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Clinical evidence for a dominant mode of inheritance and anticipation in periodic catatonia, a distinct subtype of schizophrenia, indicates that genes with triplet repeat expansions or other unstable repetitive elements affecting gene expression may be involved in the etiology of this disorder. Because patients affected with dentatorubral-pallidoluysian atrophy (DRPLA) may present with "schizophrenic" symptoms, we have investigated the DRPLA (B 37 CAG repeat) locus on chromosome 12 in 41 patients with periodic catatonia. The B 37 CAG repeat locus was highly polymorphic but all alleles in both the patient and control group had repeat sizes within the normal range. We conclude that variation at the DRPLA locus is unlikely to be associated with periodic catatonia. The evidence for dominant inheritance and anticipation as well as the high prevalence of human brain genes containing trinucleotide repeats justifies further screening for triplet repeat expansions in periodic catatonia.
Low P300 amplitudes and topographical asymmetries have been reponed in schizophrenic patients, but reference-independent amplitude assessment failed to replicate reduced amplitudes. P300 amplitude is conventially assessed at midline electrodes (PZ), anti asymmetric topography as reported in schizophrenics, may conj'ound this measurement. We lnvestigated the possible Interaction between P300 ropography and assessments of amplitudes. ln 41 clinically stable schizophrenics and 31 normal controls, the generalfinding ofreduced amplitudes at the P'l electrode and topographical asymmetrles in the patient group were replicated. ln both groups, a.symmetries of the P300 field (lateralized peaks) reduced the standard amplitude assessment at the midline parletal electrode, but did not Qjfoct the reference-independent, global amplitude assessment. This shows thal asymmetry per se does not imply reduced field strength. in addition, in schizophreraics. but not in controls, there was a significcmt effect oftlae direction of asymmetry on both amplltude measures, amplitudes belng lower with increasing shift ofthe P300 peak to the right side. Considering also the slightly left-lateralized peaks in the normal controls. this suggests rhat only right lateralized P300 peaks upressfunctional deficits in schizophrenics, whereas left lateralized pealcs fall wlthin the physiological variability of the P3OO field. Tht refonnce-independent amplitude assessment is proposed for unambiguous amplitude assessment in order to better define the clinical, psychological and physiopathological mtaning of the P3OO alterations in schizophrenics.
In a retrospective study of 80 chronic DSM 111-R schizophrenics and 80 controls, the occurrence of obstetric complications (OCs) into the development of chronic schizophrenias was investigated using Leonhard s distinction in systematic schizophrenia (no obvious familial loading) and unsystematic schizophrenia (mainly genetically determined according to Leonhard). The Lewis & Murray and Fuchs scales were used for evaluation. In both scales, unsystematic schizophrenias did not differ from controls, but those with OCs were significantly (p < 0.01) earlier hospitalized (20.5 years) than those without OCs (25.6 years). Systematic schizophrenics had an increased frequency, severity and total score of OCs compared to controls in the Fuchs scale (p < 0.0 I). Likewise, in the Lewis & Murray scale systematic schizophrenia showed an increased presence ofOCs compared to controls (p < 0.05) and to unsystematic schizophrenia (p < 0.1 ). Systematic schizophrenias were significantly allocated to matemal infectious diseases during mid-gestation. Patients with matemal infections showed moreadditional OCs than those without (p < 0.05; Lewis & Murray scale). In systematic schizophrenia, a history of OC was not associated with an early onset of the disease. In the genetic determined schizophrenias prenatal and perinatal disturbanccs Iead to an early onset of the disease, however, in systematic schizophrenias they seem to be of causal importance for the development of the disease.
The total nerve cell numbers in the right and in the left human entorhinal areas have been calculated by volume estimations with the Cavalieri principle and by cell density determinations with the optical disector. Thick gallocyanin-stained serial frozen sections through the parahippocampal gyrus of 22 human subjects (10 female, 12 male) ranging from 18 to 86 years were analysed. The laminar composition of gallocyanin (Nissl)-stained sections could easily be compared with Braak's (1972, 1980) pigmentoarchitectonic study, and Braak's nomenclature of the entorhinal laminas was adopted. Cellsparse laminae dissecantes can more clearly be distinguished in Nissl than in aldehydefuchsin preparations. These cell-poor dissecantes, lamina dissecans extema (dis-ext), lamina dissecans 1 (dis-1) and lamina dissecans 2 (dis-2), were excluded from nerve cell nurober determinations. An exact delineation of the entorhinal area is indispensable for any kind of quantitative investigation. We have defined the entorhinal area by the presence of pre-alpha ceil clusters and the deeper layers of lamina principalis externa (pre-beta and gamma) separated from lamina principalis interna (pri) by lamina dissecans 1 (dis-1). The human entorhinal area is quantitatively characterized by a left-sided (asymmetric) higher pre-alpha cell number and an age-related nerve cell loss in pre as well as pri layers. At variance with other CNS cortical and subcortical structures, the neuronal number of the entorhinal area appears to decrease continuously from the earliest stages analysed, although a secular trend has to be considered. The asymmetry in pre-alpha cell number is discussed in the context of higher human mental capabilities, especially language.
Ultrastructural changes including reduced electron density, reduction in polysemes and cisternae of rough endoplasmic reticulum occur in the cytoplasrn of endothelial cells and pericytes in the cerebellar cortex of senile virgin female Han: WIST-rats in cornparison to 3-month old virgin rats. Processes of pericytes cover less of the capillary surface in the cerebellar cortex of senile rats; moreover, arithmetic and harmonic mean thickness of the endothelium and relative volume of mitochondria in endothelial cells and pericytes are reduced, w hereas the luminal diameter of the capillaries, harmonic and arithmetic mean thickness of pericytes and their processes and of the basal laminae between endothelial cells and astrocytes (abbreviated BAL 1), pericytes and astrocytes (BAL 2) and endothelial cells and pericytes (BAL 3) increase. The increase in harmonic mean thickness of the basal laminae is statistically significant (α<=0.05) and compensates for a decrease in thickness of capillary endothelium. Consequently, the total barrier mass and thickness of cerebellar cortical capillaries in senile animals is higher than in young individuals.
The distribution of lipofuscin in the perikarya of Purkin je cells of vermal and hemispheric lobules has been determined quantitatively in 7 rats, 30-38 months old, by the point-counting method. On the basis of morphologically and statistically significant differences a pigmentarchitectonics of the cerebellar cortex is established. The Purkinje cells of lobule VIa (Larsell 1952) are extremely lipofuscin-rich. The Purkinje cells of the hemispheres, lobules V, Vlb + c and VII contain considerable amounts of a finely granular lipofuscin, the Purkinje cells of lobules I-III and VIII- IXa a globular type of lipofuscin. The Purkinje cells of sublobule XI d c and X are lipofuscin-poor cells. Three types of lipofuscin ha ve been identified in the light microscope.
The ultrastructure of autofluorescent, PAS-positive lipofuscin in Purkinje, granule, Golgi epithelial, basket and stellate, microglial and perivascular cells in the cerebellar cortex of senescent rats is described. The membrane- bounded pigment is composed ofthree elements: 1) electron-lucent homogeneaus droplets, 2) a granular matrix and 3) intensely osmiophilic patches. The proportians ofthese three components vary between cell types and one can grossly differentiate a neuronal and a gliallipofuscin. The lipofuscin granules of stellate and perivscular cells are different from lipofuscin of other cerebellar neurons and glia. lt can be concluded from these morphological observations that each cerebellar cell type has its distinct lipofuscin.
Quantitative anatomical studies on the postnatal development of the cerebellum of the albino rat
(1977)
The quantitative postnatal changes of the cerebella of 65 Wistar rats aged 2-120 days have been examined. The cerebellar volume increases in two phases: The first phase lasts from birth to the seventh postnatal week. The second phase begins ten weeks post parturn and lasts for a Ionger period than the first phase. The cerebellar surface increases continuously from birth to the end of the seventh week. The volume of the external granular layer is maximal when the organ grows rapidly. The external granular layer has nearly disappeared 24 days after birth; the volume of the interaal granular layer is maximal at this time. Later on, the volume and the width of the interaal granular layer decrease. Myelinization of the cerebellar fibers and growth of the molecular layer run parallel to this decrease. The second late, but protracted growth of the cerebellum, ten weeks after birth, is due to an increase of the molecular and medullary layer. These findings are in good accord with histological, histochemical, and ultrastructural observations of other authors.