouth in movies of a human face with/without mouth motion, upright and inverted biological motion in movies showing these stimuli simultaneously, people and geometry in preference paradigm movies showing these stimuli simultaneously, and objects with/without finger-pointing in a movie showing a woman pointing toward an object). We conducted a three-way analysis of variance, 2 (diagnosis: ASD and TD) by 2 (sex: male and female) by 3 (age group: 0-5, 6-11, and 12-18 years) and locally weighted the scatterplot smoothing (LOESS) regression curve on each AoI. RESULTS: In the face stimuli, the percentage fixation time to the eye region for the TD group increased with age, whereas the one for the ASD group did not. In the ASD group, the LOESS curves of the gaze ratios at the eye region increased up to approximately 10 years of age and thereafter tended to decrease. For the percentage fixation time to the people region in the preference paradigm, the ASD group gazed more briefly at people than did the TD group. LIMITATIONS: It is possible that due to the cross-sectional design, the degree of severity and of social interest might have differed according to the subjects' age. CONCLUSIONS: There may be qualitative differences in abnormal eye contact in ASD between individuals in early childhood and those older than 10 years.

Effects of cognitive and visual loads on driving performance after take-over request (TOR) in automated driving.

The present study investigated effects of cognitive and visual loads on driving performance after take-over request (TOR) in an automated driving task. Participants completed automated driving in a driving simulator without a non-driving related task, with an easy non-driving related task, and with a difficult non-driving related task. The primary task was to monitor the environment and the system state. An N-back task and a Surrogate Reference Task (SuRT) were adapted to induce cognitive and visual loads respectively. The system followed a front vehicle automatically. Driving performance was measured by responses to a critical event (appearance of a broken-down car) after the automated system issued TOR and then terminated. High subjective difficulty of the N-back task was related to increased time and increased steering angle variance in the time course from onset of steering control to lane change, while high subjective difficulty of SuRT was related to increased steering angle variance in the time course after lane change. This suggests that both cognitive and visual loads affect driving performance after TOR in automated driving, but the effects appear in different time courses.

Association of Genetic Risks With Autism Spectrum Disorder and Early Neurodevelopmental Delays Among Children Without Intellectual Disability.

Importance: Autism spectrum disorder (ASD) is highly heritable, and modest contributions of common genetic variants to ASD have been reported. However, the association of genetic risks derived from common risk variants with ASD traits in children from the general population is not clear, and the association of these genetic risks with neurodevelopment in infants has not been well understood. Objective: To test whether a polygenic risk score (PRS) for ASD is associated with neurodevelopmental progress at age 18 months and ASD traits at age 6 years among children from the general population. Design, Setting, and Participants: In this cohort study, 876 children in the Hamamatsu Birth Cohort for Mothers and Children in Hamamatsu, Japan, underwent testing for the association of an ASD PRS with neurodevelopmental progress and ASD traits. Data collection began in December 2007 and is ongoing. Data analysis was conducted from April to December 2019. Main Outcomes and Measures: Summary data from the largest genome-wide association study were used to generate ASD PRSs, and significance of thresholds was calculated for each outcome. The Autism Diagnostic Observation Schedule 2 was used to measure ASD traits at age 6 years, and the Mullen Scales of Early Learning was used to measure neurodevelopmental progress at age 18 months. Results: Of 876 participants (mean [SD] gestational age at birth, 38.9 [1.6] weeks; 438 [50.0%] boys; 868 [99.1%] Japanese), 734 were analyzed. The ASD PRS was associated with ASD traits (R2 = 0.024; ß, 0.71; SE, 0.24; P = .03). The association of ASD PRS with infant neurodevelopment was most pronounced in gross motor (R2 = 0.015; ß, -1.25; SE, 0.39; P = .01) and receptive language (R2 = 0.014; ß, -1.19; SE, 0.39; P = .02) scores on the Mullen Scales of Early Learning. Gene set enrichment analyses found that several pathways, such as cell maturation (R2 = 0.057; ß, -5.28; SE, 1.40; P < .001) and adenylyl cyclase activity and cyclic adenosine monophosphate concentration (R2 = 0.064; ß, -5.30; SE 1.30; P < .001), were associated with ASD traits. Gene sets associated with inflammation were commonly enriched with ASD traits and gross motor skills (eg, chemokine motif ligand 2 production: R2 = 0.051; ß, -6.04; SE, 1.75; P = .001; regulation of monocyte differentiation: R2 = 0.052; ß, -6.63; SE, 1.90; P = .001; and B-cell differentiation: R2 = 0.051; ß, 7.37; SE, 2.15; P = .001); glutamatergic signaling-associated gene sets were commonly enriched with ASD traits and receptive language skills (eg, regulation of glutamate secretion: R2 = 0.052; ß, -5.82; SE, 1.68; P = .001; ionotropic glutamate receptor signaling pathway: R2 = 0.047; ß, 3.54; SE, 1.09; P = .001; and negative regulation of glutamate secretion: R2 = 0.045; ß, -5.38; SE, 1.74; P = .002). Conclusions and Relevance: In this study, the ASD PRS was associated with ASD traits among children from the general population. Genetic risks for ASD might be associated with delays in some neurodevelopmental domains, such as gross motor and receptive language skills.

Interaction effect of oxytocin receptor (OXTR) rs53576 genotype and maternal postpartum depression on child behavioural problems.

Previous studies have reported interaction effects of oxytocin receptor genotype (rs53576) and environmental factors on mental health in youth. However, the findings are mixed, especially regarding the type of allele (i.e., A vs. G), and it remains unanswered whether such an interaction presents at an early stage of development. Thus, using a unique longitudinal birth cohort sample in Japan (n = 568), we examined whether there was an effect of the interaction between the OXTR rs53576 genotype and maternal postpartum depression, as an environmental risk, on behavioural problems in children. Child behavioural problems (internalising and externalising problems) were ascertained using the Strengths and Difficulties Questionnaire when children were 6 years old. Maternal postpartum depression was measured using the Edinburgh Postnatal Depression Scale when children were at 2 months and 10 months of age. The results revealed a significant effect in the interaction between OXTR rs53576 genotype and maternal postpartum depression on externalising problems in children with AA genotype (ß = 0.136, 95% CI 0.032 to 0.240), but not in those with GG/GA genotype. This indicates that an interaction of vulnerable genotypes (i.e., A allele of OXTR rs53576) with an environmental burden (i.e. maternal postpartum depression) may be one of the potential elements that predisposes the infant to developing behavioural problems early in life. Hence, special attention needs to be paid to children exposed to environmental risks such as maternal postpartum depression, to facilitate the provision of appropriate care.

Associations between the oxytocin receptor gene (OXTR) rs53576 polymorphism and emotional processing of social and nonsocial cues: an event-related potential (ERP) study.

BACKGROUND: Oxytocin receptor (OXTR) gene polymorphisms are related to individual differences in emotional processing of social cues. However, whether OXTR polymorphisms affect emotional processing of nonsocial cues remains unclear. The present study investigated the relationship between the OXTR rs53576 polymorphism and emotional processing of social cues and nonsocial cues. METHODS: Event-related potentials were recorded from 88 male participants while images of humans and images of objects were presented as social cues and nonsocial cues, respectively. RESULTS: First, the results showed that GG carriers of OXTR rs53576 showed more negative N1 (50-200 ms) than AA carriers in response to images of both humans and objects. Second, GG carriers showed more negative N2 (200-320 ms) than AA carriers in response to images of humans but not in response to images of objects. Third, GG carriers showed more negative N2 in response to images of humans than images of objects, whereas AA carriers showed the opposite pattern. Fourth, we observed no difference in late positive potential (600-1000 ms) to images of humans or objects that depended on the OXTR rs53576 polymorphism. CONCLUSIONS: These results suggest that the OXTR rs53576 polymorphism affects emotional processing of not only social cues but also nonsocial cues in the very early stage (reflected in N1); however, the data also suggest that the OXTR rs53576 polymorphism is related specifically to increased emotional processing of social cues in the middle stage (reflected in N2).

Relative left frontal activity in reappraisal and suppression of negative emotion: Evidence from frontal alpha asymmetry (FAA).

Previous studies have shown that reappraisal (changing the way that one thinks about emotional events) is an effective strategy for regulating emotion, compared with suppression (reducing emotion-expressive behavior). In the present study, we investigated relative left frontal activity when participants were instructed to use reappraisal and suppression of negative emotion, by measuring frontal alpha asymmetry (FAA). Two electroencephalography (EEG) experiments were conducted; FAA was analyzed while 102 healthy participants (59 men, 43 women) watched negative images after being instructed to perform reappraisal (Experiment 1) and suppression (Experiment 2). Habitual use of reappraisal and suppression was also assessed using the emotion regulation questionnaire (ERQ). The results of Experiment 1 showed that relative left frontal activity was greater when instructed to use reappraisal of negative images than when normally viewing negative images. In contrast, we observed no difference between conditions of instructed suppression and normal viewing in Experiment 2. In addition, in male participants, habitual use of reappraisal was positively correlated with increased relative left frontal activity for instructed reappraisal, while habitual use of suppression did not show a significant correlation with changes in relative left frontal activity for instructed suppression. These results suggest that emotional responses to negative images might be decreased for instructed reappraisal, but not suppression. These findings support previous reports that reappraisal is an effective emotion regulation strategy, compared with suppression.

Does cigarette smoking relieve stress? Evidence from the event-related potential (ERP).

Previous studies have reported a paradox that cigarette smoking reduces stress psychologically; however, it increases the arousal level physiologically. To examine this issue, our study aimed to investigate whether cigarette smoking relieves stress by measuring the late positive potential (LPP), a component of the event-related potential (ERP). In Experiment 1, participants first watched emotionally neutral images; second, they received a break; and finally, they watched emotionally neutral images again. In the break, they smoked a cigarette (smoking condition) or simply rested without smoking (non-smoking condition). The procedure of Experiment 2 was the same as that of Experiment 1, except that the participants watched unpleasant images as stress stimuli before the break. In Experiment 1, the LPP decreased from before to after the break in the smoking condition, but not in the non-smoking condition, suggesting that smoking cigarettes in the neutral state reduces the arousal level. In Experiment 2, the LPP for 400-600 ms decreased from before to after the break, both in the smoking and non-smoking conditions; however, the LPP for 200-400 ms decreased from before to after the break only in the smoking condition. This suggests the possibility that cigarette smoking in the unpleasant state may facilitate a decrease in the arousal level faster than with non-smoking. In both Experiments 1 and 2, the subjective rating results also suggested that cigarette smoking decreased anxiety. Taken together, both the physiological (LPP) and the psychological responses from our study suggest that cigarette smoking perhaps relieves stress.

Gender difference in N170 elicited under oddball task.

BACKGROUND: Some studies have reported gender differences in N170, a face-selective event-related potential (ERP) component. This study investigated gender differences in N170 elicited under oddball paradigm in order to clarify the effect of task demand on gender differences in early facial processing. FINDINGS: Twelve males and 10 females discriminated targets (emotional faces) from non-targets (emotionally neutral faces) under an oddball paradigm, pressing a button as quickly as possible in response to the target. Clear N170 was elicited in response to target and non-target stimuli in both males and females. However, females showed more negative amplitude of N170 in response to target compared with non-target, while males did not show different N170 responses between target and non-target. CONCLUSIONS: The present results suggest that females have a characteristic of allocating attention at an early stage when responding to faces actively (target) compared to viewing faces passively (non-target). This supports previous findings suggesting that task demand is an important factor in gender differences in N170.

Effect of emotional arousal on inter-temporal decision-making: an fMRI study.

BACKGROUND: Previous research has shown that emotion can significantly impact decision-making in humans. The current study examined whether or not and how situationally induced emotion influences people to make inter-temporal choices. METHODS: Affective pictures were used as experiment stimuli to provoke emotion, immediately followed by subjects' performance of a delay-discounting task to measure impulsivity during functional magnetic resonance imaging. RESULTS: Results demonstrate a subsequent process of increased impulsive decision-making following a prior exposure to both high positive and negative arousal stimuli, compared to the experiment subjects' experiences with neutral stimuli. Findings indicate that increased impulsive decision-making behaviors can occur with high arousal and can be characterized by decreased activities in the cognitive control regions such as prefronto-parietal regions. CONCLUSIONS: These results suggest that 'stabilization of high emotional arousal' may facilitate a reduction of impulsive decision-making and implementation of longer term goals.

Seasonal variation of non-shivering thermogenesis (NST) during mild cold exposure.

BACKGROUND: The physiological function of non-shivering thermogenesis (NST) has been investigated in recent years, and some studies have discussed the importance of NST with respect to human cold adaptation. The present study aimed to clarify individual and seasonal variations in NST that occurred as a result of mild cold exposure. METHODS: Seventeen male university students participated in the present study during summer and winter. The climate chamber used was programmed so that ambient temperature dropped from 28°C to 16°C over an 80-min period. Physiological parameters of test subjects were recorded during the experiments. RESULTS: Increases in oxygen intake (VO2) during cold exposure were significantly greater without shivering in winter than they were in summer. Respiratory exchange ratio (RER) was significantly lower during thermoneutral baseline and cold exposure in winter than it was during the same periods in summer. In addition, there was a significant negative correlation between ΔVO2 and ΔRER. CONCLUSIONS: Increase of VO2 without shivering indicated increase of NST, and decrease of RER depends on the metabolization of fat in winter. These results suggested that NST activity was activated by seasonal acclimatization, and individual variation of NST depends on individual variation of fat metabolism.

Nonthermal sensory input and altered human thermoregulation: effects of visual information depicting hot or cold environments.

A recent study showed that thermoregulatory-like cardiovascular responses can be invoked simply by exposure to visual information, even though the thermal environments are neutral and unchanged. However, it was not clear how such responses affect actual human body temperature regulation. We investigated whether such visually invoked physiological responses can substantively affect human core body temperature in a thermally challenging cold environment. Participants comprised 13 graduate or undergraduate students viewing different video images containing hot, cold, or no scenery, while room temperature was gradually lowered from 28 to 16 °C over 80 min. Rectal temperature, mean skin temperature, core to skin temperature gradient, and oxygen consumption were measured during the experiment. Rectal temperature was significantly lower when hot video images were presented compared to when control video images were presented. Oxygen consumption was comparable among all video images, but core to skin temperature gradient was significantly lower when hot video images were presented. This result suggests that visual information, even in the absence of thermal energy, can affect human thermodynamics and core body temperature.

Effect of empathy trait on attention to various facial expressions: evidence from N170 and late positive potential (LPP).

BACKGROUND: The present study sought to clarify the relationship between empathy trait and attention responses to happy, angry, surprised, afraid, and sad facial expressions. As indices of attention, we recorded event-related potentials (ERP) and focused on N170 and late positive potential (LPP) components. METHODS: Twenty-two participants (12 males, 10 females) discriminated facial expressions (happy, angry, surprised, afraid, and sad) from emotionally neutral faces under an oddball paradigm. The empathy trait of participants was measured using the Interpersonal Reactivity Index (IRI, J Pers Soc Psychol 44:113-126, 1983). RESULTS: Participants with higher IRI scores showed: 1) more negative amplitude of N170 (140 to 200 ms) in the right posterior temporal area elicited by happy, angry, surprised, and afraid faces; 2) more positive amplitude of early LPP (300 to 600 ms) in the parietal area elicited in response to angry and afraid faces; and 3) more positive amplitude of late LPP (600 to 800 ms) in the frontal area elicited in response to happy, angry, surprised, afraid, and sad faces, compared to participants with lower IRI scores. CONCLUSIONS: These results suggest that individuals with high empathy pay attention to various facial expressions more than those with low empathy, from very-early stage (reflected in N170) to late-stage (reflected in LPP) processing of faces.

Time window for cognitive activity involved in emotional processing.

BACKGROUND: From previous studies it is becoming evident that the processing of unpleasant stimuli occurs early (0 to 300 ms); however, it is not clear how cognitive processing related to pleasant/unpleasant emotions occurs at later time windows (≥ 300 ms). On the other hand, as evident from the previous reports, BIS and BAS personality traits are strongly associated with unpleasant and pleasant responses, respectively. Therefore, in the present study, we aim to identify the time window involved in human pleasant/unpleasant emotional processing by investigating ERP components correlated with BIS/BAS personality traits. METHODS: Twenty-nine men took part in the study and recording ERP during presented sounds. BIS/BAS score was calculated using the Japanese edition of the BIS/BAS questionnaire. RESULTS: Significant correlation was not observed between BIS and BAS scores. A significant and positive correlation was observed between N100 amplitude and BIS score. A positive correlation was found between BAS fun seeking subscale score and LPP amplitude. Our findings did not contradict previous study results. CONCLUSIONS: Our results suggest that the processing of unpleasant emotions takes place early on, since N100 response was larger in high BIS subjects who are known to be sensitive to unpleasant emotions. LPP was larger in high BAS subjects who are known to be sensitive to pleasant emotions. The LPP was considered to be augmented because the ACC activity level during pleasant emotions reflected on LPP.

Effect of empathy trait on attention to faces: an event-related potential (ERP) study.

BACKGROUND: Empathy is deeply linked with the ability to adapt to human social environments. The present study investigated the relationship between the empathy trait and attention elicited by discriminating facial expressions. METHODS: Event-related potentials were measured while 32 participants (17 men and 15 women) discriminated facial expressions (happy or angry) and colors of flowers (yellow or purple) under an oddball paradigm. The empathy trait of participants was measured using the Interpersonal Reactivity Index (Davis, 1980). RESULTS: The empathy trait correlated positively with both the early portion (300 to 600 ms after stimulus onset) and late portion (600 to 800 ms after stimulus onset) of late positive potential (LPP) amplitude elicited by faces, but not with LPP elicited by flowers. CONCLUSIONS: This result suggests that, compared to people with low empathy, people with high empathy pay more attention when discriminating facial expressions. The present study suggests that differences exist in methods of adapting to social environments between people with high and low empathy.