Minor physical anomalies in schizophrenia

This study was conducted to investigate the value of using physical anomalies (PAs) to evaluate early prenatal injury in schizophrenia. PAs are minor abnormalities in development of the head, hands, and feet that are presumably associated with insult during the first trimester. Sixty-seven schizophrenic inpatients and 88 normal controls were evaluated for PAs. The schizophrenic patients showed significantly more anomalies than the controls. The difference remained significant even when patients were compared to controls of low socioeconomic status. Both male and female patients showed a high incidence of mouth abnormalities, and female patients showed a high incidence of abnormalities in head circumference. Patients with early age of onset (less than or equal to 18 years) had more physical anomalies than did later onset patients. This relationship was most noticeable for males. Physical anomalies were not associated with deficits on measures of vigilance, selective attention, or orientation.     

A study of cranial computertomograms in very early and early onset schizophrenia

Summary. The cranial computer-assisted tomograms of 19 patients suffering from schizophrenic psychoses with onset by age of 14 were examined. The emphasis was on the extent of the inner liquor spaces. Compared to healthy controls, at the beginning of illness a significant enlargement was revealed only in the patient group with very early onset schizophrenia (VEOS, onset prior to the age of 12), whereas children with early onset (EOS, 12 to 14 years of age) showed no significant brain pathology. As a second result, an increase in the extent of the inner liquor spaces seems to correlate with the duration of illness. It is therefore concluded that psychoses interfere with neurodevelopmental processes and cause more severe brain pathology in very young children, already detectable at the onset of the illness. EOS, on the other hand, induces progressive morphological abnormalities over the course of the illness. Received February 2, 2001; accepted July 11, 2001     

晚发性和早发性精神分裂症临床特征比较

目的：了解早发性和晚发性精神分裂症的临床特征。方法：用阳性症状量表（SAPS）、阴性症状量表（SANS）评定临床症状;临床疗效总评量表（CGI）、治疗中出现的症状量表（TESS）评定临床疗效及不良反应;用躯体异常量表（Waldrop scale）N量软体征。对早发性精神分裂症和晚发性精神分裂症患者各50例进行对照研究。结果：早发性精神分裂症遗传倾向明显,软体征异常率高,有更明显的阴性症状,治疗效果较差,不良反应更明显。晚发性精神分裂症女性明显多于男性,以幻觉、妄想、偏执观念为主要临床特征．结论：早发性和晚发性精神分裂症各有其临床特征。早发性比晚发性精神分裂症的遗传负荷和胚胎发育异常程度高,治疗效果和预后较差。     

Relationship between physical anomalies and age at onset of schizophrenia

Among 50 schizophrenic patients grouped by age at onset, the group with onset at or before age 18 had significantly more subjects with minor physical anomalies. These findings suggest that early-onset schizophrenia is associated with a more compromised CNS.     

锚蛋白重复序列3基因在早发性精神分裂症发生过程中的作用

目的探讨锚蛋白重复序列3(Ankyrin repeat 3,ANK3)基因在早发性精神分裂症发生过程中的作用。方法采用TaqMan探针等位基因分型技术检测310例早发性精神分裂症患者和399例健康对照ANK3基因rs10761482位点多态性,分析该位点与早发性精神分裂症的关联及其与发病年龄的关系,并调查患者母亲怀孕早期的环境因素,进一步分析ANK3基因与环境因素的交互作用。结果患者组与对照组ANK3基因rs10761482位点的基因型频率组间差异无统计学意义(x2=5.410,P=0.067),而患者组rs10761482 C等位基因频率高于对照组,有统计学意义(83.06%vs.78.07%,P=0.019);携带rs10761482 C等位基因患者发病年龄(13.7±0.1岁)明显早于不携带C等位基因患者发病年龄(16.1±0.3岁)(P=0.028);未发现ANK3基因与环境因素间之间存在交互作用(P>0.05)。结论 ANK3基因与早发性精神分裂症存在关联,其rs10761482多态位点可能是导致患者发病年龄提前的重要因素。     

Relationship of extrapyramidal symptoms to age at onset and drug treatment in middle-aged and elderly schizophrenic patients

The relationship between antipsychotic drugs and dyskinesias and other extrapyramidal symptoms (EPS) in schizophrenia is not simple. There is a need to study variables that may influence the occurrence of EPS in schizophrenic patients receiving drugs. The present study examined the relationship of age at onset of illness and treatment to the development of EPS in 122 middle-aged and elderly schizophrenic patients, 84 treated and 38 who had never received antipsychotic drugs. The illness had an early onset (before 45years, EOS) in 68 patients and a late onset (after 45years, LOS) in 54 patients. The patients were evaluated for dyskinesia and parkinsonism using abnormal involuntary movements scale (AIMS) and Simpson-Angus scale. The prevalence of dyskinesia and parkinsonism was similar in all the patient groups. The scores on limb-axial and severity subscales of AIMS were significantly higher in the treated than the untreated patients of the early onset group. This was not so with the late onset patients. The total parkinsonism score was higher among the treated, notably the LOS patients. The development of dyskinesia and parkinsonism in schizophrenia is possibly related to the age at onset of the illness. In late onset forms the ageing of the patient and a possible neurological abnormality related to schizophrenia might enhance the EPS-inducing effect of drugs.     

From bench to bedside: translating new research from genetics and neuroimaging into treatment development for early-onset schizophrenia

Objective: Children and adolescents with schizophrenia share a similar pattern of phenomenological, genetic and cognitive abnormalities to adults with schizophrenia. However, an early‐onset of schizophrenia (EOS) (prior to 18 years of age) is associated with a higher frequency of risk indicators associated with schizophrenia (e.g. developmental delays and familial spectrum disorders) and a worse long‐term outcome. This overview examines recent research on the neurobiological alterations, possible causes, developmental trajectory and treatment of EOS and attempts to identify gaps in the field. Method: The authors provide a selective review of major findings from genetics, neuroimaging and treatment studies of pediatric schizophrenia that were presented at a workshop sponsored by the National Institute of Mental Health. These data are synthesized in conjunction with preclinical studies into a model of the pathophysiology of EOS. Results: EOS is associated with a high frequency of cytogenetic abnormalities (e.g. velocardiofacial syndrome, sex chromosome anomalies) and other rare denovo chromosomal aberrations. Brain imaging research in adolescents with EOS has revealed a progressive loss of cortical grey matter post‐onset of psychosis and subtle abnormalities in white matter microstructure. Although EOS patients are more likely to be treatment‐refractory than their adult counterparts, there are substantial data that this subgroup is particularly responsive to clozapine. Conclusions: Genetic or environmental factors operating during adolescence that reduce frontal capacity might contribute to an EOS in susceptible individuals. Additional longitudinal studies of adolescents with schizophrenia are needed to better understand the relationship between structural changes in fronto‐limbic regions, stress responsivity, and cognitive and neurochemical development.     

Association between minor physical anomalies and lateral ventricular enlargement in childhood and adolescent onset schizophrenia

OBJECTIVE: The primary purpose of this study was to investigate the association between morphological abnormalities of brain and minor physical anomalies (MPAs) in childhood and adolescent onset schizophrenia. METHOD: Twenty-seven patients who had been diagnosed with schizophrenia according to DSM-IV criteria before 18 years of age were included in the study. MPAs were evaluated with the modified version of Waldrop scale (WS) by Green et al. Morphological abnormalities of brain was evaluated with ventricular-brain ratio (VBR) by using cerebral magnetic resonance imaging (MRI) examination. RESULTS: A significant positive correlation was observed between WS scores and VBRs. CONCLUSION: This result indicates a relationship between MPAs and lateral ventricular enlargement, and supports neurodevelopmental etiology in childhood or adolescent onset schizophrenia.     

Neurodevelopmental significance of minor and major congenital anomalies in neonatal high risk children

Minor and major congenital anomalies were studied in 395 neonatal risk children and 107 normal school children at the age of nine in the context of follow-up of the risk children. The purpose of the study was to evaluate the impact of early prenatal disturbances on the long term prognosis. Minor physical anomalies (MPA) were scored by a weighted scoring system modified from that of Waldrop and Halverson. The children with minor or major congenital anomalies performed worse in a cognitive test (WISC) and in a motor performance test. The differences were significant in the neonatal risk group. There were more small for gestational age (SGA) children in the anomaly group of the neonatal risk group as a whole and in the low birthweight group than in the non-anomaly group. Hyperactivity was associated with a high MPA score in the comparison group, but not in the study group. The results are consistent with earlier reports of associations between intrauterine growth disturbance and minor physical anomalies. Our findings suggest an additive effect of prenatal insults and neonatal risk factors in the origin of neurodevelopmental disturbances.     

Internal consistency of Waldrop Physical Anomaly Scale in schizophrenic patients

The aim of the study is to investigate the reliability (internal consistency) of the Waldrop Physical Anomaly Scale in patients with schizophrenia. The subjects were 76 schizophrenic patients (43 men, 33 women) and 82 normal controls (42 men, 40 women) of Bulgarian origin who were examined for minor physical anomalies. The correlations between the anomalies are low in schizophrenia, which indicates poor internal consistency of the scale, probably due to the heterogeneity of the anomalies in terms of location, character, and time of prenatal development. Some sex-related differences in the scale's reliability are indicated. The findings suggest the necessity of a more comprehensive scale by including informative morphogenetic variants, which can provide reliable anomaly assessment, distinguishing between minor malformations and phenogenetic variants and indicating the possible period of prenatal adversity.     

Influence of Sex on Age at Onset of Schizophrenia

Abstract: The age at onset of schizophrenia was investigated in 2,417 inpatients (1,433 males and 984 females) meeting the DSM-III criteria for schizophrenia. About 80% of the patients became schizophrenic before the age of 30. The mean age at onset of the male patients was slightly earlier than that of the female patients. There was a higher cumulative percentage of the male patients who became affected at each age quinquennium. More men than women became schizophrenic before the age of 30.     

Do Women without a Family History of Schizophrenia Have a Later Onset of Schizophrenia ?

Abstract: The relation among age at onset of schizophrenia, sex and the presence or absence of first-degree relatives with schizophrenia was investigated in 2,417 inpatients meeting the DSM-111 criteria for schizophrenia. The mean age at onset of female schizophrenic patients without a family history of this illness was slightly later than that of any of the other three groups (male familial, female familial and male nonfamilial groups). The female nonfamilial group developed schizophrenia after the age of 25 and 30 more frequently than the male familial group and female familial or male nonfamilial group, respectively.     

Very early onset and greater vulnerability in schizophrenia: A clinical and neuroimaging study

Although schizophrenia has been diagnosed in children, this group of disorders has received too little attention in the clinical and research literature. Preliminary data suggest that early onset schizophrenia (EOS) and very early onset schizophrenia (VEOS) tend to have a worse outcome than adult onset schizophrenia, and seem to be related to a greater familial vulnerability, due to genetic, psychosocial, and environmental factors. Recently, advanced neuroimaging techniques have revealed structural and functional brain abnormalities in some cerebral areas. This paper reports on a case diagnosed as VEOS, with premorbid year-long psychopathological history. The patient showed atypical proton magnetic resonance spectroscopy findings, and normal brain and spine computer tomography and brain magnetic resonance images.     

早发精神分裂症静息态脑功能低频振幅研究

目的通过静息态功能磁共振研究早发未用药精神分裂症患者局部脑功能低频振幅(amplitude of low-frequency fluctuation,ALFF)的变化,探讨其静息态下功能异常的脑区。方法收集20例早发未用药精神分裂症患者与20名性别、年龄、受教育年限相匹配的正常对照,分别对其进行全脑静息态功能磁共振扫描,计算ALFF值。结果与对照组相比,患者组左侧额上回、左侧楔前叶、左侧扣带回、左侧枕叶、左侧海马旁回、左侧距状沟ALFF值增高(P0.05,Alpha Sim校正),右侧颞上回和右侧小脑后叶ALFF值降低(P0.05,Alpha Sim校正)。结论早发精神分裂症患者在静息态下有多处脑区ALFF值改变,提示其在静息态下存在脑功能异常。     

晚发性精神分裂症的磁共振对照研究

目的：了解晚发生性精神分裂症患者脑共振的变化特征。方法：选择１７例晚发性精神分裂症病人,和正常对照组１７例检测脑的磁共振,以第三脑室宽距,侧脑室间距,侧脑室体部最大间距、左、右颞角宽度,额叶脑兆宽度及顶叶脑沟宽度为观察点。结果：发现病例组异常率为５２．９４％,海马异常诲为４１．１８％,与正常对照组相比,第三脑室、左颞角宽度、额叶脑沟宽度和顶叶脑沟宽度有显著差异。结论：晚发性精神分裂症病人的海马、左     

Does family history of schizophrenia influence age at onset of schizophrenia?

The relation between age at onset of schizophrenia diagnosed using DSM-III criteria and the presence or absence of this illness among first-degree relatives was investigated in 2417 patients. The mean age at onset among those with a family history of schizophrenia was slightly and nonsignificantly earlier than that of schizophrenic patients without a positive family history. The former developed their illness before the age of 25 years more frequently than did the latter.     

Schizophrenia: age at onset, gender and familial risk

In a family history study of 366 schizophrenic probands and their 1851 first-degree relatives, we found a relationship between age at onset of psychosis in the male probands and the risk for schizophrenia in their relatives. The relatives of male schizophrenic probands whose onset of psychosis occurred when they were younger than 17 years of age had an increased risk of schizophrenia when compared with the relatives of male probands with an age at onset greater than 17. We did not find an association between age at onset of psychosis in the female probands and familial risk. Cox proportional hazards models permitted us to examine the relationship between age at onset of psychosis in the probands and familial risk while controlling for possible confounding effects.     

Minor physical anomalies and schizophrenia spectrum disorders: a prospective investigation

OBJECTIVE: The authors prospectively assessed the relationship between minor physical anomalies identified in childhood and adult psychiatric outcome. METHOD: In 1972, minor physical anomalies were measured in a group of 265 Danish children ages 11-13. The examination was part of a larger study investigating early signs of schizophrenia spectrum disorders. Many of the subjects had a parent with schizophrenia, leaving them at high risk for developing a schizophrenia spectrum disorder. In 1991, adult psychiatric outcome data were obtained for 91.3% (N=242) of the original subjects, including 81 who were at high risk. RESULTS: Individuals with a high number of minor physical anomalies developed schizophrenia spectrum disorders significantly more often than they developed a no mental illness outcome. Further, individuals with a high number of minor physical anomalies tended to develop schizophrenia spectrum disorders more often than other psychopathology. Among individuals at genetic high risk, higher numbers of minor physical anomalies may interact with pre-existing vulnerabilities for schizophrenia to increase the likelihood of a schizophrenia spectrum disorder outcome. CONCLUSIONS: Minor physical anomalies may provide important clues to understanding schizophrenia spectrum disorders from a neurodevelopmental perspective. Minor physical anomalies appear to signal stressors relevant to schizophrenia spectrum development, especially in those at genetic risk for schizophrenia.     

有遗传史的精神分裂症患者某些特征研究

目的:探讨首发精神分裂症患者的微小躯体异常(MPAs)与阴性症状及语词记忆缺陷的关系。方法:对36例有家族史和50例无家族史的首发精神分裂症患者进行躯体异常量表(W S)、阳性和阴性症状量表(PANSS)评定,并在恢复期进行选择性提醒测验。结果:有家族史组MPAs评分异常的比例显著高于无家族史组(P<0.05);有家族史组PANSS总分、阴性因子分显著高于无家族史组,其中阴性症状子项目中情感迟钝、抽象思维困难、交流缺乏自发性和流畅性3项评分显著高于无家族史组;有家族史组语词记忆10次通过率低;回忆总数、保持数、长时再现数及恒定长时再现数均低于无家族史组。结论:有家族史的精神分裂症患者MPAs异常比例高,阴性症状较多,语词记忆能力也明显较差,反映遗传可产生多方面影响。     

Study of anticipation in Chinese families with schizophrenia

The anticipation phenomenon is an important aspect in several genetic disorders in which the age at onset (AAO) decreases and the severity of illness increases in successive generations. This phenomenon has been reported in several schizophrenic family studies, and expanded repeat mutations are implicated. In the present study, we investigate the anticipation phenomenon in Chinese schizophrenic families. We compare the AAO between two generations of 38 unilinear schizophrenic families. Intergenerational comparisons show that the AAO was significantly earlier in the offspring generation (mean AAO, 22.2 years) than that in the parental generation (mean AAO, 31.0 years) (P < 0.001). When only including the offspring generation who married, the AAO difference between the two generations was not significant (28.4 years vs 31.0 years, P = 0.151). Our findings suggest that a selection bias in the parental group might greatly impact the study of anticipation in schizophrenia. Other unavoidable biases associated with these analyses are discussed in the text.