VBR in schizophrenia: relationship to family history of psychosis and season of birth

Ventricular enlargement has been consistently demonstrated in schizophrenia using both CT and MRI. Despite this, the structural changes that underlie increased ventricle-brain ratio (VBR) and its relationship to environmental factors (intrauterine viral exposure, obstetric complications, etc.) and family history of schizophrenia remain poorly defined. Increased VBR has been shown in some studies to correlate with an absence of family history of schizophrenia and with Winter-Spring birth. In an attempt to obtain a clearer picture of the contribution of environmental and genetic factors to VBR, we studied 54 patients with DSM III-R schizophrenia. VBR was determined from head CT scans via computerized planimetry. Family history of psychosis and non-psychotic mood disorder was determined with the family informant method. Season of birth was encoded in several ways, including season, trimester and dichotomously. Patients without a family history of psychosis had significantly larger VBR than patients with such a history; family history of mood disorder was not related to VBR. Season of birth was not predictive of VBR. Family history of psychosis and season of birth were not related to each other. These results are in line with prior work demonstrating an association between increased VBR and sporadic (non-familial) schizophrenia. We did not find a relationship between VBR and season of birth, which suggests that risk of perinatal viral exposure and other seasonal environmental factors may not account for the ventricular enlargement in non-familial schizophrenia observed in our sample.     

Structural brain abnormalities in schizophrenia: a family study

Structural brain abnormalities such as ventricular enlargement are robust correlates of schizophrenia, but the degree of difference compared with unrelated normal controls is only moderate (< 1 standard deviation), and only 40% of patients have values on these measures that fall outside of the normal distribution. Family studies can help to clarify the meaning of this overlap by controlling for some of the non-schizophrenia-related genetic variation in neuroanatomical traits. Computerized tomographic scans of the brain were used to measure ventricular and sulcal cerebrospinal fluid (CSF) to brain ratios (VBR and SBR) for each hemisphere in 16 pairs of discordant siblings from the Copenhagen Schizophrenia High-Risk Project. Schizophrenics' values for VBR and SBR exceeded those of their nonschizophrenic siblings in 75% of the pairs; on average, patients' values on these measures were 1 and 5 standard deviations larger, respectively, than those of their nonschizophrenic siblings. Sulcal and left hemisphere effects were significantly more pronounced than ventricular and right hemisphere effects. After controlling for between-family variation, structural brain abnormalities appear to be more prevalent and more pronounced in schizophrenia than has previously been assumed, with relatively greater deviation observed for cortical and left hemisphere measures of CSF space enlargement.     

Low birth weight and ventricular enlargement in a high-risk sample.

Studied the relation between adult ventricle size and perinatal complications and birth weight using Ss from a Danish high-risk sample previously studied by 2 of the present authors (1965) in a longitudinal study of children and subsequently diagnosed in a study by F. Endicott and R. Spitzer (1972). Of the 58 28–37 yr olds available for the present study, 15 had been diagnosed as schizophrenic, 18 as borderline, and 25 as having no mental illness. 10 schizophrenics, 10 borderlines, and 14 normals were given computerized tomography scans. Results show ventricular enlargement was significantly negatively related to length and weight at birth and to midwife ratings of neonate prematurity. A lack of association was found between ventricle brain ration (VBR) and composite complication score. Results suggest that enlarged ventricles might be associated with insults occurring in utero. The possibility that a fetal viral infection caused CNS system damage and consequent atrophy as measured by VBR is hypothesized. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

White matter atrophy, ventricular dilation, and intellectual functioning following traumatic brain injury.

Examined the role in traumatic brain injury (TBI) of injury severity measured by the Glasgow Coma Scale (GCS), white matter atrophy identified by various magnetic resonance imaging (MRI) morphometric techniques, and postinjury intellectual functioning measured with the Wechsler Adult Intelligence Scale—Revised (WAIS—R). MR images of 31 female and 33 male TBI patients were used to calculate corpus callosum (CC) areas, ventricular volumes (estimates of white matter loss), and parenchymal volumes. Results indicated that the men were on the average more severely injured, as indicated by significantly lower GCS scores. CC size correlated significantly with the ventricle-to-brain ratio (VBR), but no significant correlations were found between CC size and WAIS—R scores. Significant correlations were found for men only between VBR and Performance IQ and between VBR and the Digit Symbol subtest of the WAIS—R. Implications for the roles of white matter atrophy and intellectual functioning in TBI are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive functioning and neuroanatomic volume measures in schizophrenia.

Magnetic resonance imaging (MRI) and neuropsychological tests were administered to 68 patients with schizophrenia and 68 healthy controls. MRIs were analyzed with a partially automated segmentation method that quantifies the volume of each cerebral hemisphere and its cerebrospinal fluid (CSF). Whereas patients had higher ventricular-brain ratio (VBR), ventricular CSF (vCSF) volume was equivalent to controls. Brain volume was lower. Cognitive function did not correlate with VBR or vCSF volume in either group, but cognitive function did correlate with brain volume. Divided as deficit (DF) and nondeficit (NDF), only DF patients had lower brain volume than controls. Whereas NDF patients showed little correlation between anatomy and cognitive function, there were more correlations between brain volume and cognition in DF patients. Changes in DF/NDF subtype with time and treatment reduced the significance of these findings. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"White matter atrophy, ventricular dilation, and intellectual functioning following traumatic brain injury": Correction.

Reports an error in the original article by S. C. Johnson et al (Neuropsychology, 1994[July], Vol 8[3], 301–315). On page 309, Figure 2 was printed upside down. Figures are provided in the correct position. (The following abstract of this article originally appeared in record 1994-38110-001.) Examined the role in traumatic brain injury (TBI) of injury severity measured by the Glasgow Coma Scale (GCS), white matter atrophy identified by various magnetic resonance imaging (MRI) morphometric techniques, and postinjury intellectual functioning measured with the Wechsler Adult Intelligence Scale—Revised (WAIS—R). MR images of 31 female and 33 male TBI patients were used to calculate corpus callosum (CC) areas, ventricular volumes (estimates of white matter loss), and parenchymal volumes. Results indicated that the men were on the average more severely injured, as indicated by significantly lower GCS scores. CC size correlated significantly with the ventricle-to-brain ratio (VBR), but no significant correlations were found between CC size and WAIS—R scores. Significant correlations were found for men only between VBR and Performance IQ and between VBR and the Digit Symbol subtest of the WAIS—R. Implications for the roles of white matter atrophy and intellectual functioning in TBI are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neighborhood risk factors for low birthweight in Baltimore: a multilevel analysis

OBJECTIVES: Past research on low birthweight has focused on individual-level risk factors. We sought to assess the contribution of macrolevel social factors by using census tract-level data on social stratification, community empowerment, and environmental stressors. METHODS: Census tract-level information on social risk was linked to birth certificate records from Baltimore, Md, for the period 1985 through 1989. Individual level factors included maternal education, maternal age, medical assistance health insurance (Medicaid), and trimester of prenatal care initiation. Methods of multilevel modeling using two-stage regression analyses were employed. RESULTS: Macrolevel factors had both direct associations and interactions with low birthweight. All individual risk factors showed interaction with macrolevel variables; that is, individual-level risk factors for low birthweight behaved differently depending upon the characteristics of the neighborhood of residence. For example, women living in high-risk neighborhoods benefited less from prenatal care than did women living in lower-risk neighborhoods. CONCLUSIONS: Multilevel modeling is an important tool that allows simultaneous study of macro- and individual-level risk factors. Multilevel analyses should play a larger role in the formulation of public health policies.     

Inhibition of bFGF activity by complement C1s: covalent binding of C1s with bFGF

Several recent studies have reported an association between midline cerebral malformations (e.g., corpus callosum, cavum septum pellucidum) and schizophrenia. The authors investigated whether absence of the adhesio interthalamica (AI), a midline structure that develops in concert with prominent features of the ventricular system soon after the bridge from the late embryonic stages to early fetal life, might constitute a marker of early developmental neuropathologic changes in schizophrenia. Eighty-two patients (54 men, 28 women) with a diagnosis of first-episode schizophrenia (FES) were recruited from consecutive admissions to a psychiatric inpatient service. Fifty-two healthy control subjects (30 men, 22 women) were recruited and matched to the patient sample on distributions of sex and age. Magnetic resonance imaging studies were performed, and the presence versus absence of the AI was determined for each subject. The length and volume of the third ventricle were measured for each subject. The AI was found to be absent more often among patients with FES compared with control subjects, and patients without an observable AI also had larger third-ventricle volumes. These differences in presence or absence of the AI observed in vivo (but not in a comparable postmortem sample of histologically fixed and prepared brain slices), which are likely related to third-ventricle enlargement, may represent yet another early developmental marker of cerebral malformation among patients with FES.     

Abnormal neurological findings at first admission in patients with schizophrenia or schizophreniform disorders. Results of computer tomography and measurement of regional cerebral blood flow

Forty-five patients with schizophrenia or schizophreniform disorder admitted to hospital for the first time had a neurological examination, including integrative sensory and complex motor acts, by a trained neurologist. The patients were studied by CT and regional cerebral blood flow as well. A control group of 24 healthy volunteers was included. The patients had significantly more neurological abnormalities (NA) than the healthy volunteers. Medication did not explain the discrepancy. The NA were associated with sulcal enlargement and smaller brains as visualized by CT but not with ventricular enlargement. There was no association between the regional flow values and NA.     

Somatosensory Processing and Schizophrenia Liability: Proprioception, Exteroceptive Sensitivity, and Graphesthesia Performance in the Biological Relatives of Schizophrenia Patients.

In the present study, the authors examined somatosensory processing in 30 biological relatives of persons with schizophrenia (hereafter called "schizophrenia relatives"), 30 biological relatives of persons with bipolar affective disorder (psychiatric family control subjects), and 30 healthy control subjects with no family history of psychopathology. All 3 groups completed a weight discrimination task, a 2-point discrimination task, and a complex cognitive somatosensory task (i.e., graphesthesia). The schizophrenia relatives performed significantly worse on all 3 somatosensory tasks compared with both the healthy control subjects and the bipolar relatives. The healthy control subjects and psychiatric family control subjects showed no significant differences on any of the somatosensory tasks. Within the weight discrimination and 2-point discrimination tasks, schizophrenia relatives showed group differences on the d' index, the measure of sensitivity, whereas all 3 groups did not differ on lnβ, the measure of response bias, suggesting a genuine difference in weight and touch sensitivity. The d' value of the weight discrimination task was significantly associated with both the cognitive-perceptual factor and negative symptom factor of the clinical questionnaire (e.g., Schizotypal Personality Questionnaire; SPQ), whereas the 2-point discrimination d' value and graphesthesia scores were significantly associated only with the cognitive-perceptual factor of the SPQ. Implications for the possible relation between somatosensory task performance and schizophrenia liability are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Maternal nutrition and socio-economic status as determinants of birthweight in chronically malnourished African women

The birthweight is the most important determinant of mortality and morbidity in the neonatal period and may have an influence on health in adult life. The high rate of low birthweight in developing countries is therefore a major health problem. Maternal malnutrition is usually assumed to be a causal factor but other environmental factors are also involved. In this study we analysed maternal nutritional and socio-economic factors as determinants of birthweight in term infants from a rural African society characterised by a high rate of chronic malnutrition. Relations of maternal weight, gestational weight gain, parity, socio-economic status and infant sex with birthweight were analysed in 1,477 women and child pairs. The selected women were followed from early pregnancy and had an uncomplicated delivery at term of a living singleton child. The gestational weight gain was 5.6 (SD 6.0) kg and the mean birthweight 2.933 kg (SD 408). Maternal weight, representing the maternal long-term nutritional situation, was the most important independent determinant of birthweight, accounting for 13.0% of the variance in birthweight. The weight gain, representing the short-term nutritional situation, explained only 5.6% of the variance. Birthweight increased by 20 g (CI 18-23) for each kg maternal weight and by 15 g (CI 12-18) for each kg gestational weight gained. The socio-economic difference in birth-weight was 153 g (CI 109-196) 88 of which (CI 48-128) remained unexplained after adjustment for differences in maternal weight, parity and gender. Improved long-term nutritional situation and living conditions seems to be the most important prerequisites to counteract low birthweight in developing countries.     

Structural brain abnormalities in the major psychoses: A quantitative review of the evidence from computerized imaging.

The neuroimaging literature on structural brain abnormalities in the major psychoses is quantitatively reviewed. The mean effect size for studies of lateral ventriculomegaly in schizophrenia (d?=?.70) corresponded to 43% nonoverlap between the distributions of schizophrenics and control Ss. Planimetry yielded larger effects than linear methods of ventricular size estimation. Although enlargement of the third ventricle was comparable to that of lateral ventriculomegaly (d?=?.66), it was found to be significantly greater after differences in measurement method were taken into account. The average cumulative length of hospitalization, adjusted for patients' age and duration of illness, predicted ventriculomegaly in schizophrenia. Studies on schizophrenia and affective disorder differed neither in the extent of reported ventriculomegaly nor in the amount of "cortical atrophy." (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurogenic inflammation in the gastrointestinal tract of the rat

To estimate the risk of repeat low birthweight deliveries among women whose first child was very low birthweight (less than 1500 g), a retrospective cohort of women who had their first and second children in Washington state between 1984 and 1991 was studied. After adjustment for potential confounding factors, a woman whose first infant was very low birthweight experienced an 11.5-fold increased risk of delivering a low birthweight (less than 2500 g) second infant (relative risk 11.5, 95% confidence interval 5.4 to 24.4). Women with a very low birthweight first infant also had a significantly increased risk of repeat very low birthweight infant (p < 0.0001). Women with a previous very low birthweight delivery are at increased risk of repeat low and very low birthweight infants. This high-risk group may benefit from education regarding recurrence risk and modification of factors associated with low birthweight, as well as good prenatal care.     

Quantitative MR volumetry in Alzheimer's disease. Topographic markers and the effects of sex and education

We determined topographic selectivity and diagnostic utility of brain atrophy in probable Alzheimer's disease (AD) and correlations with demographic factors such as age, sex, and education. Computerized imaging analysis techniques were applied to MR images in 32 patients with probable AD and 20 age- and sex-matched normal control subjects using tissue segmentation and three-dimensional surface rendering to obtain individualized lobar volumes, corrected for head size by a residualization technique. Group differences emerged in gray and white matter compartments particularly in parietal and temporal lobes. Logistic regression demonstrated that larger parietal and temporal ventricular CSF compartments and smaller temporal gray matter predicted AD group membership with an area under the receiver operating characteristic curve of 0.92. On multiple regression analysis using age, sex, education, duration, and severity of cognitive decline to predict regional atrophy in the AD subjects, sex consistently entered the model for the frontal, temporal, and parietal ventricular compartments. In the parietal region, for example, sex accounted for 27% of the variance in the parietal CSF compartment and years of education accounted for an additional 15%, with women showing less ventricular enlargement and individuals with more years of education showing more ventricular enlargement in this region. Topographic selectivity of atrophic changes can be detected using quantitative volumetry and can differentiate AD from normal aging. Differential effects of sex and years of education can also be detected by these methods. Quantification of tissue volumes in vulnerable regions offers the potential for monitoring longitudinal change in response to treatment.     

The relationship between structural brain imaging and histopathologic findings in schizophrenia research

The suggestion that schizophrenia may involve a neurodegenerative process has emanated from the highly replicated finding of ventricular enlargement in brain images of patients with this disorder. These investigations have provided a direct impetus for recent histopathologic studies seeking evidence of a neurodegenerative process in the brains of subjects with schizophrenia. Whereas most postmortem studies have reported the presence of atrophy and/or neuronal loss in several corticolimbic regions of subjects with schizophrenia, no quantitative study, to date, has detected an increase in the number of glial cells. For this reason the changes observed in postmortem schizophrenic brain are not consistent with a typical adult pattern of neuronal degeneration, such as that seen in Huntington's disease. Because several studies have reported various changes in layer II of the anterior cingulate, prefrontal, and entorhinal cortices, the histopathologic findings described are compatible with the idea that schizophrenia involves a disturbance of the "inside-out" migration or differentiation of cortical neurons that normally occurs during ontogenesis. A neurodevelopmental perturbation early in life could result in discrete alterations of corticolimbic circuitry that eventually contribute to the appearance of schizophrenic symptoms during adolescence and adulthood.     

Birthweight-specific trends in perinatal mortality by hospital category in South Australia, 1985-1990

OBJECTIVE: To investigate differences by birthweight in risk of perinatal death between level 3 hospitals (which provide care for high risk pregnancies and neonatal intensive care) and other hospitals in South Australia, using perinatal data for the 1985-1990 period. DESIGN: Analysis of birthweight-specific trends in risk of perinatal death by hospital category for singleton births, adjusting for risk factors. SUBJECTS: 114 725 singleton births of at least 400 g birthweight (or at least 20 weeks' gestation) born in hospitals in the 1985-1990 period and notified to the perinatal data collection. MAIN OUTCOME MEASURE: The relative odds of a perinatal death, as opposed to a live birth which survived the neonatal period. RESULTS: Births at level 3 hospitals had a higher crude risk of perinatal death than those at other hospitals, but this was due to the higher frequency of low birthweights at level 3 hospitals. For birthweights under 2000 g, and especially for the very low birth-weights, there was a higher risk at non-level-3 than level 3 hospitals. There was also the unexpected finding that births at level 3 hospitals in the 2500-2999 g range had a comparatively high risk of perinatal death. There was little difference in risk for births of higher birthweight. CONCLUSIONS: The greatly reduced risk of perinatal death in level 3 hospitals for babies with birthweights under 2000 g seems likely to be due to the specialist services in these hospitals. Further investigation is required to determine why babies in the 2500-2999 g range of birthweights had a comparatively high risk of perinatal death at these hospitals. This appears to be due, at least in part, to an excess contribution of deaths from congenital abnormalities. Also, it seems that the higher prevalence of complications in pregnancy in level 3 hospitals, and the transfers for induction of labour after intrauterine fetal death, would have made a contribution. These same factors may also have affected the risk in level 3 hospitals for higher birthweight births.     

Association study of a functional catechol-O-methyltransferase gene polymorphism in Japanese schizophrenics

Catechol-O-methyltransferase (COMT) is an enzyme which inactivates catecholamine neurotransmitters by methylation, and is considered a candidate for involvement in schizophrenia. A functional COMT gene polymorphism influencing the enzyme activities, the high activity (val-108) and the low activity allele (met-108), was recently confirmed. We investigated a genetic association between schizophrenia and the COMT gene polymorphism in 150 Japanese schizophrenics and controls. We detected the low activity met-108 allele more frequently in schizophrenics than in the controls, and found that subjects sharing the met-108 allele (val/met and met/met) are significantly more common in the patients than in the controls. The results suggest that the low activity met-108 allele may be involved in susceptibility for schizophrenia.     

Chromosomal variability in the genus Nycticebus

The outcome of pregnancy was studied in 148 women over a two year period in a rural area of Kenya as part of a prospective longitudinal study whose main objective was to study the functional effects of mild to moderate malnutrition. Data were collected on maternal anthropometric variables monthly, haemoglobin levels were determined by blood samples taken every six months, food intake was based on two days each month of actual weight and recall. Each woman's past reproductive history was established at the beginning of the study. Birth weight was taken and recorded within seventy two hours of delivery. Discriminant analysis was used to identify predictors of low birthweight. The analysis was based on 123 cases who had complete data on all the variables used in the equation. Of those included in the analysis, 14 women (11%) delivered low birthweight babies and 109 had normal birthweight babies. Results of the discriminant analysis showed that mid upper arm circumference (MUAC), body mass index (BMI), Blood haemoglobin levels (HB) and socioeconomic status (SES), are the best predictors of low birthweight. Ranked in order of relative contribution to birthweight they are BMI, HB, MUAC and SES. Low birthweight prevalence was determined as being 11.2 per cent. Eighty per cent of all known cases were correctly classified using the four variables. As a screening tool for low birthweight this model with four variables has 93% sensitivity, 78.4% specificity, 35.13% positive predictive value and 98.98% negative predictive value. The results suggest that it is possible to identify women at high risk for delivering low birthweight babies at the community level.     

Determinants of Benton Facial Recognition Test performance in normal adults.

Clinical investigations have found that lesions of the right cerebral hemisphere can disrupt face perception. Much less is known about the determinants of facial discrimination in healthy adults, although age-related differences in many cognitive abilities have been shown to correlate with simple processing speed and variation in regional brain volumes. In this study, 174 healthy adults between the ages of 20 and 92 were asked to match pictures of unfamiliar faces. After their performance was regressed on age, sex, education, and perceptual comparison speed, adding terms for frontal lobe volume, nonfrontal volume, and ventricle-to-brain ratio (VBR) derived from magnetic resonance imaging improved the model and accounted for 35% of the variance in facial discrimination. VBR and processing speed alone accounted for nearly 34% of the variance. These findings suggest that both normal atrophic brain changes and decreases in processing speed contributes to individual differences in facial discrimination. (PsycINFO Database Record (c) 2010 APA, all rights reserved)