Clinical Neuroscience Research

Introduction: Reports document children with attention deficit hyperactivity disorder (ADHD) and irritability, aggression or mood lability. Whether these additional symptoms represent severe ADHD, juvenile bipolar disorder, or other comorbidities is often unclear and has both diagnostic and treatment implications. We use the Cantwell modifications of the Robins and Guze diagnostic construct to examine the diagnostic validity and treatment implications of children with ADHD and some manic symptoms. Methods: We examined 579 children with ADHD from the multimodal treatment study of children with ADHD (MTA) and compared those with manic symptoms to those without manic symptoms in the domains of clinical phenomenology, demographic factors, psychosocial factors, biological factors, family genetic factors, family environmental factors, natural history, and intervention response. Results: Children with manic symptoms were more symptomatic at baseline and had more comorbidities and psychosocial and family environmental stressors. There were few differences in parental psychopathology and no biological differences. While ADHD children with manic symptoms were more symptomatic at 14 months, most differences were not significant when controlling for baseline symptoms. They were not more likely to have manic-like side effects except for moderate or severe worries. Discussion: Children with ADHD and manic symptoms compared to ADHD children without manic symptoms were more symptomatic and had more comorbidities at baseline. They nonetheless showed no systematic pattern of differences according to the Robins/Guze/Cantwell criteria. Moreover, they improved over time with standard ADHD treatments and were generally not found to have more adverse effects from stimulants.

Cathryn A. Galanter

Dana L. Pagar

Mark Davies

Wei Li

Gabrielle A. Carlson

Howard B. Abikoff

L. Eugene Arnold

Oscar G. Bukstein

William Pelham

Glen R. Elliott

Stephen Hinshaw

Jeff N. Epstein

Karen Wells

Lily Hechtman

Jeffrey H. Newcorn

Larry Greenhill

Timothy Wigal

James M. Swanson

Peter S. Jensen

ADHD and manic symptoms: Diagnostic and treatment implications

注意缺陷多动障碍与躁狂症状：诊断与治疗的影响

Objective: To examine relationships among early smoke exposure (ESE), attention-deficit/hyperactivity disorder (ADHD), oppositional-defiant or conduct disorder (ODD/CD), and whether ESE affects symptom severity, comorbidity, and later treatment response. Study design: The Multimodal Treatment Study of Children with ADHD (MTA) had 468 children with ADHD and 279 others from the same classrooms (local normative comparison group, LNCG) with smoke-exposure data. We compared ESE as 'gestational' or 'postnatal' (ambient house smoke only, without gestational) between ADHD and LNCG, and tested its association with ADHD severity, comorbid ODD/CD, methylphenidate response, and differential treatment response to four randomly assigned treatments. Results: About 1/3 more ADHD than LNCG children had ESE (both types), but association with gestational smoke attenuated from P=0.024 to 0.094 when subjects with comorbid ODD/CD were excluded, although total smoke exposure retained significance (P=0.006). In the MTA/ADHD participants, comorbid ODD/CD, and parent/teacher-rated ADHD and ODD symptom severity were not associated with gestational smoking, but severity of ODD was associated with postnatal smoke, and for boys only, ADHD severity at 14 months associated with postnatal smoke. When ODD and CD were 'unbundled', CD was associated (P=0.005) with gestational smoke. Neither ESE moderated response to methylphenidate, optimal dose, 2-year growth slowing, or differential ODD symptom response to 14-months of 4 randomly assigned treatments. However, for ADHD symptoms, postnatal smoke moderated (P=0.008) the 14-month advantage of behavioral treatment (Beh) over community-treated comparison (CC): postnatally exposed boys benefited relatively more from Beh (d>0.5). ADHD symptom improvement also showed significant interaction of sex with gestational (P=0.015) and postnatal (P=0.044) smoke moderator effect for the contrast of MTA medication algorithm vs. Beh and CC: smoke-exposed girls did not show the usual algorithm superiority. Conclusions: These findings suggest possible moderating effects of postnatal ESE on the advantage of intensive behavioral treatment and sex-differential moderating effects of ESE on the advantage of intensive medication over behavioral treatment. This exploratory result requires replication. The findings do not convincingly support the hypothesis that the association of gestational smoking with offspring ADHD is accounted for by comorbid ODD/CD.

Michael Elliott

Ronald L. Lindsay

Brooke Molina

Marie D. Cornelius

Benedetto Vitiello

Jeffrey Newcorn

Jeffery N. Epstein

Gestational and postnatal tobacco smoke exposure as predictor of ADHD, comorbid ODD/CD, and treatment response in the MTA

妊娠期和产后烟草烟雾暴露作为多动症、共病对立违抗性障碍/品行障碍及治疗反应的预测因素：MTA研究

Despite considerable research, the validity of attention-deficit/hyperactivity disorder (ADHD) remains controversial. This paper summarizes the results of a comprehensive review of the internal and external validity of ADHD as defined in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Results indicate that for most individuals DSM-IV ADHD is a valid disorder in the sense that it is associated with significant impairment in social, academic, and occupational functioning and increased risk of accidental injury across the life span. Additional research is needed, however, to clarify the diagnostic validity of the hyperactive-impulsive type and the discriminant validity of the combined and inattentive subtypes. Other areas in need of further study include potential modifications to the diagnostic conceptualization of the inattentive subtype, developmental trajectories of the subtypes, and methods to address cross-informant diagnostic inconsistencies. Such research is likely to benefit from an etiologically informed approach to examining heterogeneity both across and within subtypes.

Erik G. Willcutt

Caryn L. Carlson

The diagnostic validity of attention-deficit/hyperactivity disorder

注意缺陷/多动障碍的诊断效度

Cantwell [Cantwell DP. Empircism and child psychiatry. In: The 1990 C. Charles Burlingame, M.D., Award Lecture, Hartford, Connecticut: The institute of living; 1990 [1]] recognized age and ethnicity as important factors that should be considered in evaluating the clinical phenomenology of childhood disorders. Here we describe how these factors have been addressed in CHOC-UCI Initiative for the Development of Attention and Readiness (CUIDAR), an early intervention and prevention model for children at risk for diagnosis with Attention-Deficit/Hyperactivity Disorder (ADHD). CUIDAR was developed to address age by focusing on needs of families with young children and ethnicity by focusing on the needs of Hispanic families that speak Spanish. This program provides ‘service before diagnosis’ by removing barriers and offering psychosocial intervention (parent training) before the usual first-line treatment of ADHD (i.e. pharmacological intervention). We present data from the start-up phase of CUIDAR to evaluate differences in ethnic groups on the basis of important measures of effectiveness, such as parental satisfaction, gains in parenting skills, and reductions in child behavior problems. Cantwell [Cantwell DP. Empircism and child psychiatry. In: The 1990 C. Charles Burlingame, M.D., Award Lecture, Hartford, Connecticut: The institute of living; 1990 [1]] also recognized that clinicians often must provide treatment with a great deal of ‘therapeutic enthusiasm’ even though the intervention may be based on inadequate research data, and in this situation he recommended creating an atmosphere in which systematic observations could be made in the existing clinical context even when controlled research was not feasible. The data we report here were accumulated in this fashion during the development of CUIDAR, which was funded by the Children's and Families Commission of Orange County as a service delivery program.

Leanne Tamm

Marc A. Lerner

Craig Childress

Brett Patterson

Kimberley Lakes

Annamarie Stehli Nguyen

Mily Kudo

Wendy Altamirano

Joel Miller

Rosa Santoyo

Veronica Camarero-Morse

John M. Watkins

Steve Simpson

Feizal Waffarn

Chuck Cunningham

Intervention for preschoolers at risk for Attention-Deficit/Hyperactivity Disorder (ADHD): Service before diagnosis

针对有注意力缺陷/多动障碍（ADHD）风险的学龄前儿童的干预：诊断前的服务

Culture can be defined as unique behaviour, lifestyle and attitudes which are formed as a result of customs, habits, beliefs and values that are common to a group and shape their emotions, behaviours and life patterns; it serves as a core behaviour that regulates life. Culture can be pathogenic, pathoplastic or pathoprotective in mental disorders. There is no doubt that culture will determine how distress is identified and pathologized and how pathways into folk, social or professional care are identified. Culture can also be pathoselective, pathofacilitory or pathodiscriminatory (see Figure 1).

Dennis P. Cantwell

THE 1990 C. CHARLES BURLINGAME, M.D. AWARD LECTURE

1990年C.查尔斯·伯林格姆医学博士奖演讲

Network approaches to analysis of functional neuroimaging data provide a powerful means with which to understand the complex functioning of the brain in health and disease. To illustrate how such approaches can be used to investigate sex differences in neurocognition, we applied the multivariate technique of Principal Components Analysis (PCA) to an fMRI dataset obtained during performance of mental rotation – a classic visuospatial task known to give rise to sex differences in performance. In agreement with prior results obtained using univariate methods, PCA identified a core mental rotation network (principal component [PC]1, accounting for 53.1% of total variance) that included activation of bilateral frontal, parietal, occipital and occipitotemporal regions. Expression of PC1 was similar in men and women, and was positively correlated with level of education. PC2, which accounted for 5.7% of total variance, was differentially expressed by men and women, and indicated greater mental rotation-associated neural activity in women in such high-order cortical regions such as prefrontal cortex and superior parietal lobule, in accord with prior findings, and with the idea that women may take a more "top-down" approach to mental rotation. By quantifying, in a data-driven fashion, the contribution of factors such as sex and education to patterns of brain activity, these findings put the magnitude of neural sex differences during mental rotation into perspective, confirming the commonsense notion that, as humans, men and women are more alike than they are different, with between-individual variability (such as level of education, which, importantly, is modifiable) generally outweighing between-sex variability. This work exemplifies the role that multivariate analysis can play in identifying brain functional networks, and in quantifying their involvement under specific conditions and in different populations.

Tracy Butler

Hong Pan

Julianne Imperato-McGinley

Daniel Voyer

Amy Christine Cunningham-Bussel

Juan J. Cordero

Yuan-Shan Zhu

David Silbersweig

Emily Stern

A network approach to fMRI condition-dependent cognitive activation studies as applied to understanding sex differences

一种基于网络的fMRI条件依赖性认知激活研究方法及其在理解性别差异中的应用

Functional neuroimaging, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT), provides a valuable technique for detecting regional changes in brain metabolic activity and blood flow associated with mild cognitive impairment (MCI) and dementia. Multivariate analysis techniques have recently received increasing attention. The results of multivariate analysis can be more easily interpreted as a signature of neuronal networks, which lend themselves to prospective application of results from the analysis of one dataset to entirely new datasets. They are well placed to provide information about mean differences and correlations with behavior with potentially greater statistical power and better reproducibility. This article will focus on investigating the baseline and progression of MCI using functional brain imaging techniques and multivariate analysis in order to understand the genesis and natural history of cognitive impairment in Alzheimer's disease (AD) and Parkinson's disease (PD), respectively.

Chaorui Huang

Paul Mattis

Per Julin

Identifying functional imaging markers of mild cognitive impairment in early Alzheimer’s and Parkinson’s disease using multivariate analysis

使用多元分析识别早期阿尔茨海默病和帕金森病轻度认知障碍的功能影像标志物

Idiopathic torsion dystonia and Huntington’s disease represent autosomal dominant inherited hyperkinetic disorders that vary considerably with regard to pathologic mechanisms and clinical penetrance. To study these mechanisms, non-manifesting DYT1 mutation carriers (nmDYT1) and presymptomatic HD gene carriers (p-HD), as well as age-matched controls were scanned with (i) FDG PET in the resting state, and (ii) 15O-labeled water PET while performing a motor sequence learning task and motor execution task. We used voxel-based principal components analysis (PCA) to isolate the effects of genotype on regional metabolism in the resting state and on patterns of activation during motor performance. We detected two specific genotype-related metabolic patterns in the resting state. The torsion dystonia-related pattern was characterized by hypermetabolism of the basal ganglia, cerebellum and the supplementary motor area (SMA). By contrast, the voxel-based HD-related pattern displayed reductions in caudate and putamen metabolic activity associated with relative increases in the thalamus, the calcarine cortex, and primary motor cortex. Both mutations were associated with sequence learning deficits compared to controls. Carriers of each genotype activated different networks while performing the sequence learning task. In nmDYT1, learning was associated with activation of a specific network involving the cerebellar hemispheres, the left pre-SMA and anterior cingulate region, as well as inferior prefrontal and occipital association cortices. In p-HD, the learning network involved activation of the orbitofrontal and occipital association regions bilaterally, the left mediodorsal thalamus, and the right cerebellar hemisphere. These topographies illustrate the utility of PCA in identifying functional abnormalities in fronto-striatal loops and related pathways.

Maren Carbon

Andrew Feigin

David Eidelberg

Multivariate analysis: Applications to the study of hereditary movement disorders

多变量分析：应用于遗传性运动障碍的研究

To report functional urethral obstruction (FUO) following the tubularised incised plate (TIP) procedure for hypospadias repair and its management.Between January 2003 and December 2010, 263 patients were referred with complications following TIP repair and who were reviewed on regular follow up after further correction. One hundred and twenty-nine of these patients presented with persistent obstructive voiding signs and symptoms in spite of apparently successful calibration or dilatation, 32 presented with persistent stenosis, and 97 with recurrent fistula. The mean age at surgery was 2.9 years (range 1–4). The complications were corrected using 1 of 2 techniques: modified Mathieu (112) and lateral onlay flap (17). The mean follow-up was 4 years (range 1–9).The obstructive symptoms were corrected with a single procedure in 120 (93%). Nine patients (7%) developed complications in the form of fistula (7 patients) and glanular dehiscence (2 patients) that were corrected successfully in a second operation.The incised urethral plate may heal forming a deep narrow groove resulting in FUO. Patients with FUO present with obstructive voiding symptoms in spite of successful calibration or dilatation. These symptoms disappear after reconstruction of a wide fully epithelised neo-urethra.

Yilong Ma

Multivariate brain mapping in clinical neuroscience research

临床神经科学研究中的多变量脑图谱

Abstract Although approximately 1–3% of the population over age 65 have Parkinson’s disease (PD), only about 75% of the patients diagnosed with parkinsonism have PD. The differential diagnosis of parkinsonian disorders based on clinical symptoms alone is particularly difficult during the early stages of the disease. A number of imaging strategies have been developed to differentiate between these clinically similar conditions. The assessment of abnormal patterns of brain metabolism, either by visual inspection or using computer-assisted algorithms, can be used to discriminate between classical PD and atypical variant conditions such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), or corticobasal ganglionic degeneration (CBGD). Recent advances in network quantification routines have created the basis for fully automated differential diagnosis. Using PET, investigators have identified specific disease-related spatial covariance patterns that are characteristic of PD and its variants. By computing pattern expression in individual patient scans, it has become possible to determine the likelihood of a specific diagnosis. In this review, we describe the various imaging techniques that have been used to diagnose PD with emphasis on the application of network tools. Analogous methods may have value in the assessment of other neurodegenerative and neuropsychiatric conditions.

Thomas Eckert

Christine Edwards

The application of network mapping in differential diagnosis of parkinsonian disorders

网络映射在帕金森病鉴别诊断中的应用

Publication Information	Publisher: Elsevier B.V.，Publishing cycle: ，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2001，Proportion of original research papers: ，Self Citation Rate:， Gold OA Rate:

Clinical Neuroscience Research

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