Exploration of electroencephalogram response to MPH treatment in ADHD patients.

Attention-deficit/hyperactivity disorder (ADHD) is known to be associated with several diagnostic resting-state electroencephalography (EEG) patterns, including the theta/beta ratio, but no objective predictive markers for each medication. In this study, we explored EEG markers with which the therapeutic efficacy of medications could be estimated at the 1st clinical visit. Thirty-two ADHD patients and thirty-one healthy subjects participated in this study. EEG was recorded during eyes-closed resting conditions, and ADHD symptoms were scored before and after the therapeutic intervention (8 ± 2 weeks). Although comparing EEG patterns between ADHD patients and healthy subjects showed significant differences, EEG dynamics, e.g., theta/beta ratio, in ADHD patients before and after MPH treatment were not significantly different despite improvements in ADHD symptoms. We demonstrated that MPH good responders and poor responders, defined by the efficacy of MPH, had significantly different theta band power in right temporal areas, alpha in left occipital and frontal areas, and beta in left frontal areas. Moreover, we showed that MPH good responders had significant improvements toward normalization in several coherence measures after MPH treatment. Our study implies the possibility of these EEG indices as predictive markers for ADHD therapeutic efficacy.

Decision aid development and its acceptability among adults with attention-deficit/hyperactivity disorders regarding treatment discontinuation after remission.

Aim: Current clinical guidelines for attention-deficit/hyperactivity disorder (ADHD) put shared decision making (SDM) at the center of care. However, there remain challenges in SDM in ADHD management, particularly regarding the decision to continue or discontinue medication after ADHD remission in adult patients. We aimed to develop a decision aid (DA) for adult patients with ADHD regarding the continuation or discontinuation of their ongoing ADHD medications after they have attained remission. Method: We systematically developed a DA according to the International Patient Decision Aid Standard (IPDAS). First, we created a DA prototype using the results of our previous systematic review and meta-analysis that identified the consequences of continuing and discontinuing ADHD medications. Second, we administered a mixed-method questionnaire (alpha acceptability testing) to adult patients with ADHD and healthcare providers to improve the DA prototype and develop it into a final version that is acceptable for clinical settings. Results: Our DA consisted of ADHD description, the option to continue or discontinue ADHD medications, the advantages and disadvantages of the consequences, as well as value clarification exercises for each option. Patients (n = 20) reported that the DA had acceptable language (85%), adequate information (75%), and a well-balanced presentation (53%). Healthcare providers (n = 19) provided favorable feedback. The final DA met all six IPDAS requisite criteria. Conclusions: Our results could facilitate the SDM process between patients and healthcare providers on the continuation or discontinuation of ADHD medication following remission. Further studies should verify the effects of using the DA during the SDM process among patients across the age spectrum with ADHD and healthcare providers.

Efficacy and Safety of Medication for Attention-Deficit Hyperactivity Disorder in Children and Adolescents with Common Comorbidities: A Systematic Review.

INTRODUCTION: Comorbid psychiatric conditions in children and adolescents with attention-deficit hyperactivity disorder (ADHD) occur frequently, complicate management, and are associated with substantial burden on patients and caregivers. Very few systematic reviews have assessed the efficacy and safety of medications for ADHD in children and adolescents with comorbidities. Of those that were conducted, most focused on a particular comorbidity or medication. In this systematic literature review, we summarize the efficacy and safety of treatments for children and adolescents with ADHD and comorbid autism spectrum disorders, oppositional defiant disorder, Tourette's disorder and other tic disorders, generalized anxiety disorder, and major depressive disorder. METHODS: We searched MEDLINE, Embase, and ClinicalTrials.gov (to October 2019) for studies of patients (aged < 18 years) with an ADHD diagnosis and the specified comorbidities treated with amphetamines, methylphenidate and derivatives, atomoxetine (ATX), and guanfacine extended-release (GXR). For efficacy, placebo-controlled randomized controlled trials (RCTs) or meta-analyses of RCTs were eligible for inclusion; for safety, all study types were eligible. The primary efficacy outcome measure was ADHD Rating Scale IV (ADHD-RS-IV) total score. RESULTS: Of 2177 publications/trials retrieved, 69 were included in this systematic literature review (5 meta-analyses, 37 placebo-controlled RCTs, 16 cohort studies, 11 case reports). A systematic narrative synthesis is provided because insufficient data were retrieved to combine ADHD-RS-IV total scores or effect sizes. Effect sizes for ADHD-RS-IV total scores were available for ten RCTs and ranged from 0.46 to 1.0 for ATX and from 0.92 to 2.0 for GXR across comorbidities. The numbers and types of adverse events in children with comorbidities were consistent with those in children without comorbidities, but treatment should be individualized to ensure children can tolerate the lowest effective dose. CONCLUSION: Limited information is available from placebo-controlled RCTs on the efficacy (by ADHD-RS-IV) or safety of medication in children with ADHD and psychiatric comorbidities. Further studies are required to support evidence-based drug selection for these populations.

Trajectories of Healthcare Utilization Among Children and Adolescents With Autism Spectrum Disorder and/or Attention-Deficit/Hyperactivity Disorder in Japan.

BACKGROUND: Early intervention and prevention of psychiatric comorbidities of children with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are urgent issues. However, the differences in the diagnoses of ASD and ADHD and psychiatric comorbidities associated with age, long-term healthcare utilization trajectories, and its associated diagnostic features have not been fully elucidated in Japan. METHOD: We conducted a retrospective observational study using the medical records. Member hospitals of three major consortiums of hospitals providing child and adolescent psychiatric services in Japan were recruited for the study. Children who accessed the psychiatry services of the participating hospitals in April 2015 were followed up for 5 years, and data on their clinical diagnoses, consultation numbers, and hospitalizations were collected. Non-hierarchical clustering was performed using two 10-timepoint longitudinal variables: consultation numbers and hospitalization. Among the major clusters, the differences in the prevalence of ASD, ADHD, comorbid intellectual disability, neurotic disorders, and other psychiatric disorders were assessed. RESULTS: A total of 44 facilities participated in the study (59.5%), and 1,003 participants were enrolled. Among them, 591 diagnosed with ASD and/or ADHD (58.9%) and 589 without missing data were assessed. The mean age was 10.1 years, and 363 (70.9%) were boys. Compared with the pre-schoolers, the school-aged children and adolescents had fewer ASD, more ADHD, and fewer comorbid intellectual disability diagnoses, as well as more diagnoses of other psychiatric disorders. A total of 309 participants (54.7%) continued consultation for 2 years, and 207 (35.1%) continued for 5 years. Clustering analysis identified three, two, and three major clusters among pre-schoolers, school-aged children, and adolescents, respectively. The largest cluster was characterized by early termination of the consultation and accounted for 55.4, 70.6, and 73.4% of pre-schoolers, school-aged children, and adolescents, respectively. Among the school-aged children, the diagnosis of ADHD was associated with a cluster that required longer periods of consultations. Among the adolescents, comorbid psychiatric disorders other than intellectual disability and neurotic disorders were associated with clusters that required hospitalization. CONCLUSION: Continuous healthcare needs were common and psychiatric comorbidities were associated with complex trajectory among adolescents. The promotion of early intervention and prevention of comorbidities are important.

Associations of childhood experiences with event-related potentials in adults with autism spectrum disorder.

Childhood maltreatment is defined as experiencing of physical, emotional and sexual abuse and neglect in childhood. Maltreatment in childhood leads to substantial psychosocial problems later in life in the general population. Individuals with autism spectrum disorder (ASD) have a higher risk of experiencing stressful and traumatic events, such as maltreatment, during childhood. Although childhood maltreatment reportedly leads to psychosocial problems in adults with ASD, the biological associations between childhood experiences and brain function in this population remain understudied. Here, we evaluated the relationships between childhood experiences and event-related potential (ERP) components during the auditory odd-ball task in adults with ASD (N = 21) and typically developed (TD) individuals (N = 22). We found that the higher the severity of sexual abuse, the larger the amplitude of P300 at Fz, Cz, C3, and C4 in individuals with ASD. Conversely, the severity of child maltreatment was associated with P300 latency at Cz and C3 in TD individuals. Moreover, full IQ was significantly associated with the MMN amplitude at Fz, Cz, C3, and C4 in TD individuals. These findings provide the first evidence that ERPs could be used to study the impacts childhood experiences on the brain of individuals with ASD and that childhood sexual abuse has salient impacts on brain function in this population.

Delayed prefrontal hemodynamic response associated with suicide risk in autism spectrum disorder.

Adults diagnosed with Autism spectrum disorder (ASD) are at high risk of experiencing suicidality compared with other clinical groups. Recently, near-infrared spectroscopy (NIRS) studies have investigated the association between frontotemporal functional abnormalities and suicidality in patients with mood disorders. However, whether these prefrontal hemodynamic responses are associated with suicide vulnerability in individuals with ASD remains unclear. Here, we used 24-channel NIRS to examine the characteristics of prefrontal hemodynamic responses during a verbal fluency task in 20 adults with ASD and in age-, sex-, and intelligence quotient-matched healthy controls. In addition, we used Spearman's correlation analysis to identify the relationship between the time-course of prefrontal hemodynamic activation and the current suicide risk in patients with ASD. We found no significant differences between the verbal fluency task-induced prefrontal hemodynamic responses in the ASD vs. control group. However, we found a significant positive correlation between the current suicide risk score and the time-course of prefrontal hemodynamic activation in the ASD group. Thus, the 24-channel NIRS system appears to be useful in assessing suicide risk in individuals with ASD.

Influence of Self-Esteem and Psychiatric Diagnosis on Health-Related Quality of Life in Children and Adolescents with School Refusal Behavior.

BACKGROUND: School refusal behavior (SRB), which is the refusal to attend or remain in school, has been associated with emotional, psychological, and other behavioral problems, as well as a lower health-related quality of life (HRQOL). However, the effects of self-esteem and a psychiatric diagnosis in students with SRB on HRQOL are not yet known. Understanding these relationships could help to develop more effective therapeutic interventions. METHODS: A total of 175 young people (aged 8-18 years old) who visited our medical centers and outpatient clinics participated in the study. This comprised the SRB group (n = 70) and an age- and sex-matched control group (n = 105). Information about any psychiatric diagnosis was collected from medical records, HRQOL was measured using the J-KIDSCREEN-52, SRB was assessed using the School Refusal Assessment Scale-Revised for Japanese Attendance at School, self-esteem was measured using the Rosenberg Self-Esteem Scale, children's mental health status was measured using the Strengths and Difficulties Questionnaire, and social support was measured using the Oslo 3-item Social Support Scale. We performed between-group comparisons and multiple regression analysis. RESULTS: The SRB had a significantly lower HRQOL than the control group in several of the KIDSCREEN-52 dimensions. In the SRB group, 35.7% had chronic disease and 35.7% of their parents had health problems and were receiving treatment. The multiple regression analysis revealed that, within the SRB group, a psychiatric diagnosis was associated with a lower HRQOL. However, this was not the case for a diagnosis of autistic spectrum disorder. Self-esteem positively affected HRQOL in six dimensions of the KIDSCREEN-52 within the SRB group. CONCLUSION: Our results could inform the development of support strategies for young people with SRB. Namely, support that enhances self-esteem could be used to increase HRQOL in young people with SRB. Furthermore, the presence of psychiatric disorders should be assessed as early as possible.

Effect of Continuing and Discontinuing Medications on Quality of Life After Symptomatic Remission in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aimed to compare the effect of continuing and discontinuing medications on quality of life of patients with attention-deficit/hyperactivity disorder (ADHD). DATA SOURCES: PubMed, Cochrane Library, and Embase databases were searched using generic terms for ADHD, discontinuing, continuing, pharmacotherapy, and randomized controlled trials without date or language restrictions. STUDY SELECTION: Of the 3,672 screened studies, 9 met the predefined inclusion criteria on patients with ADHD; 5 of these 9 studies reporting on 1,463 patients (children and adolescents, n = 894; adults, n = 569) measured quality of life and were included in this meta-analysis. Only randomized, double-blind, placebo-controlled withdrawal trials of ADHD medications were included. DATA EXTRACTION: Data were independently extracted according to the Cochrane Handbook for Systematic Reviews of Interventions. Analyses were based on random-effects models. RESULTS: Compared with continuing medications, discontinuing them significantly worsened quality of life score in patients with ADHD (standardized mean difference [SMD] = 0.19; 95% CI, 0.08 to 0.30]). Moreover, discontinuing medications worsened this score in children and adolescents with ADHD (SMD = 0.21; 95% CI, 0.06 to 0.36) but not in adults with ADHD (SMD = 0.02; 95% CI, -0.46 to 0.50). CONCLUSIONS: Discontinuing medications was associated with a small but statistically significant decrease in quality of life among children and adolescents with ADHD but not in adults with ADHD. Quality of life can be applied in pharmacologic interventions regarding continuing and discontinuing medication because this concept is related to individuals' appraisal of their situation. Quality of life is an important factor for planning individualized ADHD medication treatment.

Reduced prefrontal hemodynamic response in pediatric autism spectrum disorder measured with near-infrared spectroscopy.

BACKGROUND: Functional neuroimaging studies suggest that prefrontal cortex dysfunction is present in people with autism spectrum disorder (ASD). Near-infrared spectroscopy is a noninvasive optical tool for examining oxygenation and hemodynamic changes in the cerebral cortex by measuring changes in oxygenated hemoglobin. METHODS: Twelve drug-naïve male participants, aged 7-15 years and diagnosed with ASD according to DSM-5 criteria, and 12 age- and intelligence quotient (IQ)-matched healthy control males participated in the present study after giving informed consent. Relative concentrations of oxyhemoglobin were measured with frontal probes every 0.1 s during the Stroop color-word task, using 24-channel near-infrared spectroscopy. RESULTS: Oxyhemoglobin changes during the Stroop color-word task in the ASD group were significantly smaller than those in the control group at channels 12 and 13, located over the dorsolateral prefrontal cortex (FDR-corrected P: 0.0021-0.0063). CONCLUSION: The results suggest that male children with ASD have reduced prefrontal hemodynamic responses, measured with near-infrared spectroscopy.

Guanfacine monotherapy for ADHD/ASD comorbid with Tourette syndrome: a case report.

BACKGROUND: Patients with attention deficit/hyperactivity disorder (ADHD) often experience comorbid conditions, such as autism spectrum disorder (ASD) and Tourette syndrome (TS). Although pharmacotherapies are effective for treating ADHD, they are likely to elicit a variety of adverse effects. It is, thus, important to select an effective and well-tolerated pharmacotherapeutic treatment for patients with ADHD/ASD comorbid with TS. CASE PRESENTATION: We report the case of a 10-year-old boy with ADHD/ASD comorbid with TS who was treated with guanfacine (GUAN). He experienced several side effects of atomoxetine (ATX) and methylphenidate (MPH) before being treated with GUAN. In the presented case, symptoms of ADHD as well as tic symptoms were improved by treatment with GUAN. CONCLUSION: GUAN might be effective and well tolerated in the treatment of patients with ADHD/ASD comorbid with TS who experience side effects of ATX and MPH.

Glucose and Prolactin Monitoring in Children and Adolescents Initiating Antipsychotic Therapy.

OBJECTIVE: We aimed to evaluate glucose and prolactin monitoring in children and adolescents initiating antipsychotic therapy using a nationwide claims database. METHODS: A retrospective 15-month cohort study was conducted using the National Database of Health Insurance Claim Information and Specified Medical Checkups in Japan. Patients aged ≤18 years, who were newly prescribed antipsychotics between April 2014 and March 2015, were followed up for 450 days. Outcomes were the use of glucose and prolactin testing through 15 months after drug initiation (index date) with consideration of persistence with antipsychotic therapy. The incidence proportion of patients monitored was assessed within the following four time windows: baseline (between 30 days before the index date and the index date), at 1-3 months (between 1 and 90 days after the index date), at 4-9 months (between 91 and 270 days after the index date), and at 10-15 months (between 271 and 450 days after the index date). RESULTS: Of 43,608 new users in 6620 medical institutions, the percentage of persistent antipsychotic users was 46.4% at 90 days, 29.7% at 270 days, and 23.8% at 450 days after the index date. The proportion of patients who received monitoring within the baseline period was 13.5% (95% confidence interval [CI], 13.2-13.8) for glucose and 0.6% (95% CI, 0.5-0.6) for prolactin, respectively. The proportion of patients who received glucose monitoring at all time windows decreased to 0.9%. The proportion of patients who received prolactin monitoring by the second time window decreased to 0.1%. CONCLUSIONS: Our study shows that monitoring for glucose and prolactin is infrequent in children and adolescents initiating antipsychotic therapy. Strategies for physicians, patients, and guardians are needed to overcome the barriers in glucose and prolactin monitoring.

Intra-individual variability across cognitive task in drug-naïve pediatric patients with obsessive compulsive disorder.

Attention deficit is commonly observed in several psychiatric conditions. In particular, patients with attention deficit hyperactivity disorder exhibit not only attention deficit, but also intra-individual variability in response times (IIV-RT) during the performance of cognitive tasks related to attention span and sustained attention. Although obsessive compulsive disorder (OCD) is commonly observed across childhood, little is known about abnormalities in IIV-RT during the auditory odd-ball task, and how these changes relate to event-related potentials (ERPs) components. In the present study, we compared the ERPs of 15 adolescent and pediatric patients with OCD with 15 healthy age, sex, and IQ-matched controls. We found that tau of IIV-TR was not significantly different between the OCD group and controls, whereas the OCD group exhibited lower mu and sigma compared to controls. Furthermore, we revealed that P300 amplitude was significantly attenuated in the OCD group at Fz, C3, and C4, compared with controls. The present study thereby provided the first evidence that individuals with pediatric or adolescent OCD exhibit lower variability in reaction time in IIV-RT during an auditory odd-ball task than controls. These results suggest that there are no impairments in attention span and sustained attention in pediatric and adolescent patients with OCD.

Distinct patterns of blood oxygenation in the prefrontal cortex in clinical phenotypes of schizophrenia and bipolar disorder.

BACKGROUND: Schizophrenia (SZ) and bipolar disorder (BD) are characterized by different clinical symptoms, and have previously been considered as categorically separate. However, several lines of evidence controversially suggest that these two disorders may run on a continuum. While it is therefore important to evaluate the subtle differences between SZ and BD, few studies have investigated the difference of brain functioning between the two by focusing on the common symptoms of cognitive functioning and impulsivity, rather than positive/negative and mood symptoms. Recent developments in near-infrared spectroscopy (NIRS) technology have enabled noninvasive assessment of brain function in people with psychiatric disorders. METHODS: Near-infrared spectroscopy (NIRS) using 24-channels was conducted during the verbal fluency task (VFT) and Stroop color-word task (SCWT) in 38 patients diagnosed with SZ, 34 patients with BD, and 26 age- and sex-matched healthy controls. RESULTS: Oxyhemoglobin changes in the prefrontal cortex (PFC) were significantly lower particularly in the SZ compared to control group during the VFT. On the other hand, these were significantly lower particularly in the BD and SZ group to control group during the SCWT. Regression analysis showed that hemodynamic changes were significantly correlated with verbal memory and impulsivity in both disorders. CONCLUSION: These findings suggest that different hemodynamic responses in the prefrontal cortex might reflect cognitive functioning and impulsivity, providing a greater insight into SZ and BD pathophysiology.

Reduced prefrontal hemodynamic response in adult attention-deficit hyperactivity disorder as measured by near-infrared spectroscopy.

AIM: Recent developments in near-infrared spectroscopy (NIRS) have enabled non-invasive clarification of brain functions in psychiatric disorders. In pediatric attention-deficit hyperactivity disorder (ADHD), reduced prefrontal hemodynamic responses have been observed with NIRS repeatedly. However, there are few studies of adult ADHD by multi-channel NIRS. Therefore, in this study, we used multi-channel NIRS to examine the characteristics of prefrontal hemodynamic responses during the Stroop Color-Word Task (SCWT) in adult ADHD patients and in age- and sex-matched control subjects. METHODS: Twelve treatment-naïve adults with ADHD and 12 age- and sex-matched healthy control subjects participated in the present study after giving consent. We used 24-channel NIRS to measure the oxygenated hemoglobin (oxy-Hb) changes at the frontal lobes of participants during the SCWT. We compared the oxy-Hb changes between adults with ADHD and control subjects by t-tests with Bonferroni correction. RESULTS: During the SCWT, the oxy-Hb changes observed in the ADHD group were significantly smaller than those in the control group in channels 11, 16, 18, 21, 22, 23, and 24, corresponding to the prefrontal cortex. At channels 16, 21, 23, and 24 of the ADHD group, there were negative correlations between the symptomatic severity and the oxy-Hb changes. CONCLUSION: The present study suggests that adults with ADHD have reduced prefrontal hemodynamic response as measured by NIRS.

Left dorsolateral prefrontal cortex atrophy is associated with frontal lobe function in Alzheimer's disease and contributes to caregiver burden.

OBJECTIVE: Caregivers of patients with dementia experience physical and mental deterioration. We have previously reported a correlation between caregiver burden and the Frontal Assessment Battery (FAB) total scores of patients with Alzheimer's disease (AD), especially regarding the dependency factor from the Zarit Burden Interview. The present study aimed to identify an objective biomarker for predicting caregiver burden. METHODS: The participants were 26 pairs of caregivers and patients with AD and mild-to-moderate dementia. Correlations between regional gray matter volumes in the patients with AD and the FAB total scores were explored by using whole-brain voxel-based morphometric analysis. Path analysis was used to estimate the relationships between regional gray matter volumes, FAB total scores, and caregiver burden based on the Zarit Burden Interview. RESULTS: The voxel-based morphometric revealed a significant positive correlation between the FAB total scores and the volume of the left dorsolateral prefrontal cortex. This positive correlation persisted after controlling for the effect of general cognitive dysfunction, which was assessed by using the Mini-Mental State Examination. Path analysis revealed that decreases in FAB scores, caused by reduced frontal lobe volumes, negatively affected caregiver burden. CONCLUSIONS: The present study revealed that frontal lobe function, based on FAB scores, was affected by the volume of the left dorsolateral prefrontal cortex. Decreased scores were associated with greater caregiver burden, especially for the dependency factor. These findings may facilitate the development of an objective biomarker for predicting caregiver burden.

Differential therapeutic effects of atomoxetine and methylphenidate in childhood attention deficit/hyperactivity disorder as measured by near-infrared spectroscopy.

BACKGROUND: The stimulant methylphenidate (MPH) and the nonstimulant atomoxetine (ATX) are the most commonly-prescribed pharmacological treatments for attention deficit/hyperactivity disorder (ADHD). However, the drug-specific mechanism of action on brain function in ADHD patients is not well known. This study examined differences in prefrontal hemodynamic activity between MPH and ATX in children with ADHD as measured by near-infrared spectroscopy (NIRS) using the Stroop color-word task. METHODS: Thirty children with ADHD participated in the present study. We used 24-channel NIRS (ETG-4000) to measure the relative concentrations of oxyhemoglobin in the frontal lobes of participants in the drug-naïve condition and those who had received MPH (n = 16) or ATX (n = 14) for 12 weeks. Measurements were conducted every 0.1 s during the Stroop color-word task. We used the ADHD RS-IV-J (Home Version) to evaluate ADHD symptoms. RESULTS: Treatment with either MPH or ATX significantly reduced ADHD symptoms, as measured by the ADHD RS-IV-J, and improved performance on the Stroop color-word task in terms of number of correct words. We found significantly higher levels of oxyhemoglobin changes in the prefrontal cortex of participants in the ATX condition compared with the values seen at baseline (pre-ATX). In contrast, we found no oxyhemoglobin changes between pre- and post-treatment with MPH. CONCLUSIONS: The present study suggests that MPH and ATX have differential effects on prefrontal hemodynamic activity in children with ADHD.

Pharmacotherapy for the treatment of aggression in pediatric and adolescent patients with autism spectrum disorder comorbid with attention-deficit hyperactivity disorder: A questionnaire survey of 571 psychiatrists.

AIM: Both attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are frequently accompanied by serious aggression that requires psychiatric treatment. However, little is known about the experiences psychiatrists have had using pharmacotherapy to treat aggression in patients who have both ASD and ADHD (ASD/ADHD). The purpose of this study was to examine the experiences of Japanese child and adolescent psychiatrists in prescribing medication for aggression in patients with ASD/ADHD. METHODS: A prospective questionnaire was mailed to 2001 psychiatrists affiliated with the Japanese Society for Child and Adolescent Psychiatry. Multivariate logistic regression analysis was used to identify factors predicting the outcome of pharmacotherapeutic treatment of aggression in pediatric and adolescent patients with ASD/ADHD. RESULTS: Of 2001 psychiatrists, 571 (28.5%) completed the full questionnaire (final sample). Of these, 488 (85.4%) prescribed psychotropic medication in treating pediatric and adolescent patients with ASD/ADHD, 299 (61.3%) of them doing so to treat aggression. Prescribers' duration of practice (odds ratio, 1.055; P = 0.038) and patient symptoms of residual impulsivity (odds ratio, 2.479; P = 0.039) increased the odds of prescribing psychotropic medications to treat aggression in these patients. The respondents reported a similar effect for patients with ADHD/ASD compared with those with ADHD only in treating aggression. CONCLUSION: Japanese psychiatrists tended to prescribe psychotropic medication for aggression in pediatric and adolescent patients with ASD/ADHD. Future studies examining aggression in pediatric and adolescent patients with ASD/ADHD should aim to accumulate evidence for the use of psychotropic medications, which could help clinicians make better decisions.

Frontal lobe function in elderly patients with Alzheimer's disease and caregiver burden.

AIM: Understanding of the relationship between caregiver burden and the degree of behavioural deficits in patients with Alzheimer's disease (AD) is relatively limited. Therefore, it is worthwhile to examine the correlations between the various relevant factors to improve the efficacy of care for patients with AD. The aim of this study was to investigate the specific contributions of frontal lobe dysfunction in AD patients to caregiver burden, while controlling for other predictor variables. METHODS: Participants included 30 pairs of caregivers and patients with AD. The Zarit Burden Interview and Frontal Assessment Battery were used to measure the caregiver burden and patients' frontal lobe function, respectively. To investigate the effects of frontal lobe dysfunction on caregiver burden, hierarchical regression equations with steps incorporating additional predictor variables were fitted. We also performed a correlation analysis between the individual subdomains of the Zarit Burden Interview and the predictor variables. RESULTS: Our study suggests that the degree of frontal lobe dysfunction in AD patients predicts their caregiver burden, when other factors of daily functional limitations and neuropsychiatric symptoms are controlled. Daily functional limitations and neuropsychiatric symptoms affected caregivers' psychosocial burden, whereas frontal lobe dysfunction affected caregivers' burden due to the increase in the dependency of the patients. CONCLUSION: Our findings indicate that to ameliorate the disabilities of patients and reduce caregiver burden, there is a need for interventions that focus on psychosocial burdens, as shown in previous studies, as well as on excessive dependency due to frontal lobe dysfunction.

Persistence of impulsivity in pediatric and adolescent patients with obsessive-compulsive disorder.

AIM: Increasing clinical evidence points to impulsivity as a symptom of obsessive-compulsive disorder (OCD). However, little is known about its persistence over time. METHODS: In this study, we evaluated the performance of 12 pediatric patients with OCD on the Stroop color-word task, which assesses impulsivity, and compared this with age- and sex-matched controls. In parallel, we measured changes in hemodynamic responses during the task, using near-infrared spectroscopy. As patients in the OCD group were naïve to treatment, we compared results before and after 3-year medication with serotonin reuptake inhibitors. RESULTS: We report that, compared with controls, the OCD group had significantly poorer performance and less activation in the prefrontal cortex during the Stroop color-word task. Surprisingly, while serotonin-reuptake-inhibitors treatment reduced OCD symptomology, it did not improve the diminished hemodynamic responses or task performance of these patients. CONCLUSION: Our findings suggest that a persistent deficit exists in the inhibitory control of pediatric patients with OCD; they also provide insight into the pathophysiology of OCD.

Associations between the mismatch-negativity component and symptom severity in children and adolescents with attention deficit/hyperactivity disorder.

AIM: Cognitive impairment is an important predictor of functional outcome in patients with attention deficit/hyperactivity disorder (ADHD). However, the neurophysiology of ADHD-related cognitive impairments remains unclear. Event-related potentials (ERPs) represent the noninvasive measurement of neural correlates of cognitive function. Mismatch negativity (MMN) is an ERP component that is presumed to index the preattentive monitoring of changes in the auditory environment. MATERIALS AND METHODS: Previous studies have shown altered MMN amplitude and latency in patients with ADHD. However, little is known about the relationship between MMN and ADHD-symptom severity. To address this, we measured the amplitude and latency of MMN in ERPs and assessed correlations with the clinical severity of ADHD, as measured by the ADHD Rating Scale IV - Japanese version. Participants were 51 treatment-naïve children and adolescents with ADHD (mean age 10.42±3.35 years) and 15 normally developing age- and sex-matched children (mean age 11.8±3.36 years). RESULTS: In the ADHD group, MMN amplitudes were attenuated at the central electrode and MMN latencies prolonged at the parietal electrode (Pz) relative to those in the control group. Furthermore, MMN amplitudes at Pz were negatively correlated with ADHD full-scale and hyperactivity-impulsivity and inattention subscale scores, and MMN latency at Pz was positively correlated with ADHD hyperactivity-impulsivity subscale scores. CONCLUSION: Our data suggest that MMN reflects the severity of ADHD symptoms in children and adolescents, and provides support for the use of ERPs in evaluating ADHD symptoms in patients.