Yoko Nakanishi

Event-related potentials in drug-naïve pediatric patients with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is one of the most common mental health disorders, characterized by obsessive thoughts and/or compulsive behaviors, which may involve specific disorders in cognition and/or information processing. Event-related potentials (ERPs) are commonly used as physiological measures of cognitive function as they are easily measured and noninvasive. In the present study, 20 drug-naïve pediatric patients with OCD were compared with 20 healthy control participants who were age- and sex-matched to perform the ERP. Based on the guidelines for evoked potential measurement, the P300 and mismatch negativity (MMN) were obtained by auditory odd-ball tasks. We found that the amplitudes of the P300 components in the Fz, Cz, Pz, C3, and C4 regions were significantly smaller in the OCD group compared with the control group. There were no between-group differences in P300 latency, MMN amplitude, or MMN latency. Moreover, we found significant correlations between scores on the Childrens Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) and P300 amplitudes at Cz, Pz, and C3. The present study is the first to report smaller P300s and the associations between P300 abnormalities and CY-BOCS scores.

Event-related potentials reflect the efficacy of pharmaceutical treatments in children and adolescents with attention deficit/hyperactivity disorder.

Few objective biological measures of pharmacological treatment efficacy exist for attention deficit/hyperactivity disorder (ADHD). Although we have previously demonstrated that event-related potentials (ERPs) reflect the effects of osmotic-release methylphenidate in treatment of naïve pediatric patients with ADHD, whether this is true for the therapeutic effects of atomoxetine (ATX) is unknown. Here, we used the Japanese version of the ADHD rating-scale IV to evaluate 14 patients with ADHD, and compared their ERP data with 14 age- and sex-matched controls. We measured P300 and mismatch negativity (MMN) components during an auditory oddball task before treatment (treatment naïve) and after 2 months of ATX treatment. Compared with controls, P300 components at baseline were attenuated and prolonged in the ADHD group at Fz (fronto-central), Cz (centro-parietal), Pz (parietal regions), C3 and C4 electrodes. ATX treatment reduced ADHD symptomology, and after 2 months of treatment, P300 latencies at Fz, Cz, Pz, C3, and C4 electrodes were significantly shorter than those at baseline. Moreover, MMN amplitudes at Cz and C3 electrodes were significantly greater than those at baseline. Thus, ERPs may be useful for evaluating the pharmacological effects of ATX in pediatric and adolescent patients with ADHD.

Early onset of cardiomyopathy and intellectual disability in a girl with Danon disease associated with a de novo novel mutation of the LAMP2 gene

Danon disease, primary lysosome‐associated membrane protein‐2 (LAMP‐2) deficiency, is characterized clinically by cardiomyopathy, myopathy and intellectual disability in boys. Because Danon disease is inherited in an X‐linked dominant fashion, males are more severely affected than females, who usually have only cardiomyopathy without myopathy or intellectual disability; moreover, the onset of symptoms in females is usually in adulthood. We describe a girl with Danon disease who presented with hypertrophic cardiomyopathy and Wolff‐Parkinson‐White (WPW) syndrome at 12 years of age. Subsequently, she showed signs of mild learning disability and intellectual disability on psychological examinations. She had a de novo novel mutation in the LAMP‐2 gene and harbored an identical c.749C > A (p.Ser250X) variant, resulting in a stop codon in exon 6. She showed decreased, but not completely absent LAMP‐2 expression on immunohistochemical and Western blot analyses of a skeletal muscle biopsy specimen, which has been suggested to be caused by a 50% reduction in LAMP‐2 expression (LAMP‐2 haploinsufficiency) in female patients with Danon disease caused by a heterozygous null mutation. To our knowledge, our patient is one of the youngest female patients to have been given a diagnosis of Danon disease. In addition, this is the first documented case in a girl that was clearly associated with intellectual disability, which is very rare in females with Danon disease. Our findings suggest that studies of female patients with Danon disease can extend our understanding of the clinical features of this rare disease.

Comparison of pervasive developmental disorder and schizophrenia by the Japanese version of the National Adult Reading Test

Abstract Objective. In adults, it is sometimes difficult to discriminate between pervasive developmental disorder (PDD) and schizophrenia (SCH) when positive symptoms are not outstanding. We examined whether the Japanese version of the National Adult Reading Test (JART), is a valid scale for evaluating pre-morbid intelligence quotient (IQ) in patients with SCH, and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) are useful for helping to discriminate between PDD and SCH. Methods. Sixteen patients with adult PDD and 16 age-, education- and sex-matched patients with SCH participated in the present study. In addition, two groups were matched for JART and GAF scores. All subjects were scored on the JART and WAIS-R after informed consent on the aim of this study. Examiners who were blind to the diagnoses measured JART and WAIS-R. Results. Significant diagnosis-by-IQ examination interactions were found (F[1,30] = 10.049, P = 0.003). Furthermore, WAIS-R scores of the PDD group were higher than those of the SCH group (P = 0.002) considering two groups were matched for JART. Conclusions. The comparison of IQ in the PDD group and in the SCH group by JART and WAIS-R might be an easy and useful method for helping to discriminate between PDD and SCH.

Reduced Prefrontal Cortex Hemodynamic Response in Adults with Methamphetamine Induced Psychosis: Relevance for Impulsivity.

Patients with methamphetamine abuse/dependence often exhibit high levels of impulsivity, which may be associated with the structural abnormalities and functional hypoactivities observed in the frontal cortex of these subjects. Although near-infrared spectroscopy (NIRS) is a simple and non-invasive method for characterizing the clinical features of various psychiatric illnesses, few studies have used NIRS to directly investigate the association between prefrontal cortical activity and inhibitory control in patients with methamphetamine-induced psychosis (MAP). Using a 24-channel NIRS system, we compared hemodynamic responses during the Stroop color-word task in 14 patients with MAP and 21 healthy controls matched for age, sex and premorbid IQ. In addition, we used the Barrett Impulsivity Scale-11 (BIS-11) to assess impulsivity between subject groups. The MAP group exhibited significantly less activation in the anterior and frontopolar prefrontal cortex accompanied by lower Stroop color-word task performance, compared with controls. Moreover, BIS-11 scores were significantly higher in the MAP group, and were negatively correlated with the hemodynamic responses in prefrontal cortex. Our data suggest that reduced hemodynamic responses in the prefrontal cortex might reflect higher levels of impulsivity in patients with MAP, providing new insights into disrupted inhibitory control observed in MAP.

A longitudinal event-related potential study of selective serotonin reuptake inhibitor therapy in treatment-naïve pediatric obsessive compulsive disorder patients

Obsessive-compulsive disorder (OCD) is characterized by obsessive thoughts and/or compulsive behaviors, involving specific cognition and/or information processing disorders. Event-related potentials (ERPs) are commonly used as physiological measures of cognitive function. In conscious patients, ERPs are easily and non-invasively measured. Previous ERP studies have revealed differences between OCD patients and control subjects. Whether ERPs reflect the pharmacological effects of OCD treatment, particularly in treatment-naïve pediatric patients, remains unknown. We used the Childs Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) to evaluate the symptomatic severity of 12 treatment-naïve pediatric OCD patients. Comparisons were made with 12 age-, sex-, and intelligence-matched controls. The P300 and mismatch negativity (MMN) components were measured during an auditory odd-ball task at baseline in both groups and after the 3-year serotonin reuptake inhibitor (SSRI) treatment in OCD patients. Compared with controls, P300 amplitudes were smaller n the OCD group at Fz, Cz, Pz, C3, and C4. After SSRI treatment, P300 amplitudes increased partly at Fz and C4 in association with symptomatic improvements. We found a significant positive correlation between P300 amplitude in C4 and CY-BOCS scores. Our findings confirm the utility of SSRIs in pediatric OCD, and suggest the utility of ERPs for evaluating pharmacological effects in treatment-naïve pediatric OCD patients.

Event-Related Potentials Correlate with the Severity of Child and Adolescent Patients with Attention Deficit/Hyperactivity Disorder

Background: Attention deficit/hyperactivity disorder (ADHD) symptoms can continue through adolescence and adulthood, including difficulty in staying focused, paying attention, and controlling behavior, as well as hyperactivity. While children and adolescents with ADHD have functional impairments at multiple dimensions, there are no objective biological indicators to assess the severity of ADHD. Event-related potentials (ERPs) are widely used as a noninvasive method for evaluating sensory and cognitive processes involved in attention tasks. Previous studies have shown that P300 amplitude or latency, a main component in ERPs, is altered in patients with ADHD. However, little is known about the relationship between P300 and the severity of ADHD symptoms. Method: We sought to measure both P300 amplitude and latency in ERPs during auditory oddball tasks in 44 patients with ADHD (mean age ± SD 10.28 ± 3.43 years) and 15 age- and gender-matched normally developing children (11.40 ± 3.02 years). In ADHD patients, we also assessed symptom severity using the ADHD rating scale-IV-Japanese version. Result: In ADHD groups, P300 amplitude and latency were attenuated and prolonged compared to controls at the frontocentral, centroparietal, and parietal positions. Furthermore, levels of P300 latency at these positions are positively correlated with the inattention subscale scores measured by the ADHD rating scale-IV-Japanese version. Conclusions: The present study revealed that the degree of P300 latency might reflect the severity of ADHD symptoms with children and adolescents, suggesting that ERPs are a useful technique to evaluate the severity of ADHD symptoms.

Increased prefrontal hemodynamic change after atomoxetine administration in pediatric attention-deficit/hyperactivity disorder as measured by near-infrared spectroscopy.

Atomoxetine, approved in Japan for the treatment of pediatric attention‐deficit/hyperactivity disorder (ADHD) in April 2009, is a nonstimulant that is thought to act presynaptically via the inhibition of norepinephrine reuptake. Near‐infrared spectroscopy is a non‐invasive optical tool that can be used to study oxygenation and hemodynamic changes in the cerebral cortex. The present study examined the effects of a clinical dose of atomoxetine on changes in prefrontal hemodynamic activity in children with ADHD, as measured by near‐infrared spectroscopy using the Stroop Color–Word Task.

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

Increasing clinical evidence points to impulsivity as a symptom of obsessive–compulsive disorder (OCD). However, little is known about its persistence over time.

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.