Biomedical subjects

Hilleke E Hulshoff Pol

Publications and source records attributed to Hilleke E Hulshoff Pol.

At least 19 recordsLinked to original sources

PubMed2021

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

Brain↗

PubMed2007

Hippocampal volume and subcortical white matter lesions in late life depression: comparison of early and late onset depression.

BACKGROUND: Reduced hippocampal volume and increased prevalence of subcortical white matter lesions are associated with both recurrent early onset depression (EOD) and late onset depression (LOD). It is not clear whether these two factors differentially affect the age of onset of first depression. Therefore, we wished to investigate the relationship between age of first depression onset and hippocampal volume, with adjustment for subcortical white matter lesions. METHODS: MRI brain scans were used to compare hippocampal volumes and white matter lesions between age matched female patients (>60 years) with recurrent EOD and LOD and healthy controls. RESULTS: When comparing the three groups and adjusting for age, the Mini-Mental State Examination score, total brain volume and total hippocampal volume were significantly smaller in patients with EOD compared with controls (5.6 vs 6.1 ml; p = 0.04). The prevalence of larger subcortical white matter lesions was higher in patients with LOD compared with patients with EOD (47% vs 8%; p = 0.002). Patients with LOD did not differ in hippocampal volume from patients with EOD or from controls. CONCLUSIONS: In late life depression, age of first depression onset may distinguish between different independent neuropathological mechanisms. A small hippocampus volume may be a neuroanatomical marker of EOD depression and larger subcortical white matter lesions could be an intermediate between cerebrovascular disease and LOD.

Age of Onset↗

PubMed2006

Genetic contributions to human brain morphology and intelligence.

Variation in gray matter (GM) and white matter (WM) volume of the adult human brain is primarily genetically determined. Moreover, total brain volume is positively correlated with general intelligence, and both share a common genetic origin. However, although genetic effects on morphology of specific GM areas in the brain have been studied, the heritability of focal WM is unknown. Similarly, it is unresolved whether there is a common genetic origin of focal GM and WM structures with intelligence. We explored the genetic influence on focal GM and WM densities in magnetic resonance brain images of 54 monozygotic and 58 dizygotic twin pairs and 34 of their siblings. For genetic analyses, we used structural equation modeling and voxel-based morphometry. To explore the common genetic origin of focal GM and WM areas with intelligence, we obtained cross-trait/cross-twin correlations in which the focal GM and WM densities of each twin are correlated with the psychometric intelligence quotient of his/her cotwin. Genes influenced individual differences in left and right superior occipitofrontal fascicle (heritability up to 0.79 and 0.77), corpus callosum (0.82, 0.80), optic radiation (0.69, 0.79), corticospinal tract (0.78, 0.79), medial frontal cortex (0.78, 0.83), superior frontal cortex (0.76, 0.80), superior temporal cortex (0.80, 0.77), left occipital cortex (0.85), left postcentral cortex (0.83), left posterior cingulate cortex (0.83), right parahippocampal cortex (0.69), and amygdala (0.80, 0.55). Intelligence shared a common genetic origin with superior occipitofrontal, callosal, and left optical radiation WM and frontal, occipital, and parahippocampal GM (phenotypic correlations up to 0.35). These findings point to a neural network that shares a common genetic origin with human intelligence.

Adolescent↗

PubMed2006

Gray and white matter density changes in monozygotic and same-sex dizygotic twins discordant for schizophrenia using voxel-based morphometry.

Global gray matter brain tissue volume decreases in schizophrenia have been associated to disease-related (possibly nongenetic) factors. Global white matter brain tissue volume decreases were related to genetic risk factors for the disease. However, which focal gray and white matter brain regions best reflect the genetic and environmental risk factors in the brains of patients with schizophrenia remains unresolved. 1.5-T MRI brain scans of 11 monozygotic and 11 same-sex dizygotic twin-pairs discordant for schizophrenia were compared to 11 monozygotic and 11 same-sex dizygotic healthy control twin-pairs using voxel-based morphometry. Linear regression analysis was done in each voxel for the average and difference in gray and white matter density separately, in each twin-pair, with group (discordant, healthy) and zygosity (monozygotic, dizygotic) as between subject variables, and age, sex and handedness as covariates. The t-maps (critical threshold value mid R:tmid R: > 6.0, P < 0.05) revealed a focal decrease in gray matter density accompanied by a focal increase in white matter density in the left medial orbitofrontal gyrus and a focal decrease in white matter density in the left sensory motor gyrus in twin-pairs discordant for schizophrenia as compared to healthy twin-pairs. Focal changes in left medial (orbito)frontal and left sensory motor gyri may reflect the increased genetic risk to develop schizophrenia. Focal changes in the left anterior hemisphere may therefore be particularly relevant as endophenotype in genetic studies of schizophrenia.

Brain↗

PubMed2006

MRI, volumetry, 1H spectroscopy, and cerebropetal blood flowmetry in childhood idiopathic anatomic megalencephaly.

PURPOSE: To evaluate cerebral abnormalities in childhood idiopathic anatomic megalencephaly (MC) by means of different magnetic resonance (MR) modalities. MATERIALS AND METHODS: MRI, volumetry, spectroscopy, and cerebropetal blood flowmetry were performed in six children with idiopathic anatomic MC, and seven volunteers. RESULTS: MRI revealed an increased ventricular system in five of six patients. A thalamic hamartoma was found in one patient and a Chiari I malformation was found in two. Volumetric analysis showed a disproportional increase of ventricular volume but normal subarachnoid cerebrospinal fluid (CSF) volume. Supratentorial volume was disproportionally increased compared to cerebellar volume. Intracranial volume correlated significantly with skull circumference. MR spectroscopy (MRS) N-acetyl aspartate/choline (NAA/Cho) peak ratios in WM were significantly higher in patients than in controls. Choline/creatine (Cho/Cr) peak ratios in WM were significantly lower in patients. Cortical gray matter (GM) MRS ratios were unaltered. Cerebropetal flow was increased in MC, possibly related to increased brain volume. CONCLUSION: This study reveals associated developmental anomalies for idiopathic anatomic MC. A relative ventriculomegaly was found, which should not be misinterpreted as true hydrocephalus. In contrast to metabolic MC, MRS showed no severe disturbances. Total intracranial volume is correlated to skull circumference and cerebropetal blood flow.

Aspartic Acid↗

PubMed2005

Focal brain matter differences associated with lifetime alcohol intake and visual attention in male but not in female non-alcohol-dependent drinkers.

The purpose of this study was to investigate whether current or lifetime alcohol intake is related to focal gray and white matter in healthy non-alcohol-dependent drinkers, and, if so, whether these densities are related to functional brain activity associated with visual attention. Voxel-based morphometric analyses of gray- and white-matter densities, and event-related potentials in response to a visual-attention task were determined in 47 male drinkers (current alcohol intake 20 drinks per week, lifetime alcohol intake 240 kg) and 44 female drinkers (current alcohol intake 15 drinks per week, lifetime alcohol intake 170 kg). All participants had a negative personal and family history of alcohol dependence to reduce possible confounding by genetic factors related to alcohol dependence. In males, mean lifetime alcohol intake was negatively associated with gray-matter density and positively associated with white-matter density in the right frontal gyrus (BA 6) and the right parietal region (BA 40). Right frontal (but not right parietal) gray and white matter in males correlated with the P3 amplitude of the event-related potentials elicited in a visual-attention task. In females, mean lifetime alcohol intake was not associated with gray- or white-matter density. Current alcohol intake was unrelated to gray or white matter in both males and females. In conclusion, lifetime alcohol intake is associated with focal gray-matter decreases and white-matter increases in the right frontal and right parietal brain regions in non-alcohol-dependent males, but not in females. These alcohol-related differences in focal brain matter in males are associated with differences in brain function related to visual attention. As the confounding effects of genetic factors were reduced, the present results may selectively relate to the effects of alcohol intake on focal brain matter.

Alcohol Drinking↗

PubMed2005

Increased gray-matter volume in medication-naive high-functioning children with autism spectrum disorder.

BACKGROUND: To establish whether high-functioning children with autism spectrum disorder (ASD) have enlarged brains in later childhood, and if so, whether this enlargement is confined to the gray and/or to the white matter and whether it is global or more prominent in specific brain regions. METHOD: Brain MRI scans were acquired from 21 medication-naive, high-functioning children with ASD between 7 and 15 years of age and 21 comparison subjects matched for gender, age, IQ, height, weight, handedness, and parental education, but not pubertal status. RESULTS: Patients showed a significant increase of 6% in intracranium, total brain, cerebral gray matter, cerebellum, and of more than 40% in lateral and third ventricles compared to controls. The cortical gray-matter volume was evenly affected in all lobes. After correction for brain volume, ventricular volumes remained significantly larger in patients. CONCLUSIONS: High-functioning children with ASD showed a global increase in gray-matter, but not white-matter and cerebellar volume, proportional to the increase in brain volume, and a disproportional increase in ventricular volumes, still present after correction for brain volume. Advanced pubertal development in the patients compared to the age-matched controls may have contributed to the findings reported in the present study.

Adolescent↗

PubMed2005

Brain anatomy in non-affected parents of autistic probands: a MRI study.

BACKGROUND: Autism is a neurodevelopmental disorder with an estimated genetic origin of 90%. Previous studies have reported an increase in brain volume of approximately 5% in autistic subjects, especially in children. If this increase in brain volume is genetically determined, biological parents of autistic probands might be expected to show brain enlargement, or at least intracranial enlargement, as well. Identifying structural brain abnormalities under genetic control is of particular importance as these could represent endophenotypes of autism. METHOD: Using quantitative anatomic brain magnetic resonance imaging, volumes of intracranial, total brain, frontal, parietal, temporal and occipital lobe, cerebral and cortical gray and white matter, cerebellum, lateral ventricle, and third ventricle were measured in biological, non-affected parents of autistic probands (19 couples) and in healthy, closely matched control subjects (20 couples). RESULTS: No significant differences were found between the parents of the autistic probands and healthy control couples in any of the brain volumes. Adding gender as a factor in a second analysis did not reveal a significant interaction effect of gender by group. CONCLUSIONS: The present sample of biological, non-affected parents of autistic probands did not show brain enlargements. As the intracranium is not enlarged, it is unlikely that the brain volumes of the parents of autistic probands have originally been enlarged and have been normalized. Thus, increased brain volume in autism might be caused by the interaction of paternal and maternal genes, possibly with an additional effect of environmental factors, or increased brain volumes might reflect phenotypes of autism.

Autistic Disorder↗

PubMed2005

Associations between alcohol intake and brain volumes in male and female moderate drinkers.

BACKGROUND: Alcohol-dependent individuals have brain volume loss. Possibly, moderate drinkers who are not alcohol dependent have similar but less prominent brain damage. The authors investigated whether current or lifetime alcohol intake is related to volumes of total brain, cerebellum, ventricles, peripheral cerebrospinal fluid, and cerebral gray and white matter in moderate drinkers. METHODS: The relation between current or lifetime alcohol intake and brain volumes of 47 male moderate drinkers (current alcohol intake 20 drinks per week, lifetime alcohol intake 240 kg) and 44 female moderate drinkers (current alcohol intake 15 drinks per week, lifetime alcohol intake 170 kg), all without a personal or family history of alcohol dependence, was determined using high-resolution magnetic resonance images, corrected for intracranial volume, age, and sex. RESULTS: In males, mean lifetime alcohol intake was positively associated with cerebral white matter volume, particularly in the frontal region. In females, mean lifetime alcohol intake was not associated with brain volumes. Current alcohol intake was unrelated to brain volumes in either males or females. CONCLUSIONS: Neither current nor lifetime alcohol intake is associated with decreases in brain volumes in male or female moderate drinkers. Because all participants had a negative personal and family history of alcohol dependence, the current results relatively purely concern the effects of moderate alcohol intake on brain volumes.

Adult↗

PubMed2004

Hippocampal changes and white matter lesions in early-onset depression.

BACKGROUND: Hippocampal volume reduction and increased prevalence of subcortical white matter lesions have been reported in late-life depression. We aimed to examine whether total number of subcortical white matter lesions were associated with reduced hippocampal volume in aged female subjects with early-onset depression (< 45 years) and healthy comparison subjects. METHODS: The study included 28 middle-aged and elderly subjects with major depression and 41 age-matched control subjects. Hippocampal, parahippocampal gyrus, and orbitofrontal cortex volumes were determined using manual tracing methods. White matter lesions were rated from T2-weighted MRI scans using a semiquantitative classification scale. RESULTS: After controlling for total brain volume and age, patients had reduced hippocampal volume due to right hippocampal volume decrease (2.84 mL vs. 3.12 mL, F = 16.6, p < .001). Parahippocampal and orbitofrontal volumes did not differ significantly between groups. Multiple linear regression analysis indicated that reduced hippocampal volume did not significantly correlate with total number of subcortical white matter lesions (t = .673, p = .518). CONCLUSIONS: Right hippocampal volume was reduced in aged female early-onset subjects with depression. Total number of subcortical white matter lesions was not associated with the decrease in right hippocampal volume. Our data suggest hippocampal involvement, independent of subcortical white matter lesions, in the neuropathology of early-onset depression.

Age of Onset↗

PubMed2004

A controlled study of brain structure in monozygotic twins concordant and discordant for schizophrenia.

BACKGROUND: We examined monozygotic twins concordant and discordant for schizophrenia to clarify the role of genetic and environmental factors in determining brain abnormalities. METHODS: Magnetic resonance imaging brain scans were obtained from 14 monozygotic twin pairs concordant and 10 monozygotic pairs discordant for schizophrenia, as well as 17 pairs of monozygotic control twins. Twenty-two discordant sibling-pairs and 56 pairs of unrelated control subjects were included to assess the extent of genetic control over these structures. RESULTS: Within-pair similarities for whole brain volume increased as pair members were more closely related genetically (monozygotic twins > siblings > unrelated control subjects). Schizophrenic twins, whether from concordant or discordant pairs, had smaller whole brain volumes than control twins. The probands of discordant pairs showed more abnormalities in hippocampal, third and lateral ventricular volumes than concordant twins. CONCLUSIONS: Whole brain volume is under high genetic control and smaller whole brain volume is a reflection of the genetic liability to develop schizophrenia. The variation in hippocampal and ventricular volumes within discordant monozygotic pairs indicates a role for environmental factors in determining these volume abnormalities in schizophrenia. Such factors may also underlie the more extensive morphometric deviations in patients from monozygotic discordant twins than in their counterparts from concordant twins.

Adolescent↗

PubMed2004

Gray and white matter volume abnormalities in monozygotic and same-gender dizygotic twins discordant for schizophrenia.

BACKGROUND: Whole brain tissue volume decreases in schizophrenia have been related to both genetic risk factors and disease-related (possibly nongenetic) factors; however, whether genetic and environmental risk factors in the brains of patients with schizophrenia are differentially reflected in gray or white matter volume change is not known. METHODS: Magnetic resonance imaging (1.5 T) brain scans of 11 monozygotic and 11 same-gender dizygotic twin pairs discordant for schizophrenia were acquired and compared with 11 monozygotic and 11 same-gender dizygotic healthy control twin pairs. RESULTS: Repeated-measures volume analysis of covariance revealed decreased whole brain volume in the patients with schizophrenia as compared with their co-twins and with healthy twin pairs. Decreased white matter volume was found in discordant twin pairs compared with healthy twin pairs, particularly in the monozygotic twin pairs. A decrease in gray matter was found in the patients compared with their co-twins and compared with the healthy twins. CONCLUSIONS: The results suggest that the decreases in white matter volume reflect the increased genetic risk to develop schizophrenia, whereas the decreases in gray matter volume are related to environmental risk factors. Study of genes involved in the (maintenance) of white matter structures may be particularly fruitful in schizophrenia.

Adult↗

PubMed2004

Reliability of brain volumes from multicenter MRI acquisition: a calibration study.

Multicenter studies can provide additional information over single center studies because of their increased statistical power. Because similar acquisition protocols are being used internationally for structural magnetic resonance imaging (MRI) studies of the human brain, volumetric MRI data studies seem suitable for this purpose. Possible systematic differences between sites should be avoided, however, particularly when subtle differences in tissue volume are being searched for, such as in neuropsychiatric diseases. In this calibration study, the brains of six healthy volunteers were (re)scanned with MR scanners from four different manufacturers at five different sites, using the local acquisition protocols. The images were segmented at a central reference site. The intraclass correlation coefficient (ICC) was determined for the whole brain, gray and white matter, cerebellum, and lateral and third ventricle volumes. When required, the processing algorithms were calibrated for each site. Calibration of the histogram analysis was needed for segmentation of total brain volume at one site and for gray and white matter volume at all sites. No (additional) calibration was needed for cerebellum and ventricle volumes. The ICCs were > or = 0.96 for total brain, > or = 0.92 for cerebellum, > or = 0.96 for lateral ventricle, > or = 0.21 for third ventricle, > or = 0.84 for gray matter, and > or = 0.78 for white matter volume. Calibration of segmentation procedures allows morphologic MRI data acquired at different research sites to be combined reliably in multicenter studies.

Adult↗

PubMed2004

Larger brains in medication naive high-functioning subjects with pervasive developmental disorder.

BACKGROUND: Are brain volumes of individuals with Pervasive Developmental Disorder (PDD) still enlarged in adolescence and adulthood, and if so, is this enlargement confined to the gray and/or the white matter and is it global or more prominent in specific brain regions. METHODS: Brain MRI scans were made of 21 adolescents with PDD and 21 closely matched controls. RESULTS: All brain volumes, except the white matter, were significantly larger in patients. After correction for brain volume, ventricular volumes remained significantly larger in patients. CONCLUSIONS: Patients showed a proportional, global increase in gray matter and cerebellum volume, and a disproportional increase in ventricular volumes. Thus, at least in high-functioning patients with PDD, brain enlargement may still be present in adult life.

Adult↗

PubMed2004

Focal white matter density changes in schizophrenia: reduced inter-hemispheric connectivity.

Gray matter changes have been demonstrated in several regions in schizophrenia. Particularly, the frontal and temporal cortices and amygdala-hippocampal region have been found decreased in volume and density in magnetic resonance imaging (MRI) studies. These abnormalities may reflect an aberrant neuronal network in schizophrenia, suggesting that white matter fibers connecting these regions may also be affected. However, it is unclear if particular white matter areas are (progressively) affected in schizophrenia and if these are related to the gray matter changes. Focal white matter changes in schizophrenia were studied in whole brain magnetic resonance images acquired from 159 patients with schizophrenia or schizophreniform disorder and 158 healthy comparison subjects using voxel-based morphometry. White matter density changes in the patients with schizophrenia were correlated to gray matter density changes and to illness severity. In the patients with schizophrenia, significant decreases in white matter density were found in the genu and truncus of the corpus callosum in the left and right hemisphere, in the right anterior internal capsule and in the right anterior commissure. No interactions between diagnosis and age were found. Increased illness severity was correlated with low density of the corpus callosum and anterior commissure. Decreased corpus callosum density correlated with decreased density of thalamus, lateral inferior frontal and insular gray matter in patients and controls and with decreased density of medial orbitofrontal and superior temporal gyri in patients. Decreased internal capsule and anterior commissure density correlated with increased caudate, and globus pallidus density in patients and controls. These findings suggest aberrant inter-hemispheric connectivity of anterior cortical and sub-cortical brain regions in schizophrenia, reflecting decreased hemispheric specialisation in schizophrenia.

Adult↗

PubMed2004

Magnetic resonance imaging of boys with attention-deficit/hyperactivity disorder and their unaffected siblings.

OBJECTIVE: To study the influence of increased familial risk for attention-deficit/hyperactivity disorder (ADHD) on brain morphology. METHOD: Volumetric cerebral measures based on whole brain magnetic resonance imaging scans from 30 boys with ADHD, 30 of their unaffected siblings, and 30 matched controls were compared. RESULTS: Both subjects with ADHD and their unaffected siblings displayed reductions in right prefrontal gray matter and left occipital gray and white matter of up to 9.1% (p < 0.05). Right cerebellar volume was reduced by 4.9% in subjects with ADHD (p = 0.026) but not in their unaffected siblings (p = 0.308). A 4.0% reduction in intracranial volume was found in subjects with ADHD (p = 0.031), while a trend was observed in their unaffected siblings (p = 0.068). CONCLUSIONS: The volumetric reductions in cortical gray and white matter in subjects with ADHD are also present in their unaffected siblings, suggesting that they are related to an increased familial risk for the disorder. In contrast, the cerebellum is unaffected in siblings, suggesting that the reduction in volume observed in subjects with ADHD may be more directly related to the pathophysiology of this disorder.

Adolescent↗

PubMed2003

Brain volumes as predictor of outcome in recent-onset schizophrenia: a multi-center MRI study.

Gray matter brain volume decreases have been found in patients with schizophrenia as compared to healthy control subjects measured by using Magnetic Resonance Imaging (MRI). An association has been suggested between decreased gray matter volume and poor outcome in chronically ill patients with schizophrenia. The present longitudinal multi-center study investigated whether gray matter volume at illness onset can predict poor outcome in recent-onset schizophrenia after a follow-up of approximately 2 years. An MRI calibration study was performed since scans of patients with recent-onset psychosis were conducted at three sites with 1.5 T MR scanners from two different manufacturers. Applying a linear scaling procedure on the histogram improved comparability between volume measurements acquired from images from the different scanners. Brain scans were obtained from 109 patients with recent-onset schizophrenia. Volumes of intracranium, total brain, cerebral gray and white matter, third and lateral ventricles, and cerebellum were measured. After a mean follow-up period of approximately 2 years, measurements of symptoms, functioning, need for care, and illness history variables were assessed. No significant correlations were found between the brain volume measures and any of these measures. Gray matter volume at illness onset does not predict outcome after 2 years in recent-onset schizophrenia.

Adolescent↗

PubMed2003

Global intellectual impairment does not accelerate with age in patients with schizophrenia: a cross-sectional analysis.

Neuropsychological studies show impairment in intellectual functions in schizophrenia patients. It is still unclear, however, whether intelligence scores decline progressively during the illness as compared to healthy subjects' scores. Longitudinal studies conducted so far have been restricted to relatively short time spans. The aim of this study is to investigate whether changes in intelligence scores accelerate with age in schizophrenia patients. In a cross-sectional design, performance of four subtests of the Wechsler Adult Intelligence Scale (WAIS) was analyzed in 112 schizophrenia patients and compared to that of 70 healthy subjects, across an age span of 40 years (16-56 years). A linear regression analysis was performed. A main effect on the total ratio score of the four tests was demonstrated between the two groups. No main effect of age and no interaction effect of age with group for the total ratio score were found. The results confirm that there is global intellectual impairment in schizophrenia patients at the onset of illness but no age-accelerated decline and are consistent with the neurodevelopmental hypothesis of schizophrenia.

Adolescent↗