九州大学 研究者情報
論文一覧
中尾 智博(なかお ともひろ) データ更新日:2020.06.24

教授 /  医学研究院 臨床医学部門


原著論文
1. Keisuke Ikari, Tomohiro Nakao, Kiyotaka Nemoto, Kayo Okada, Keitaro Murayama, Shinichi Honda, Masumi Kuwano, Satoshi Yamada, Hirofumi Tomiyama, Mayumi Tomita, Osamu Togao, Akio Hiwatashi, Shigenobu Kanba, Corrigendum to “Morphologic and clinical differences between early- and late-onset obsessive-compulsive disorder
Voxel-based morphometric study” (Journal of Obsessive-Compulsive and Related Disorders (2017) (35–41)(S2211364916301580)(10.1016/j.jocrd.2017.02.005)), Journal of Obsessive-Compulsive and Related Disorders, 10.1016/j.jocrd.2017.11.005, 16, 112-113, 2018.01, [URL], We regret that Table 1 and Fig. 2 need correction. As for Table 1, we found a few critical errors. The patients' age is not 18–64 years old, correctly 17–64 years old. The patients' age of onset is not 4–38 years old, correctly 6–54 years old. The patients' duration of illness is not 0.6–42 years, correctly 0.6–51 years. As for Fig.2, several readers pointed us that it was difficult to see. So we would like to make corrections. We coloured the lines to make it distinguishable, and enlarged letters to make it more visible. We explained in footnote which line colour corresponds to which group. We attached the modified files. We are sorry to trouble you, but we hope that you will correct and replace them by the following files. We would like to apologise for any inconvenience caused..
2. Ashley E. Nordsletten, Lorena Fernández de la Cruz, Elena Aluco, Pino Alonso, Clara López-Solà, José M. Menchón, Tomohiro Nakao, Masumi Kuwano, Satoshi Yamada, Leonardo F. Fontenelle, André Luís Campos-Lima, David Mataix-Cols, A transcultural study of hoarding disorder
Insights from the United Kingdom, Spain, Japan, and Brazil, Transcultural Psychiatry, 10.1177/1363461518759203, 55, 2, 261-285, 2018.04, [URL], Though problematic hoarding is believed to be a universal human behavior, investigations of clinically-defined hoarding disorder (HD) have been confined almost exclusively to Western countries. The current investigation sought to describe and directly compare the features of individuals meeting diagnostic criteria for HD across four distinct cultural settings. Participants were 82 individuals meeting DSM-5 diagnostic criteria for HD, recruited and assessed by trained clinicians at one of four project sites: London, Barcelona, Fukuoka, and Rio de Janeiro. A series of semi-structured interviews and self-report scales were administered, including assessments of socio-demographic characteristics, psychiatric comorbidity, and severity of hoarding and related features. Results indicate that the severity and core features of HD, as well as the cognitions and behaviors commonly associated with this condition, are largely stable across cultures. However, some differences in patient demographics—in particular age, marital status, and clinical expression—as well as comorbid psychiatric features also emerged. These findings confirm that HD, as defined in DSM-5, exists and presents with similar phenomenology across the studied cultures. Future, more fine-grained, research will be needed to study the features of the disorder in additional cultures (e.g., non-industrialized nations) and to evaluate the impact of these cultural aspects on the design of interventions for the disorder..
3. Premika S.W. Boedhoe, Lianne Schmaal, Yoshinari Abe, Pino Alonso, Stephanie H. Ameis, Alan Anticevic, Paul D. Arnold, Marcelo C. Batistuzzo, Francesco Benedetti, Jan C. Beucke, Irene Bollettini, Anushree Bose, Silvia Brem, Anna Calvo, Rosa Calvo, Yuqi Cheng, Kang Ik K. Cho, Valentina Ciullo, Sara Dallaspezia, Damiaan Denys, Jamie D. Feusner, Kate D. Fitzgerald, Jean Paul Fouche, Egill A. Fridgeirsson, Patricia Gruner, Gregory L. Hanna, Derrek P. Hibar, Marcelo Q. Hoexter, Hao Hu, Chaim Huyser, Neda Jahanshad, Anthony James, Norbert Kathmann, Christian Kaufmann, Kathrin Koch, Jun Soo Kwon, Luisa Lazaro, Christine Lochner, Rachel Marsh, Ignacio Martínez-Zalacaín, David Mataix-Cols, José M. Menchón, Luciano Minuzzi, Astrid Morer, Takashi Nakamae, Tomohiro Nakao, Janardhanan C. Narayanaswamy, Seiji Nishida, Erika Nurmi, Joseph O'Neill, John Piacentini, Fabrizio Piras, Federica Piras, Y. C.Janardhan Reddy, Tim J. Reess, Yuki Sakai, Joao R. Sato, H. Blair Simpson, Noam Soreni, Carles Soriano-Mas, Gianfranco Spalletta, Michael C. Stevens, Philip R. Szeszko, David F. Tolin, Guido A. Van Wingen, Ganesan Venkatasubramanian, Susanne Walitza, Zhen Wang, Je Yeon Yun, Paul M. Thompson, Dan J. Stein, Odile A. Van Den Heuvel, Cortical abnormalities associated with pediatric and adult obsessive-compulsive disorder
Findings from the enigma obsessive-compulsive disorder working group, American Journal of Psychiatry, 10.1176/appi.ajp.2017.17050485, 175, 5, 453-462, 2018.05, [URL], Objective: Brain imaging studies of structural abnormalities in OCD have yielded inconsistent results, partly because of limited statistical power, clinical heterogeneity, and methodological differences. The authors conducted meta- and mega-analyses comprising the largest study of cortical morphometry in OCD ever undertaken. Method: T1-weighted MRI scans of 1,905 OCD patients and 1,760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer to assess cortical thickness and surface area. Effect sizes for differences between patients and controls, and associations with clinical characteristics, were calculated using linear regression models controlling for age, sex, site, and intracranial volume. Results: In adult OCD patients versus controls, we found a significantly lower surface area for the transverse temporal cortexand a thinner inferiorparietalcortex.Medicated adult OCD patients also showed thinner cortices throughout the brain. In pediatric OCD patients compared with controls, we found significantly thinner inferior and superior parietal cortices, but none of the regions analyzed showedsignificant differences in surface area. However, medicated pediatric OCD patients had lower surface area in frontal regions. Cohen's d effect sizes varied from 20.10 to 20.33. Conclusions: The parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication..
4. Satoshi Yamada, Tomohiro Nakao, Keisuke Ikari, Masumi Kuwano, Keitaro Murayama, Hirofumi Tomiyama, Suguru Hasuzawa, Osamu Togao, Akio Hiwatashi, Shigenobu Kanba, A unique increase in prefrontal gray matter volume in hoarding disorder compared to obsessive-compulsive disorder, PloS one, 10.1371/journal.pone.0200814, 13, 7, 2018.07, [URL], Background Hoarding disorder (HD) is a disease concept newly presented in DSM-5. As far as we know, no studies have examined the structural changes relevant to hoarding by applying the diagnostic criteria of HD in DSM-5. In the present study, we aimed to find abnormalities in gray matter (GM) structures of patients with HD. Methods Seventeen patients who met the DSM-5 criteria for HD, 17 obsessive-compulsive disorder (OCD) patients, and 17 healthy controls (HCs) participated in this study. All participants underwent MRI scanning of the brain by a 3.0-Tesla MRI scanner. In a voxel-based morphometric procedure, preprocessed GM structural images were used to compare the three groups. Thereafter we investigated the correlation between the clinical data (age of onset, symptomatic severity) and GM volume. Results The HD group showed a significantly increased GM volume compared to the OCD and healthy control groups (p<0.05) in both Brodmann area (BA)10 and BA11. There was no significant difference between OCD and healthy control groups. No significant correlation between the clinical data including age of onset, symptom severity score, and GM volume was observed in HD and OCD groups. Conclusions The results might help to explain the inconsistency of previous studies. As with OCD, HD is considered to have cognitive dysfunction as its basis. This result is convincing after considering the clinical features of HD and suggested that structural abnormalities in the prefrontal regions might relate to the pathophysiology of HD..
5. Hirofumi Tomiyama, Tomohiro Nakao, Keitaro Murayama, Kiyotaka Nemoto, Keisuke Ikari, Satoshi Yamada, Masumi Kuwano, Suguru Hasuzawa, Osamu Togao, Akio Hiwatashi, Shigenobu Kanba, Dysfunction between dorsal caudate and salience network associated with impaired cognitive flexibility in obsessive-compulsive disorder
A resting-state fMRI study, NeuroImage: Clinical, 10.1016/j.nicl.2019.102004, 24, 2019, [URL], Background: Impaired cognitive flexibility has been implicated in the genetic basis of obsessive-compulsive disorder (OCD). Recent endophenotype studies of OCD showed neural inefficiency in the cognitive control network and interference by the limbic network of the cognitive control network. Exploring the relationship between the functional brain network and impaired cognitive flexibility may provide novel information about the neurobiological basis of OCD. Methods: We obtained resting-state functional magnetic resonance imaging (rsfMRI) scans and measured the cognitive flexibility of 37 medication-free OCD patients and 40 healthy control (HC) participants using the Wisconsin Card Sorting Test (WCST). We explored the difference between OCD and HC groups in the functional brain network related to impaired cognitive flexibility from the amygdala and dorsal striatal regions of interest (ROIs) by using a seed-based approach. Results: Significant differences between the OCD and HC groups were identified in the resting state functional network from the dorsal caudate. Increased functional connectivity from the dorsal caudate to the dorsal anterior cingulate cortex (dACC) and anterior insula (AI) was associated with poorer cognitive flexibility in the OCD group, but better cognitive flexibility in the HC group. Conclusions: These results provide evidence that the impaired cognitive flexibility of OCD may be associated with dysfunctions of the brain network from the dorsal caudate (DC) to important nodes of the salience network. Our results extend the neuropsychological model of OCD by showing intrinsically different associations between OCD and HC in functional network and cognitive flexibility..
6. , Xiang Zhen Kong, Premika S.W. Boedhoe, Yoshinari Abe, Pino Alonso, Stephanie H. Ameis, Paul D. Arnold, Francesca Assogna, Justin T. Baker, Marcelo C. Batistuzzo, Francesco Benedetti, Jan C. Beucke, Irene Bollettini, Anushree Bose, Silvia Brem, Brian P. Brennan, Jan Buitelaar, Rosa Calvo, Yuqi Cheng, Kang Ik K. Cho, Sara Dallaspezia, Damiaan Denys, Benjamin A. Ely, Jamie Feusner, Kate D. Fitzgerald, Jean Paul Fouche, Egill A. Fridgeirsson, David C. Glahn, Patricia Gruner, Deniz A. Gürsel, Tobias U. Hauser, Yoshiyuki Hirano, Marcelo Q. Hoexter, Hao Hu, Chaim Huyser, Anthony James, Fern Jaspers-Fayer, Norbert Kathmann, Christian Kaufmann, Kathrin Koch, Masaru Kuno, Gerd Kvale, Jun Soo Kwon, Luisa Lazaro, Yanni Liu, Christine Lochner, Paulo Marques, Rachel Marsh, Ignacio Martínez-Zalacaín, David Mataix-Cols, Sarah E. Medland, Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder
Findings From the ENIGMA Consortium, Biological Psychiatry, 10.1016/j.biopsych.2019.04.022, 2019.01, [URL], Background: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD. Methods: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status. Results: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = −0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets. Conclusions: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD..
7. Kosuke Kajitani, Rikako Tsuchimoto, Jun Nagano, Tomohiro Nakao, Relevance of hoarding behavior and the traits of developmental disorders among university students
A self-reported assessment study, BioPsychoSocial Medicine, 10.1186/s13030-019-0156-1, 13, 1, 2019.06, [URL], Background: Previous studies have shown that hoarding behavior usually starts at a subclinical level in early adolescence and gradually worsens; however, a limited number of studies have examined the prevalence of hoarding behavior and its association with developmental disorders in young adults. The aims of this study were to estimate the prevalence of hoarding behavior and to identify correlations between hoarding behavior and developmental disorder traits in university students. Methods: The study participants included 801 university students (616 men, 185 women) who completed questionnaires (ASRS: Adult ADHD Self-Report Scale version 1.1, AQ16: Autism-Spectrum Quotient with 16 items, and CIR: Clutter Image Rating). Results: Among 801 participants, 27 (3.4%) exceeded the CIR cut-off score. Moreover, the participants with hoarding behavior had a significantly higher percentage of ADHD traits compared to participants without hoarding behavior (HB(+) vs HB(-), 40.7% vs 21.7%). In addition, 7.4% of HB(+) participants had autism spectrum disorder (ASD) traits, compared to 4.1% of HB(-) participants. A correlation analysis revealed that the CIR composite score had a stronger correlation with the ASRS inattentive score than with the hyperactivity/impulsivity score (CIR composite vs ASRS IA, r = 0.283; CIR composite vs ASRS H/I, r = 0.147). Conclusions: The results showed a high prevalence of ADHD traits in the university students with hoarding behavior. Moreover, we found that the hoarding behavior was more strongly correlated with inattentive symptoms rather than with hyperactivity/impulsivity symptoms. Our results support the concept of a common pathophysiology behind hoarding behavior and ADHD in young adults..
8. Tomohiro Nakao, Shigenobu Kanba, Pathophysiology and treatment of hoarding disorder, Psychiatry and clinical neurosciences, 10.1111/pcn.12853, 73, 7, 370-375, 2019.07, [URL], Hoarding disorder (HD) is a newly listed disease in the new category of Obsessive–Compulsive and Related Disorders in the DSM-5. Patients with HD find it difficult to discard possessions regardless of their actual value and to organize those things. As a result, the possessions overflow the living space and hinder living functions. Though the hoarding symptom had been regarded as a subtype of obsessive–compulsive disorder (OCD) to date, recent studies have revealed many differences in clinical characteristics, including onset, course, degree of insight, and treatment responses, between hoarding and other subtypes. Moreover, several neuroimaging studies have found specific changes of brain structure and function in OCD patients with hoarding symptoms compared to patients with non-hoarding OCD. Meanwhile, strategies for treatment of HD have not been standardized. At present, psychological treatment using cognitive behavioral therapy techniques has a certain effect. In this review, we outline the pathophysiology and treatment of HD..
9. , Je Yeon Yun, Premika S.W. Boedhoe, Chris Vriend, Neda Jahanshad, Yoshinari Abe, Stephanie H. Ameis, Alan Anticevic, Paul D. Arnold, Marcelo C. Batistuzzo, Francesco Benedetti, Jan C. Beucke, Irene Bollettini, Anushree Bose, Silvia Brem, Anna Calvo, Yuqi Cheng, Kang Ik K. Cho, Valentina Ciullo, Sara Dallaspezia, Damiaan Denys, Jamie D. Feusner, Jean Paul Fouche, Mònica Giménez, Patricia Gruner, Derrek P. Hibar, Marcelo Q. Hoexter, Hao Hu, Chaim Huyser, Keisuke Ikari, Norbert Kathmann, Christian Kaufmann, Kathrin Koch, Luisa Lazaro, Christine Lochner, Paulo Marques, Rachel Marsh, Ignacio Martínez-Zalacaín, David Mataix-Cols, José M. Menchón, Luciano Minuzzi, Pedro Morgado, Pedro Moreira, Takashi Nakamae, Tomohiro Nakao, Janardhanan C. Narayanaswamy, Erika L. Nurmi, Joseph O’Neill, John Piacentini, Fabrizio Piras, Federica Piras, Brain structural covariance networks in obsessive-compulsive disorder
A graph analysis from the ENIGMA consortium, Brain, 10.1093/brain/awaa001, 143, 2, 684-700, 2020.01, [URL], Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10–0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P 5 0.0001), lower modularity (P 5 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions..
10. Masumi Kuwano, Tomohiro Nakao, Koji Yonemoto, Satoshi Yamada, Keitaro Murayama, Kayo Okada, Shinichi Honda, Keisuke Ikari, Hirofumi Tomiyama, Suguru Hasuzawa, Shigenobu Kanba, Clinical characteristics of hoarding disorder in Japanese patients, Heliyon, 10.1016/j.heliyon.2020.e03527, 6, 3, 2020.03, [URL], Previous studies have reported clinical characteristics of hoarding disorder (HD), such as early onset, a chronic course, familiality, high unmarried rate, and high rates of comorbidities. However, clinical research targeting Japanese HD patients has been very limited. As a result, there is a low recognition of HD in Japan, leading to insufficient evaluation and treatment of Japanese HD patients. The aim of the current study was to delineate the clinical characteristics of Japanese HD patients. Thirty HD patients, 20 obsessive-compulsive disorder (OCD) patients, and 21 normal controls (NC) were targeted in this study. The HD group had a tendency toward higher familiality, earlier onset, and longer disease duration compared to the OCD group. In addition, the HD group showed a significantly higher unmarried rate than the NC group. The top two comorbidities in the HD group were major depressive disorder (56.7%) and attention-deficit/hyperactivity disorder (26.7%). The HD group had significantly higher scores on hoarding rating scales and lower scores on the Global Assessment of Functioning Scale than the other two groups. The current study showed a clinical trend in Japanese HD patients similar to previous studies in various countries, suggesting that HD may be a universal disease with consistent clinical symptoms..
11. Tomohiro Nakao, [Treatment-refractory OCD and its biological pathophysiology]., Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica, 115, 9, 981-989, 2013.01, Recently, ample evidence has suggested that selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy are highly effective treatments for OCD. There are, however, certain patients who are refractory to almost all types of therapeutic intervention. In recent studies, atypical antipsychotic augmentation of SSRIs and deep brain stimulation have been suggested to be effective for these refractory-type patients. Dysfunction of neuro-circuits throughout the frontal cortex and associated subcortical structures is considered to be due to both serotonergic and dopaminergic nerve system impairment. A large number of previous neuroimaging studies identified abnormally high metabolic activities throughout the frontal cortex as well as subcortical and limbic structures. These over-activities are suggested to be biological markers of the treatment response. In addition, structural and nerve connective dysfunction of these regions may be associated with a severe, treatment-resistant, and treatment-refractory status. A treatment-refractory state may be attributable to the clinical subtypes of OCD. Associations between the symptom subtype and brain activity reveal the heterogeneity of OCD. Several correlative analyses have shown distinct neural correlations associated with specific OCD symptom dimensions such as aggression/checking, contamination/cleaning, and hoarding. Overlapping of these neural disturbances will cause treatment-refractory OCD. Another reason for a treatment-refractory state may be comorbid disorders such as major depression and tic disorders. Comorbid depression will aggravate metabolic impairments in the hippocampus and thalamus and cause more severe disturbance of neuro-circuits in OCD. Obsessive-compulsive symptom with Tourette syndrome or pervasive developmental disorders will become refractory because of fixation caused by developmental factors and a perceptual element called "just right feeling". There should be a close relationship between neuro-circuit disturbance and a treatment-refractory state. The pathophysiology becomes more complicated due to the symptom subtype and comorbidity. Further investigations are needed to develop effective treatment strategies based on biological evidence..
12. Keitaro Murayama, Tomohiro Nakao, Shigenobu Kanba, [Neuro-pathophysiological hypothesis of obsessive compulsive disorder based on the findings from neuroimaging studies]., Unknown Journal, 104, 5, 81-88, 2013.01.
13. Heledd Hart, Joaquim Radua, Tomohiro Nakao, David Mataix-Cols, Katya Rubia, Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder
Exploring task-specific, stimulant medication, and age effects, JAMA Psychiatry, 10.1001/jamapsychiatry.2013.277, 70, 2, 185-198, 2013.01, [URL], Context: Functional magnetic resonance imaging studies in attention-deficit/hyperactivity disorder (ADHD) revealed fronto-striato-parietal dysfunctions during tasks of inhibition and attention. However, it is unclear whether task-dissociated dysfunctions exist and to what extent they may be influenced by age and by long-term stimulant medication use. Objective: To conduct a meta-analysis of functional magnetic resonance imaging studies in ADHD during inhibition and attention tasks, exploring age and long-term stimulant medication use effects. Data Sources: Pub-Med, Science-Direct, Web of Knowledge, Google Scholar, and Scopus databases were searched up to May 2012 for meta-analyses. Meta-regression methods explored age and long-term stimulant medication use effects. Study Selection: Twenty-one data sets were included for inhibition (287 patients with ADHD and 320 control subjects), and 13 data sets were included for attention (171 patients with ADHD and 178 control subjects). Data Extraction: Peak coordinates of clusters of significant group differences, as well as demographic, clinical, and methodological variables, were extracted for each study or were obtained from the authors. Data Synthesis: Patients with ADHD relative to controls showed reduced activation for inhibition in the right inferior frontal cortex, supplementary motor area, and anterior cingulate cortex, as well as striato-thalamic areas, and showed reduced activation for attention in the right dorsolateral prefrontal cortex, posterior basal ganglia, and thalamic and parietal regions. Furthermore, the meta-regression analysis for the attention domain showed that long-term stimulant medication use was associated with more similar right caudate activation relative to controls. Age effects could be analyzed only for the inhibition meta-analysis, showing that the supplementary motor area and basal ganglia were underactivated solely in children with ADHD relative to controls, while the inferior frontal cortex and thalamus were underactivated solely in adults with ADHD relative to controls. Conclusions: Patients with ADHD have consistent functional abnormalities in 2 distinct domain-dissociated right hemispheric fronto-basal ganglia networks, including the inferior frontal cortex, supplementary motor area, and anterior cingulate cortex for inhibition and dorsolateral prefrontal cortex, parietal, and cerebellar areas for attention. Furthermore, preliminary evidence suggests that long-term stimulant medication use may be associated with more normal activation in right caudate during the attention domain..
14. Keitaro Murayama, Tomohiro Nakao, Hirokuni Sanematsu, Kayo Okada, Takashi Yoshiura, Mayumi Tomita, Yusuke Masuda, Kayoko Isomura, Akiko Nakagawa, Shigenobu Kanba, Differential neural network of checking versus washing symptoms in obsessive-compulsive disorder, Progress in Neuro-Psychopharmacology and Biological Psychiatry, 10.1016/j.pnpbp.2012.09.002, 40, 1, 160-166, 2013.01, [URL], Obsessive-compulsive disorder (OCD) is clinically heterogeneous. The aim of this study was to investigate differential neural responses to a symptom provocation task in drug-free patients who have predominantly aggression/checking symptoms (Checkers) and patients with contamination/washing symptoms (Washers). We compared the Checkers (n = 10) and the Washers (n = 12) separately to normal controls during the symptom provocation tasks using fMRI (functional magnetic resonance imaging). Moreover, we performed correlative analysis in each OCD group between brain activation and symptom severity. The Checkers showed hypoactivation in the left caudate and left anterior cingulate cortex (ACC) compared to the normal controls and a positive correlation between activated brain areas and symptom severity in the left ACC. The Washers showed hyperactivation in several bilateral cortico-cerebellar regions and a positive correlation between symptom severity and the bilateral fronto-temporal gyrus. We suggest that the caudate and ACC are associated with checking rituals and that large cortical brain regions are related to washing rituals..
15. Tomohiro Nakao, Kayo Okada, Shigenobu Kanba, Neurobiological model of obsessive-compulsive disorder
Evidence from recent neuropsychological and neuroimaging findings, Psychiatry and Clinical Neurosciences, 10.1111/pcn.12195, 68, 8, 587-605, 2014.01, [URL], Obsessive-compulsive disorder (OCD) was previously considered refractory to most types of therapeutic intervention. There is now, however, ample evidence that selective serotonin reuptake inhibitors and behavior therapy are highly effective methods for treatment of OCD. Furthermore, recent neurobiological studies of OCD have found a close correlation between clinical symptoms, cognitive function, and brain function. A large number of previous neuroimaging studies using positron emission tomography, single-photon emission computed tomography or functional magnetic resonance imaging (fMRI) have identified abnormally high activities throughout the frontal cortex and subcortical structures in patients with OCD. Most studies reported excessive activation of these areas during symptom provocation. Furthermore, these hyperactivities were decreased after successful treatment using either selective serotonin reuptake inhibitors or behavioral therapy. Based on these findings, an orbitofronto-striatal model has been postulated as an abnormal neural circuit that mediates symptomatic expression of OCD. On the other hand, previous neuropsychological studies of OCD have reported cognitive dysfunction in executive function, attention, nonverbal memory, and visuospatial skills. Moreover, recent fMRI studies have revealed a correlation between neuropsychological dysfunction and clinical symptoms in OCD by using neuropsychological tasks during fMRI. The evidence from fMRI studies suggests that broader regions, including dorsolateral prefrontal and posterior regions, might be involved in the pathophysiology of OCD. Further, we should consider that OCD is heterogeneous and might have several different neural systems related to clinical factors, such as symptom dimensions. This review outlines recent neuropsychological and neuroimaging studies of OCD. We will also describe several neurobiological models that have been developed recently. Advanced findings in these fields will update the conventional biological model of OCD..
16. Tomohiro Nakao, Hirokuni Sanematsu, Takashi Yoshiura, Osamu Togao, Keitaro Murayama, Mayumi Tomita, Yusuke Masuda, Shigenobu Kanba, Erratum to "fMRI of patients with social anxiety disorder during a social situation task" [Neuroscience Research 69 (2011) 67-72], Neuroscience Research, 10.1016/j.neures.2010.12.008, 81-82, 2014.01, [URL].
17. Yuta Aoki, Ryota Inokuchi, Tomohiro Nakao, Hidenori Yamasue, Neural bases of antisocial behavior
A voxel-based meta-analysis, Social Cognitive and Affective Neuroscience, 10.1093/scan/nst104, 9, 8, 1223-1231, 2014.08, [URL], Individuals with antisocial behavior place a great physical and economic burden on society. Deficits in emotional processing have been recognized as a fundamental cause of antisocial behavior. Emerging evidence also highlights a significant contribution of attention allocation deficits to such behavior. A comprehensive literature search identified 12 studies that were eligible for inclusion in the meta-analysis, which compared 291 individuals with antisocial problems and 247 controls. Signed Differential Mapping revealed that compared with controls, gray matter volume (GMV) in subjects with antisocial behavior was reduced in the right lentiform nucleus (P < 0.0001), left insula (P=0.0002) and left frontopolar cortex (FPC) (P=0.0006), and was increased in the right fusiform gyrus (P < 0.0001), right inferior parietal lobule (P=0.0003), right superior parietal lobule (P=0.0004), right cingulate gyrus (P=0.0004) and the right postcentral gyrus (P=0.0004). Given the well-known contributions of limbic and paralimbic areas to emotional processing, the observed reductions in GMV in these regions might represent neural correlates of disturbance in emotional processing underlying antisocial behavior. Previous studies have suggested an FPC role in attention allocation during emotional processing. Therefore, GMV deviations in this area may constitute a neural basis of deficits in attention allocation linked with antisocial behavior..
18. Yuta Aoki, Ryota Inokuchi, Tomohiro Nakao, Hidenori Yamasue, Neural bases of antisocial behavior
a voxel-based meta-analysis, Social Cognitive and Affective Neuroscience, 10.1093/scan/nst104, 9, 8, 1223-1231, 2014.08, [URL], Individuals with antisocial behavior place a great physical and economic burden on society. Deficits in emotional processing have been recognized as a fundamental cause of antisocial behavior. Emerging evidence also highlights a significant contribution of attention allocation deficits to such behavior. A comprehensive literature search identified 12 studies that were eligible for inclusion in the meta-analysis, which compared 291 individuals with antisocial problems and 247 controls. Signed Differential Mapping revealed that compared with controls, gray matter volume (GMV) in subjects with antisocial behavior was reduced in the right lentiform nucleus (P < 0.0001), left insula (P = 0.0002) and left frontopolar cortex (FPC) (P = 0.0006), and was increased in the right fusiform gyrus (P < 0.0001), right inferior parietal lobule (P = 0.0003), right superior parietal lobule (P = 0.0004), right cingulate gyrus (P = 0.0004) and the right postcentral gyrus (P = 0.0004). Given the well-known contributions of limbic and paralimbic areas to emotional processing, the observed reductions in GMV in these regions might represent neural correlates of disturbance in emotional processing underlying antisocial behavior. Previous studies have suggested an FPC role in attention allocation during emotional processing. Therefore, GMV deviations in this area may constitute a neural basis of deficits in attention allocation linked with antisocial behavior..
19. Tomohiro Nakao, Behavioral Activation for Depression
Theory and Practice, Psychiatria et Neurologia Japonica - Seishin Shinkeigaku Zasshi, 117, 1, 18-25, 2015, Behavioral activation (BA) has recently attracted marked attention. While cognitive therapy focuses on the cognitive distortion of patients with depression and asks them to change their behaviors as the process of altering the cognitive distortion, BA pays attention to behavior to avoid an unpleasant situation or social situation as a key symptom that leads to persistence of the depression. Avoidance behaviors are often seen during every process of depression, from onset to recurrence. Avoidance behaviors, a decrease in pleasant phenomena, or increase in unpleasant phenomena, result in reinforcing a depressive mood. If patients can set appropriate behavioral targets and achieve them, the beneficial behaviors will be further promoted with positive feed-back. The behavioral change, as-a consequence, will result in improvement of the mood, cognition, and depression itself. In this manuscript, the author presents two clinical cases, in which BA assisted the patients in recovering from their depression. The first case was a male in his thirties who repeatedly took sick leave from his work because of maladjustment, which resulted in persistent depression. The second case was a female in her thirties who suffered from OCD and then became maladjusted to her place of work, depressive, and emotionally unstable. In both cases, avoidant behaviors caused their conditions to persist. Appropriate activities formed by BA improved their moods, and their self-efficacies were gradually regained. It was suggested that BA is markedly effective, especially in patients whose avoidant behaviors mainly cause the persistence of their depressive symptoms..
20. Kayo Okada, Tomohiro Nakao, Hirokuni Sanematsu, Keitaro Murayama, Shinichi Honda, Mayumi Tomita, Osamu Togao, Takashi Yoshiura, Shigenobu Kanba, Biological heterogeneity of obsessive-compulsive disorder
A voxel-based morphometric study based on dimensional assessment, Psychiatry and Clinical Neurosciences, 10.1111/pcn.12269, 69, 7, 411-421, 2015.07, [URL], Aim Although many neuroimaging studies of obsessive-compulsive disorder (OCD) have reported broad abnormalities in gray matter (GM), their results remain inconsistent. One reason for this inconsistency could be the heterogeneity of OCD. In the present study, we aimed to classify alterations in brain anatomy by OCD subtype. Methods Magnetic resonance imaging examinations of 37 OCD patients and 37 matched healthy controls were conducted using a 3.0-Tesla scanner. In the voxel-based morphometric procedure, preprocessed GM structural images were used to compare the two groups, and multiple regression analysis was used to investigate the correlation between regional GM volume in OCD patients and the OCD symptom dimension type assessed by using the Dimensional Yale-Brown Obsessive-Compulsive Scale. Results We found significant reductions in GM volume in broad areas of the left prefrontal, right orbitofrontal, right parietal, right temporal, and right posterior cingulate cortex in the OCD patients compared to healthy controls. In addition, we found specific negative correlations between symptomatic dimension scores and regional GM volumes, mainly as decreased right cerebellum in 'aggression/checking' and decreased right insula in 'contamination/washing'. Conclusion The pathophysiology of OCD may involve widely distributed neural systems. Moreover, there are distinct correlations among symptomatic dimensions and structural abnormalities..
21. 中尾智博, DSM-5の強迫関連症群の概要と臨床的意義—ためこみ症を中心に—, 精神科治療学, 2017.03.
22. Keisuke Ikari, Tomohiro Nakao, Keitaro Murayama, Morphologic and clinical differences between Early- and Late-onset obsessive-compulsive disorder: Voxel-Based Morphometric study, Journal of Obsessive-Compulsive and Related Disorders, 2017.06.
23. Shinichi Honda, Tomohiro Nakao, Keitaro Murayama, A pilot study exploring the association of morphological changes with 5-HTTLPR polymorphism in OCD patients, Annals of General Psychiatry, 2017.06.
24. Okada Kayo, Tomohiro Nakao, Sanematsu Hirokuni, Biological heterogeneity of obsessive-compulsive disorder: A voxel-based morphometric study based on dimensional assessment, Psychiatry Clin Neurosci. 69:411-21, 2015, 2015.06.
25. Tomohiro Nakao, Biological heterogeneity of obsessive-compulsive disorder: A voxel-based morphometric study based on dimensional assessment, Psychiatry Clin Neurosci, 2014.12.
26. Murayama K, Tomohiro Nakao, Differential neural network of checking versus washing symptoms in obsessive-compulsive disorder. , 2012.12.
27. Nakao T, Radua J, Rubia K, Mataix-Cols D, Gray Matter Volume Abnormalities in ADHD: Voxel-Based Meta-Analysis Exploring the Effects of Age and Stimulant Medication. , Am J Psychiatry, 2011.08.
28. Nabeyama M, Nakagawa A, Yoshiura T, Nakao T, Nakatani E, Togao O, Yoshizato C, Yoshioka K, Tomita M, Kanba S, functional MRI study of brain-activation alterations in patients with obsessive-compulsive disorder after symptom improvement., Psychiatry res neuroimaging, 2008.03.
29. Nakao T, Nakagawa A, Yoshiura T, Nakatani E, Nabeyama M, Sanematsu H, Togao O, Yoshioka K, Tomita M, Kuroki T, Kanba S, Duration effect of obsessive-compulsive disorder on cognitive function: a functional MRI study, Depression and Anxiety, 2008.03.
30. 中尾智博, 強迫性障害の行動療法, 月刊精神科, 2007.08.
31. 中尾智博, 黒木俊秀, 機能的脳画像と認知機能評価によるOCDの病態解明—SSRIの効果をめぐって—, 精神神経誌, 2007.02.
32. 吉里千佳, 海老原竜二, 吉岡和子, 飯倉康郎, 鍋山麻衣子, 中尾智博, 加藤奈子, 多田恭子, 中川彰子, インターネットを利用した実態調査—強迫性障害の行動療法について—, 九神精医, 52:153-160, 2006.12.
33. 中尾智博,中谷江利子,鍋山麻衣子,吉岡和子,富田真弓,中川彰子, 強迫性障害の神経心理機能と治療反応性に罹病期間が与える影響, 精神神経誌, 107:P1286-1298, 2005.01.
34. Nakao T, Nakagawa A, Yoshiura T, Nakatani E, Nabeyama M, Yoshizato C, Kudoh A, Tada K, Yoshioka K, Kawamoto M, Togao O, Kanba S, Brain activation of patients with obsessive-compulsive disorder during neuropsychological and symptom provocation tasks before and after symptom improvement, Biological psychiatry, 10.1016/j.biopsycg.2004.12.039, 57, 8, 901-910, 57:901-910, 2005.01.
35. Nakao T, Nakagawa A, Yoshiura T, Nakatani E, Nabeyama M, Yoshizato C, Kudoh A, Tada K, Yoshioka K, Kawamoto M, A functional MRI comparison of patients with obsessive-compulsive disorder and normal controls during a Chinese character Stroop task, Psychiatry research neuroimaging, 10.1016/j.pscychresns.2004.12.004, 139, 2, 101-114, 139:101-114, 2005.01.

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