Initial Impact of the COVID-19 Outbreak on ADHD Symptoms Among University Students in Japan.

Objectives: The coronavirus disease 2019 pandemic and its associated societal responses are anticipated to have wide-ranging effects on youth development and mental health. Depression, anxiety, and attention deficit hyperactivity disorder (ADHD) are the three most common mental health problems among university students. Many factors that can threaten mental health during the outbreak affect these three conditions, as well as sleep conditions, in undergraduate students. Thus, determining how these abrupt changes in students' circumstances impact their mental health is very important from a public health perspective. Methods: We investigated the usual conditions and changes in ADHD symptoms during the outbreak, in relation to depressive and sleep-related symptoms among undergraduate students. A total of 252 students, primarily juniors, completed the online survey. Results: The results showed that 12% of the students exceeded the cut-off score of the ADHD questionnaire before the pandemic. Approximately 6%-21% of the university students, especially those with ADHD traits, rated their ADHD behaviors as worse during the outbreak than that before the outbreak. Conclusion: Female students and undergraduates with ADHD traits are more susceptible to experiencing further deterioration of ADHD (inattention) symptoms during the pandemic. In cases where it is difficult to intervene with ADHD symptoms, approaching circadian rhythm or depression will be of considerable clinical use.

Asymmetric Complexity in a Pupil Control Model With Laterally Imbalanced Neural Activity in the Locus Coeruleus: A Potential Biomarker for Attention-Deficit/Hyperactivity Disorder.

Locus coeruleus (LC) overactivity, especially in the right hemisphere, is a recognized pathophysiology of attention-deficit/hyperactivity disorder (ADHD) and may be related to inattention. LC activity synchronizes with the kinetics of the pupil diameter and reflects neural activity related to cognitive functions such as attention and arousal. Recent studies highlight the importance of the complexity of the temporal patterns of pupil diameter. Moreover, asymmetrical pupil diameter, which correlates with the severity of inattention, impulsivity, and hyperactivity in ADHD, might be attributed to a left-right imbalance in LC activity. We recently constructed a computational model of pupil diameter based on the newly discovered contralateral projection from the LC to the Edinger-Westphal nucleus (EWN), which demonstrated mechanisms for the complex temporal patterns of pupil kinetics; however, it remains unclear how LC overactivity and its asymmetry affect pupil diameter. We hypothesized that a neural model of pupil diameter control featuring left-right differences in LC activity and projections onto two opponent sides may clarify the role of pupil behavior in ADHD studies. Therefore, we developed a pupil diameter control model reflecting LC overactivity in the right hemisphere by incorporating a contralateral projection from the LC to EWN and evaluated the complexity of the temporal patterns of pupil diameter generated by the model. Upon comparisons with experimentally measured pupil diameters in adult patients with ADHD, the parameter region of interest of the neural model was estimated, which was a region in the two-dimensional plot of complexity versus left-side LC baseline activity and that of the right. A region resulting in relatively high right-side complexity, which corresponded to the pathophysiological indexes, was identified. We anticipate that the discovery of lateralization of complexity in pupil diameter fluctuations will facilitate the development of biomarkers for accurate diagnosis of ADHD.

Identification of attention-deficit hyperactivity disorder based on the complexity and symmetricity of pupil diameter.

Adult attention-deficit/hyperactivity disorder (ADHD) frequently leads to psychological/social dysfunction if unaddressed. Identifying a reliable biomarker would assist the diagnosis of adult ADHD and ensure that adults with ADHD receive treatment. Pupil diameter can reflect inherent neural activity and deficits of attention or arousal characteristic of ADHD. Furthermore, distinct profiles of the complexity and symmetricity of neural activity are associated with some psychiatric disorders. We hypothesized that analysing the relationship between the size, complexity of temporal patterns, and asymmetricity of pupil diameters will help characterize the nervous systems of adults with ADHD and that an identification method combining these features would ease the diagnosis of adult ADHD. To validate this hypothesis, we evaluated the resting state hippus in adult participants with or without ADHD by examining the pupil diameter and its temporal complexity using sample entropy and the asymmetricity of the left and right pupils using transfer entropy. We found that large pupil diameters and low temporal complexity and symmetry were associated with ADHD. Moreover, the combination of these factors by the classifier enhanced the accuracy of ADHD identification. These findings may contribute to the development of tools to diagnose adult ADHD.

Pupillometric Complexity and Symmetricity Follow Inverted-U Curves Against Baseline Diameter Due to Crossed Locus Coeruleus Projections to the Edinger-Westphal Nucleus.

In addition to photic reflex function, the temporal behavior of the pupil diameter reflects levels of arousal and attention and thus internal cognitive neural activity. Recent studies have reported that these behaviors are characterized by baseline activity, temporal complexity, and symmetricity (i.e., degree of symmetry) between the right and left pupil diameters. We hypothesized that experimental analysis to reveal relationships among these characteristics and model-based analysis focusing on the newly discovered contralateral projection from the locus coeruleus (LC) to the Edinger-Westphal nucleus (EWN) within the neural system for controlling pupil diameter could contribute to another dimension of understanding of complex pupil dynamics. In this study, we aimed to validate our hypothesis by analyzing the pupillary hippus in the healthy resting state in terms of sample entropy (SampEn), to capture complexity, and transfer entropy (TranEn), to capture symmetricity. We also constructed a neural model embedded with the new findings on neural pathways. The following results were observed: first, according to surrogate data analysis, the complexity and symmetricity of pupil diameter changes reflect a non-linear deterministic process. Second, both the complexity and the symmetricity are unimodal, peaking at intermediate pupil diameters. Third, according to simulation results, the neural network that controls pupil diameter has an inverted U-shaped profile of complexity and symmetricity vs. baseline LC activity; this tendency is enhanced by the contralateral synaptic projections from the LCs to the EWNs. Thus, we characterized the typical relationships between the baseline activity and the complexity and symmetricity of the pupillometric data in terms of SampEn and TranEn. Our evaluation method and findings may facilitate the development of estimation and diagnostic tools for exploring states of the healthy brain and psychiatric disorders based on measurements of pupil diameter.

A Qualitative Study of Impacts of the COVID-19 Pandemic on Lives in Adults with Attention Deficit Hyperactive Disorder in Japan.

(1) Background: COVID-19 may deteriorate some aspects among individuals with attention deficit hyperactivity disorder (ADHD). Although some positive aspects were reported during the pandemic, it remains unclear how COVID-19 qualitatively influences their living context; (2) Methods: this study employed interviews with four participants with ADHD during the declaration of emergency issued in Japan. The study was a part of ongoing coaching as a psychosocial intervention for ADHD, which was initiated long before the pandemic. The data were the answers to the question: "how are things going with participants during this pandemic?". In a qualitative analysis, the researchers coded the data to identify different themes and sub-themes; (3) Results and Discussion: the qualitative data analysis yielded five themes: (1) Terrible feeling caused by frustration, stress, and anger; (2) Closeness due to the internal difficulties and conflict; (3) Deteriorating ADHD symptoms and executive function related matters; (4) Condition is the same as usual; and (5) Positive aspects associated with the self-lockdown. As a whole, these results show that the COVID-19 pandemic could be a factor in inducing psychological distress in the participants who adjust relatively better at work/school but did not do well at home before the pandemic; (4) Conclusions: this study indicates the need for special support for individuals with ADHD, especially those who originally had difficulties at home.

Atypical alert state control in adult patients with ADHD: A pupillometry study.

Although behavioral studies have repeatedly demonstrated that individuals with attention-deficit/hyperactivity disorder (ADHD) have deficits in alertness, little is known about its underlying neural basis. It is hypothesized that pupil diameter reflects the firing of norepinephrine (NE) neurons in the locus coeruleus (LC), and that the LC-NE neuromodulatory system for regulating alertness may be dysfunctional in ADHD. To clinically and non-invasively examine this hypothesis, we monitored the kinetics of pupil diameter in response to stimuli and compared them between adults with ADHD (n = 17) and typically developing (TD) adults (n = 23) during an auditory continuous performance task. Individuals in the ADHD group exhibited a significantly larger tonic pupil diameter, and a suppressed stimulus-evoked phasic pupil dilation, compared to those in the TD group. These findings provide support for the idea that the aberrant regulatory control of pupil diameter in adults with ADHD may be consistent with a compromised state of alertness resulting from a hyperactivated LC-NE system.

Discrepancies in Wechsler Adult Intelligent Scale III profile in adult with and without attention-deficit hyperactivity disorder.

AIM: The Wechsler Adult Intelligent Scale (WAIS) is the most frequently administered cognitive assessment for adult Attention-deficit hyperactivity disorder (ADHD); therefore, identifying discrepancies in WAIS profile in patients and comparing with matched controls would be clinically and diagnostically beneficial. METHODS: The WAIS-III profiles of 50 adults with ADHD were compared to an age-matched typical development (TD) group. RESULTS: The adult ADHD group exhibited significantly lower WAIS-III working memory (WM) and processing speed (PS) indices. However, these differences disappeared when intelligence quotient (IQ), Beck Depression Inventory (BDI) score, or Autism Quotient (AQ) score was included as a covariate. The adult ADHD group also demonstrated significantly lower scores in several WM- and PS-domain subscales, while crystallized abilities were comparatively preserved. Additionally, only a small portion of participants in both groups lacked any significant gaps between WAIS-III verbal and performance IQ scores (VIQ-PIQ) or associated indices. DISCUSSION: This study confirms previous findings that adult ADHD patients have deficits in WM and PS. However, it is highly likely that comorbidities such as depression and autism spectrum disorder contribute to lower WM and PS scores in adult ADHD. Unexpectedly, a "flat profile" is uncommon even in TD adults. Therefore, clinician should assess how WAIS deficits affect daily life rather than merely considering an uneven WAIS profile when diagnosing and treating adult ADHD.

Factors Associated With Discrepancy in Parent-Teacher Reporting of Symptoms of ADHD in a Large Clinic-Referred Sample of Children.

Objective: To identify factors associated with discrepancy in parent-teacher reporting of symptoms of ADHD. Method: Parents and teachers rated 1,364 children using an ADHD rating scale. Data were analyzed using multiple regressions and ANOVA. Results: Demographic variables predicted greater parent-teacher discrepancy for ethnic minority families than for Caucasian families. Comorbidity variables predicted greater discrepancy for children who had a comorbid externalizing disorder. Academic performance variables predicted discrepancy for children who showed more homework problems. When all significant predictors were entered together, externalizing disorders and homework problems emerged as significant predictors. Participants whose parents reported higher levels of symptoms were of significantly higher socioeconomic status. Participants whose teachers reported higher levels of symptoms were significantly less likely to have a comorbid externalizing disorder and parent-reported homework problems. Conclusion: Parent-teacher discrepancies are likely to occur when the child has significant homework and externalizing behavior problems.

Psychometric properties of a sluggish cognitive tempo scale in Japanese adults with and without ADHD.

This study examined the psychometric properties, convergent validity, and divergent validity of a Japanese translation of Barkley (The Barkley adult ADHD rating scale-IV, Guilford Press, New York, 2011) rating scale for assessing sluggish cognitive tempo (SCT) in adults. In total, 429 Japanese adults participated across three samples: 26 diagnosed with attention-deficit/hyperactivity disorder (ADHD; ages 19-50), 81 adults without ADHD (ages 22-65), and 322 university students (ages 18-27). All participants completed rating scales of SCT, ADHD, anxiety, and depressive symptoms. A subset of participants completed the SCT measure at two time points two weeks apart. The SCT measure (5 items) showed acceptable levels of internal consistency and test-retest reliability. This scale also demonstrated convergent and discriminant validity, as evidenced by factor analyses between SCT and ADHD inattention (ADHD-IN) symptoms as well as adequate fit of a four-factor model involving SCT, ADHD-IN, ADHD-hyperactivity/impulsivity (ADHD-HI), and internalizing symptoms. Additionally, SCT and ADHD-IN dimensions were differentially associated with ADHD-HI and internalizing factors. The ADHD group scored higher on SCT ratings compared to the student and adult non-ADHD groups even after controlling for the severity of ADHD and internalizing symptoms. The 5-item SCT measure appears reliable and demonstrates preliminary evidence of validity in Japanese adults, providing initial support for the transcultural validity of the SCT construct. Additional studies are needed to further evaluate the SCT items that did not meet criteria for convergent and discriminant validity in the current study, and to examine functional outcomes of individuals recruited based on clinically elevated SCT symptoms.

Psychometric properties of the Japanese version of the Adult Attention-deficit hyperactivity disorder (ADHD) Self-Report Scale (ASRS-J) and its short scale in accordance with DSM-5 diagnostic criteria.

We developed the Japanese version of the Adult ADHD Self-Report Scale (ASRS-J) and report its psychometric properties. The ASRS-J and other questionnaires were administered to 48 adults with ADHD, 46 adults with non-ADHD psychiatric disorders, 96 non-clinical adults, and 894 university students. ADHD diagnoses were made using the Japanese semi-structured diagnostic interview for adult ADHD, which is compatible with the DSM-5. The ASRS-J, its subscales, and the short form, all had Cronbach's α values of around 0.80. Total scores on the ASRS-J and the ASRS-J-6 were highly correlated with readministration after a two-week interval. The total and 18 individual item scores in the ASRS-J were significantly higher in the ADHD group than the other three groups. ASRS-J scores were correlated with scores on the Japanese version of Conners' Adult ADHD Rating Scales-Self Report subscales (0.59≤r≤0.77), with one exception. ASRS-J scores were also correlated (albeit more weakly; r=0.38) with Beck Depression Inventory-II total scores. Employing optimal cut-offs, sensitivity, specificity, and positive and negative predictive values of the ASRS-J and ASRS-J-6 are all above 0.69. The ASRS-J and ASRS-J-6 showed acceptable psychometric properties, although further study is necessary.

Psychometric properties of the Japanese version of the Weiss Functional Impairment Rating Scale: Self-Report.

The Weiss Functional Impairment Rating Scale Self-Report has been translated into nine languages and has been widely used in assessing functional impairment of adults with ADHD. This study is a psychometric validation of the WFIRS-S in Japanese. The WFIRS-S-J and other questionnaires were administered to 46 adults with attention-deficit-hyperactivity disorder (ADHD), 104 control adults, and 889 university students. ADHD diagnoses were made using the Japanese semi-structured diagnostic interview for adult ADHD, which is compatible with the DSM-5. All subscales of the WFIRS-S-J had Cronbach's α values of around 0.80. Total scores on the WFIRS-S-J had high test-retest reliability after a 2-week interval. The total score, subscale scores, and 59 of the individual item scores of the 70 items in the WFIRS-S-J were significantly higher in the ADHD group than in the other two groups, although more than half of the items in subdomain G (risk) showed floor effects and did not reach significance. Generally WFIRS-S-J subdomain scores were moderately correlated with scores on the Japanese version of Conners' Adult ADHD Rating Scales Self-Report subscales. WFIRS-S-J scores were also correlated (albeit more weakly; 0.31 ≤ r ≤ 0.55) with Beck Depression Inventory II total scores. The WFIRS-S-J showed acceptable psychometric properties, although further study is necessary.

Psychometric properties of the self-rating organization scale with adult samples.

Organization skills are defined broadly to include both materials and temporal features. Given its symptoms and neurobiological features, attention-deficit hyperactivity disorder (ADHD) should be susceptible to impairment in organization. A valid organization scale is imperative to assess and intervene individuals with ADHD. However, there is no validated organization scale in Japan. Referring to existing scales and clinical experience, the self-rating organization scale (SOS) was developed and tested in terms of its psychometric properties with 1,017 adults and students including 47 adults with ADHD. Additionally, cutoffs for disorganization were set for clinical utility. Three factors (materials disorganization, temporal disorganization, and mess) were extracted by factor analyses. The index for reliability and validity of the SOS was acceptable. The factor "mess" could reflect the unique aspect of the Japanese environment. Further study is needed to enhance the clinical utility of the SOS.

Reliability and validity of ADHD diagnostic criteria in the Assessment System for Individuals with ADHD (ASIA): a Japanese semi-structured diagnostic interview.

BACKGROUND: With reports of a high prevalence of attention-deficit/hyperactivity disorder (ADHD) in adults, publication of ADHD diagnostic criteria in DSM-5, and the urgent need for a relevant diagnostic instrument conforming to DSM-5, we developed the Assessment System for Individuals with ADHD (ASIA), a Japanese semi-structured diagnostic interview. We report here the reliability and validity of ASIA ADHD diagnostic criteria. METHODS: ASIA ADHD criterion A corresponds to DSM-5 ADHD criterion A and has 144 original questions assessing nine inattention symptoms and nine hyperactivity-impulsivity symptoms, each having four childhood and four adulthood questions. The 144 questions are evaluated on a 3-point frequency scale. ASIA ADHD criteria B to E correspond to DSM-5 ADHD criteria B to E and are evaluated on a 2-point scale. ASIA was administered to 60 adults (mean age, 29.9 ± 9.0 years; 28 males; 36 ADHD and 24 non-ADHD participants diagnosed by consensus of two experts). RESULTS: For ASIA ADHD criterion A, values of Cronbach's α for the adulthood and childhood inattention and hyperactivity-impulsivity symptoms ranged from 0.64 to 0.90. Values of κ for two independent raters ranged from 0.98 to 1.00 for the 144 questions and raw agreement rates ranged from 0.97 to 1.00 for criteria B, C, D, and E. The consensus DSM-5 diagnoses endorsed 59 of the 60 ASIA diagnoses (ADHD and non-ADHD). The ADHD group scored significantly higher on 125 of the 144 questions for criterion A than the non-ADHD group. Correlations between ASIA total and subscale scores in adulthood and corresponding scores on the Japanese version of the Conners' Adult ADHD Scales-Self Report were high. CONCLUSIONS: ASIA ADHD criteria showed acceptable psychometric properties, although further investigation is necessary. The use of ASIA ADHD criteria could facilitate clinical practice and research into adult ADHD in Japan.

Attention deficit and attention training in early twentieth-century Japan.

Yuzero Motora (1856-1912), regarded as the first professional Japanese psychologist, tried to address students' attention difficulties through attention training methods of his own design. His reports contain the first description of ADHD-like symptoms in the history of Japan. Motora viewed "distractibility" as the irregular transition of attention. Students with low scores and attention difficulties who participated in Motora's exercises showed improvement in arithmetic, psychological testing, and certain aspects of daily life. This article describes Motora's theoretical conception of attention and attention training methodology, the history of attention deficit and attention training, and the significance of Motora's experiments.

What can ADHD without comorbidity teach us about comorbidity?

Neuropsychiatric comorbidity in ADHD is frequent, impairing and poorly understood. In this report, characteristics of comorbid and comorbid-free ADHD subjects are investigated in an attempt to identify differences that could potentially advance our understanding of risk factors. In a clinically-referred ADHD cohort of 449 youths (ages 6-18), age, gender, IQ, SES and ADHD symptoms were compared among ADHD comorbid free subjects and ADHD with internalizing and externalizing disorders. Logistic regression analyses were also carried out to investigate the relationship between comorbidity and parental psychiatric status. Age range was younger in the ADHD without comorbidity and older in ADHD+internalizing disorders. No significant difference in IQ or SES was found among ADHD comorbid and comorbid-free groups. ADHD with internalizing disorder has a significantly greater association with paternal psychiatric conditions. After matching by age, gender, IQ and SES, ADHD with externalizing disorders had significantly higher total ADHD, hyperactivity/impulsivity score and single item score of difficulty awaiting turn than ADHD without comorbidity and ADHD with internalizing disorders. Older age ranges, ADHD symptom severity and parental psychopathology may be risk factors for comorbidity.

Methylphenidate transdermal system: clinical applications for attention-deficit/hyperactivity disorder.

The methylphenidate transdermal system (MTS) provides a novel method of delivery for methylphenidate, a well-studied and effective medication for attention-deficit/hyperactivity disorder. The MTS achieves two major goals. First, the delivery system allows for administration throughout the day with a single patch, thus improving adherence. Second, it is the first approved attention-deficit/hyperactivity disorder medication that is not administered orally, thus bypassing gastrointestinal absorption and first-pass metabolism through the enteric circulation. In this article, we review the current data on MTS, including preclinical, clinical and post-marketing studies, and compare efficacy and tolerability to currently available treatments.

Parental ADHD status and its association with proband ADHD subtype and severity.

OBJECTIVE: To better understand the familial transmission of attention deficit hyperactivity disorder (ADHD), a highly heritable disorder, the effects of paternal and maternal ADHD status on probands' ADHD symptoms and subtypes were investigated. STUDY DESIGN: In 323 trios with ADHD, data from a structured interview and a self-report scale (score of >21) were used to determine ADHD probands' diagnostic status and parental ADHD status, respectively. Parental ADHD status on proband ADHD severity and subtypes was investigated. RESULTS: ADHD criteria were endorsed by 23% of fathers and 27% of mothers, and by at least one parent in 41% of the cases. ADHD severity was higher for children whose parents had ADHD versus those whose parents were without it. Paternal ADHD was associated with an increased likelihood of ADHD combined subtype (odds ratio = 3.56) and a decreased likelihood of the inattentive subtype (odds ratio = 0.34) in male children. CONCLUSIONS: Parental ADHD status appears to confer different risks for the severity of hyperactive-impulsive and inattentive symptoms depending on parental sex; however, parental ADHD self-report scale score has low to negligible correlation with proband's ADHD severity. Biparental ADHD does not appear to have an additive or synergistic effect on the proband's ADHD severity.

Nocturnal enuresis: a suggestive endophenotype marker for a subgroup of inattentive attention-deficit/hyperactivity disorder.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) and enuresis co-occur at a higher rate than expected; the cause for this is unclear. STUDY DESIGN: Diagnostic and demographic variables were compared in 344 children ages 6 to 12 years, with and without enuresis, recruited in an ADHD genetic study. Sleep variables were investigated in a subgroup of 44 enuretic children with age- and sex-matched nonenuretic controls. The association of enuresis with single nucleotide polymorphisms located in regions reported in linkage with enuresis was explored. RESULTS: The prevalence rate of nocturnal enuresis was 16.9% for the entire cohort. There were no differences in sex, age, socioeconomic status, intelligence quotient, medication treatment, or comorbidities. The enuresis group had a higher likelihood of inattentive symptoms than the nonenuretic group. Night wakings and ability of children to wake themselves in the morning were both significantly decreased in children with enuresis compared with control children in the Child Sleep Habits Questionnaire Night Wakings subscale. No significant association was found with chromosomal regions previously reported in linkage with enuresis. CONCLUSIONS: Deficits in arousal may contribute to both enuresis and inattentive ADHD. Nocturnal enuresis may be a useful clinical marker in identifying a subgroup of the inattentive phenotype in ADHD genetic studies.

Comparison of developmental/intellectual changes between autistic disorder and pervasive developmental disorder not otherwise specified in preschool years.

This study is the first to compare the change in developmental quotient (DQ) or IQ between autistic disorder (AD) and pervasive developmental disorder not otherwise specified (PDDNOS) in preschool years. Forty-nine AD children and 77 PDDNOS children were evaluated at age 2 and at age > or =5. The AD children were significantly lower in DQ/IQ at initial evaluation and outcome evaluation (also with initial DQ being controlled for) than the PDDNOS children.