Meta-analysis of corpus callosum size in schizophrenia.

Studies with MRI have shown differences in corpus callosum size between schizophrenic patients and controls. Most have found that the corpus callosum is smaller in schizophrenic patients, but in only a minority was this finding statistically significant, perhaps due to small sample sizes. Therefore a meta-analysis of 11 published studies of corpus callosum morphology in schizophrenia was conducted to ascertain whether there was a significant difference in corpus callosum size between schizophrenic patients and normal controls. These studies combined comprised 313 patients and 281 controls. Measures of corpus callosum midsagittal area, length, and corpus callosum area:brain area ratio were used in the meta-analysis. There was overall a statistically significant reduction in corpus callosum area in schizophrenic patients compared with controls (P < 0.02). Differences between patients and controls in measures of corpus callosum: brain area and corpus callosum length were not statistically significant. Age and corpus callosum area were related in both patients and controls. The influences on the corpus callosum of overall alterations of brain size, sex, handedness, and psychiatric illness in general remains to be determined.     

Age at onset and sex differences in corpus callosum area in schizophrenia

Previous research on neuropsychological function among schizophrenia patients suggests that typical onset males (first psychiatric hospital admission before age 25) and typical onset females (first admission after age 25) may exhibit less lateralization of behavioral function (‘hypolateralization’) than atypical onset males and atypical onset females. To explore whether these differences were reflected in corpus callosum area, brain morphometric data from a large sample of subjects diagnosed with schizophrenia were analyzed. Typical onset females and typical onset males were compared to atypical onset females and atypical onset males on corpus callosum area. While neither sex nor onset effect on total corpus callosum area was statistically significant, analysis of standard subregions of the corpus callosum revealed a significant interaction effect on the posterior 20% area of the corpus callosum, with typical onset women having particularly large corpora callosa. The anterior 50% area did not differ among the groups. The results are discussed in terms of the role of anomalies in the integration and hemispheric transfer of information as underlying mechanisms of schizophrenia.     

Corpus callosum area and functioning in schizophrenic patients with auditory--verbal hallucinations

Auditory--verbal hallucinations (AVH) are a characteristic feature of schizophrenia. Patients with AVHs have been found to differ from non-hallucinating patients in volumes of certain asymmetrical brain structures on MRI, and on certain neuropsychological measures. There is also evidence of corpus callosum (CC) abnormalities in schizophrenia, and it has been proposed that abnormalities of inter-hemispheric transmission may underlie hallucinations and other symptoms. The aim of this study was to examine whether patients with AVHs have smaller corpora callosa than those without AVH, and whether CC size is related to performance on neuropsychological tests of functional cerebral asymmetry. Seventy-one DSM-IV male schizophrenics were recruited on the basis of their hallucination history plus 33 matched normal controls. Twenty-nine patients had no history of AVH, and 42 had a strong history of AVH. The mid-sagittal surface area and longitudinal length of the CC were measured from T(1)-weighted spin echo images. Callosal area was divided into four sections. There were no significant differences in any of the measurements between the two patient groups, or between patients with schizophrenia and controls. There was no association between CC measures and handedness, or performance on dichotic listening or finger tapping tasks. The results of this study do not lend support for there being a major morphological abnormality of the corpus callosum in schizophrenic patients, or for a specific relationship to AVH. However, a significant association between CC area and overall grey and white matter volumes was noted in the hallucinating patients and, to a lesser extent, in the non-hallucinators, which may point to differing influences on brain development or degeneration in such patients compared with normal controls.     

Corpus callosum size in schizophrenia – a magnetic resonance imaging analysis

Previous MRI studies have shown differences in corpus callosum size between schizophrenic patients and controls. The corpus callosum (CC), as the main interhemispheric fiber tract, plays an important role in interhemispheric integration and communication. Though MRI studies suggest smaller CC in schizophrenia, there are still conflicting findings. Using in vivo magnetic resonance imaging, it was investigated whether the midsagittal area of CC differs between twenty-three right-handed male schizophrenic patients and twenty-three matched controls. Total CC area, five subregions of CC, total brain volume, gray and white matter were measured. No differences between schizophrenic patients and controls were found regarding all CC measurements, total brain volume, and gray matter tissue. However, a significant reduction of white matter tissue in the patient group emerged. There was no correlation between CC morphology and clinical variables such as age of onset, length of illness or symptom severity. Interestingly, five schizophrenic patients with a positive family history of schizophrenia showed significant reduction of the subregion C3, associated with a reduced total brain and gray and white matter volume. Significant reduction in the CC and its subregions was not confirmed in this group of patients with schizophrenia. In the subgroup of schizophrenic patients with a positive family history of schizophrenia, a significant reduction of the subregion corresponding to a part of the trunk of the CC was found. Received: 16 August 1999 / Accepted: 5 October 1999     

Corpus callosum and P300 in schizophrenia

Functional abnormalities in the interhemispheric transfer via the corpus callosum in schizophrenia may result in filtering problems and information processing problems, which may in turn be related to the synchronization of cortical event-related activity. To explore whether a relationship exists between corpus callosum (CC) size, measured with in-vivo magnetic resonance imaging, and late auditory event-related P300 potentials, 50 patients with schizophrenia as well as 50 healthy controls were examined. The absolute CC size and subregional areas, as well as the CC areas adjusted for total brain volume, were not significantly different between patients with schizophrenia and controls. While no significant group differences were observed for P3a-, P3b-, PSW-amplitudes and P3b-latencies, P3a- and PSW-latencies were significantly prolonged for patients with schizophrenia. Absolute CC total size was significantly correlated with P3b-amplitudes in healthy controls (r=0.29; P=0.044). In patients with schizophrenia, significant correlations were observed between the subregion of the posterior body of the CC and positive slow wave (PSW; r=0.47; P=0.001). P3a-, P3b- and PSW-latencies were not significantly correlated to CC size in either patients with schizophrenia or healthy controls. The results are discussed in terms of the possibility that abnormalities in interhemispheric transfer may underlie the mechanisms of schizophrenia.     

Patterns of cranial, brain and sulcal CSF volumes in male and female deficit and nondeficit patients with schizophrenia

Recent evidence suggests that schizophrenia reflects a neurodegenerative process. The studies have not compared brain change patterns in male and female patients with schizophrenia or examined the relation of these patterns to patient subgroups defined by specific symptom domains. Maximum Total Brain Volume (TBVmax), total cranial (TCV), total brain (TBV), sulcal CSF (sCSF), and ventricular (VV) volumes were measured in 66 normal controls (32 females, 34 males), and 85 patients with schizophrenia (21 females, 64 males). Sixty-six patients were categorized as nondeficit and 19 as deficit patients. Patients had smaller TBV and larger VV than normal controls. Patients also showed significant excessive brain volume loss after, but not before, TBVmax was achieved compared with normal controls. Although male patients had larger brain volume loss compared with male normal controls than female patients had compared with female normal controls, there were no significant gender x diagnosis interactions. Male patients with the deficit syndrome, but not those without the deficit syndrome, had significantly larger ventricles than normal controls. There were no other significant deficit/nondeficit differences. The present study suggests that brain volume loss in schizophrenia occurs after TBVmax and that male and female patients and deficit and nondeficit patients with schizophrenia do not demonstrate any differences in the time course of their brain volume reductions.     

Corpus callosal area differences and gender dimorphism in neuroleptic-naïve, recent-onset schizophrenia and healthy control subjects

The study of corpus callosal morphometry is important to unravel the underlying connectivity disturbance in schizophrenia. We studied the corpus callosal area in schizophrenia subjects compared to healthy subjects, while controlling for several confounders that could affect morphometric measures of the corpus callosum (CC). Areas of the whole CC and its sub-regions obtained by two geometric partitioning schemes were studied in 23 right-handed neuroleptic-na?ve, recent-onset, schizophrenia patients and compared with 23 right-handed age-, sex- and education-matched healthy subjects. The patients did not differ from controls in whole CC area. On tripartite division of the CC, the area of the anterior sub-region was significantly higher in patients compared to controls. On radial division into 5 sub-regions, the anterior truncus area was significantly higher in patients compared to controls. There was a significant effect of gender (F>M) on the area measures; however there was no significant diagnosis()gender effect. Age, age of onset, duration of illness and psychopathology ratings did not show any significant correlations with whole CC area and area of CC sub-regions. The finding of increased area of the anterior truncus that possibly comprises white fibres connecting the temporal association cortices could be indicative of an "abnormal functional hyperconnection" involving these regions in positive symptom schizophrenia. Additionally, the finding of females having larger areas of the whole CC and of the anterior and middle sub-regions could reflect a "normal hyperconnection" underlying increased ambilaterality in females.     

Behavioral correlates of corpus callosum size: Anatomical/behavioral relationships vary across sex/handedness groups

There are substantial individual differences in the size and shape of the corpus callosum and such differences are thought to relate to behavioral lateralization. We report findings from a large scale investigation of relationships between brain anatomy and behavioral asymmetry on a battery of visual word recognition tasks. A sample of 200 individuals was divided into groups on the basis of sex and consistency of handedness. We investigated differences between sex/handedness groups in callosal area and relationships between callosal area and behavioral predictors. Sex/handedness groups did not show systematic differences in callosal area or behavioral asymmetry. However, the groups differed in the relationships between area of the corpus callosum and behavioral asymmetry. Among consistent-handed males, callosal area was negatively related to behavioral laterality. Among mixed-handed males and consistent-handed females, behavioral laterality was not predictive of callosal area. The most robust relationship was observed in mixed-handed females, in whom behavioral asymmetry was positively related to callosal area. Our study demonstrates the importance of considering brain/behavior relationships within sub-populations, as relationships between behavioral asymmetry and callosal anatomy varied across subject groups.     

Corpus callosum morphology from magnetic resonance images in Tourette's syndrome

We measured the midline cross-sectional area and other morphologic features of the corpus callosum (CC) from magnetic resonance (MR) images in 14 unmedicated patients with Tourette's syndrome (TS) and 14 normal control subjects matched for age, sex, handedness, and socioeconomic status. Each CC was manually circumscribed on midline images from a T1-weighted sagittal series, and the area of the entire CC and five anatomic subdivisions were measured. CC circumference, regional width, and mean callosal curvature were also measured. CC cross-sectional area correlated positively with brain size and basal ganglia volumes. The magnitude of reduction (17.7%) in total CC area in TS patients compared with control subjects was similar to the reductions seen in all CC subdivision areas. Analyses of covariance with total midsagittal cross-sectional head area as a covariate revealed the reductions to be statistically significant for the overall CC area and all subregion areas. CC width tended to be nonsignificantly thinner in all subdivisions (from 5% to 11%), and the overall length of the center line measured from rostrum to splenium was significantly reduced in the TS group (by 5.3%). Measures of mean callosal curvature suggested that CCs in TS patients are less rounded than those of normal control subjects. Worst-ever motor tic symptoms showed the strongest significant correlation with the length of the CC center line in TS patients (r = 0.88). These findings suggest that structural interhemispheric connectivity may be aberrant in the central nervous systems of TS patients, and they provide indirect supportive evidence for the presence of altered cerebral lateralization in the disorder.     

Morphology of the corpus callosum in treatment‐resistant schizophrenia and major depression

Objective: To identify possible differences in the mean midsagittal corpus callosum (CC) total and subdivision areas in treatment‐resistant schizophrenia and depression (TRS and TRD) patients. Method: Areas of the total CC and its five equidistant subregions (from CC1 to CC5) obtained by parallel grid partitioning schemes were manually segmented from brain MRI of 42 TRS, 45 TRD patients and 30 healthy controls. The intracranial volume (ICV) normalized areas were calculated and compared between groups. Results: When compared with controls, patients with TRS had reduced ICV and a larger CC5, and TRD patients had a smaller CC4 while no significant difference in CC total area in patients with TRS or TRD was found. Multiple individual segments and total CC areas were significantly larger in TRS than TRD patients after normalization. Conclusion: Patients with TRS and TRD have different CC morphological characteristics, and therefore there may be aberrant interhemispheric connectivity in schizophrenia and major depressive disorder patients.     

Abnormalities of the corpus callosum in first episode,treatment naive schizophrenia

BACKGROUND: Structural alterations in the association cortices as well as in the corpus callosum (CC) have been described in schizophrenia, and have been considered to reflect developmental abnormalities. Areas of primary and association cortices have been topographically mapped in the CC. OBJECTIVE: To investigate whether, in schizophrenia, there are alterations in CC subdivisions that connect association, but not primary, cortices, and also to see if the normative, developmentally mediated increase in CC size with age is absent in this disorder. METHODS: The midsagittal magnetic resonance imaging scans of 31 first episode, neuroleptic naive, schizophrenic patients, 12 non-schizophrenic, psychotic patients, and 31 healthy controls were compared. The total area of CC as well as that of anterior, middle and posterior genu, body, isthmus, and anterior, middle, and posterior splenii were measured. RESULTS: Patients with schizophrenia as a group had a smaller CC, anterior genu, anterior body, isthmus, and anterior splenium than normal controls. Furthermore, the age related increase in CC size seen in normal subjects was absent in the patients. CONCLUSIONS: The observed reductions in size in selected regions of CC suggest a reduction in axonal connections between the heteromodal association cortices, which typically involve small diameter fibres. Furthermore, the absence of an age related increase in CC size in patients with schizophrenia suggests a neurodevelopmental abnormality that may extend into adolescence and early adulthood.     

Gender differences in brain volume and size of corpus callosum and amygdala of rhesus monkey measured from MRI images

While it has been established that the weight of the female rhesus monkey brain is less than that of the male, the sexual dimorphism of specific brain structures has not been well-documented. To further understand potential sex differences, we measured the whole brain volume and the size of the corpus callosum (mid-sagittal) and amygdala (largest coronal section) in MRI images from juvenile to adult male and female rhesus monkeys between 8 months and 7.2 years of age. The mean volume of the male brain was 89.2 +/- 1.9 (S.E.M.) compared to the female brain volume of 70.8 +/- 0.72 cm3. The average area of the corpus callosum increased from 8 months to 4.5 years; 0.56 to 0.93 cm2 in males and 0.45 to 0.66 cm2 in females. However, the average area of splenium is significantly greater in females (0.280 cm2), than males (0.184 cm2). The average area of the amygdala did not change with age; it was 1.07 +/- 0.037 (S.E.M.) in males and 1.08 +/- 0.022 cm2 in females. This data suggests that the whole brain volume and the size of the entire corpus callosum of young adult female rhesus monkeys are approximately 20% smaller than those of young adult males. Interestingly, the area of the splenial portion of the corpus callosum is larger in female monkeys. The size of the amygdala showed no sex difference.     

Interfrontal commissural abnormality in schizophrenia: tractography-assisted callosal parcellation

Previous studies have indicated abnormal fiber connectivity of the corpus callosum (CC) in schizophrenia. This study investigated whether the interfrontal commissural region of the CC is decreased in schizophrenia, by partitioning the CC using a function-anatomically relevant internal landmark derived from tractographic analysis of diffusion tensor imaging (DTI). T1 weighted and DTI images were acquired by 3T-MRI. Using tractography, the interfrontal commissural region (anterior part) was partitioned from the rest of the CC in 40 schizophrenia patients and 36 healthy controls. Schizophrenia patients showed smaller anterior/total CC length and area rates. These results suggested interfrontal hypoconnectivity in schizophrenia.     

Corpus callosum development in childhood-onset schizophrenia

OBJECTIVE: Corpus callosum (CC) size and interhemispheric communication differences have been reported between patients with schizophrenia and normal controls. Childhood-onset schizophrenia (COS) is a severe form of the disorder that is continuous with later-onset disorder. Corpus callosal area was examined for COS at initial scan and prospectively through adolescence, and related to other developmental abnormalities for this group. METHOD: A total of 113 anatomic brain MRI scans were obtained from 55 COS (22 female) and 110 scans from 56 age- and gender-matched healthy volunteers (22 female), across ages 8-24. Baseline and prospective rescans were obtained at approximately 2-year intervals. The midsagittal areas for total corpus callosum and seven subregions were calculated using an automated system. Cross-sectional and longitudinal data were combined using mixed model regression analysis to compare developmental changes for the two groups. RESULTS: No diagnostic differences were seen at time of initial scan. Longitudinally, and in contrast to healthy volunteers, patients with schizophrenia showed a significant difference in developmental trajectory for the area of the splenium, both before (p=0.012) and after (p=0.05) adjustment for total cerebral volume. The area of the splenium becomes significantly smaller in COS, starting at about age 22. CONCLUSION: Patients with schizophrenia showed a significant difference in developmental trajectory for the splenial area, which seems to decline for COS. If replicated, this may reflect anticipated late occipital and extrastriate changes in brain regions.     

Size of the corpus callosum in normal subjects and patients with Alzheimer's disease--magnetic resonance imaging study

The area of the corpus callosum (CC) on midsagittal spin-echo sequence magnetic resonance (MR) scans was measured in 64 normal subjects and 12 patients with Alzheimer's disease (AD). The normal subjects consisted of 32 males and 32 females, aged 25 to 83 years old. There was no significant age difference between males and females. Fifty-five out of 64 subjects were right-handed (RH) and 9 were left-handed or ambidextrous (NRH). Among patients with AD, 5 were males and 7 were females, aged 53 to 79 years old. Diagnosis of AD was performed mainly based on clinical history, magnetic resonance image (MRI) and positron emission tomographic findings. The outline of the CC on midsagittal MR film was traced and the total callosal sectional area (CCT) as well as the anterior half (CCA), posterior half (CCP) and posterior 5th or splenium (CCS) area measurements were performed using a planimeter. In either normal males or females, the CCA showed a significant negative correlation with age, but the CCP and the CCS did not correlate with age. Total CC (CCT) area was 691.2 +/- 91.0 sq. mm for the whole group and no difference was found between males and females. When the CC area was normalized with respect to the midsagittal area of the supratentorial portion of the brain (MSB), females were found to have a larger CC than males. No portion of the CC area was significantly different between RH and NRH subjects in absolute or normalized measures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gender differences in the corpus callosum of neonates

The gender difference of corpus callosum is a long standing controversy. Some investigators have reported that adult females have a more bulbous splenium and larger area relative to brain size, but others failed to replicate this. Few studies have reported on sexual dimorphism during development. Midsagittal ultrasonographs were obtained through the anterior fontanelle of healthy Korean neonates (100 males, 100 females) and were analyzed with NIH Image. The total area of corpus callosum and sub-regions of corpus callosum showed no gender differences. However, the male corpus callosum had significantly more height than that of the female whereas there was no difference in width of the corpus callosum. The estimated average thickness of corpus callosum was greater in the female splenium.     

Prenatal protein deprivation increases defects of the corpus callosum in laboratory mice

The development of two forebrain fiber tracts, the anterior commissure (CA) and corpus callosum (CC), was examined in laboratory mice in relation to the maternal dietary protein concentration during gestation. The diets contained either 8 or 27% casein. The strain was used because it is prone to having a corpus callosum which is either deficient in size or absent. Female mice were assigned to the low-protein diet either 2 weeks prior to mating (chronic malnutrition) or on the seventh day of gestation (acute malnutrition), and fetal brain development was assessed at 18.5 days after conception. Protein deficiency increased the number of animals which did not have a corpus callosum present in a midsagittal section. In those animals in which the structure was present, it was evident that the cross-sectional area was smaller in the chronically deprived animals than in the control group. In addition to CC area, both CA area and brain weight were reduced by protein deprivation. When brain weight was used as a covariate in an analysis of covariance the effect on CA area was no longer apparent. Part of the effect on the corpus callosum was, however, independent of the effect on brain weight and CA area.     

Abnormalities in MRI-measured signal intensity in the corpus callosum in schizophrenia

The microstructural integrity of the corpus callosum (CC) in first-episode schizophrenia patients was assessed by measuring the signal intensity (SI) in T1-weighted MRI images. Analyses revealed that compared to both healthy controls and non-schizophrenic patients, schizophrenia patients showed reductions in SI in all the callosal subregions, the genu, body, isthmus and splenium in first-episode schizophrenia. These results indicate that schizophrenia is characterized by pathology of this principal interhemispheric commissure; the abnormalities may reflect distributed (rather than localized) interhemispheric disconnectivity that extends beyond the heteromodal association cortices.     

A controlled magnetic resonance imaging study of corpus callosum thickness in schizophrenia

Two previous postmortem studies reported an increased thickness of the corpus callosum in schizophrenic patients compared to psychiatric controls. We report an in vivo study of the corpus callosum in schizophrenic patients (n = 38) and healthy controls (n = 41) using magnetic resonance (MR) brain imaging. A significant increase in mean callosal thickness was found in the middle and anterior, but not the posterior, parts of the callosal body. However, when the patients and controls were compared by gender and handedness, schizophrenic men were found not to differ from control men in callosal thickness, regardless of handedness, whereas schizophrenic women were found to have a highly significant increase in callosal middle and anterior thickness compared to control women. The data suggest that increased callosal thickness in schizophrenia is gender related, a factor that is not considered by postmortem studies. The implications of increased callosal dimensions in female schizophrenics are discussed.     

Corpus callosum atrophy associated with the degree of cognitive decline in patients with Alzheimer's dementia or mild cognitive impairment: A meta-analysis of the region of interest structural imaging studies

Individual structural neuroimaging studies of the corpus callosum (CC) in Alzheimer's disease (AD) and mild cognitive impairment (MCI) with the region of interest (ROI) analysis have yielded inconsistent findings. The aim of this study was to conduct a meta-analysis of structural imaging studies using ROI technique to measure the CC midsagittal area changes in patients with AD or MCI. Databases of PubMed, the Cochrane Library, the ISI Web of Science, and Science Direct from inception to June 2014 were searched with key words “corpus callosum” or “callosal”, plus “Alzheimer's disease” or “mild cognitive impairment”. Twenty-three studies with 603 patients with AD, 146 with MCI, and 638 healthy controls were included in this meta-analysis. Effect size was used to measure the difference between patients with AD or MCI and healthy controls. Significant callosal atrophy was found in MCI patients with an effect size of −0.36 (95% CI, -0.57 to −0.14; P = 0.001). The degree of the CC atrophy in mild AD was less severe than that in moderate AD with a mean effect size −0.69 (95% CI, -0.89 to −0.49) versus −0.92 (95% CI, -1.16 to −0.69), respectively. Comparing with healthy controls, patients with MCI had atrophy in the anterior portion of the CC (i.e., rostrum and genu). In contrast, patients with AD had atrophy in both anterior and posterior portions (i.e., splenium). These results suggest that callosal atrophy may be related to the degree of cognitive decline in patients with MCI and AD, and it may be used as a biomarker for patients with cognitive deficit even before meeting the criteria for AD.