The development concept of "endogenous psychoses".

Several structural deviances in the brain in "endogenous psychoses" have been described over the last decades. The enlargement of the lateral ventricles and the subtle structural deficits in temporobasal and orbital frontal structures (hypofrontality) are reasonably well established in the majority of schizophrenic patients. We examined the cytoarchitecture of these important central structures, namely the entorhinal region and the orbitofrontal cortex (Brodmann area 11), which have been under meticulous investigation in our laboratories over the last few decades. In a new series of schizophrenic patients and normal controls, we made serial cuts of the whole rostral entorhinal cortex on both sides. For this report, we selected two cases with very different psychopathologies, and present the serial cuts through both hemispheres and the malformations found. We report on the differing magnitude of the heterotopic malformations (for definition see page 103), either bilaterally or unilaterally.

Morphological abnormalities in nitric-oxide-synthase-positive striatal interneurons of schizophrenic patients.

Schizophrenia has been suggested to be a neurodevelopmental disorder, and nitric-oxide-synthase (NOS)-positive neurons were shown to be involved in distorted cortical development in schizophrenia. Here we investigated whether nitrinergic neurons in the striatum of schizophrenic patients also display abnormalities regarding distribution or morphology. To do so, postmortem putaminal sections of schizophrenic subjects were examined by means of nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) staining and NOS immunohistochemistry. NOS-positive neurons were counted and analyzed morphologically. Abnormalities regarding morphology or number of NOS-containing neurons could be found in the putamen of schizophrenics (n = 3), but not controls (n = 5). Neurons were either of abnormal size and branching pattern, or they were markedly reduced (130 +/- 44 vs. 54 +/- 62 NADPHd-positive somata/mm(3) putamen; p < 0.0001). Striatal nitrinergic interneurons might thus be involved in the pathogenesis of at least some forms of schizophrenia. Studies on larger samples are however needed to further corroborate this finding.

NADPH-diaphorase staining reveals new types of interneurons in human putamen.

Neurons in the human striatum have been divided into five or seven different types, respectively. To further characterize these interneurons, we investigated the putamen of five brains by means of NADPH-diaphorase staining and compared our results to previous classifications in man. The NADPH-diaphorase method is selective for nitric oxide synthase (NOS); in the human striatum, predominantly interneurons were stained. NADPH-diaphorase positive neurons were then further examined. They showed clear morphological differences and could be classified into 12 different types, which only partially corresponded to previously described neuron types. Thus, we suggest at least three novel types of neostriatal interneurons. Furthermore, a special class of large neurons thought to be efferent in nature, stained NOS-positive.

Histomorphology of angiogenesis in human perinatal orbitofrontal cortex: a Golgi and electron microscopic study of anastomosis formation.

We demonstrate here for the first time the formation of vascular anastomoses in the human neocortex. The orbitofrontal cortex (OFC) of the perinatal human brain is structurally immature, so that the maturation of neurons, neuroglia and intracortical capillaries can be conveniently studied by comparison with these elements in motor and striatal cortex of the same brain. In OFC of the perinatal human brain, indication of prominent anastomosis formation in the upper layers (lamina II and III) is observed. Golgi silver impregnation and electron microscopic techniques were employed to demonstrate individual stages of vascular anastomosis development. Along with capillary angiogenesis, vascular anastomosis formation is of major importance for the ontogenesis of neuronal and glial elements of the CNS, particularly with respect to optimal metabolic support of structural elements of the mature brain. In the neocortex of the adult human brain, a characteristic three-dimensional capillary angioarchitecture is observed, contrasting with the two-dimensional arrangement in the immature perinatal cortex. Abnormal OFC angioarchitecture was also found in 14% of histomorphologically investigated brains from persons with endogenous psychoses. For the pathogenesis of functional disorders of the human brain, including endogenous psychoses, knowledge about the processes of structural maturation of neurons and neuroglia, but also of capillary architecture, is essential.

Increased frequency of dentate granule cells with basal dendrites in the hippocampal formation of schizophrenics.

In the hippocampal formation of schizophrenics, the detailed morphology of Golgi-impregnated granule cells was examined. These granule cells of the dentate gyrus are interposed between the rostral entorhinal cortex and the hippocampus proper. In these limbic regions significant cytoarchitectural alterations in schizophrenics are reported, giving rise to the concept of a prenatal limbic maldevelopment in schizophrenia. Compared to controls, the frequency of dentate granule cells with basal dendrites was significantly increased in schizophrenics [43% (+/-3)] vs. [22% (+/-2) in the control group]. In epilepsy, dentate granule cells of epileptic patients also develop basal dendrites, which is explained as an adaptive process of plasticity. Similarly, the hippocampal alterations described in schizophrenics could be the sequela of primary entorhinal cytoarchitectural alterations. Since the increase in basal dendrites seems to reflect a process of continuous plasticity, suggesting an increased rate of postnatal granule cell generation, the synthesis of a prenatal limbic maldevelopment with an ongoing process of plasticity might, therefore, supersede the hypothesis of a neurodegeneration in schizophrenia.