Cortical gray and white brain tissue volume in adolescents and adults with autism.

BACKGROUND: A number of studies have found brain enlargement in autism, but there is disagreement as to whether this enlargement is limited to early development or continues into adulthood. In this study, cortical gray and white tissue volumes were examined in a sample of adolescents and adults with autism who had demonstrated total brain enlargement in a previous magnetic resonance imaging (MRI) study. METHODS: An automated tissue segmentation program was applied to structural MRI scans to obtain volumes of gray, white, and cerebrospinal fluid (CSF) tissue on a sample of adolescent and adult males ages 13-29 with autism (n = 23) and controls (n = 15). Regional differences for brain lobes and brain hemispheres were also examined. RESULTS: Significant enlargement in gray matter volume was found for the individuals with autism, with a disproportionate increase in left-sided gray matter volume. Lobe volume enlargements were detected for frontal and temporal, but not parietal or occipital lobes, in the subjects with autism. Age and nonverbal IQ effects on tissue volume were also observed. CONCLUSIONS: These findings give evidence for left-lateralized gray tissue enlargement in adolescents and adults with autism, and demonstrate a regional pattern of cortical lobe volumes underlying this effect.     

Cerebral cortical gray matter overgrowth and functional variation of the serotonin transporter gene in autism

CONTEXT: Autism is a heritable neurodevelopmental disorder characterized biologically by enlargement of the head and brain and abnormalities of serotonin neurotransmission. OBJECTIVE: To evaluate whether 5-HTTLPR, a functional promoter polymorphism of the serotonin transporter gene SLC6A4, influences cerebral cortical structure volumes in young male children with autism. DESIGN: Association study of a genetic variant with quantitative traits. SETTING: Autism research centers at the University of North Carolina (UNC), Chapel Hill, and the University of Washington (UW), Seattle. PARTICIPANTS: Forty-four male children, 2 to 4 years old, with autism participating in longitudinal brain magnetic resonance imaging studies. MAIN OUTCOME MEASURES: Cerebral cortical and cerebellar gray and white matter volumes. RESULTS: We found that 5-HTTLPR genotype influenced gray matter volumes of the cerebral cortex (F(2,23) = 7.29, P = .004) and of 3 lobe-based subregions in the UNC sample of 29 children (frontal lobe gray matter: F(2,23) = 6.36, P = .01). The 5-HTTLPR short allele appeared to be additively associated with increasing gray matter volumes, an observation affirmed by tests of linear genotype effects (cortical gray matter: F(1,24) = 14.11, P = .001; frontal lobe gray matter: F(1,24) = 13.20, P = .001). Genotype did not influence cerebellar volumes. Confirmation was pursued by means of the UW sample of 15 children. While effects were not significant in the UW sample alone, the patterns of adjusted means resembled those found in the UNC sample. Positive Cochran-Mantel-Haenszel test results supported the concordance of relationships across the 2 sites, and analyses of covariance of the combined sample that included a site covariate showed significant linear genotype effects on structure volumes (cortical gray matter: F(1,38) = 5.73, P = .02; frontal lobe gray matter: F(1,38) = 11.73, P = .002). Effect sizes of 5-HTTLPR genotype on total cortical and frontal lobe gray matter volumes were 10% and 16%, respectively. CONCLUSION: The SLC6A4 promoter polymorphism 5-HTTLPR influences cerebral cortical gray matter volumes in young male children with autism.     

MRI neuroanatomy in young girls with autism: a preliminary study

OBJECTIVE: To test the hypothesis that young girls and boys with autism exhibit different profiles of neuroanatomical abnormality relative to each other and relative to typically developing children. METHOD: Structural magnetic resonance imaging was used to measure gray and white matter volumes (whole cerebrum, cerebral lobes, and cerebellum) and total brain volume in nine girls (ages 2.29-5.16) and 27 boys (ages 1.96-5.33) with autism and 14 girls (ages 2.17-5.71) and 13 boys (ages 1.72-5.50) with typical development. Structure size and the relationship between size and age were examined. Diagnostic and cognitive outcome data were obtained after the children reached 4 to 5 years of age. RESULTS: Girls with autism exhibited nearly every size-related abnormality exhibited by boys with autism. Furthermore, additional sites of abnormality were observed in girls, including enlargement in temporal white and gray matter volumes and reduction in cerebellar gray matter volume. Significant correlations were observed between age and white matter volumes (e.g., cerebral white matter rs = 0.950) for the girls with autism, whereas no significant age-structure size relationships were observed for the boys with autism. CONCLUSIONS: Results suggest sex differences in etiological factors and the biological time course of the disorder.     

Evidence for cortical dysfunction in autism: a proton magnetic resonance spectroscopic imaging study.

BACKGROUND: Although brain imaging studies have reported neurobiological abnormalities in autism, the nature and distribution of the underlying neurochemical irregularities are unknown. The purpose of this study was to examine cerebral gray and white matter cellular neurochemistry in autism with proton magnetic resonance spectroscopic imaging (MRSI). METHODS: Proton MRSI examinations were conducted in 26 males with autism (age 9.8 +/- 3.2 years) and 29 male comparison subjects (age 11.1 +/- 2.4 years). Estimates of cerebral gray and white matter concentrations of N-acetylaspartate (NAA), creatine + phosphocreatine, choline-containing compounds, myo-inositol, and glutamate + glutamine (Glx) were made by linear regression analysis of multi-slice MRSI data and compared between groups. Regional estimates of metabolite concentration were also made with multivariate linear regression, allowing for comparisons of frontal, temporal, and occipital gray matter, cerebral white matter, and the cerebellum. RESULTS: Patients with autism exhibited significantly lower levels of gray matter NAA and Glx than control subjects. Deficits were widespread, affecting most cerebral lobes and the cerebellum. No significant differences were detected in cerebral white matter or cerebellar metabolite levels. CONCLUSIONS: These results suggest widespread reductions in gray matter neuronal integrity and dysfunction of cortical and cerebellar glutamatergic neurons in patients with autism.     

Outcome classification of preschool children with autism spectrum disorders using MRI brain measures

OBJECTIVE: To test the hypothesis that a combination of magnetic resonance imaging (MRI) brain measures obtained during early childhood distinguish children with autism spectrum disorders (ASD) from typically developing children and is associated with functional outcome. METHOD: Quantitative MRI technology was used to measure gray and white matter volumes (cerebrum and cerebellum), total brain volume, and the area of the cerebellar vermis in 52 boys with a provisional diagnosis of autism (aged 1.9-5.2 years) and 15 typically developing young children (aged 1.7-5.2 years). Diagnostic confirmation and cognitive outcome data were obtained after the children reached 5 years of age. RESULTS: A discriminant function analysis of the MRI brain measures correctly classified 95.8% of the ASD cases and 92.3% of the control cases. This set of variables also correctly classified 85% of the ASD cases as lower functioning and 68% of the ASD cases as higher functioning. CONCLUSIONS: These results indicate that variability in cerebellar and cerebral size is correlated with diagnostic and functional outcome in very young children with ASD.     

Structural brain abnormalities in chronic schizophrenia at the extremes of the outcome spectrum.

OBJECTIVE: This study investigated the relationship between outcome and structural brain abnormalities in schizophrenia. METHOD: Intracranial volume and volumes of the cerebrum, gray and white matter, lateral and third ventricles, frontal lobes, thalamus, and cerebellum were measured in 20 patients with a poor outcome, 25 with a favorable outcome, and 23 healthy comparison subjects with magnetic resonance imaging. RESULTS: Thalamic volume was significantly smaller both in poor-outcome patients and good-outcome patients. In contrast, only poor-outcome patients displayed significantly smaller cerebral gray matter, particularly prefrontal, and enlargement of the lateral and third ventricles. No significant differences were found for intracranial, cerebellar, or cortical CSF volumes. CONCLUSIONS: Smaller thalamic volumes in schizophrenia may reflect a greater susceptibility for the disorder and seem unrelated to outcome. In contrast, gray matter volume loss of the cerebrum, particularly in the frontal lobes, and lateral and third ventricular enlargement appear related to outcome in schizophrenia.     

Does an Increase in Sulcal or Ventricular Fluid Predict Where Brain Tissue Is Lost?

Quantitative volumes of cerebrospinal fluid (CSF) and brain tissue were measured on magnetic resonance images (MRIs) of 287 individuals from 5 diagnostic groups: Alzheimer's disease (AD), chronic alcoholics (ALC), individuals positive for human immunodeficiency virus (HIV), schizophrenia subjects (SZ), and normal comparison subjects (NC) older than 50 years of age. Within each group, mean volumes were calculated for ventricular CSF, cortical (sulcal) CSF, cortical gray matter, total white matter, basal ganglia gray matter, and thalamic gray matter. Correlations of CSF measures with brain tissue measures were determined, and multiple regression analyses were performed to try and predict volume of gray matter or white matter region from volume of CSF compartment. Results indicated the following: 1. Enlarged cortical fluid volume significantly predicts cortical gray matter deficits for subjects with AD and those who are ALC and SZ but not for subjects with HIV or NC. 2. Enlarged cortical fluid volume also significantly predicts white matter deficits in all five groups. 3. Enlarged ventricular fluid volume significantly predicts basal ganglia deficits in AD, HIV, and NC but not in SZ or ALC. 4. Enlarged ventricular volume has no predictive value for thalamic volume for any of the groups. This study supports the clinical practice of predicting brain tissue volume loss from CSF enlargement but not for all brain regions in all diagnoses.     

Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study

OBJECTIVE: To quantify developmental abnormalities in cerebral and cerebellar volume in autism. METHODS: The authors studied 60 autistic and 52 normal boys (age, 2 to 16 years) using MRI. Thirty autistic boys were diagnosed and scanned when 5 years or older. The other 30 were scanned when 2 through 4 years of age and then diagnosed with autism at least 2.5 years later, at an age when the diagnosis of autism is more reliable. RESULTS: Neonatal head circumferences from clinical records were available for 14 of 15 autistic 2- to 5-year-olds and, on average, were normal (35.1 +/- 1.3 cm versus clinical norms: 34.6 +/- 1.6 cm), indicative of normal overall brain volume at birth; one measure was above the 95th percentile. By ages 2 to 4 years, 90% of autistic boys had a brain volume larger than normal average, and 37% met criteria for developmental macrencephaly. Autistic 2- to 3-year-olds had more cerebral (18%) and cerebellar (39%) white matter, and more cerebral cortical gray matter (12%) than normal, whereas older autistic children and adolescents did not have such enlarged gray and white matter volumes. In the cerebellum, autistic boys had less gray matter, smaller ratio of gray to white matter, and smaller vermis lobules VI-VII than normal controls. CONCLUSIONS: Abnormal regulation of brain growth in autism results in early overgrowth followed by abnormally slowed growth. Hyperplasia was present in cerebral gray matter and cerebral and cerebellar white matter in early life in patients with autism.     

Effects of age on brain volume and head circumference in autism

OBJECTIVE: To determine whether brain volume, as assessed on MRI scans, differs between individuals with autism and control subjects, and whether such differences are affected by age. BACKGROUND: Previous studies have found increased brain weight, head circumference, and MRI brain volume in children with autism. However, studies of brain size in adults with autism have yielded conflicting results. The authors hypothesize that enlargement of the brain may be a feature of brain development during early childhood in autism that normalizes with maturational processes. METHODS: The authors measured total brain volumes from 1.5-mm coronal MRI scans in 67 non-mentally retarded children and adults with autism and 83 healthy community volunteers, ranging in age from 8 to 46 years. Head circumference was also measured. Groups did not differ on age, sex, verbal IQ, or socioeconomic status. RESULTS: Brain volumes were significantly larger for children with autism 12 years old and younger compared with normally developing children, when controlling for height. Brain volumes for individuals older than age 12 did not differ between the autism and control groups. Head circumference was increased in both younger and older groups of subjects with autism, suggesting that those subjects older than age 12 had increased brain volumes as children. CONCLUSIONS: Brain development in autism follows an abnormal pattern, with accelerated growth in early life that results in brain enlargement in childhood. Brain volume in adolescents and adults with autism is, however, normal, and appears to be due to a slight decrease in brain volume for these individuals at the same time that normal children are experiencing a slight increase.     

Neuroanatomic variation in monozygotic twin pairs discordant for the narrow phenotype for autism

OBJECTIVE: The broader autism phenotype includes relatives of individuals with autism who display social and language deficits that are qualitatively similar to those of autism but less severe. In previous studies of monozygotic twins discordant for autism, more than 75% of the twins without autism displayed the broader phenotype. Differences in neuroanatomy between discordant monozygotic twins might be associated with the narrow and broader behavioral phenotypes. The authors examined the relationship of twin pair differences in clinical phenotype to differences in neuroanatomic phenotype. METHOD: The subjects were 16 monozygotic twin pairs between the ages of 5 and 14 years and 16 matched singleton comparison subjects. Seven twin pairs were clinically concordant and nine twin pairs were clinically discordant for strictly defined autism. After magnetic resonance imaging, a semiautomated procedure was applied to images in which the brain tissue was subdivided into neurofunctional regions and segmented into gray, white, and ventricular compartments. RESULTS: Both the concordant and discordant twin pairs exhibited concordance in cerebral gray and white matter volumes. However, only the clinically concordant pairs exhibited concordance in cerebellar gray and white matter volumes. Within the discordant twin pairs, both the twins with autism and their co-twins exhibited frontal, temporal, and occipital white matter volumes that were lower than those of the comparison subjects. CONCLUSIONS: These findings support the role and the limits of genetic liability in autism. Continuing to clarify the neuroanatomic pathways in autistic spectrum disorders could illuminate the etiology of autism and, ultimately, contribute to treatments.     

Sex differences in the effects of alcohol on brain structure

OBJECTIVE: This study investigated whether alcoholic women manifest deficits in cortical gray and white matter volumes and ventricular enlargement similar to those seen in alcoholic men. METHOD: Volumetric measures of intracranium, cortical gray matter, white matter and sulci, and lateral and third ventricles were obtained from magnetic resonance images of 42 women and 44 men with DSM-III-R alcoholism and age-matched healthy comparison groups (37 women and 48 men). Groups of alcoholic men and women were matched on age and length of sobriety, but men had a 2.5 times higher lifetime alcohol consumption than women. RESULTS: Women, regardless of diagnosis, had less cortical gray and white matter and smaller third ventricles than men, consistent with sex-related differences in intracranial volume. Alcoholics had larger volumes of cortical sulci and lateral and third ventricles than comparison subjects. Diagnosis-by-sex interactions for cortical white matter and sulcal volumes were due to abnormalities in alcoholic men but not alcoholic women, relative to same-sex comparison subjects. This interaction persisted for cortical sulci after covarying for lifetime alcohol consumption. Slopes relating cortical gray matter and sulcal volumes to age were steeper in alcoholic than in comparison men. Slopes relating lateral ventricle volume to age were steeper in alcoholic than in comparison women. In alcoholic women, longer sobriety was associated with larger white matter volumes. CONCLUSIONS: Alcoholic men and women show different brain morphological deficits, relative to same-sex comparison subjects. However, age and alcoholism interact in both sexes, which puts all older alcoholics at particular risk for the negative sequelae of alcoholism.     

Dorsolateral prefrontal and anterior cingulate cortex volumetric abnormalities in adults with attention-deficit/hyperactivity disorder identified by magnetic resonance imaging.

OBJECTIVES: Gray and white matter volume deficits have been reported in a number of studies of children with attention-deficit/hyperactivity disorder (ADHD); however, there is a paucity of structural magnetic resonance imaging (MRI) studies of adults with ADHD. This structural MRI study used an a priori region of interest approach. METHODS: Twenty-four adults with DSM-IV ADHD and 18 healthy controls comparable on age, socioeconomic status, sex, handedness, education, IQ, and achievement test performance had an MRI on a 1.5T Siemens scanner. Cortical and sub-cortical gray and white matter were segmented. Image parcellation divided the neocortex into 48 gyral-based units per hemisphere. Based on a priori hypotheses we focused on prefrontal, anterior cingulate cortex (ACC) and overall gray matter volumes. General linear analyses of the volumes of brain regions, adjusting for age, sex, and total cerebral volumes, were used to compare groups. RESULTS: Relative to controls, ADHD adults had significantly smaller overall cortical gray matter, prefrontal and ACC volumes. CONCLUSIONS: Adults with ADHD have volume differences in brain regions in areas involved in attention and executive control. These data, largely consistent with studies of children, support the idea that adults with ADHD have a valid disorder with persistent biological features.     

Smaller frontal lobe white matter volumes in depressed adolescents.

BACKGROUND: Prior studies have demonstrated reduced frontal lobe volumes in depressed adolescents. In this study, frontal lobe gray and white matter volumes in adolescents with major depressive disorder were evaluated. METHODS: Nineteen depressed and thirty-eight healthy comparison adolescents were recruited for a magnetic resonance imaging study. Images were segmented into gray matter, white matter, and cerebrospinal fluid. Morphometric measurements of the whole brain and frontal lobe region were completed. RESULTS: Whole brain volumes were significantly smaller in depressed subjects compared with the healthy comparison subjects. Significantly smaller frontal white matter volumes and significantly larger frontal gray matter volumes were found in the depressed subjects, after controlling for age and whole brain volume. CONCLUSIONS: These results are consistent with the hypothesis that a deficit in frontal volume exists during cortical development in adolescents with depression. Further studies are needed to assess whether volume differences resolve over time and the extent to which these differences influence response to treatment.     

White matter volume as a major predictor of cognitive function in Sturge-Weber syndrome

OBJECTIVE: To assess the role of gray and white matter volume loss vs seizures in cognitive impairment of children with Sturge-Weber syndrome with unilateral involvement. DESIGN: Patients were enrolled in this prospective cohort during a period of 3 years. SETTING: Pediatric neurology clinic with national referral through the Sturge-Weber Foundation. PARTICIPANTS: Twenty-one children (age range, 1 year 6 months to 10 years 4 months) with unilateral Sturge-Weber syndrome. MAIN OUTCOME MEASURES: Cortical gray matter and hemispheric white matter volumes were measured on segmented volumetric magnetic resonance imaging and correlated with the age of the participants. Global intellectual function (IQ) was correlated with magnetic resonance imaging and seizure variables in both univariate and multivariate analyses. RESULTS: Both gray and white matter volumes showed an age-related linear increase. Tissue volumes on the side of the angioma showed a positive correlation with IQ after controlling for age in univariate regression analyses (white matter, r = 0.71, P < .001; gray matter, r = 0.48, P = .03), while seizure variables did not correlate with IQ (P > .1). A multivariate regression showed that hemispheric white matter volume ipsilateral to the angioma was an independent predictor of IQ (R = 61, P = .006), which also showed a negative correlation with age (R = - 0.52, P = .022) but no correlation with gray matter volumes. CONCLUSIONS: Early hemispheric white matter loss may play a major role in cognitive impairment in children with Sturge-Weber syndrome. Future therapeutic approaches should aim at preserving white matter integrity in addition to seizure control to improve cognitive outcome.     

Widespread cerebral gray matter volume deficits in schizophrenia.

Magnetic resonance imaging was used to investigate whether the structural brain differences commonly observed in patients with schizophrenia as compared with normal control subjects are specific to gray or white matter, and furthermore whether such abnormalities are localizable to circumscribed cortical regions. Accordingly, 22 patients meeting DSM-III-R criteria for schizophrenia and 20 healthy community volunteers, all 23 to 45 years old, received magnetic resonance imaging scans. Seven axial magnetic resonance imaging sections of 5-mm thickness were segmented into cerebrospinal fluid, gray matter, and white matter compartments and used for volumetric quantification. For the healthy control subjects, age correlated significantly with the percentage of all magnetic resonance imaging sections taken up by gray matter but not white matter. After correcting for the normal effect of age, the schizophrenic group was found to have significantly less gray matter than the control group but no difference in white matter; ventricular volume was 34% greater in the schizophrenic group. The schizophrenic group had less gray matter in all six cortical subregions analyzed; these differences attained statistical significance for all but the parietal measure. These findings have implications for studies of localized gray matter abnormalities and suggest that regional brain volume measurements need to be expressed in the context of possible widespread gray matter volume deficits in schizophrenia.     

Neuroanatomy of Down's syndrome: a high-resolution MRI study

OBJECTIVE: Down's syndrome, the most common genetic cause of mental retardation, results in characteristic physical and neuropsychological findings, including mental retardation and deficits in language and memory. This study was undertaken to confirm previously reported abnormalities of regional brain volumes in Down's syndrome by using high-resolution magnetic resonance imaging (MRI), determine whether these volumetric abnormalities are present from childhood, and consider the relationship between neuroanatomic abnormalities and the cognitive profile of Down's syndrome. METHOD: Sixteen children and young adults with Down's syndrome (age range=5-23 years) were matched for age and gender with 15 normal comparison subjects. High-resolution MRI scans were quantitatively analyzed for measures of overall and regional brain volumes and by tissue composition. RESULTS: Consistent with prior imaging studies, subjects with Down's syndrome had smaller overall brain volumes, with disproportionately smaller cerebellar volumes and relatively larger subcortical gray matter volumes. Also noted was relative preservation of parietal lobe gray and temporal lobe white matter in subjects with Down's syndrome versus comparison subjects. No abnormalities in pattern of brain asymmetry were noted in Down's syndrome subjects. CONCLUSIONS: The results largely confirm findings of previous studies with respect to overall patterns of brain volumes in Down's syndrome and also provide new evidence for abnormal volumes of specific regional tissue components. The presence of these abnormalities from an early age suggests that fetal or early postnatal developmental differences may underlie the observed pattern of neuroanatomic abnormalities and contribute to the specific cognitive and developmental deficits seen in individuals with Down's syndrome.     

Brain structure and aging in chronic temporal lobe epilepsy

Purpose: To characterize differences in brain structure and their patterns of age‐related change in individuals with chronic childhood/adolescent onset temporal lobe epilepsy compared with healthy controls. Methods: Subjects included participants with chronic temporal lobe epilepsy (n = 55) of mean childhood/adolescent onset and healthy controls (n = 53), age 14–60 years. Brain magnetic resonance imaging (MRI) studies (1.5 T) were processed using FreeSurfer to obtain measures of lobar thickness, area, and volume as well as volumes of diverse subcortical structures and cerebellum. Group differences were explored followed by cross‐sectional lifespan modeling as a function of age. Key Findings: Anatomic abnormalities were extensive in participants with chronic temporal lobe epilepsy including distributed subcortical structures (hippocampus, thalamus, caudate, and pallidum), cerebellar gray and white matter, total cerebral gray and white matter; and measures of cortical gray matter thickness, area, or volume in temporal (medial, lateral) and extratemporal lobes (frontal, parietal). Increasing chronologic age was associated with progressive changes in diverse cortical, subcortical, and cerebellar regions for both participants with epilepsy and controls. Age‐accelerated changes in epilepsy participants were seen in selected areas (third and lateral ventricles), with largely comparable patterns of age‐related change across other regions of interest. Significance: Extensive cortical, subcortical, and cerebellar abnormalities are present in participants with mean chronic childhood/adolescent onset temporal lobe epilepsy implicating a significant neurodevelopmental impact on brain structure. With increasing chronologic age, the brain changes occurring in epilepsy appear to proceed in a largely age‐appropriate fashion compared to healthy controls, the primary exception being age‐accelerated ventricular expansion (lateral and third ventricles). These cumulative structural abnormalities appear to represent a significant anatomic burden for persons with epilepsy, the consequences of which remain to be determined as they progress into elder years.     

Association between the scores of the Japanese version of the Brief Assessment of Cognition in Schizophrenia and whole‐brain structure in patients with chronic schizophrenia: A voxel‐based morphometry and diffusion tensor imaging study

Aim

The Brief Assessment of Cognition in Schizophrenia (BACS) is a concise tool designed to evaluate cognitive deficits in schizophrenia. We examined the possible association between BACS scores and whole‐brain structure, as observed using magnetic resonance imaging with a relatively large sample.

Methods

The study sample comprised 116 patients with schizophrenia (mean age, 39.3 ± 11.1 years; 66 men) and 118 healthy controls (HC; mean age, 40.0 ± 13.6 years; 58 men) who completed the Japanese version of the BACS (BACS‐J). All participants were of Japanese ethnicity. The magnetic resonance imaging volume and diffusion tensor imaging data were processed with voxel‐based morphometry and tract‐based spatial statistics, respectively.

Results

There were significant reductions in the regional gray matter volumes and white matter fractional anisotropy values in patients with schizophrenia compared to HC. For the gray matter areas, the working memory score had a significant positive correlation with the anterior cingulate and medial frontal cortices volumes in the patients. For the white matter areas, the motor speed score had a significant positive correlation with fractional anisotropy values in the corpus callosum, internal capsule, superior corona radiata, and superior longitudinal fasciculus in the patients. However, there was no significant correlation among either the gray or white matter areas in the HC.

Conclusion

Our results suggest that among the BACS‐J measures, the working memory and motor speed scores are associated with several structural alterations in the brains of patients with schizophrenia.     

Age, rapid-cycling, and pharmacotherapy effects on ventral prefrontal cortex in bipolar disorder: a cross-sectional study.

BACKGROUND: Neuroimaging data suggest that deficits in ventral prefrontal cortex (VPFC) function in bipolar disorder (BD) progress during adolescence and young adulthood. However, the developmental trajectory of VPFC morphological abnormalities in BD is unknown. This study investigated potential age-dependent volume abnormalities in VPFC in BD. METHODS: Thirty-seven individuals diagnosed with BD I (14 adolescents, 10 young adults and 13 older adults) and 56 healthy comparison subjects (HC) participated in imaging. Gray and white matter volumes of VPFC were measured using high-resolution structural magnetic resonance imaging (MRI). We used a mixed model, repeated measures analysis to examine VPFC volumes across age groups while co-varying for total brain volume. Potential effects of illness features including rapid-cycling and medication were explored. RESULTS: VPFC volumes declined with age (p < .001). The diagnosis-by-age group interaction was significant (p = .01). Relative to HC subjects, VPFC gray and white matter volumes were significantly smaller in BD patients only in young adulthood (p = .04). In participants with BD, VPFC volumes were significantly smaller in participants with rapid-cycling than participants without rapid-cycling (p = .02). Conversely, current use of medication was associated with larger VPFC gray matter volumes (p = .005), independent of age. CONCLUSIONS: These preliminary findings suggest the presence of a more rapid initial decline in VPFC volumes with age in adolescents and young adults with BD than HC. These findings also suggest that the rapid-cycling subtype of BD is associated with larger VPFC volume deficits than the non-rapid-cycling subtype, and that pharmacotherapy may have trophic or protective effects on VPFC volumes in BD patients.     

Brain imaging in normal and abnormal brain development: new perspectives for child psychiatry

Non-invasive brain imaging permits the study of normal and abnormal brain development in childhood and adolescence. This paper summarizes current knowledge of brain development for healthy adolescents and for patients with childhood-onset schizophrenia (COS), a rare form of the disorder. The implications of these findings are explored. Cross-sectional and longitudinal brain magnetic resonance imaging (MRI) studies are reviewed. The pattern and temporal characteristics of anatomic brain MRI in adult-onset schizophrenia (AOS) and COS are reviewed, and discussed in terms of normal brain development and candidate mechanisms. A consistent, abnormal pattern of childhood brain development is found for COS. Normal children show non-linear regionally specific changes in gray matter volume and linear increase in white matter. COS children have smaller brain volumes due to a 10% decrease in cortical gray matter with white matter sparing. Moreover, there is a progressive loss of regional gray matter particularly in parietal, frontal and temporal regions during adolescence that is more striking for COS than that seen for AOS. In COS, developmental data are consistent with models of time limited diagnostically specific abnormalities of synaptic and dendritic production and pruning. Selected human postmortem brain and developmental animal studies relevant to such models are reviewed.