Development of O4+/O1- immunopanned pro-oligodendroglia in vitro.

In this study, O4+/O1- pro-oligodendroglia isolated by immunopanning from cerebral hemispheres of P3-P5 rats were evaluated during their maturation in culture. Immunopanning yielded 3-4 x 10(5) cells/cerebrum, with 98% O4+ and 6% O1+. There was heterogeneity in the morphologies of immunopanned cells ranging from simple bipolar cells to more complex multipolar cells. As a first step in determining potential differentiative responses of mature oligodendroglia, we examined glial fibrillary acidic protein (GFAP) expression in response to fetal bovine serum (FBS) by cultures established from O4+/O1- immunopanned cells grown for 1, 14, or 21 days, exposed to 20% FBS for 6-7 days and fixed and immunostained on days 7, 21 or 28 in culture (DIC). When immunopanned cells were exposed to FBS following 1 day in serum-free medium, 88% expressed GFAP and when immunopanned cells were cultured for 14 days prior to FBS exposure, 78% expressed GFAP. By contrast, when cells were cultured for 21 days prior to FBS exposure (when a majority of the cells expressed O1 and myelin basic protein (MBP)), only 19% of the cells expressed GFAP (p < 0.001). Cells that were O4+/GFAP- even in the presence of FBS often exhibited a mature oligodendroglial morphology. Among immunopanned cells that responded to FBS by expression of GFAP, both process-bearing (similar to type 2 astroglia) and flattened, polygonal (similar to type 1 astroglia) GFAP+ cells were observed. These results confirm the utility of immunopanning for the isolation of pro-oligodendroglia and demonstrate that oligodendroglia that develop in vitro from O4+/O1- immunopanned cells become resistant to GFAP induction by FBS.

Resolution of parental bereavement after a perinatal loss.

This is a follow-up study of 25 middle-class, expectant, married couples who had experienced a perinatal loss (16 miscarriages, seven stillbirths, and two neonatal deaths) within the previous 2 years and who subsequently gave birth to a healthy child. The Perinatal Bereavement Scale (PBS) had been previously completed during the 8th month of the subsequent pregnancy and at 6 weeks postnatally. In this study, the PBS was completed 16 months after the birth of the subsequent child. The hypothesis was that the parents who experienced a late perinatal loss (stillbirth and neonatal death) would display more unresolved grief 16 months after the subsequent child was born compared to parents who had experienced an early loss (miscarriage). The late group mothers had significantly higher PBS scores than either the early group mothers or early group fathers at 16 months postnatally.

Brain-imaging approaches in psychiatry: early developmental considerations.

Recent advances in the neurosciences have provided important new approaches to understanding mental illness. Historically, the application of these approaches has followed patterns that parallel the scientific process of repeated testing and reexamination. In the investigation of schizophrenia, this process has focused particular attention on the frontal lobes. Special considerations should be weighed in assimilating and integrating these new approaches into our field.

Perinatal loss and parental bereavement.

The authors studied 25 middle-class pregnant women and their husbands who had experienced perinatal losses (16 miscarriages, seven stillbirths, and two neonatal deaths) within the previous 2 years. The Perinatal Bereavement Scale was designed to determine whether parents who have experienced a late perinatal loss (stillbirth or neonatal death) display more unresolved grief during a subsequent pregnancy and during the postnatal period than parents who have experienced a miscarriage. A three-factor repeated measures analysis of variance indicated significantly greater grief for the late-loss group, for the mothers, and during the pregnancy preceding the birth of the viable child.

Increased temporal lobe glucose use in chronic schizophrenic patients.

Temporal lobe glucose metabolic rate was assessed in 21 off-medication patients with schizophrenia and 19 normal controls by positron emission tomography with 18F-deoxyglucose. Patients with schizophrenia had significantly greater metabolic activity in the left than the right anterior temporal lobe, and the extent of this lateralization was in proportion to the severity of psychopathology.

Antisomatostatin IgG in major depressive disorder. A preliminary study with implications for an autoimmune mechanism of depression.

IgG reactive with somatostatin 1-14 was identified in human plasma by enzyme linked immunosorbent assay. From a sample of 25 subjects, six (60%) of ten individuals with major depressive disorder demonstrated antibody reactive with somatostatin 1-14, in contrast to one (7%) of 15 controls. Overall, antisomatostatin reactivity was significantly higher in patients with major depressive disorder (0.233 +/- 0.177) than in the normal volunteers (0.084 +/- 0.039; t = 3.18, P less than .01). Antisomatostatin IgG was isolated by affinity chromatography. The recognition site for somatostatin was retained by F(ab)'2 fragments. Although there has been little previous exploration of the existence of antibodies to endogenous neuropeptides, such antibodies could prove of relevance to neuropsychiatric and other human disorders.

Human antiidiotypic antibody against opiate receptors.

Sera containing antibodies to beta-endorphin from 2 patients with major depressive disorder were shown to have antidiotypic antibodies that specifically inhibited reactivity between anti-beta-endorphin IgG and beta-endorphin. Autologous and homologous antiidiotypic anti-anti-beta-endorphin IgG antibodies were isolated by affinity chromatography. The purified antiidiotypic antibody did not bind beta-endorphin but competed with [125I]beta-endorphin for rat brain opiate receptors. Normal IgG that was similarly treated had negligible competitive effects. The antibody bound to the membrane preparation; such binding was inhibited by opiate receptor ligands. Binding of the antiidiotype to a 60,000-dalton protein from rat brain was detected by Western immunoblot analysis. This protein corresponds in molecular weight to proteins proposed to be components of opiate receptors. These findings imply that immune reactivity to neuropeptides could contribute to psychiatric impairment.

Clinical neuroscience approaches in psychiatry.

Recent advances in the clinical neurosciences have begun to expand and change our understanding of how the brain functions. As further neuroscientific principles are delineated we may gain insights into the underlying pathophysiology of some psychiatric disorders and through this new understanding we may be able to define new therapeutic interventions. Two illustrative examples of neuroscientific research are discussed and reviewed both in terms of the promises and dangers inherent in these new approaches to the mind.

Computed electroencephalographic activity mapping in schizophrenia. The resting state reconsidered.

Several topographic mapping studies of electroencephalographic (EEG) power spectra have reported increased slow (delta) activity in the frontal regions of schizophrenic patients. Using supraorbital and lateral canthus electrodes to detect eye movement, we deleted EEG epochs during eye movement in 15 medication-free patients with schizophrenia and in 13 normal control subjects. Power spectral analysis of the 28-channel EEG demonstrated a diffuse mild increase in delta activity in schizophrenic patients compared with normal control subjects but no tendency for frontal localization of this slow activity. There were no differences between schizophrenic patients and normal control subjects in other frequency bands. These results, which replicate earlier findings of increased delta activity in schizophrenia, emphasize the importance of excluding the slow activity due to eye movement in the comparisons of summed EEG spectra. This emphasis can best be ensured by equating the summed spectra from extraocular movement channels of experimental and control groups.

Dysfunction in a prefrontal substrate of sustained attention in schizophrenia.

Regional brain metabolism was measured in normal subjects and patients with schizophrenia while they performed an auditory discrimination task designed to emphasize sustained attention. A direct relationship was found in the normal subjects between metabolic rate in the middle prefrontal cortex and accuracy of performance. The metabolic rate in the middle prefrontal cortex of patients with schizophrenia, even those who performed as well as normals, was found to be significantly lower than normal and unrelated to performance. The findings point to a role of the mid-prefrontal region in sustained attention and to dysfunction of this region in schizophrenia.

Topographic differences between normals and schizophrenics: the N120 evoked potential component.

Topographic differences in evoked potentials were measured in 20 off-medication chronic schizophrenics and 24 normal controls. Four intensities of brief electrical shocks were administered to the subject's right forearm in a random order at 1-second intervals. Evoked potentials (EPs) were recorded from the scalp over the left hemisphere. The EP data from 16 left hemisphere leads were used to generate EP maps of brain response for individual subjects. The maps were normalized by z transformation. Group mean maps of EP activity and unpaired t tests were then computed. Normals showed strongly localized activity in the pre- and postcentral gyri, with increasing intensity resulting in the attenuation of parietal response. Schizophrenics showed more diffuse EP activity which did not vary with intensity. Significant differences between normals and schizophrenics were found for all four intensities in posterior frontal and anterior parietal cortex. This is consistent with the findings of small EPs reported by others in the somatosensory, visual and auditory modalities.

Positron emission tomography in schizophrenic patients with and without neuroleptic medication.

Positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose was performed in nine chronic schizophrenic patients both when medication-free and when medicated with neuroleptics. Total brain cortex, temporal cortex, and basal ganglia glucose use was significantly increased with medication; however, there was no change in anterior/posterior metabolic gradients.