Interstitial cells of the white matter in the inferior parietal cortex in schizophrenia: An unbiased cell-counting study

Abstract

Previous studies have found an increased density of the interstitial cells of the white matter (ICWMs) in the frontal and temporal cortex in schizophrenia. Some data suggested this abnormality was restricted to a subgroup of patients, whose clinical features were consistent with the presence of the deficit syndrome. Clinical studies suggest deficit features are due to an abnormality in a cortical-subcortical circuit that includes dorsolateral prefrontal and inferior parietal cortex. We compared the density of ICWMs labeled for MAP2 immunoreactivity in Brodmann area 39 (inferior parietal cortex) from nine schizophrenia subjects (three deficit and six nondeficit) and nine matched controls using an unbiased cell-counting technique. The density of ICWMs was significantly greater in the deficit syndrome subjects compared to the nondeficit schizophrenia group (respective means +/- SEM, 0.22 +/- 0.04, and 0. 13 +/- 0.02; P < 0.05). The density of ICWMs in the deficit group was also significantly greater (P < 0.05) than that of the control group (0.09 +/- 0.02), but the nondeficit and control groups were not significantly different. These findings 1) confirm that an abnormal placement of neurons in the white matter is found in schizophrenia, 2) provide evidence for a microscopic anatomical abnormality in the inferior parietal cortex, and 3) suggest the ICWM abnormality may be confined to deficit patients.

Schizophrenia Breakdown in the Well-regulated Lifelong Process of Brain Development and Maturation

“…These findings are consistent with recent evidence that in addition to neurons, mature oligodendrocytes also produce N-acetyl aspartate (NAA) (Bhakoo and Pearce 2000) and may contribute to the NAA signal observed in proton spectroscopy studies (Lim et al 1998). In addition, the post-mortem literature may be consistent in reports of increased density of interstitial cells in white matter (Akbarian et al 1996;Kirkpatrick et al 1999). This finding could be reinterpreted in the context of the model to suggest that the reduced white matter volume in schizophrenia causes the increased density as opposed to an altered production of these cells.…”

Schizophrenia Breakdown in the Well-regulated Lifelong Process of Brain Development and Maturation

“…These findings are consistent with recent evidence that in addition to neurons, mature oligodendrocytes also produce N-acetyl aspartate (NAA) (Bhakoo and Pearce 2000) and may contribute to the NAA signal observed in proton spectroscopy studies (Lim et al 1998). In addition, the post-mortem literature may be consistent in reports of increased density of interstitial cells in white matter (Akbarian et al 1996;Kirkpatrick et al 1999). This finding could be reinterpreted in the context of the model to suggest that the reduced white matter volume in schizophrenia causes the increased density as opposed to an altered production of these cells.…”

Interstitial white matter neurons express less reelin and are abnormally distributed in schizophrenia: towards an integration of molecular and morphologic aspects of the neurodevelopmental hypothesis

“…28,42,44 The finding also implies that reelin may be part of the molecular cascade underlying morphometric involvement of IWMNs in schizophrenia. Notably, the heterozygous reeler mouse shows increased superficial IWMN density, 47 providing direct evidence that decreased reelin expression can produce a similar change in IWMNs as found here and previously 18,20 in schizophrenia. The reduced reelin expression by IWMNs in schizophrenia ( Figure 6a,b) likely contributes to the overall loss of reelin mRNA and protein in the cortex in the disorder.…”

“…In particular, our observation that IWMN density is increased selectively in the superficial white matter in schizophrenia corroborates two earlier studies. 18,20 The results support the basic view, given the premises outlined in the Introduction, that schizophrenia may be associated with a neurodevelopmental disturbance, most likely in the second trimester. Our data suggesting a greater IWMN disturbance in patients with prominent negative symptoms support, to an extent limited by our small sample size, the finding in patients with deficit syndrome.…”

Magnetization transfer imaging alterations and its diagnostic value in antipsychotic-naïve first-episode schizophrenia

“…As noted above, a higher MTR could indicate greater neuronal remyelination, which might contribute to a volume increase [ 48 ]. Previous studies found a greater density of interstitial neurons in the parietal [ 49 ] and occipital areas [ 50 ] in individuals with schizophrenia, which is suggestive of neurodevelopmental abnormalities that might also contribute to the present findings.…”

Schizophrenia Breakdown in the Well-regulated Lifelong Process of Brain Development and Maturation

“…These findings are consistent with recent evidence that in addition to neurons, mature oligodendrocytes also produce N-acetyl aspartate (NAA) (Bhakoo and Pearce 2000) and may contribute to the NAA signal observed in proton spectroscopy studies (Lim et al 1998). In addition, the post-mortem literature may be consistent in reports of increased density of interstitial cells in white matter (Akbarian et al 1996;Kirkpatrick et al 1999). This finding could be reinterpreted in the context of the model to suggest that the reduced white matter volume in schizophrenia causes the increased density as opposed to an altered production of these cells.…”

Interstitial white matter neurons express less reelin and are abnormally distributed in schizophrenia: towards an integration of molecular and morphologic aspects of the neurodevelopmental hypothesis

“…28,42,44 The finding also implies that reelin may be part of the molecular cascade underlying morphometric involvement of IWMNs in schizophrenia. Notably, the heterozygous reeler mouse shows increased superficial IWMN density, 47 providing direct evidence that decreased reelin expression can produce a similar change in IWMNs as found here and previously 18,20 in schizophrenia. The reduced reelin expression by IWMNs in schizophrenia ( Figure 6a,b) likely contributes to the overall loss of reelin mRNA and protein in the cortex in the disorder.…”

“…In particular, our observation that IWMN density is increased selectively in the superficial white matter in schizophrenia corroborates two earlier studies. 18,20 The results support the basic view, given the premises outlined in the Introduction, that schizophrenia may be associated with a neurodevelopmental disturbance, most likely in the second trimester. Our data suggesting a greater IWMN disturbance in patients with prominent negative symptoms support, to an extent limited by our small sample size, the finding in patients with deficit syndrome.…”

Magnetization transfer imaging alterations and its diagnostic value in antipsychotic-naïve first-episode schizophrenia

“…As noted above, a higher MTR could indicate greater neuronal remyelination, which might contribute to a volume increase [ 48 ]. Previous studies found a greater density of interstitial neurons in the parietal [ 49 ] and occipital areas [ 50 ] in individuals with schizophrenia, which is suggestive of neurodevelopmental abnormalities that might also contribute to the present findings.…”

Schizophrenia Breakdown in the Well-regulated Lifelong Process of Brain Development and Maturation

“…These findings are consistent with recent evidence that in addition to neurons, mature oligodendrocytes also produce N-acetyl aspartate (NAA) (Bhakoo and Pearce 2000) and may contribute to the NAA signal observed in proton spectroscopy studies (Lim et al 1998). In addition, the post-mortem literature may be consistent in reports of increased density of interstitial cells in white matter (Akbarian et al 1996;Kirkpatrick et al 1999). This finding could be reinterpreted in the context of the model to suggest that the reduced white matter volume in schizophrenia causes the increased density as opposed to an altered production of these cells.…”

Interstitial white matter neurons express less reelin and are abnormally distributed in schizophrenia: towards an integration of molecular and morphologic aspects of the neurodevelopmental hypothesis

“…28,42,44 The finding also implies that reelin may be part of the molecular cascade underlying morphometric involvement of IWMNs in schizophrenia. Notably, the heterozygous reeler mouse shows increased superficial IWMN density, 47 providing direct evidence that decreased reelin expression can produce a similar change in IWMNs as found here and previously 18,20 in schizophrenia. The reduced reelin expression by IWMNs in schizophrenia ( Figure 6a,b) likely contributes to the overall loss of reelin mRNA and protein in the cortex in the disorder.…”

“…In particular, our observation that IWMN density is increased selectively in the superficial white matter in schizophrenia corroborates two earlier studies. 18,20 The results support the basic view, given the premises outlined in the Introduction, that schizophrenia may be associated with a neurodevelopmental disturbance, most likely in the second trimester. Our data suggesting a greater IWMN disturbance in patients with prominent negative symptoms support, to an extent limited by our small sample size, the finding in patients with deficit syndrome.…”

Magnetization transfer imaging alterations and its diagnostic value in antipsychotic-naïve first-episode schizophrenia

“…As noted above, a higher MTR could indicate greater neuronal remyelination, which might contribute to a volume increase [ 48 ]. Previous studies found a greater density of interstitial neurons in the parietal [ 49 ] and occipital areas [ 50 ] in individuals with schizophrenia, which is suggestive of neurodevelopmental abnormalities that might also contribute to the present findings.…”