Causal models of attention-deficit/hyperactivity disorder: from common simple deficits to multiple developmental pathways.

Until recently, causal models of attention-deficit/hyperactivity disorder (ADHD) have tended to focus on the role of common, simple, core deficits. One such model highlights the role of executive dysfunction due to deficient inhibitory control resulting from disturbances in the frontodorsal striatal circuit and associated mesocortical dopaminergic branches. An alternative model presents ADHD as resulting from impaired signaling of delayed rewards arising from disturbances in motivational processes, involving frontoventral striatal reward circuits and mesolimbic branches terminating in the ventral striatum, particularly the nucleus accumbens. In the present article, these models are elaborated in two ways. First, they are each placed within their developmental context by consideration of the role of person x environment correlation and interaction and individual adaptation to developmental constraint. Second, their relationship to one another is reviewed in the light of recent data suggesting that delay aversion and executive functions might each make distinctive contributions to the development of the disorder. This provides an impetus for theoretical models built around the idea of multiple neurodevelopmental pathways. The possibility of neuropathologic heterogeneity in ADHD is likely to have important implications for the clinical management of the condition, potentially impacting on both diagnostic strategies and treatment options.     

Visualization of maturation of the corpus callosum during childhood and adolescence using T2 relaxometry

Previous studies have shown that maturation of the white matter in terms of its relative signal intensity changes on MRI is almost complete at 2-3 years of age. We hypothesized that quantitative analysis may show maturation of the white matter during childhood and adolescence. In the present study we performed multi-echo T2 relaxometry in 33 healthy subjects (girls, 15; boys, 18) aged 3-15 years. T2 relaxation times of the genu and splenium were measured. In healthy subjects, the T2 relaxation times were significantly correlated with age in both girls (r=0.611, p=.016) and boys (r=0.721, p=.001) in the splenium, but not in the genu (p>.05). To further confirm genu-to-splenium signal intensity ratio changes, a total of 389 brain MRIs were retrospectively selected from the patients who had normal results (189 girls/women, 200 boys/men; age range, 3-20 years). The genu-to-splenium signal intensity ratio was obtained from the T2-weighted images. In patients with normal MRI, the genu-to-splenium signal intensity ratio was significantly decreased with age (p<.001) by 16 years. The T2 relaxation times gradually increase in the splenium during childhood and adolescence, suggestive of maturation.     

西部区域经济跨越式发展的动力建构和路径选择

跨越式发展是经济发展相对落后地区在借鉴和吸收先进国家和地区成功经验和优秀成果的基础上 ,通过技术和生产力的跨越、管理和制度的创新、产业结构的优化升级、经济运行质量的提升、速度和效益的并进 ,不平衡推进和超常规增长 ,最终实现经济整体跃升的一种新的发展模式。在国家宏观政策和市场机制的双重作用下 ,充分利用各种有利条件 ,努力实现区域经济跨越式发展已成为西部地区的必然选择。积极推进区域制度创新、技术创新和文化创新 ,构建西部区域经济跨越式发展的动力系统 ,既是西部区域经济跨越式发展的必由之路 ,也是西部地区当前面临的主要任务。在路径选择上必须把发挥比较优势和发挥后发优势有机结合起来 ,使二者相得益彰 ,从而走出一条具有西部特色的跨越式发展之路。     

唇腭裂患者手术后上颌骨发育的评价研究

目的　研究唇腭裂术后患者上颌骨发育特征及手术对发育造成的影响。方法　将 6 0例婴幼儿期手术的完全性唇腭裂患者作为研究对象 ,采用X线头影测量方法进行测量 ,拍摄标准侧位头影测量片 ,并选择 12个标志点及 12个测量项目 ,并与同年龄段正常患者的测量值进行比较分析。结果　单纯唇裂患者与正常对照组比较出现∠SNA [(76 .4± 3.0 6 )° ,P 0 .0 5 ]、N A Pg[(- 4 .8± 6 .31)mm ,P 0 .0 5 ]值变小 ;单纯腭裂及唇腭裂患者出现∠SNA[(74 .5± 4 .0 1)° ,P 0 .0 5 ;(75 .1± 1.0 7)°,P 0 .0 1]、N ANS[(47.3± 2 .4 1)mm ,P 0 .0 1;(49.8± 1.91)mm ,P 0 .0 1]等多项指标均小于正常对照 ,提示不同程度、不同表现形式的上颌骨发育受限。结论　唇腭裂患者术后上颌发育不足是先天及后天因素综合影响的结果。唇裂修复术是影响上颌前后向发育的重要因素之一 ,腭裂修复术是影响上颌骨高度及宽度发育的重要因素之一。     

大鼠上丘一氧化氮合酶阳性神经元的发育

目的：研究大鼠胚胎时期及生后早期一氧化氮合酶(NOS)阳性神经元在上丘的分布，进一步探讨一氧化氮(NO)在上丘发育过程中的作用。方法：应用还原型尼克酰胺腺嘌呤二核苷酸脱氢酶(NADPH—d)组织化学方法观察孕17d起至生后14d大鼠上丘NOS阳性神经元的发育。结果：孕20d上丘深白层与深灰层出现NOS阳性神经元。P0上丘中层也观察到NOS阳性神经元。随着发育，阳性神经元增多，胞体增大，染色加深。到P14，视神经层出现少许：NOS阳性神经元，浅灰层观察到大量的NOS阳性神经元。结论：胚胎20天上丘深层首先出现NOS阳性神经元并沿腹背方向发生，提示NO在上丘发育过程中起着重要作用。     

Risperidone exerts potent anti-aggressive effects in a developmentally immature animal model of escalated aggression.

BACKGROUND: Risperidone has been shown to be clinically effective for the treatment of aggressive behavior in children, yet no information is available regarding whether risperidone exhibits aggression-specific suppression in preclinical studies that use validated developmentally immature animal models of escalated aggression. Previously, we have shown that exposure to low doses of the psychostimulant cocaine-hydrochloride (.5 mg/kg intraperitoneally) during the majority of pubertal development (postnatal days [P]27-57) generates animals that exhibit a high level of offensive aggression. This study examined whether risperidone exerts selective aggression-suppressing effects by using this pharmacologic animal model of highly escalated offensive aggression. METHODS: Experimental hamsters were tested for offensive aggression after the acute administration of risperidone (.05-1.0 mg/kg, intraperitoneally). RESULTS: Risperidone dose-dependently reduced the highly aggressive phenotype, with a significant reduction observed at .1-.2 mg/kg for most aggressive responses measured. Experimental animals treated with higher doses of risperidone (.3-1.0 mg/kg) showed significant reductions in aggression and social interest toward intruders, indicating more general behavioral inhibition. CONCLUSIONS: These studies provide evidence that risperidone exerts specific aggression-suppressing effects in a developmentally immature animal model of escalated aggression.     

Maturation of executive function in autism.

BACKGROUND: Executive dysfunction has been reported at different ages in autism. It is not clear however, when this impairment emerges or how its expression is affected by development. METHODS: 61 non-mentally retarded autism participants (AUT) and 61 age, gender, and IQ matched typically developing participants (CON) were assessed with two oculomotor executive function tasks, the oculomotor delayed response task (ODR) and the antisaccade task (AS), as well as a visually-guided saccade sensorimotor task (VGS). RESULTS: The AUT group demonstrated impairments in response inhibition and spatial working memory at all ages tested. Developmental improvements in speed of sensorimotor processing and voluntary response inhibition were similar in both groups indicating sparing of some attentional control of behavior. Developmental progression in the speed of initiating a cognitive plan and maintaining information on line over time, however, was impaired in the AUT group indicating abnormal development of working memory. CONCLUSIONS: These results indicate that while executive dysfunction is present throughout development, there is evidence for both typical and atypical developmental progression of executive functions in autism. The plasticity suggested by the developmental improvements may have implications regarding appropriate developmental epochs and types of interventions aimed at enhancing cognitive capacities in individuals with autism.     

Leukaemia Inhibitory Factor or Related Factors Promote the Differentiation of Neuronal and Astrocytic Precursors within the Developing Murine Spinal Cord

Previously we have shown that leukaemia inhibitory factor (LIF) potentiates the development of murine spinal cord neurons in vitro , suggesting that it, or related factors, may play an important regulatory role in neuronal development. We have further investigated this role and show here that the generation of neurons in cultures of embryonic day 10 spinal cord cells is inhibited by antibodies to the β subunit of the LIF receptor. Since there are more undifferentiated precursors in antibody-treated cultures than in control and LIF-treated cultures, it is concluded that the primary action of LIF, or related molecules, is to promote neuronal differentiation, not precursor survival. In addition, the failure of LIF to support neuronal survival in the period immediately following differentiation suggests that the increased numbers of neurons generated with LIF are not attributable to its neurotrophic action. By selecting neuronal precursors on the basis of their inability to express class I major histocompatibility complex molecules, it was shown that LIF acted directly upon these cells and not via an intermediary cell. LIF also appears to be involved in regulating the differentiation of astrocytes, since it increases the number of glial fibrillary protein (GFAP)-positive cells present in the cultures and since the spontaneous production of GFAP-positive cells is blocked by antibodies to the LIF β receptor. These findings suggest that LIF or related factors promote the differentiation of neural precursors in the spinal cord, but that they are not involved in preferentially promoting precursors down a specific differentiation pathway.     

Expressed-emotion development and course of schizophrenic illness: considerations based on results of a CFI replication

This study examines the correlation between development of expressed emotion (EE) in relatives and course of illness of 99 DSM-III schizophrenic patients. Patients whose relatives were high EE at baseline and at the 2nd CFI approximately 20 months later had a poor prognosis at the very outset of the study and an unfavourable course of illness. They had a higher rehospitalisation rate, more symptoms, lower psychosocial assessment, and a poorer 2-year and even 8-year outcome. Patients from families with a fluctuating EE or a consistently low EE had better courses. Expessed emotion is therefore a valid predictor not only of symptomatic relapses, but also of other important aspects of schizophrenia. The connection between EE index and course of illness seerns not to be simply reactive or causal, but complex and non-uniform.