Michio Hiratani

Increased urine phenylethylamine after methylphenidate treatment in children with ADHD

The urine levels of β‐phenylethylamine, 3‐methoxy‐4‐hydroxyphenyl glycol, homovanillic acid, and 5‐hydroxyindoleacetic acid were measured to clarify the neurochemical mechanism in attention deficit hyperactivity disorder. β‐Phenylethylamine levels were significantly lower in attention deficit hyperactivity disorder individuals (n = 37) than in controls (n = 21). The 22 children with attention deficit hyperactivity disorder were treated with methylphenidate, and they were further divided into methylphenidate responders (n = 18) and nonresponders (n = 4). β‐Phenylethylamine levels significantly increased after methylphenidate therapy in responders, whereas they did not increase in nonresponders.

Distinguishing between autism spectrum disorder and attention deficit hyperactivity disorder by using behavioral checklists, cognitive assessments, and neuropsychological test battery

Children with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share many common symptoms, including attention deficit, behavioral problems, and difficulties with social skills. The aim of this study was to distinguish between ASD and ADHD by identifying the characteristic features of both the disorders, by using multidimensional assessments, including screening behavioral checklists, cognitive assessments, and comprehensive neurological battery. After screening for comorbid disorders, we carefully selected age-, sex-, IQ-, and socio-economic status-matched children with typical development (TD). In the Wechsler Intelligence Scale for children, a lower score was observed for the ASD group than for the TD group in Picture concept, which is a subscale of perceptual reasoning. A lower score was shown by the ADHD group than by the TD group in the spatial working memory test in the Cambridge Neuropsychological Test Automated Battery (CANTAB(®)). Although ASD and ADHD have many similar symptoms, they can be differentiated by focusing on the behavioral and cognitive characteristics of executive function.

The prevalence of Rett syndrome in Fukui prefecture

The present study was performed to estimate the prevalence of Rett syndrome in Fukui prefecture by sending questionnaires to special classes (classes for handicapped children in schools for normal children) and schools for mentally/physically handicapped children, and observing children suspected of having this syndrome on the basis of answers to the questionnaire. The subjects were girls aged 6-14 years who were attending 11 special classes and 7 schools for handicapped children. The prevalence of Rett syndrome was estimated to be 0.22 per 10,000 girls aged 6-14 years in Fukui prefecture, as of April 1, 1993. The prevalence noted in this study was lower than those found in previous studies in Japan and Western countries.

Effects of methylphenidate in children with attention deficit hyperactivity disorder: a near-infrared spectroscopy study with CANTAB®

BackgroundA wide range of evidence supports the methylphenidate (MPH)-induced enhancement of prefrontal cortex (PFC) functioning and improvements in behavioral symptoms in patients with attention deficit hyperactivity disorder (ADHD). Although working memory (WM) has been hypothesized to be impaired in patients with ADHD, no pharmacological studies have examined visuospatial WM (VSWM) with near-infrared spectroscopy (NIRS).Study aimThe present study was designed to investigate the acute effects of MPH on neuropsychological performance and hemodynamic activation in children with ADHD during VSWM tasks.MethodsThe subject group included 10 boys and 1 girl previously diagnosed with ADHD. Two VSWM tasks of differing degrees of difficulty were conducted. This is the first study on the pharmacological effects of MPH in children with ADHD to evaluate hemodynamic responses in the PFC with simultaneous NIRS.ResultsNo significant differences were found in the scores for both spatial working memory (SWM) and score of spatial span (SSP) tasks between the MPH-off and MPH–on conditions. However, a significant MPH-effect on changes in oxy-hemoglobin levels in the PFC was found only in the SWM task.ConclusionThese findings suggest that PFC activation might be affected by MPH, depending on the degree of difficulty of the particular task. Although the MPH-induced change on behavior may or may not be obvious, NIRS measurements might be useful for assessing the psychological effects of MPH even when performance changes were not observed in the cognitive tasks.

Ventral striatum dysfunction in children and adolescents with reactive attachment disorder: functional MRI study

Background Child maltreatment is a major risk factor for psychopathology, including reactive attachment disorder (RAD). Aims To examine whether neural activity during reward processing was altered in children and adolescents with RAD. Method Sixteen children and adolescents with RAD and 20 typically developing (TD) individuals performed tasks with high and low monetary rewards while undergoing functional magnetic resonance imaging. Results Significantly reduced activity in the caudate and nucleus accumbens was observed during the high monetary reward condition in the RAD group compared with the TD group (P=0.015, family-wise error-corrected cluster level). Significant negative correlations between bilateral striatal activity and avoidant attachment were observed in the RAD and TD groups. Conclusions Striatal neural reward activity in the RAD group was markedly decreased. The present results suggest that dopaminergic dysfunction occurs in the striatum of children and adolescents with RAD, leading towards potential future risks for psychopathology. Declaration of interest None. Copyright and usage

Altered frontal pole development affects self-generated spatial working memory in ADHD.

BACKGROUND Spatial working memory (SWM) dysfunction is a feature of attention deficit hyperactivity disorder (ADHD). Previous studies suggested that behavioral performance in self-generated SWM improves through development in children with and without ADHD. Nevertheless, developmental changes in the neural underpinnings of self-generated SWM are unknown. METHOD Using near-infrared spectroscopy, hemodynamic activity in the prefrontal cortex (PFC) was measured in 30 children with ADHD (9.5 ± 1.6 years-old) and 35 TD children (9.0 ± 1.6 years-old) while they performed a self-generated SWM task. We then investigated correlations between age and behavioral performance, and between age and hemodynamic activity in the PFC for each group. RESULTS Both groups showed a negative correlation with age and number of errors [ADHD: r(28)=-0.37, p=0.040; TD: r(33)=-0.59, p<0.001], indicating that self-generated SWM improves through development. The TD group showed a positive correlation between age and oxygenated hemoglobin in the frontal pole [10ch: r(33)=0.41, p=0.013; 11ch; r(33)=0.44, p=0.008] and bilateral lateral PFC [4ch: r(33)=0.34, p=0.049; 13ch; r(33)=0.54, p=0.001], while no significant correlation was found in the ADHD group. Furthermore, regression slopes for the frontal pole significantly differed between the TD and ADHD groups [10ch: t(61)=2.35, p=0.021; 11ch: t(61)=2.05, p=0.044]. CONCLUSION Children with ADHD showed abnormalities in functional maturation of the frontal pole, which plays a role in manipulating and maintaining information associated with self-generated behavior.

Effectiveness and tolerability of switching to aripiprazole from risperidone in subjects with autism spectrum disorders: a prospective open-label study.

BackgroundSubjects with autism spectrum disorders (ASDs) often exhibit behavioral symptoms such as aggressiveness and irritability. The purpose of this study was to examine the efficacy and the tolerability of aripiprazole switched from risperidone in children and adolescents with ASD. MethodsThis prospective, 12-week, open-label study included 9 male subjects with ASD (age range, 9–22 years; mean ± SD age, 14.8 ± 4.0 years) followed up for 12 weeks after switching to aripiprazole from risperidone. The primary outcome measures were the Clinical Global Impression–Improvement scales and the irritability subscale of the Aberrant Behavior Checklist. ResultsThe mean ± SD maintenance dosages of risperidone and aripiprazole were 0.6 ± 0.4 mg/d and 4.8 ± 4.0 mg/d, respectively. The mean ± SD scores of the irritability subscale of the Aberrant Behavior Checklist before switching to aripiprazole (baseline) and 12 weeks after switching to aripiprazole (end point) were 14.8 ± 7.6 and 13.1 ± 8.0, respectively. The mean ± SD Clinical Global Impression–Improvement score, a comparison from baseline to end point, was 2.4 ± 0.7. Mild somnolence was observed only in 1 subject. No significant changes in vital signs, weight, electrocardiogram, or laboratory measures occurred during switching to aripiprazole. Serum prolactin levels decreased significantly from 17.3 ± 9.4 ng/mL (baseline) to 2.3 ± 1.7 ng/mL (end point). ConclusionsThe results show that aripiprazole might be generally well tolerated and might constitute an alternative treatment of subjects with ASD who experience poor efficacy or tolerability issues with risperidone treatment. Additional long-term controlled studies are needed to evaluate the efficacy and the safety of switching to aripiprazole from other antipsychotics in subjects with ASD.

Switching to aripiprazole in subjects with pervasive developmental disorders showing tolerability issues with risperidone.

BACKGROUND Subjects with Pervasive Developmental Disorders (PDD) often exhibit behavioral symptoms such as aggressiveness and irritability, which are targets of psychopharmacologic intervention. This retrospective study was designed to examine children and adolescents with PDD experiencing tolerability issues with risperidone treatment, and thereby assess the efficacy and tolerability of switching to aripiprazole. METHODS This naturalistic study included 23 subjects with PDD (16 males, 7 females, age range 9-24 years, mean age 15.1±3.9 years) diagnosed according to DSM-IV criteria and followed up for 14.9±8.4 weeks after switching to aripiprazole from risperidone. Outcome measures were the Clinical Global Impression-Severity (CGI-S) and CGI Improvement (CGI-I) scales. RESULTS The mean CGI-S scores of pre-aripiprazole treatment and post-aripiprazole treatment were, respectively 4.7±1.4 and 4.6±1.3. Mean maintenance dosages of risperidone and aripiprazole were, respectively, 0.7±0.5mg/day and 2.8±1.3mg/day. The mean CGI-I score, which shows the difference induced by switching from risperidone to aripiprazole, was 3.4±0.8 for the whole sample, suggesting that the efficacy of risperidone for treating behavioral problems of PDD was maintained by aripiprazole. Some improvement of safety/tolerability issues such as increased appetite, somnolence, hyperprolactinemia, and amenorrhea occurred after switching to aripiprazole. CONCLUSION Results show that switching to aripiprazole might be generally well tolerated and might constitute an alternative treatment for subjects with PDD who experience tolerability issues with risperidone treatment. Additional long-term controlled studies of PDD subjects should be undertaken to evaluate the efficacy and safety of switching to aripiprazole from other antipsychotics.

Quetiapine responsive catatonia in an autistic patient with comorbid bipolar disorder and idiopathic basal ganglia calcification.

BACKGROUND Bipolar disorder (BD) has been linked with the manifestation of catatonia in subjects with autism spectrum disorders (ASD). Idiopathic basal ganglia calcification (IBGC) is characterized by movement disorders and various neuropsychiatric disturbances including mood disorder. CASE We present a patient with ASD and IBGC who developed catatonia presenting with prominent dystonic feature caused by comorbid BD, which was treated effectively with quetiapine. CONCLUSION In addition to considering the possibility of neurodegenerative disease, careful psychiatric interventions are important to avoid overlooking treatable catatonia associated with BD in cases of ASD presenting with both prominent dystonic features and apparent fluctuation of the mood state.

Spatial Short-Term Memory in Children With Nonverbal Learning Disabilities: Impairment in Encoding Spatial Configuration

ABSTRACT The authors investigated whether impaired spatial short-term memory exhibited by children with nonverbal learning disabilities is due to a problem in the encoding process. Children with or without nonverbal learning disabilities performed a simple spatial test that required them to remember 3, 5, or 7 spatial items presented simultaneously in random positions (i.e., spatial configuration) and to decide if a target item was changed or all items including the target were in the same position. The results showed that, even when the spatial positions in the encoding and probe phases were similar, the mean proportion correct of children with nonverbal learning disabilities was 0.58 while that of children without nonverbal learning disabilities was 0.84. The authors argue with the results that children with nonverbal learning disabilities have difficulty encoding relational information between spatial items, and that this difficulty is responsible for their impaired spatial short-term memory.