Frontal and temporal volume size of grey and white matter in patients with schizophrenia

We previously performed a magnetic resonance imaging (MRI) parcellation study that showed smaller grey and white matter volumes of the temporal lobes and increased CSF volumes in the frontal and temporal lobe in men with schizophrenia. One question that arose from this earlier study was whether similar structural changes in the brain are found in a large group of schizophrenic patients consisting of both men and women. In the present study, MRI scans were acquired from 94 patients of both genders with schizophrenia and 101 healthy subjects. After the automatic segmentation of grey matter, white matter, and cerebrospinal fluid, the frontal, temporal, parietal, and occipital lobes were automatically parcellated according to the Talairach atlas. Compared with healthy subjects, schizophrenic patients showed significantly smaller volumes of grey matter in the temporal lobe and white matter in the frontal lobe. Schizophrenic patients had a greater CSF volume in the frontal and temporal lobes. These results suggest that volume reduction in the cerebrum is prominent in the frontal and temporal lobes in both men and women with schizophrenia.     

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.     

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.     

Optimized voxel-based morphometry of gray matter volume in first-episode, antipsychotic-naive schizophrenia

This study examined gray matter (GM) volume abnormalities in first-episode, antipsychotic-na?ve Indian schizophrenia patients. Magnetic resonance images of 18 schizophrenia patients and 18 matched healthy comparison subjects were analyzed by optimized voxel-based morphometry. Schizophrenia patients had significantly smaller global GM and greater global CSF volumes and smaller regional GM volume in superior frontal, inferior frontal, cingulate, post-central, superior temporal and parahippocampal gyri, inferior parietal lobule, insula, caudate nuclei, thalamus and cerebellum. Findings suggest limbic, heteromodal cortical, striatal, thalamic and cerebellar abnormalities in schizophrenia.     

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.     

Structural brain abnormalities in patients with schizophrenia and their healthy siblings

OBJECTIVE: The authors sought to investigate the contribution of genotype on structural brain abnormalities in schizophrenia. METHOD: Intracranial volumes and volumes of the cerebrum, white and gray matter, lateral and third ventricles, frontal lobes, caudate nucleus, amygdala, hippocampus, parahippocampal gyrus, and the cerebellum were measured in 32 same-sex siblings discordant for schizophrenia and 32 matched comparison subjects by means of magnetic resonance imaging. RESULTS: Third ventricle volumes did not differ between the schizophrenic patients and their healthy siblings. However, both had higher third ventricle volumes than did the comparison subjects. The schizophrenic patients had lower cerebrum volumes than did the comparison subjects, whereas the cerebrum volume of the healthy siblings did not significantly differ from the patients or comparison subjects. Additionally, patients with schizophrenia displayed a volume reduction of the frontal lobe gray matter and a volume increase of the caudate nuclei and lateral ventricles compared to both their healthy siblings and comparison subjects. Intracranial volume, CSF volume, or volumes of the cerebellum, amygdala, hippocampus, or the parahippocampal gyrus did not significantly differ among the patients, siblings, and comparison subjects. CONCLUSIONS: Healthy siblings share third ventricle enlargement with their affected relatives and may partially display a reduction in cerebral volume. These findings suggest that third ventricular enlargement, and to some extent cerebral volume decrease, may be related to genetic defects that produce a susceptibility to schizophrenia.     

Middle and inferior temporal gyrus gray matter volume abnormalities in first-episode schizophrenia: an MRI study

OBJECTIVE: Magnetic resonance imaging (MRI) studies of schizophrenia reveal temporal lobe structural brain abnormalities in the superior temporal gyrus and the amygdala-hippocampal complex. However, the middle and inferior temporal gyri have received little investigation, especially in first-episode schizophrenia. METHOD: High-spatial-resolution MRI was used to measure gray matter volume in the inferior, middle, and superior temporal gyri in 20 patients with first-episode schizophrenia, 20 patients with first-episode affective psychosis, and 23 healthy comparison subjects. RESULTS: Gray matter volume in the middle temporal gyrus was smaller bilaterally in patients with first-episode schizophrenia than in comparison subjects and in patients with first-episode affective psychosis. Posterior gray matter volume in the inferior temporal gyrus was smaller bilaterally in both patient groups than in comparison subjects. Among the superior, middle, and inferior temporal gyri, the left posterior superior temporal gyrus gray matter in the schizophrenia group had the smallest volume, the greatest percentage difference, and the largest effect size in comparisons with healthy comparison subjects and with affective psychosis patients. CONCLUSIONS: Smaller gray matter volumes in the left and right middle temporal gyri and left posterior superior temporal gyrus were present in schizophrenia but not in affective psychosis at first hospitalization. In contrast, smaller bilateral posterior inferior temporal gyrus gray matter volume is present in both schizophrenia and affective psychosis at first hospitalization. These findings suggest that smaller gray matter volumes in the dorsal temporal lobe (superior and middle temporal gyri) may be specific to schizophrenia, whereas smaller posterior inferior temporal gyrus gray matter volumes may be related to pathology common to both schizophrenia and affective psychosis.     

Correlations between MRI-assessed volumes of the thalamus and cortical Brodmann's areas in schizophrenia

BACKGROUND: We compared the thalamic-cortical volumetric correlational patterns in patients with schizophrenia and normal comparison subjects, and evaluated their relations to outcome. METHODS: High-resolution MR images were acquired in patients with schizophrenia (n=106) and normal comparison subjects (n=42). Patients were divided into good-outcome (n=52) and poor-outcome (Kraepelinian, n=54) subtypes based on their ability for self-care. Correlations between the relative gray and white matter volumes of the individual cortical Brodmann's areas and five dorsoventral levels of the thalamus were assessed. RESULTS: Compared to normal subjects, schizophrenia patients lacked significant thalamic gray matter volume correlations with the prefrontal and medial temporal cortical regions in the right hemisphere, and with frontal, cingulate, posterior parietal and occipital regions in the left hemisphere, while normal white matter volume cortical-thalamic correlations along the cingulate gyrus and in the temporal lobe were not found in schizophrenia patients in both hemispheres. In contrast to both normal comparison subjects and good-outcome group, schizophrenia patients with poor outcomes showed significant bilateral gray matter volume correlations between the dorsal thalamus and ventral prefrontal cortex, while the group differences in the white matter volume correlations were mostly restricted to the cingulate arch. CONCLUSIONS: Whereas patients with schizophrenia exhibit deficiencies in cortical-thalamic correlational patterns, poor outcome is associated with abnormal interregional correlations not observed in either normal subjects or patients with good outcomes. This latter finding may be explained by a core neurodevelopmental disturbance that results in aberrant cortical-thalamic connectivity in poor-outcome schizophrenia.     

Progressive decrease of left superior temporal gyrus gray matter volume in patients with first-episode schizophrenia

OBJECTIVE: Smaller temporal lobe cortical gray matter volumes, including the left superior temporal gyrus, have been reported in magnetic resonance imaging (MRI) studies of patients with chronic schizophrenia and, more recently, in patients with first-episode schizophrenia. However, it remains unknown whether there are progressive decreases in temporal lobe cortical gray matter volumes in patients with first-episode schizophrenia and whether similarly progressive volume decreases are present in patients with affective psychosis. METHOD: High-spatial-resolution MRI scans at initial hospitalization and 1.5 years later were obtained from 13 patients with first-episode schizophrenia, 15 patients with first-episode affective psychosis (mainly manic), and 14 healthy comparison subjects. MRI volumes were calculated for gray matter of superior temporal gyrus and for the amygdala-hippocampal complex. RESULTS: Patients with first-episode schizophrenia showed significant decreases in gray matter volume over time in the left superior temporal gyrus compared with patients with first-episode affective psychosis or healthy comparison subjects. This progressive decrease was more pronounced in the posterior portion of the left superior temporal gyrus (mean=9.6%) than in the anterior portions (mean=8.4%). No group differences in the rate of change over time were present in other regions. CONCLUSIONS: These findings demonstrate a progressive volume reduction of the left posterior superior temporal gyrus gray matter in patients with first-episode schizophrenia but not in patients with first-episode affective psychosis.     

Temporal lobe pathology in schizophrenia: a quantitative magnetic resonance imaging study

Although numerous studies have confirmed the presence of larger cerebral ventricles in schizophrenia, the locus of tissue loss remains elusive. By analyzing magnetic resonance scans with computerized image analysis, the authors determined gray and white matter volumes in the temporal lobes and prefrontal regions of 17 patients with schizophrenia and 17 age- and sex-matched normal subjects. The volume of temporal lobe gray matter was 20% smaller in the patients than in the control subjects. The lateral ventricular volume was 67% larger in the patients and, when normalized for brain size, correlated inversely with the volume of temporal lobe gray matter.     

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.     

The relationship of structural alterations to cognitive deficits in schizophrenia: a voxel-based morphometry study.

BACKGROUND: Region of interest studies have identified a number of structure-cognition associations in schizophrenia and revealed alterations in structure-cognition relationship in this population. METHODS: We examined the relationship of structural brain alterations, identified using voxel-based morphometry, to cognitive deficits in 45 schizophrenia patients relative to 43 healthy control subjects and tested the hypothesis that structure-cognition relationship is altered in schizophrenia. RESULTS: Patients had smaller total brain, gray matter, and white matter volumes. Regional alterations were left-hemisphere specific, including: gray matter reduction of inferior frontal, lingual, and anterior superior temporal gyri; white matter reduction of posterior and occipital lobes; and gray matter increase of the putamen and the precuneus. Smaller whole brain and gray matter volumes were associated with lower premorbid intelligence quotient (IQ) and poorer performance on IQ-dependent cognitive measures in patients and to a similar extent in control subjects. Larger precuneus was associated with better immediate verbal memory in patients, whereas verbal and nonverbal memory were positively associated with inferior frontal gyrus volume in control subjects. Smaller occipital white matter volume was associated with slower information processing speed in patients but not in control subjects. CONCLUSIONS: Regional volume alterations are associated with specific cognitive deficits in schizophrenia. Some structure-cognition relationships differentiate this population from healthy control subjects.     

Structural neuroimaging in adolescents with a first psychotic episode

OBJECTIVE: The objective of the present study is to replicate findings in first-episode psychosis reporting a smaller volume in brain structures in a population with adolescent onset. METHOD: Magnetic resonance imaging studies were performed on 23 psychotic adolescents (12-18 years old, 17 males, 6 females) consecutively admitted to an adolescent inpatient unit and on 37 normal controls (13-18 years, 23 males, 14 females) matched for age, sex, and years of education. Diagnosis was made at baseline on the basis of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version and confirmed after 12 months of follow-up. Total brain volume and gray matter, white matter, and cerebrospinal fluid (CSF) volumes of the frontal, parietal, temporal, and occipital lobes were measured bilaterally using a segmentation method based on the Talairach grid system. RESULTS: Male patients showed significantly larger volumes than did male controls in overall CSF and left frontal and right parietal sulci CSF. Male patients also showed significantly lower volumes of gray matter in the right and left frontal lobes. No significant volumetric differences were found in females. There were no differences between individuals with a diagnosis of schizophrenia at follow-up and the rest of the patients. CONCLUSIONS: This study suggests that larger CSF and lower gray matter volumes in the frontal lobes may be a nonspecific vulnerability marker for psychosis in male adolescents.     

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.     

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.     

Structural brain abnormalities in patients with schizophrenia, epilepsy, and epilepsy with chronic interictal psychosis.

Chronic interictal psychotic syndromes, often resembling schizophrenia, develop in some patients with epilepsy. Although widespread brain abnormalities are recognized as characteristic of schizophrenia, prevailing but controversial hypotheses on the co-occurrence of epilepsy and psychosis implicate left temporal lobe pathology. In this study, quantitative MRI methods were used to address the regional specificity of structural brain abnormalities in patients with epilepsy plus chronic interictal psychosis (E+PSY, n=9) relative to three comparison groups: unilateral temporal lobe epilepsy without chronic psychosis (TLE, n=18), schizophrenia (SCZ, n=46), and healthy control subjects (HC, n=57). Brain measures, derived from a coronal spin-echo MRI sequence, were adjusted for age and cerebral volume. Relative to HC, all patient groups had ventricular enlargement and smaller temporal lobe, frontoparietal, and superior temporal gyrus gray matter volumes, with the extent of these abnormalities greatest in E+PSY. Only TLE had temporal lobe white matter deficits, as well as smaller hippocampi, which were ipsilateral to the seizure focus. Structural brain abnormalities in E+PSY are not restricted to the left temporal lobe. The confluence of cortical gray matter deficits in E+PSY and SCZ suggests salience to chronic psychosis.     

Temporal lobe volume determined by magnetic resonance imaging in schizotypal personality disorder and schizophrenia

The volumes of the whole temporal lobe, the superior temporal gyrus and the corpus callosum were measured on magnetic resonance images from 13 patients with schizotypal personality disorder (SPD), 27 patients with schizophrenia, and 31 age- and sex-matched controls. Temporal lobe structures were traced on consecutive 1.2mm thick SPGR images. Both patient groups had smaller temporal lobes than normal volunteers, a difference that was more marked for the area outside the superior temporal gyrus than for the STG. Correcting for brain volume diminished differences between normal subjects and schizophrenia patients, but the differences between normal subjects and SPD patients remained. Normal volunteers and SPD patients showed significant correlations between the sagittal section area of the posterior portion of the corpus callosum, which carries temporal interhemispheric connections, and the white matter volume of the temporal lobe. While the sample size is modest, taken together, these results suggest that the psychopathological symptoms of SPD may be related to temporal gray matter loss with relatively intact white matter connectivity, while the cognitive and psychotic symptoms of schizophrenia may be related to temporal gray loss combined with disruption of normal patterns of white matter development.     

Gray matter volume deficits are associated with motor and attentional impairments in adolescents with schizophrenia

Cognitive deficits have been well described in adolescents with schizophrenia, but little is known about the neuroanatomical basis of these abnormalities. The authors examined whether neuropsychological deficits observed in adolescents with schizophrenia were associated with cortical gray matter volume deficits. Volumes of the superior frontal gyrus, anterior cingulate gyrus and orbital frontal lobe were outlined manually from contiguous MR images and automatically segmented into gray and white matter in 52 patients and 48 healthy volunteers. Subjects received a comprehensive neuropsychological test battery, assessing five different functional domains: executive, attention, verbal memory, motor and sensory motor. Children and adolescents with schizophrenia were found to have lower total cortical and lower superior frontal gyrus gray matter volumes and lower test scores across all functional domains compared to healthy volunteers. Among patients, the lower total cortical gray matter volume was associated with worse functioning on the attention and motor domains. Our findings point to widespread, perhaps multifocal, pathology as contributing to cognitive dysfunction in adolescents with schizophrenia.     

Thought disorder and frontotemporal volumes in pediatric epilepsy

The aim of this study was to determine if volumes of frontotemporal regions associated with language were related to thought disorder in 42 children, aged 5–16 years, with cryptogenic epilepsy, all of whom had complex partial seizures (CPS). The children with CPS and 41 age- and gender-matched healthy children underwent brain MRI scans at 1.5 T. Tissue was segmented, and total brain, frontal lobe, and temporal lobe volumes were computed. Thought disorder measures, IQ, and seizure information were collected for each patient. The subjects with CPS had more thought disorder, smaller total gray matter and orbital frontal gray matter volumes, as well as larger temporal lobe white matter volumes than the control group. In the CPS group, thought disorder was significantly related to smaller orbital frontal and inferior frontal gray matter volumes, increased Heschl’s gyrus gray matter volumes, and smaller superior temporal gyrus white matter volumes. However, significantly larger orbital frontal gyrus, superior temporal gyrus, and temporal lobe gray matter volumes and decreased Heschl’s gyrus white matter volumes were associated with thought disorder in the control group. These findings suggest that thought disorder might represent a developmental disability involving frontotemporal regions associated with language in pediatric CPS.     

Large CSF volume not attributable to ventricular volume in schizotypal personality disorder

OBJECTIVE: The purpose of this study was to determine whether schizotypal personality disorder, which has the same genetic diathesis as schizophrenia, manifests abnormalities in whole-brain and CSF volumes. METHOD: Sixteen right-handed and neuroleptic-naive men with schizotypal personality disorder were recruited from the community and were age-matched to 14 healthy comparison subjects. Magnetic resonance images were obtained from the subjects and automatically parcellated into CSF, gray matter, and white matter. Subsequent manual editing separated cortical from noncortical gray matter. Lateral ventricles and temporal horns were also delineated. RESULTS: The men with schizotypal personality disorder had larger CSF volumes than the comparison subjects; the difference was not attributable to larger lateral ventricles. The cortical gray matter was somewhat smaller in the men with schizotypal personality disorder, but the difference was not statistically significant. CONCLUSIONS: Consistent with many studies of schizophrenia, this examination of schizotypal personality disorder indicated abnormalities in brain CSF volumes.