Magnetic resonance imaging and head circumference study of brain size in autism: birth through age 2 years

CONTEXT: While the neuroanatomical basis of autism is not yet known, evidence suggests that brain enlargement may be characteristic of this disorder. Inferences about the timing of brain enlargement have recently come from studies of head circumference (HC). OBJECTIVES: To examine brain volume and HC in individuals with autism as compared with control individuals. DESIGN: A cross-sectional study of brain volume was conducted at the first time point in an ongoing longitudinal magnetic resonance imaging study of brain development in autism. Retrospective longitudinal HC measurements were gathered from medical records on a larger sample of individuals with autism and local control individuals. SETTING: Clinical research center. PARTICIPANTS: The magnetic resonance imaging study included 51 children with autism and 25 control children between 18 and 35 months of age (the latter included both developmentally delayed and typically developing children). Retrospective, longitudinal HC data were examined from birth to age 3 years in 113 children with autism and 189 local control children. MAIN OUTCOME MEASURES: Cerebral cortical (including cortical lobes) and cerebellar gray and white matter magnetic resonance imaging brain volumes as well as retrospective HC data from medical records were studied. RESULTS: Significant enlargement was detected in cerebral cortical volumes but not cerebellar volumes in individuals with autism. Enlargement was present in both white and gray matter, and it was generalized throughout the cerebral cortex. Head circumference appears normal at birth, with a significantly increased rate of HC growth appearing to begin around 12 months of age. CONCLUSIONS: Generalized enlargement of gray and white matter cerebral volumes, but not cerebellar volumes, are present at 2 years of age in autism. Indirect evidence suggests that this increased rate of brain growth in autism may have its onset postnatally in the latter part of the first year of life.     

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.     

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.     

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.     

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.     

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.     

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 assessment of gray and white matter distribution in Brodmann's areas of the cortex in patients with schizophrenia with good and poor outcomes

OBJECTIVE: High-resolution magnetic resonance imaging (MRI) was used to compare cortical gray and white matter and CSF volumes in schizophrenia patients with poor outcomes, schizophrenia patients with good outcomes, and healthy comparison subjects. METHOD: T(1)-weighted, 1.2-mm-thick MR images were acquired for 37 patients with schizophrenia and 37 healthy, age- and sex-matched comparison subjects. The patients were assigned to subgroups with poor outcomes (N=13) and good outcomes (N=24) on the basis of clinical characteristics. Poor-outcome patients were those who were continuously hospitalized or completely dependent on others for basic needs, were unemployed, and had severe negative symptoms and severe formal thought disorder. The MR images were reoriented to standard position parallel to the anterior commissure-posterior commissure line and segmented into CSF, gray matter, and white matter tissue types. The tissue types were assigned to Brodmann's areas by using the Perry postmortem histological atlas, and tissue-type volumes in the three subject groups were compared. RESULTS: Compared to the healthy subjects, the overall patient group had a significantly smaller mean cortical gray matter volume and significantly larger mean CSF volume, especially in the frontal lobe and left temporal lobe. The smaller frontal lobe volume in schizophrenia was confirmed for unadjusted volumes and for volumes with adjustment for whole brain volumes. Compared to patients with good outcomes, patients with poor outcomes (Kraepelinian schizophrenia) had significantly smaller gray matter volumes in the temporal and occipital lobes, but no difference between groups was found for total frontal lobe volume. Only 21% of the healthy subjects had volumes 0.5 standard deviations below the mean for healthy subjects in any area of the frontal or temporal lobes, compared with 62% of poor-outcome patients. CONCLUSIONS: Poor outcome in patients with schizophrenia may be associated with a more posterior distribution (posteriorization) of gray matter deficits across widely distributed cortical regions.     

Development of cortical and subcortical brain structures in childhood and adolescence: a structural MRI study

The purpose of the present study was to describe in greater anatomical detail the changes in brain structure that occur during maturation between childhood and adolescence. High-resolution MRI, tissue classification, and anatomical segmentation of cortical and subcortical regions were used in a sample of 35 normally developing children and adolescents between 7 and 16 years of age (mean age 11 years; 20 males, 15 females). Each cortical and subcortical measure was examined for age and sex effects on raw volumes and on the measures as proportions of total supratentorial cranial volume. Results indicate age-related increases in total supratentorial cranial volume and raw and proportional increases in total cerebral white matter. Gray-matter volume reductions were only observed once variance in total brain size was proportionally controlled. The change in total cerebral white-matter proportion was significantly greater than the change in total cerebral gray-matter proportion over this age range, suggesting that the relative gray-matter reduction is probably due to significant increases in white matter. Total raw cerebral CSF volume increases were also observed. Within the cerebrum, regional patterns varied depending on the tissue (or CSF) assessed. Only frontal and parietal cortices showed changes in gray matter, white matter, and CSF measures. Once the approximately 7% larger brain volume in males was controlled, only mesial temporal cortex, caudate, thalamus, and basomesial diencephalic structures showed sex effects with the females having greater relative volumes in these regions than the males. Overall, these results are consistent with earlier reports and describe in greater detail the regional pattern of age-related differences in gray and white matter in normally developing children and adolescents.     

Smaller frontal gray matter volume in postmortem schizophrenic brains

OBJECTIVE: The prefrontal cortex exhibits prominent functional, biochemical, and anatomic abnormalities in schizophrenic patients. However, smaller than normal volume of the frontal lobe has not been found in previous postmortem studies of schizophrenic subjects, and magnetic resonance imaging (MRI) scans of schizophrenic subjects have not consistently revealed frontal volumetric deficits. The variability in MRI findings may be related partly to difficulty in defining the posterior border of the frontal lobe. In this study, precise measurements of frontal lobe volume from postmortem brains were derived by defining the posterior border according to the brain atlas of Talairach and Tournoux and by applying stereologic methods to estimate gray and white matter volumes. METHOD: Whole, or nearly whole, formalin-fixed left hemispheres from 14 schizophrenic and 19 normal comparison subjects were analyzed. Total cortical gray and white matter volumes, as well as frontal cortical gray and white matter volumes, were measured by using the Cavalieri method. RESULTS: Only frontal gray matter volume was significantly smaller in the schizophrenic subjects than in the comparison subjects (12% difference). The differences between groups in total gray and white matter volumes and frontal white matter volume (6%-8% smaller in the schizophrenic subjects than in the comparison subjects) did not reach statistical significance. CONCLUSIONS: The smaller frontal gray matter volume observed in schizophrenic brains suggests that pathology of the frontal lobe may be more severe than that of the three posterior lobes and may account for the prominence of prefrontal dysfunction associated with schizophrenia.     

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.     

Progressive cortical change during adolescence in childhood-onset schizophrenia. A longitudinal magnetic resonance imaging study.

BACKGROUND: Adolescence provides a window to examine regional and disease-specific late abnormal brain development in schizophrenia. Because previous data showed progressive brain ventricular enlargement for a group of adolescents with childhood-onset schizophrenia at 2-year follow-up, with no significant changes for healthy controls, we hypothesized that there would be a progressive decrease in volume in other brain tissue in these patients during adolescence. METHODS: To examine cortical change, we used anatomical brain magnetic resonance imaging scans for 15 patients with childhood-onset schizophrenia (defined as onset of psychosis by age 12 years) and 34 temporally yoked, healthy adolescents at a mean (SD) age of 13.17 (2.73) years at initial baseline scan and 17.46 (2.96) years at follow-up scan. Cortical gray and white matter volumes were obtained with an automated analysis system that classifies brain tissue into gray matter, white matter, and cerebrospinal fluid and separates the cortex into anatomically defined lobar regions. RESULTS: A significant decrease in cortical gray matter volume was seen for healthy controls in the frontal (2.6%) and parietal (4.1%) regions. For the childhood-onset schizophrenia group, there was a decrease in volume in these regions (10.9% and 8.5%, respectively) as well as a 7% decrease in volume in the temporal gray matter. Thus, the childhood-onset schizophrenia group showed a distinctive disease-specific pattern (multivariate analysis of variance for change X region X diagnosis: F, 3.68; P = .004), with the frontal and temporal regions showing the greatest between-group differences. Changes in white matter volume did not differ significantly between the 2 groups. CONCLUSIONS: Patients with very early-onset schizophrenia had both a 4-fold greater decrease in cortical gray matter volume during adolescence and a disease-specific pattern of change. Etiologic models for these patients' illness, which seem clinically and neurobiologically continuous with later-onset schizophrenia, must take into account both early and late disruptions of brain development.     

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.     

Age-related brain volume reductions in amphetamine and cocaine addicts and normal controls: implications for addiction research

The study evaluated the relationship between age and frontal and temporal lobe volumes in young cohorts of cocaine-dependent (CD), amphetamine-dependent (Am), and normal control subjects. Ten CD, nine Am, and 16 age- and gender-matched control subjects underwent magnetic resonance imaging (MRI). The volume of the frontal and temporal lobes was measured from an identically positioned slab of seven contiguous 3-mm-thick coronal images. Follow-up measures of the gray and white matter subcomponents of these volumes were also obtained. Both CD and Am groups had a significantly smaller temporal lobe volumes, but only the CD group demonstrated a significantly greater decline in temporal lobe volume with age (intracranial volume, education, and race were controlled for in all statistical analyses). Segmenting the brain regions into gray and white matter revealed that the negative correlation between age and temporal lobe volume of CD patients was mostly due to a significant age-related decline in the gray matter subcomponent. Negative trends between age and gray matter volumes were also observed in the Am and normal groups. In the frontal lobes, age was negatively correlated with gray matter volume in the control, CD, and Am groups. Unlike the consistent decreases in gray matter volumes, white matter showed non-significant increases in volume with age. The data suggest that CD patients may have an accelerated age-related decline in temporal lobe gray matter volume and a smaller temporal lobe volume compared to normal controls. In the frontal lobe, age-related gray matter volume reductions occur in all three groups. These age-related cortical gray matter volume reductions may be a biological marker for the risk of addictive behavior, which also decreases with age.     

Smaller prefrontal and premotor volumes in boys with attention-deficit/hyperactivity disorder.

BACKGROUND: Anatomic magnetic resonance imaging (MRI) studies of attention-deficit/hyperactivity disorder (ADHD) have been limited by use of callosal rather than sulcal/gyral landmarks in defining cerebral lobes and functionally relevant sublobar regions (e.g., prefrontal cortex). We present an investigation of cerebral volumes in ADHD using a Talairach-based approach that uses cortical landmarks to define functionally relevant regions. METHODS: Volumes were compared between groups of 12 boys with ADHD and 12 age- and gender-matched control subjects, using a series of multiple analyses of variance. RESULTS: Boys with ADHD had (on average) 8.3% smaller total cerebral volumes. Significant reductions in lobar volumes were seen only for the frontal lobes. Within the frontal lobes, a reduction was seen in both gray and white matter volumes, with some evidence suggesting lateralization of these findings: reduction in frontal white matter volume was specific to the left hemisphere; there was a bilateral reduction in frontal gray matter volume but more so in the right hemisphere. Subparcellation of the frontal lobe revealed smaller prefrontal, premotor, and deep white matter volumes. CONCLUSIONS: Findings suggest that ADHD is associated with decreased frontal lobe gray and white matter volumes. More than one subdivision of the frontal lobes appears to be reduced in volume, suggesting that the clinical picture of ADHD encompasses dysfunctions attributable to anomalous development of both premotor and prefrontal cortices.     

Cortical gray and white matter volume in unmedicated schizotypal and schizophrenia patients

Magnetic resonance imaging (MRI) studies have revealed fronto-temporal cortical gray matter volume reductions in schizophrenia. However, to date studies have not examined whether age- and sex-matched unmedicated schizotypal personality disorder (SPD) patients share some or all of the structural brain-imaging characteristics of schizophrenia patients. We examined cortical gray/white matter volumes in a large sample of unmedicated schizophrenia-spectrum patients (n = 79 SPD, n = 57 schizophrenia) and 148 healthy controls. MRI images were reoriented to standard position parallel to the anterior–posterior commissure line, segmented into gray and white matter tissue types, and assigned to Brodmann areas (BAs) using a postmortem-histological atlas. Group differences in regional volume of gray and white matter in the BAs were examined with MANOVA. Schizophrenia patients had significantly reduced gray matter volume widely across the cortex but more marked in frontal and temporal lobes. SPD patients had reductions in the same regions but only about half that observed in schizophrenia and sparing in key regions including BA10. In schizophrenia, greater fronto-temporal volume loss was associated with greater negative symptom severity and in SPD, greater interpersonal and cognitive impairment. Overall, our findings suggest that increased prefrontal volume in BA10 and sparing of volume loss in temporal cortex (BAs 22 and 20) may be a protective factor in SPD which reduces vulnerability to psychosis.     

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.     

An MRI study of increased cortical thickness in autism

OBJECTIVE: The purpose of this study was to examine cortical thickness in autism in light of the postmortem evidence of cortical abnormalities of the disorder. METHOD: Magnetic resonance imaging (MRI) scans were acquired from 17 children with autism and 14 healthy comparison subjects, and sulcal and gyral thickness were measured for the total brain and for all lobes. RESULTS: Increases in total cerebral sulcal and gyral thickness were observed in children with autism relative to comparison subjects. Similar findings were noted in the temporal and parietal lobes but not in the frontal and occipital lobes. CONCLUSIONS: These preliminary findings indicate that increased cortical thickness may contribute to the increased gray matter volume and total brain size that have been observed in autism and may also be related to anomalies in cortical connectivity.     

Cortical gray matter deficit in patients with bipolar disorder

Background: cortical gray matter volume deficit and ventricular enlargement are well documented in schizophrenia, but their presence in bipolar disorder is less well established.

Methods: global cortical gray matter, white matter and sulcal CSF, as well as lateral and third ventricular volume measures, were derived from axial MRI brain images obtained on age-matched bipolar (n=9), schizophrenic (n=9), and control (n=16) subjects. All subjects were free of history of alcohol or other substance dependence.

Results: relative to controls, bipolar patients had widespread volume deficits of cortical gray matter but not of cortical white matter. Schizophrenic patients had an even more severe cortical gray matter deficit and greater sulcal and lateral ventricular enlargement than the bipolar patients.

Conclusions: this group of patients with bipolar disorder had a widespread deficit of cortical gray matter similar to, but less pronounced than, that observed in patients with schizophrenia.     

Differential effects of age on brain gray matter in bipolar patients and healthy individuals

This study examined possible differences in total gray and white matter brain content in bipolar patients and healthy individuals, and their relationship with age. 22 DSM-IV bipolar patients and 22 healthy controls underwent a 1.5-tesla Spoiled Gradient Recalled Acquisition (SPGR) MRI. Evaluators blind to patients' identities measured total brain, gray and white matter volumes using a semi-automated software. No differences were found for total brain volume, gray matter or white matter volumes between bipolar patients and healthy controls (MANCOVA, age as covariate, p > 0.05). Age was inversely correlated with total gray matter volume in patients (r = -0.576, p = 0.005), but not in controls (r = -0.193, p = 0.388). Our findings suggest that any existing gray matter deficits in bipolar disorder are likely to be localized to specific brain regions, rather than generalized. The inverse correlation between age and brain gray matter volumes in bipolar patients, not present in healthy controls, in this sample of mostly middle-aged adults, could possibly indicate more pronounced age-related gray matter decline in bipolar patients, and may be of potential relevance for the pathophysiology of the disorder.