维生素D在孤独症谱系障碍中作用的研究进展

孤独症谱系障碍(ASD)是影响儿童健康的严重公共问题之一,以社交沟通障碍、兴趣或活动范围狭窄以及重复刻板行为为特征。近年来越来越多的研究显示,ASD患儿维生素D(VitD)水平明显低于同龄健康儿童,VitD缺乏可能与ASD的发病机制相关。本文就VitD与ASD的相关研究进行综述。     

Parental alcohol use and brain volumes in early- and late-onset alcoholics.

BACKGROUND: Studies have shown that alcoholics have smaller brain volumes than non-alcoholic cohorts, but an effect of family history (FH) of heavy drinking on brain volume has not been demonstrated. We examined the relationship between an FH of heavy drinking and both brain shrinkage as measured by the ratio of brain volumes to intracranial volume (ICV) as well as maximal brain growth as measured by ICV in early-onset and late-onset alcoholics. METHODS: With T1-weighted resonance imaging, we measured ICV, brain volume, and white and gray matter volume in adult treatment-seeking late-onset and early-onset alcoholics with either a positive or a negative FH of heavy alcohol use, and in healthy control subjects. We also calculated brain shrinkage using a ratio of soft tissue volumes to ICV. RESULTS: The FH positive alcoholic patients had significantly smaller ICVs than FH negative patients, suggesting smaller premorbid brain growth. Brain shrinkage did not correlate with FH. Late-onset alcoholics showed a greater difference in ICV between FH positive and FH negative patients than early-onset alcoholics. Late-onset FH positive patients also had significantly lower IQ scores than late-onset FH negative patients, and IQ scores were correlated with ICV. CONCLUSIONS: These data provide evidence that parental alcohol use might increase risk for alcoholism in offspring in part by a genetic and/or environmental effect that might be related to reduced brain growth.     

C2H2-171 : A novel human cDNA representing a developmentally regulated poz domain/zinc finger protein preferentially expressed in brain

We describe a novel human zinc finger cNDA, C2H2-171. This cDNA represents an mRNA which encodes a protein of 484 amino acids and a calculated molecular weight of 54 kD. Four zinc finger-like domains are found in the C-terminal end of the protein. At the N-terminus, C2H2-171 contains a POZ/tramtrack-like domain similar to that found in the tumor associated zinc finger proteins LAZ-3/BCL-6 and PLZ-F, as well as in non-zinc finger proteins. C2H2-171 RNA is preferentially expressed in the brain, and increases during the course of murine development, with maximal expression in the adult. C2H2-171 RNA is differentially expressed in brain regions, with the highest level of expression in the cerebellum. C2H2-171 RNA was expressed at high levels in primary cerebellar granule cell neurons compared to astrocytes. The gene encoding C2H2-171 is highly conserved in vertebrates, and maps to the terminus of human chromosome 1 (1q44-ter). This chromosomal location is associated with a number of cytogenetic aberrations including those involving brain developmental anomalies and tumorigenesis. These data suggest that C2H2-171 may play an important role in vertebrate brain development and function.     

Neuropathology of schizophrenia: A mini review

The neuropathology of schizophrenia remains obscure despite the fact that many neuropathologists have investigated this area for over 100 years. While remarkable progress has been made in the neuropathological study of neurodegenerative diseases including Alzheimer's disease, progress in studying the neuropathological entity of schizophrenia has not kept pace; the phrase “schizophrenia is the graveyard of neuropathologists” has been stated in the field. Since the 1980s, the morphological or functional abnormalities in the brains of schizophrenia patients have been reported by means of CT or MRI and with advanced functional brain image technology such as positron emission tomography or single photon emission computed tomography. Results from such imaging studies have led to neuropathological examination of the post mortem brains of schizophrenia patients being undertaken again. These neuroimaging studies have influenced the neuropathological investigation of the schizophrenic brain. Not only the classical microscopic observation of neuropathology, but also measurement and statistical analysis using computer imaging software or using immunohistological techniques has been performed. Based on the neuropathological studies of schizophrenia over the last 20 years, it is clear that schizophrenia is not a pure functional disease without organic factors. Reports of neuropathological abnormalities in the post mortem schizophrenic brain indicated they were found in almost all areas of the brain, but there are more reports describing the temporal lobe and frontal lobe compared to those describing other areas of the brain. These observed neuropathological abnormalities are explained rationally by the hypothesis of a neurodevelopmental disorder in this disease. In recent molecular biology studies, several putative candidate genes were reported, and some of these genes might have the function of neurodevelopment or making neuronal networks. It is important to consider together these findings with morphometric studies in neuropathological observation, neuroimaging studies and genome studies to pursue the etiology of schizophrenia from various perspectives.     

A review of Disrupted-In-Schizophrenia-1 (DISC1): neurodevelopment, cognition, and mental conditions.

Disrupted-In-Schizophrenia-1 (DISC1) is a promising candidate gene for schizophrenia (SZ) and bipolar disorder (BP), but its basic biology remains to be elucidated. Accumulating genetic evidence supports that DISC1 is associated with some aspects of cognitive functions relevant to SZ and BP. Here, we provide a summary of the current updates in biological studies of DISC1. Disrupted-In-Schizophrenia-1, preferentially expressed in the forebrain, has multiple isoforms with potential posttranslational modifications. Disrupted-In-Schizophrenia-1 protein occurs in multiple subcellular compartments, which include the centrosome, microtubule fractions, postsynaptic densities, actin cytoskeletal fractions, the mitochondria, and the nucleus. Recent studies have clarified that DISC1 mediates at least centrosome-dynein cascade and cyclic adenosine monophosphate (cAMP) signaling. Furthermore, both cytogenetic and cell biological studies consistently suggest that an overall loss of DISC1 function (either haploinsufficiency or dominant-negative, or both) may be associated with SZ and BP. On the basis of these findings, production of DISC1 genetically engineered mice is proposed as a promising animal model for SZ and BP. Several groups are currently generating DISC1 mice and starting to characterize them. In this review, the advantages and disadvantages of each animal model are discussed.     

Pituitary volume in pediatric obsessive-compulsive disorder.

BACKGROUND: Abnormalities in the limbic-hypothalamic-pituitary-adrenal (LHPA) axis have been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). To our knowledge, however, no prior study has measured pituitary gland volume in OCD. METHODS: Volumetric magnetic resonance imaging studies were conducted in 31 psychotropic drug-na?ve children (10 boys, 21 girls) aged 8-17 years and 31 case-matched healthy comparison subjects. RESULTS: Pituitary volume was significantly smaller in patients with OCD as compared with healthy control subjects (11% smaller). Smaller pituitary volume in patients with OCD was associated with increased compulsive but not obsessive symptom severity. Boys with OCD had smaller pituitary gland volumes compared with control boys (20% smaller). No significant differences in pituitary volume were observed between girls with OCD and control girls. Boys with OCD had significantly smaller pituitary volumes than girls with OCD (31% smaller), whereas control boys also had smaller pituitary gland volumes compared with control girls (21% smaller). CONCLUSIONS: These findings provide new evidence of reduced pituitary volume in pediatric OCD that seems to be more prominent in male patients. The observed alterations in pituitary volume are consistent with neuroendocrine studies that have reported abnormalities in the LHPA axis in OCD.     

Immune activation during pregnancy in mice leads to dopaminergic hyperfunction and cognitive impairment in the offspring: a neurodevelopmental animal model of schizophrenia.

BACKGROUND: Maternal viral infection is associated with increased risk for schizophrenia. It is hypothesized that the maternal immune response to viruses may influence fetal brain development and lead to schizophrenia. METHODS: To mimic a viral infection, the synthetic double strand RNA polyriboinosinic-polyribocytidilic acid (poly I:C) was administered into pregnant mice. Behavioral evaluations (thigmotaxis, methamphetamine [MAP]-induced hyperactivity, novel-object recognition test [NORT]), sensorimotor gating (prepulse inhibition [PPI]), and biochemical evaluation of the dopaminergic function of the offspring of phosphate-buffered saline (PBS)-treated dams (PBS-mice) and that of poly I:C-treated dams (poly I:C-mice) were examined. RESULTS: In juveniles, no difference was found between the poly I:C-mice and PBS-mice. However, in adults, the poly I:C-mice exhibited attenuated thigmotaxis, greater response in MAP-induced (2 mg/kg) hyperlocomotion, deficits in PPI, and cognitive impairment in NORT compared with the PBS-mice. Cognitive impairment in the adult poly I:C-mice could be improved by subchronic administration of clozapine (5.0 mg/kg) but not haloperidol (.1 mg/kg). Increased dopamine (DA) turnover and decreased receptor binding of D2-like receptors, but not D1-like receptors, in the striatum were found in adult poly I:C-mice. CONCLUSIONS: Prenatal poly I:C administration causes maturation-dependent increased subcortical DA function and cognitive impairment in the offspring, indicating a neurodevelopmental animal model of schizophrenia.     

Patterns of dysmorphic features in schizophrenia

Congenital dysmorphic features are prevalent in schizophrenia and may reflect underlying neurodevelopmental abnormalities. A cluster analysis approach delineating patterns of dysmorphic features has been used in genetics to classify individuals into more etiologically homogeneous subgroups. In the present study, this approach was applied to schizophrenia, using a sample with a suspected genetic syndrome as a testable model. Subjects (n = 159) with schizophrenia or schizoaffective disorder were ascertained from chronic patient populations (random, n = 123) or referred with possible 22q11 deletion syndrome (referred, n = 36). All subjects were evaluated for presence or absence of 70 reliably assessed dysmorphic features, which were used in a three‐step cluster analysis. The analysis produced four major clusters with different patterns of dysmorphic features. Significant between–cluster differences were found for rates of 37 dysmorphic features (P < 0.05), median number of dysmorphic features (P = 0.0001), and validating features not used in the cluster analysis: mild mental retardation (P = 0.001) and congenital heart defects (P = 0.002). Two clusters (1 and 4) appeared to represent more developmental subgroups of schizophrenia with elevated rates of dysmorphic features and validating features. Cluster 1 (n = 27) comprised mostly referred subjects. Cluster 4 (n = 18) had a different pattern of dysmorphic features; one subject had a mosaic Turner syndrome variant. Two other clusters had lower rates and patterns of features consistent with those found in previous studies of schizophrenia. Delineating patterns of dysmorphic features may help identify subgroups that could represent neurodevelopmental forms of schizophrenia with more homogeneous origins. © 2001 Wiley‐Liss, Inc.     

18~36月龄语言发育迟缓儿童的神经发育水平特点

目的 回顾性分析18~36月龄语言发育迟缓儿童神经发育特点,为后期评估、干预提供理论依据。方法 选取苏州大学附属儿童医院2018-2019年因语言问题首次就诊的18~36月龄婴幼儿,根据“0~6岁儿童神经心理发育量表”及“早期语言发育进程量表”结果分为单纯语言发育迟缓组与多能区发育迟缓组,比较两组儿童各能区发育、早期语言水平,以及孤独症筛查阳性检出率。结果 共有700例婴幼儿入选,两组间月龄(t=-1.73,P=0.09)、性别(χ²=2.06,P=0.15)差异无统计学意义;两组间年龄构成比存在差异(χ²=9.124 ,P=0.01)。多能区发育迟缓组在语言、大运动、精细运动、适应性及社交能区均更为落后(t=15.08,20.26,25.68,18.76,39.79,P＜0.001)。在早期语言水平方面,多能区发育迟缓组在总的早期语言发展水平、语音和语言表达、听觉感受理解、视觉相关语言方面较单纯语言发育迟缓组均更低(t=8.20,10.23,9.18,11.39,P＜0.001)。单纯语言迟缓组语言能区的落后与精细运动、适应性及社交DQ存在相关性(r=0.127,0.146,0.238,P＜0.001),而多能区发育迟缓组语言能区的落后与各能区DQ均存在相关性(r=0.154,0.392,0.390,0.435,P＜0.001);多能区发育迟缓组孤独症筛查阳性检出率更高(χ²=61.69,105.17,P＜0.05)。结论 早期语言发育迟缓儿童合并多能区落后时存在语言发育的显著落后,应进一步完善检查,注意识别神经发育障碍性疾病。