二十二碳-6烯酸对注意缺陷多动障碍患儿神经生化及行为影响的研究

【目的】探讨二十二碳-6烯酸（DoCosahexaenoiCacid，DHA）对注意缺陷多动障碍（attention deficit hyperactivitydisorder，ADHD）患儿神经生化及行为影响，观察补充DHA对ADHD患儿症状行为的改变情况。【方法】通过对确诊的ADHD儿童补充DHA，检测其血清中多巴胺（dopamine，DA）、5-羟色胺（5-hydroxytryptamine，5HT）以及促肾上腺皮质激素（adrenocorticotropic hormone，ACTH）的水平在服用前后的变化，并分析这些变化对ADHD儿童行为改变的影响。【结果】①ADHD儿童血清DA、5-HT、ACTH含量在服用前后差异均有显著性（P〈0．05）。男童血清DA、ACTH水平，女童血清5-HT、ACTH水平，中学生血清DA、5-HT水平在服用前后差异也均有显著性。②服用后儿童行为问题检出率12．5％，低于服用前的37．9％（P〈0．05）。6～16岁ADHD男童Achenbach儿童行为量表（Child Behavior Checklist，CBCL）行为得分在补充DHA后有所改善（P〈0．05）。③DA水平与多动指数水平呈负相关（r=-0．300，P〈0．05）；5-HT水平与注意缺陷指数水平存在负相关（r=-0．434，P〈0．05）；ACTH水平与注意缺陷指数水平存在边缘正相关（r=0．236，P=0．047）。【结论】DHA对ADHD患儿DA、5-HT及ACTH水平有一定调控作用，对改善其临床症状有一定疗效。     

Adolescent hyperactivity and general psychopathology

The aim of this study was to explore the relationship between activity and psychopathology in adolescents. A total of 289 high school students completed the Symptom Check List-90-R (SCL-90-R) and Wender Utah Rating Scale (WURS) in December 1998. The WURS was used to measure the students' activity level and the SCL-90-R was used as a measure of general psychopathology. Forty-one students (14.18%) scored higher than 46, the cut-off point for differentiation of attention deficit hyperactivity disorder (ADHD) from the general population according to Ward's report, in the WURS (WURS(+)). The WURS(+) students scored significantly higher than the WURS(-) students in all the subscales of SCL-90-R. The prevalence rate of adolescent WURS(+) in this study is 14.18%. This result shows that ADHD adolescents have overlapping symptoms with depression.     

De novo microduplication of the FMR1 gene in a patient with developmental delay,epilepsy and hyperactivity

Loss-of-function due to expansion of a CGG repeat located in the 5''UTR of the FMR1 gene is the most frequent cause of fragile X syndrome. Less than 1% of individuals with fragile X syndrome have been reported to have a partial or full deletion or point mutation of the FMR1 gene. However, whether a copy number gain of the FMR1 gene could result in certain clinical phenotypes has not been fully investigated. Here, we report the case of a child who presented with developmental delay starting at 9 months of age, fine motor and speech delay, progressive seizures since 18 months of age and hyperactivity. Molecular workup identified a de novo microduplication in the Xq27.3 region, including the FMR1 gene and the ASFMR1 gene. The expression level of the FMR1 gene in peripheral blood did not differ from that of the controls. In addition, an inherited 363-kb duplication on the chromosome 1q44 region and an inherited deletion of 168 kb on the chromosome 4p15.31 region were detected. It is not clear whether these inherited copy number variations (CNVs) also have a modifying role in the clinical phenotype of this patient.     

A Postmarketing Clinical Experience Study of Metadate® CD

Summary

Objective:The objective of the study was to investigate the effectiveness and safety of Metadate® CD (methylphenidate HCl, USP) Extended Release Capsules in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD), in actual clinical practice.

Method:This was a multicenter, open-label, postmarketing study. Eligible patients were aged 6-17 with a diagnosis of ADHD and receiving either no treatment or maintenance treatment with another approved methylphenidate (MPH) product. Metadate® CD was administered once daily for 3 weeks, titrated against reported and observed symptoms. Clinical Global Impression (CGI) scores at Week 3 were used for the primary efficacy evaluation. Patient treatment satisfaction was determined by questionnaire at the final evaluation visit. Safety was assessed through adverse event reporting, laboratory tests and vital sign measurements.

Results: Overall, of the 308 patients in the Intent-To-Treat population, the majority (65%) demonstrated a positive response to Metadate® CD (defined as CGI Global Improvement rating of very much or much improved). In addition, patients previously treated with immediate-release or extended-release tablet formulations of MPH were successfully converted to Metadate® CD at a comparable dose. Most patients (87%) were very satisfied or moderately satisfied with study treatment, and among previously treated patients, 71% rated Metadate® CD as much better or better than their previous MPH treatment. Adverse events were consistent with current FDA-approved product labeling for Metadate® CD.

Conclusions: Metadate® CD is effective and well-tolerated in actual clinical use for ADHD.     

Positive AMPA receptor modulation in the treatment of neuropsychiatric disorders: A long and winding road

Glutamatergic transmission is widely implicated in neuropsychiatric disorders, and the discovery that ketamine elicits rapid-acting antidepressant effects by modulating α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) signaling has spurred a resurgence of interest in the field. This review explores agents in various stages of development for neuropsychiatric disorders that positively modulate AMPARs, both directly and indirectly. Despite promising preclinical research, few direct and indirect AMPAR positive modulators have progressed past early clinical development. Challenges such as low potency have created barriers to effective implementation. Nevertheless, the functional complexity of AMPARs sets them apart from other drug targets and allows for specificity in drug discovery. Additional effective treatments for neuropsychiatric disorders that work through positive AMPAR modulation may eventually be developed.     

Heterogeneity of Age-Related Neural Hyperactivity along the CA3 Transverse Axis

Age-related memory deficits are correlated with neural hyperactivity in the CA3 region of the hippocampus. Abnormal CA3 hyperactivity in aged rats has been proposed to contribute to an imbalance between pattern separation and pattern completion, resulting in overly rigid representations. Recent evidence of functional heterogeneity along the CA3 transverse axis suggests that proximal CA3 supports pattern separation while distal CA3 supports pattern completion. It is not known whether age-related CA3 hyperactivity is uniformly represented along the CA3 transverse axis. We examined the firing rates of CA3 neurons from young and aged, male, Long–Evans rats along the CA3 transverse axis. Consistent with prior studies, young CA3 cells showed an increasing gradient in mean firing rate from proximal to distal CA3. However, aged CA3 cells showed an opposite, decreasing trend, in that CA3 cells in aged rats were hyperactive in proximal CA3, but possibly hypoactive in distal CA3, compared with young (Y) rats. We suggest that, in combination with altered inputs from the entorhinal cortex and dentate gyrus (DG), the proximal CA3 region of aged rats may switch from its normal function that reflects the pattern separation output of the DG and instead performs a computation that reflects an abnormal bias toward pattern completion. In parallel, distal CA3 of aged rats may create weaker attractor basins that promote abnormal, bistable representations under certain conditions.SIGNIFICANCE STATEMENT Prior work suggested that age-related CA3 hyperactivity enhances pattern completion, resulting in rigid representations. Implicit in prior studies is the notion that hyperactivity is present throughout a functionally homogeneous CA3 network. However, more recent work has demonstrated functional heterogeneity along the CA3 transverse axis, in that proximal CA3 is involved in pattern separation and distal CA3 is involved in pattern completion. Here, we show that age-related hyperactivity is present only in proximal CA3, with potential hypoactivity in distal CA3. This result provides new insight in the role of CA3 in age-related memory impairments, suggesting that the rigid representations in aging result primarily from dysfunction of computational circuits involving the dentate gyrus (DG) and proximal CA3.