Atypical brain structure mediates reduced IQ in young adults born preterm with very low birth weight.

Preterm birth with very low birth weight (VLBW) confers heightened risk for perinatal brain injury and long-term cognitive deficits, including a reduction in IQ of up to one standard deviation. Persisting gray and white matter aberrations have been documented well into adolescence and adulthood in preterm born individuals. What has not been documented so far is a plausible causal link between reductions in cortical surface area or subcortical brain structure volumes, and the observed reduction in IQ. The NTNU Low Birth Weight in a Lifetime Perspective study is a prospective longitudinal cohort study, including a preterm born VLBW group (birthweight ≤1500 g) and a term born control group. Structural magnetic resonance imaging data were obtained from 38 participants aged 19, born preterm with VLBW, and 59 term-born peers. The FreeSurfer software suite was used to obtain measures of cortical thickness, cortical surface area, and subcortical brain structure volumes. Cognitive ability was estimated using the Wechsler Adult Intelligence Scale, 3rd Edition, including four IQ-indices: Verbal comprehension, Working memory, Perceptual organization, and Processing speed. Statistical mediation analyses were employed to test for indirect effects of preterm birth with VLBW on IQ, mediated by atypical brain structure. The mediation analyses revealed negative effects of preterm birth with VLBW on IQ that were partially mediated by reduced surface area in multiple regions of frontal, temporal, parietal and insular cortex, and by reductions in several subcortical brain structure volumes. The analyses did not yield sufficient evidence of mediation effects of cortical thickness on IQ. This is, to our knowledge, the first time a plausible causal relationship has been established between regional cortical area reductions, as well as reductions in specific subcortical and cerebellar structures, and general cognitive ability in preterm born survivors with VLBW.

Visual Event-Related Potentials under External Emotional Stimuli in Bipolar I Disorder with and without Hypersexuality.

Hypersexuality is related to functions of personality and emotion and is a salient symptom of bipolar I disorder especially during manic episode. However, it is uncertain whether bipolar I disorder with (BW) and without (BO) hypersexuality exhibits different cerebral activations under external emotion stimuli. In 54 healthy volunteers, 27 BW and 26 BO patients, we administered the visual oddball event-related potentials (ERPs) under external emotions of Disgust, Erotica, Fear, Happiness, Neutral, and Sadness. Participants' concurrent states of mania, hypomania, and depression were also evaluated. The N1 latencies under Erotica and Happiness were prolonged, and the P3b amplitudes under Fear and Sadness were decreased in BW; the P3b amplitudes under Fear were increased in BO. The parietal, frontal, and occipital activations were found in BW, and the frontal and temporal activations in BO under different external emotional stimuli, respectively. Some ERP components were correlated with the concurrent affective states in three groups of participants. The primary perception under Erotica and Happiness, and voluntary attention under Fear and Sadness, were impaired in BW, while the voluntary attention under Fear was impaired in BO. Our study indicates different patterns of visual attentional deficits under different external emotions in BW and BO.

Cortical Thickness Changes After Computerized Working Memory Training in Patients With Mild Cognitive Impairment.

Background: Adaptive computerized working memory (WM) training has shown favorable effects on cerebral cortical thickness as compared to non-adaptive training in healthy individuals. However, knowledge of WM training-related morphological changes in mild cognitive impairment (MCI) is limited. Objective: The primary objective of this double-blind randomized study was to investigate differences in longitudinal cortical thickness trajectories after adaptive and non-adaptive WM training in patients with MCI. We also investigated the genotype effects on cortical thickness trajectories after WM training combining these two training groups using longitudinal structural magnetic resonance imaging (MRI) analysis in Freesurfer. Method: Magnetic resonance imaging acquisition at 1.5 T were performed at baseline, and after four- and 16-weeks post training. A total of 81 individuals with MCI accepted invitations to undergo 25 training sessions over 5 weeks. Longitudinal Linear Mixed effect models investigated the effect of adaptive vs. non-adaptive WM training. The LME model was fitted for each location (vertex). On all statistical analyzes, a threshold was applied to yield an expected false discovery rate (FDR) of 5%. A secondary LME model investigated the effects of LMX1A and APOE-ε4 on cortical thickness trajectories after WM training. Results: A total of 62 participants/patients completed the 25 training sessions. Structural MRI showed no group difference between the two training regimes in our MCI patients, contrary to previous reports in cognitively healthy adults. No significant structural cortical changes were found after training, regardless of training type, across all participants. However, LMX1A-AA carriers displayed increased cortical thickness trajectories or lack of decrease in two regions post-training compared to those with LMX1A-GG/GA. No training or training type effects were found in relation to the APOE-ε4 gene variants. Conclusion: The MCI patients in our study, did not have improved cortical thickness after WM training with either adaptive or non-adaptive training. These results were derived from a heterogeneous population of MCI participants. The lack of changes in the cortical thickness trajectory after WM training may also suggest the lack of atrophy during this follow-up period. Our promising results of increased cortical thickness trajectory, suggesting greater neuroplasticity, in those with LMX1A-AA genotype need to be validated in future trials.

Allocentric representation in the human amygdala and ventral visual stream.

The hippocampus and the entorhinal cortex are considered the main brain structures for allocentric representation of the external environment. Here, we show that the amygdala and the ventral visual stream are involved in allocentric representation. Thirty-one young men explored 35 virtual environments during high-resolution functional magnetic resonance imaging (fMRI) of the medial temporal lobe (MTL) and were subsequently tested on recall of the allocentric pattern of the objects in each environment-in other words, the positions of the objects relative to each other and to the outer perimeter. We find increasingly unique brain activation patterns associated with increasing allocentric accuracy in distinct neural populations in the perirhinal cortex, parahippocampal cortex, fusiform cortex, amygdala, hippocampus, and entorhinal cortex. In contrast to the traditional view of a hierarchical MTL network with the hippocampus at the top, we demonstrate, using recently developed graph analyses, a hierarchical allocentric MTL network without a main connector hub.

Cerebral cortical dimensions in headache sufferers aged 50 to 66 years: a population-based imaging study in the Nord-Trøndelag Health Study (HUNT-MRI).

Based on previous clinic-based magnetic resonance imaging studies showing regional differences in the cerebral cortex between those with and without headache, we hypothesized that headache sufferers have a decrease in volume, thickness, or surface area in the anterior cingulate cortex, prefrontal cortex, and insula. In addition, exploratory analyses on volume, thickness, and surface area across the cerebral cortical mantle were performed. A total of 1006 participants (aged 50-66 years) from the general population were selected to an imaging study of the head at 1.5 T (HUNT-MRI). Two hundred eighty-three individuals suffered from headache, 80 with migraine, and 87 with tension-type headache, whereas 309 individuals did not suffer from headache and were used as controls. T1-weighted 3D scans of the brain were analysed with voxel-based morphometry and FreeSurfer. The association between cortical volume, thickness, and surface area and questionnaire-based headache diagnoses was evaluated, taking into consideration evolution of headache and frequency of attacks. There were no significant differences in cortical volume, thickness, or surface area between headache sufferers and nonsufferers in the anterior cingulate cortex, prefrontal cortex, or insula. Similarly, the exploratory analyses across the cortical mantle demonstrated no significant differences in volume, thickness, or surface area between any of the headache groups and the nonsufferers. Maps of effect sizes showed small differences in the cortical measures between headache sufferers and nonsufferers. Hence, there are probably no or only very small differences in volume, thickness, or surface area of the cerebral cortex between those with and without headache in the general population.

Reduced white matter fractional anisotropy mediates cortical thickening in adults born preterm with very low birthweight.

Development of the cerebral cortex may be affected by aberrant white matter development. Preterm birth with very low birth weight (VLBW) has been associated with reduced fractional anisotropy of white matter and changes in cortical thickness and surface area. We use a new methodological approach to combine white and gray matter data and test the hypothesis that white matter injury is primary, and acts as a mediating factor for concomitant gray matter aberrations, in the developing VLBW brain. T1 and dMRI data were obtained from 47 young adults born preterm with VLBW and 73 term-born peers (mean age = 26). Cortical thickness was measured across the cortical mantle and compared between the groups, using the FreeSurfer software suite. White matter pathways were reconstructed with the TRACULA software and projected to their cortical end regions, where cortical thickness was averaged. In the VLBW group, cortical thickness was increased in anteromedial frontal, orbitofrontal, and occipital regions, and fractional anisotropy (FA) was reduced in frontal lobe pathways, indicating compromised white matter integrity. Statistical mediation analyses demonstrated that increased cortical thickness in the frontal regions was mediated by reduced FA in the corpus callosum forceps minor, consistent with the notion that white matter injury can disrupt frontal lobe cortical development. Combining statistical mediation analysis with pathway projection onto the cortical surface offers a powerful novel tool to investigate how cortical regions are differentially affected by white matter injury.

Joint Analysis of Cortical Area and Thickness as a Replacement for the Analysis of the Volume of the Cerebral Cortex.

Cortical surface area is an increasingly used brain morphology metric that is ontogenetically and phylogenetically distinct from cortical thickness and offers a separate index of neurodevelopment and disease. However, the various existing methods for assessment of cortical surface area from magnetic resonance images have never been systematically compared. We show that the surface area method implemented in FreeSurfer corresponds closely to the exact, but computationally more demanding, mass-conservative (pycnophylactic) method, provided that images are smoothed. Thus, the data produced by this method can be interpreted as estimates of cortical surface area, as opposed to areal expansion. In addition, focusing on the joint analysis of thickness and area, we compare an improved, analytic method for measuring cortical volume to a permutation-based nonparametric combination (NPC) method. We use the methods to analyze area, thickness and volume in young adults born preterm with very low birth weight, and show that NPC analysis is a more sensitive option for studying joint effects on area and thickness, giving equal weight to variation in both of these 2 morphological features.

Cortical trajectories during adolescence in preterm born teenagers with very low birthweight.

While cross-sectional neuroimaging studies on cortical development predict reductions in cortical volume (surface area and thickness) during adolescence, this is the first study to undertake a longitudinal assessment of cortical surface area changes across the continuous cortical surface during this period. We studied the developmental dynamics of cortical surface area and thickness in adolescents and young adults (aged 15-20) born with very low birth weight (VLBW; <1500 g) as well as in term-born controls. Previous studies have demonstrated brain structural abnormalities in cortical morphology, as well as long-term motor, cognitive and behavioral impairments, in adolescents and young adults with VLBW, but the developmental dynamics throughout adolescence have not been fully explored. T1-weighted MRI scans from 51 VLBW (27 scanned twice) and 79 term-born adolescents (37 scanned twice) were used to reconstruct the cortical surface and produce longitudinal estimates of cortical surface area and cortical thickness. Linear mixed model analyses were performed, and the main effects of time and group, as well as time × group interaction effects, were investigated. In both groups, cortical surface area decreased up to 5% in some regions, and cortical thickness up to 8%, over the five-year period. The most affected regions were located on the lateral aspect of the hemispheres, in posterior temporal, parietal and to some extent frontal regions. There was no significant interaction between time and group for either morphometry variable. In conclusion, cortical thickness decreases from 15 to 20 years of age, in a similar fashion in the clinical and control groups. Moreover, we show for the first time that developmental trajectories of cortical surface area in preterm and term-born adolescents do not diverge during adolescence.

Limited microstructural and connectivity deficits despite subcortical volume reductions in school-aged children born preterm with very low birth weight.

Preterm birth and very low birth weight (VLBW, ≤1500 g) are worldwide problems that burden survivors with lifelong cognitive, psychological, and physical challenges. In this multimodal structural magnetic resonance imaging (MRI) and diffusion MRI (dMRI) study, we investigated differences in subcortical brain volumes and white matter tract properties in children born preterm with VLBW compared to term-born controls (mean age=8 years). Subcortical brain structure volumes and cortical thickness estimates were obtained, and fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were generated for 18 white matter tracts. We also assessed structural relationships between white matter tracts and cortical thickness of the tract endpoints. Compared to controls, the VLBW group had reduced volumes of thalamus, globus pallidus, corpus callosum, cerebral white matter, ventral diencephalon, and brain stem, while the ventricular system was larger in VLBW subjects, after controlling for age, sex, IQ, and estimated total intracranial volume. For the dMRI parameters, group differences were not significant at the whole-tract level, though pointwise analysis found shorter segments affected in forceps minor and left superior longitudinal fasciculus - temporal bundle. IQ did not correlate with subcortical volumes or dMRI measures in the VLBW group. While the deviations in subcortical volumes were substantial, there were few differences in dMRI measures between the two groups, which may reflect the influence of advances in perinatal care on white matter development.

Impaired Verbal Learning Is Associated with Larger Caudate Volumes in Early Onset Schizophrenia Spectrum Disorders.

BACKGROUND: Both brain structural abnormalities and neurocognitive impairments are core features of schizophrenia. We have previously reported enlargements in subcortical brain structure volumes and impairment of neurocognitive functioning as measured by the MATRICS Cognitive Consensus Battery (MCCB) in early onset schizophrenia spectrum disorders (EOS). To our knowledge, no previous study has investigated whether neurocognitive performance and volumetric abnormalities in subcortical brain structures are related in EOS. METHODS: Twenty-four patients with EOS and 33 healthy controls (HC) were included in the study. Relationships between the caudate nucleus, the lateral and fourth ventricles volumes and neurocognitive performance were investigated with multivariate linear regression analyses. Intracranial volume, age, antipsychotic medication and IQ were included as independent predictor-variables. RESULTS: The caudate volume was negatively correlated with verbal learning performance uniquely in the EOS group (r=-.454, p=.034). There were comparable positive correlations between the lateral ventricular volume and the processing speed, attention and reasoning and problem solving domains for both the EOS patients and the healthy controls. Antipsychotic medication was related to ventricular enlargements, but did not affect the brain structure-function relationship. CONCLUSION: Enlargement of the caudate volume was related to poorer verbal learning performance in patients with EOS. Despite a 32% enlargement of the lateral ventricles in the EOS group, associations to processing speed, attention and reasoning and problem solving were similar for both the EOS and the HC groups.

Cortical morphometry and IQ in VLBW children without cerebral palsy born in 2003-2007.

Children born prematurely with very low birth weight (VLBW: bw  ≤ 1500 g) have an increased risk of preterm perinatal brain injury, which may subsequently alter the maturation of the brain, including the cerebral cortex. The aim of study was to assess cortical thickness and surface area in VLBW children compared with term-born controls, and to investigate possible relationships between cortical morphology and Full IQ. In this cross-sectional study, 37 VLBW and 104 term children born between the years 2003-2007 were assessed cognitively at 5-10 years of age, using age appropriate Wechsler tests. The FreeSurfer software was used to obtain estimates of cortical thickness and surface area based on T1-weighted MRI images at 1.5 Tesla. The VLBW children had smaller cortical surface area bilaterally in the frontal, temporal, and parietal lobes. A thicker cortex in the frontal and occipital regions and a thinner cortex in posterior parietal areas were observed in the VLBW group. There were significant differences in Full IQ between groups (VLBW M = 98, SD = 9.71; controls M = 108, SD = 13.57; p < 0.001). There was a positive relationship between IQ and surface area in both groups, albeit significant only in the larger control group. In the VLBW group, reduced IQ was associated with frontal cortical thickening and temporo-parietal thinning. We conclude that cortical deviations are evident in childhood even in VLBW children born in 2003-2007 who have received state of the art medical treatment in the perinatal period and who did not present with focal brain injuries on neonatal ultrasonography. The cortical deviations were associated with reduced cognitive functioning.

Visual-motor deficits relate to altered gray and white matter in young adults born preterm with very low birth weight.

Individuals born preterm and at very low birth weight (birth weight ≤ 1500 g) are at an increased risk of perinatal brain injury and neurodevelopmental deficits over the long term. This study examined whether this clinical group has more problems with visual-motor integration, motor coordination, and visual perception compared to term-born controls, and related these findings to cortical surface area and thickness and white matter fractional anisotropy. Forty-seven preterm-born very low birth weight individuals and 56 term-born controls were examined at 18-22 years of age with a combined cognitive, morphometric MRI, and diffusion tensor imaging evaluation in Trondheim, Norway. Visual-motor skills were evaluated with the Beery-Buktenica Developmental Test of Visual-Motor Integration-V (VMI) copying test and its supplemental tests of motor coordination and visual perception. 3D T1-weighted MPRAGE images and diffusion tensor imaging were done at 1.5 T. Cortical reconstruction generated in FreeSurfer and voxelwise maps of fractional anisotropy calculated with Tract-Based Spatial Statistics were used to explore the relationship between MRI findings and cognitive results. Very low birth weight individuals had significantly lower scores on the copying and motor coordination tests compared with controls. In the very low birth weight group, VMI scores showed significant positive relationships with cortical surface area in widespread regions, with reductions of the superior temporal gyrus, insula, and medial occipital lobe in conjunction with the posterior ventral temporal lobe. Visual perception scores also showed positive relationships with cortical thickness in the very low birth weight group, primarily in the lateral occipito-temporo-parietal junction, the superior temporal gyrus, insula, and superior parietal regions. In the very low birth weight group, visual-motor performance correlated positively with fractional anisotropy especially in the corpus callosum, inferior fronto-occipital fasciculus bilaterally, and anterior thalamic radiation bilaterally, driven primarily by an increase in radial diffusivity. VMI scores did not demonstrate a significant relationship to cortical surface area, cortical thickness, or diffusion measures in the control group. Our results indicate that visual-motor integration problems persist into adulthood for very low birth weight individuals, which may be due to structural alterations in several specific gray-white matter networks. Visual-motor deficits appear related to reduced surface area of motor and visual cortices and disturbed connectivity in long association tracts containing visual and motor information. We conjecture that these outcomes may be due to perinatal brain injury or aberrant cortical development secondary to injury or due to very preterm birth.

Brain morphometry and cognition in young adults born small for gestational age at term.

OBJECTIVES: To examine brain volumes and cortical surface area and thickness and to relate these brain measures to cognitive function in young adults born small for gestational age (SGA) at term compared with non-SGA control patients. STUDY DESIGN: This population-based follow-up study at age 20 years included 58 term-born SGA (birth weight <10th percentile, mean: 2915 g) and 81 non-SGA controls (birth weight ≥ 10th percentile, mean: 3707 g). Brain volumes and cortical surface area and thickness were investigated with magnetic resonance imaging, which was successfully obtained in 47 SGA patients and 61 control patients. Cognitive function was assessed using the Wechsler Adult Intelligence Scale, 3rd edition. A subgroup analysis was performed in the SGA group among subjects diagnosed with fetal growth restriction (FGR) based on repeated fetal ultrasound measurements. RESULTS: The SGA group showed regional reductions in cortical surface area, particularly in the frontal, parietal, and temporal lobes. Total brain volume, cortical gray matter, cerebral white matter, and putamen volumes were reduced in the SGA group compared with control patients, but there were no differences in specific subcortical brain structure volumes when correcting for intracranial volume. Reductions were most pronounced among SGA subjects with FGR. No associations were found between brain measures and IQ measures in either group. CONCLUSION: Young adults born SGA at term show a global reduction in brain volume as well as regional reductions in cortical surface area. We speculate whether these reductions may be confined to those exposed to FGR. None of the brain measures correlated with cognition.

Brain volumes and cognitive function in very-low-birth-weight (VLBW) young adults.

BACKGROUND: Preterm born very-low-birth-weight (VLBW: birth weight ≤1500 g) survivors have increased risk of perinatal brain injury that may cause deviant brain development and later neuroimpairments, including reduced cognitive functioning. AIMS: In this long-term follow up study of three year-cohorts (birth years 1986-88) of VLBW subjects and term born controls with normal birth weight, the aim was to examine differences in brain volumes at age 20 years. In addition, the relationships between brain volumes and cognitive abilities and perinatal variables were explored. METHODS: Forty-four VLBW subjects and 60 controls were assessed with cognitive testing (Wechsler Adult Intelligence Scale - WAIS-III) and structural MRI at 1.5 T, using the FreeSurfer 5.1 software for volumetric analysis. A subpopulation had MRI performed also at age 15, and for this group changes in brain volumes with age were examined. RESULTS: The VLBW subjects had smaller brain volumes, especially of thalamus, globus pallidus and parts of the corpus callosum, and larger lateral ventricles than controls at age 20. However, no significant group differences in longitudinal change from age 15 to 20 were observed. The most immature and smallest VLBW subjects at birth, and those with the highest perinatal morbidity, showed most pronounced volume deviations. Positive associations between several brain volumes and full IQ, as well as three of four IQ indices in the VLBW group, were observed. CONCLUSION: Reduced volumes of grey and white matter and ventricular dilatation in VLBW young adults may indicate permanent effects on brain development from perinatal brain injury with influence on later cognitive function.

Normal birth weight variation is related to cortical morphology across the psychosis spectrum.

BACKGROUND: Normal birth weight variation affects schizophrenia risk and cognitive performance in schizophrenia patients and healthy controls. Brain cortical anatomy is altered in psychotic disorders and in low birth weight subjects, but if birth weight variation relates to cortical morphology across the psychosis spectrum is not known. METHODS: Magnetic Resonance Imaging brain scans and clinical-, neurocognitive-, and medical birth registry data were collected from 359 adults including patients with a DSM-IV diagnosis of schizophrenia (n = 90, mean age 29.4±10.2 [95% CI], 62% male), bipolar disorder (n = 79, age 29.4±11.8, 39% male) or other psychosis (n = 40, age 26.3±10.0, 56% male), and healthy controls (n = 140, age 30.8±12.0,53% male). We explored the relationship between whole-range birth weight variation and cortical surface area and thickness and their possible associations to cognitive performance. RESULTS: Across all groups, lower birth weight was associated with smaller total surface area (t = 3.87, P = .0001), within specific regions of the temporal, parietal, and frontal cortex bilaterally. There were no associations between birth weight and cortical thickness, and no diagnosis by birth weight interaction effects on cortical thickness or surface area. Smaller cortical area (t = 2.50, P = .013) and lower birth weight (t = 2.53, P = .012) were significantly related to poorer working memory performance in all diagnostic groups except schizophrenia. CONCLUSION: Birth weight relates to adult cortical surface area, but not cortical thickness, in patients across the psychosis spectrum and in healthy controls. Cortical area appears to be a diagnosis-independent general marker of early neurodevelopment, with a dose-response association to normal birth weight variation.

Reduced brain cortical folding in schizophrenia revealed in two independent samples.

The cerebral cortex is highly convoluted, and principal folding patterns are determined early in life. Degree of cortical folding in adult life may index aberrations in brain development. Results from previous studies of cortical folding in schizophrenia are inconsistent. Here we investigated cortical folding patterns in the hitherto largest sample of patients with schizophrenia drawn from two independent cohorts. Magnetic resonance imaging scans were acquired from 207 patients and 206 healthy subjects recruited to two separate research projects in Sweden and Norway. Local gyrification index (lGI) was estimated continuously across the cortex using automated methods. Group differences in lGI were analyzed using general linear models. Patients had lower lGI in three large clusters of the cortex with peak differences found in the left precentral gyrus, right middle temporal gyrus, and right precuneus. Similar, although not completely overlapping results were found when the two cohorts were analyzed separately. There were no significant interaction effects between age and diagnosis and gender and diagnosis. The finding of reduced degree of folding in large regions of the cerebral cortex across two independent samples indicates that reduced gyrification is an inherent feature of the brain pathology in schizophrenia.

Age-related cortical thickness differences in adolescents with early-onset schizophrenia compared with healthy adolescents.

The aim of the present study was to investigate the influence of age on cerebral cortical thickness in adolescents with early-onset schizophrenia (EOS) (n=22, aged 12-18 years), as compared to an age-matched healthy control group (n=32). All participants were scanned with magnetic resonance imaging. Whereas in the healthy control group there was a negative association between increasing age and cortical thickness measures in widespread brain regions, including frontal and parietal cortices, the patient group showed no significant effects of age when the groups were studied separately. There was a trend towards an age-by-group effect in the left supramarginal gyrus and the right pre- and postcentral gyri. The between-group statistical analysis indicated similar cortical thickness in the patients as in the healthy controls. There were no significant effects of medication on cortical thickness, nor was there any significant sex-by-group interaction. The results suggest that patients with EOS have a deficiency of the expected cortical thinning to occur during adolescence development. The findings are discussed in context of neurobiological processes known to be involved in brain maturation, including synaptic reorganization, pruning and myelination.

ZNF804A and cortical thickness in schizophrenia and bipolar disorder.

ZNF804A SNP rs1344706 confers genome-wide risk for schizophrenia and bipolar disorder. Both disorders affect cortical thickness. To determine if single nucleotide polymorphisms (SNPs) across ZNF804A are associated with cortical thinning, we investigated 63 SNPs (including rs1344706) in 365 psychosis patients and healthy controls. Results show no significant associations.

A 5-year follow-up study of brain cortical and subcortical abnormalities in a schizophrenia cohort.

BACKGROUND: Magnetic resonance imaging studies have demonstrated that patients with schizophrenia have thinner cortex in prefrontal and temporal brain regions, and enlarged lateral ventricles, compared to healthy subjects. Longitudinal studies have shown progressive brain tissue loss and ventricular dilatation among patients, predominantly in the early phase of the illness. Evidence for progression in more chronic phases of schizophrenia is less established. METHODS: Measurements of cortical thickness, cortical volume and subcortical volumes were obtained from 52 patients with long-term treated schizophrenia and 63 healthy subjects who were scanned twice over five years. Differences in brain measurements across time and group were investigated using general linear models. RESULTS: Compared to controls, patients had similar patterns of thinner cortex and smaller cortical volumes in prefrontal and temporal regions at both time points. In the follow-up interval regional cortical volumes decreased and lateral ventricle volumes increased in both groups. There was a trend level interaction effect of group and time for the right lateral ventricle, but not for cortical measurements. This effect was related to higher degree of negative symptoms at follow-up. CONCLUSIONS: Regional differences in cortical thickness and volume between long-term treated patients with schizophrenia and healthy subjects are stable across five years, while right lateral ventricle volumes tend to increase more in the patients. The findings indicate that brain structure abnormalities found in schizophrenia are not progressive in the chronic stage of the disease, but that some progression in subcortical structures may be present in patients with poor outcome.

Comprehensive segmentation of subcortical brain volumes in early onset schizophrenia reveals limited structural abnormalities.

Structural brain abnormalities are well documented in adult schizophrenia, but there are few studies of brain structures in early onset schizophrenia (EOS) and findings are inconsistent. Most previous EOS studies have been limited to global morphometric measures, such as whole gray matter (GM) or cerebrospinal fluid (CSF), or to single brain structures. The purpose of this study was to compare specific volumes and hemispheric lateralization in a large number of subcortical brain structures, between EOS patients and a healthy control group. High-resolution structural magnetic resonance images (MRI) and automatic brain volume segmentation were performed on 18 EOS patients and 33 healthy controls (11-18 years). A total of 29 brain structures were studied. The patients showed marked bilateral enlargements of the lateral ventricles and of the fourth ventricle, and bilateral enlargement of the caudate nuclei compared to the controls. For all other subcortical brain structures, there were no significant differences between the EOS group and the healthy control group, contrary to findings from the majority of morphometric studies of childhood or adult onset schizophrenia.