Association analysis of the −308G > A promoter polymorphism of the tumor necrosis factor alpha (TNF-α) gene in Japanese patients with schizophrenia

Summary. Two research groups have thus far reported a significant association between schizophrenia and a promoter polymorphism (–308G > A) of the gene encoding tumor necrosis factor alpha (TNF-), while contradictive negative results have also been reported. We examined the possible association in a Japanese sample of 297 schizophrenia cases and 458 controls. Allele frequencies of both the patients and controls were very low (1.5% and 0.8%, respectively), and the difference was not statistically significant. We conclude that the effect of the –308G > A polymorphism on the development of schizophrenia is, if any, weak and the majority of Japanese schizophrenics are unrelated to the –308G > A polymorphism of the TNF- gene.     

Identification of the κ and λ light chains within the CSF immunoglobulin region in multiple sclerosis and subacute sclerosing panencephalitis by immunofixation after isoelectric focusing

Summary The distribution of the and light chains within the cerebrospinal fluid (CSF) IgG oligoclonal bands of 15 multiple sclerosis (MS) and 3 subacute sclerosing panencephalitis (SSPE) patients has been studied by isoelectric focusing (IF) followed by direct immunofixation. The oligoclonal bands demonstrated by IF were both homogeneous and heterogeneous with regard to the light chain type; in the MS patients there was a prevalence of heterogeneous bands and of homogeneous bands of type, while in SSPE a slight prevalence of homogeneous bands was found. The homogeneous bands were preferentially disposed in a more cathodal position in respect to IgG bands; in some cases bands probably constituted only of free light chains of type were found. Finally, in some cases, the oligoclonal IgG pattern was more distinct after immunofixation than after basal IF.

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Zusammenfassung Die Verteilung von leichten - und -Ketten in den oligoklonalen IgG-Fraktionen des CSF ist bei 15 MS- und 3 SSPE-Patienten durch isoelektrische Fokussierung (IF) und anschließende direkte Immunofixierung untersucht worden.Die durch IF hervorgehobenen oligoklonalen Fraktionen waren sowohl homogen als auch heterogen hinsichtlich des Typs der leichten Ketten; bei den MS-Patienten waren die heterogenen und homogenen IgG-Fraktionen des Typs vorherrschend, während bei den SSPE-Patienten die homogenen IgG-Fraktionen des Typs leicht vorherrschend waren.Die homogenen IgG-Fraktionen des Typs waren im Vergleich zu den IgG-Fraktionen des Typs vorzugsweise in einer kathodennaheren Position angetroffen worden; in einigen Fällen wurden IgG-Fraktionen gefunden, die wahrscheinlich nur aus freien leichten Ketten des Typs bestehen.Schließlich waren in einigen Fällen die oligoklonalen IgG-Fraktionen nach der Immunofixierung deutlicher als nach der IF.

     

Characteristics and management of prisoners at risk of suicide behaviour

This study provides data on the characteristics and management of all prisoners identified at risk of suicidal behaviour over a 12 month period in all Scottish prisons. From a total of 44,093 admissions, 1,984 (4.5%) prisoners were identified at time of reception as at risk while 857 (1.9%) inmates were classified as at risk at some other point during custody. Of those identified at risk at time of reception, 19.1% were retained on suicidal supervision, while 58.2% of those identified at risk during custody were maintained on some form of suicidal supervision. Average length of time kept on strict suicidal supervision for those identified at time of reception was 1.87 days, and for those identified at some other point during custody was 2.59 days. Results are discussed in relation to the problems associated with suicide prediction and prevention in prison settings and the tendency for risk assessment to create significant numbers of false positives at time of reception.     

Is the DSM-III-R category of mood disorders too broad?

Summary In the DSM-III and DSM-III-R the affective or mood category has been widened and moodincongruent psychotic affective illness (MICPAI) included. The present study was undertaken to determine whether this broad mood category is still homogeneous. Personality factors were used as parameters. Minnesota Multiphasic Personality Inventory findings of 54 patients with MICPAI were compared with those of 21 probands with a DSM-III typical affective disorder and with those of 15 DSM-III schizophrenics. It was shown that MICPAI differed significantly from typical affective disorder, but not from schizophrenia, in particular regarding the subscales schizophrenia and psychopathic deviate. When MICPAI was subdivided into the depressed and manic type, the depressed type was found to be more closely related to schizophrenia (with respect to the subscales paranoia and schizophrenia), whereas the manic type hardly differed from affective disorder. Whether this result is due to diagnostic inaccuracies is discussed. Our finding that MICPAI differs from typical affective disorder with respect to personality is in accordance with heredity and outcome studies demonstrating that MICPAI is associated with a higher risk for schizophrenia in firstdegree relatives and with worse outcomes when compared with typical affective disorder. It can thus be concluded that the decision to include MICPAI in the affective or mood category of the DSM-III or DSM-III-R has rendered this category more heterogeneous.     

GSK-3β in cerebrospinal fluid of schizophrenia patients

Summary. Cerebrospinal fluid contains proteins and metabolites of brain origin and was extensively studied in psychiatry in the 1970s with few definitive results. We have recently found 40% reduced protein levels of GSK-3 in schizophrenia in postmortem prefrontal cortex, but our attempt to develop a diagnostic marker using peripheral lymphocyte GSK-3 was not successful. In this study we aimed to find whether the reduction in brain GSK-3 is reflected in CSF of schizophrenia patients. We report a significant reduction in CSF GSK-3 protein levels in six schizophrenia patients compared to seventeen healthy subjects. Our results corroborate other studies in which CSF protein levels reflect the alteration found in these proteins in schizophrenia patients postmortem brain.     

Expression of αB-crystallin in Alzheimer's disease

B-crystallin is a member of the small heatshock protein family. Under pathological conditions, the expression of B-crystallin increases in proliferating astrocytes, which suggests that this protein, in addition to glial fibrillary acidic protein (GFAP), can be a marker for gliosis in neurodegenerative diseases. Immunoblotting and immunohistochemical methods were used for the detection of B-crystallin in the brains of Alzheimer's disease (AD) patients and nondemented controls. An increase in B-cyrstallin expression was found in the brains of AD patients. Immunoreaction was present in reactive astrocytes, microglia, and oligodendrocytes, indicating that all types of glia respond to the stress associated with AD pathology. Colocalization of GFAP and B-crystallin was found in fibrous astrocytes. However, the intensity and range of B-crystallin expression appeared to be limited as compared with the large increase in the number of GFAP-positive astrocytes. This indicates that expression of B-crystallin is not a marker for gliosis in AD. Immunoreactivity to B-crystallin in both astrocytes and microglia was found mainly restricted to areas with senile plaques and neurofibrillary tangles, suggesting the association of B-crystallin with amyloid deposition in AD.Supported by a grant (No. EY08202) from the National Institutes of Health, Bethesda, USASupported by a fellowship of the Royal Netherlands Academy of Arts and Sciences     

On areas of transition between entorhinal allocortex and temporal isocortex in the human brain. Normal morphology and lamina-specific pathology in Alzheimer's disease

Summary The allocortical entorhinal region does not gradually transform into the temporal isocortex. Instead, there is an extended stretch of transentorhinal cortex with interdigitation of allocortical and isocortical laminae. The main feature of this transition zone is that the superficial layer of large multipolar nerve cells (Pre-) of the entorhinal region gradually sweeps downward and follows an oblique course through the outer layers. During this course the starshaped nerve cells of Pre- are transformed into pyramidal cells.The layer Pre- projection cells are particularly prone to the development of neurofibrillary changes of the Alzheimer type. In cases of presenile and senile dementia almost all of the layer Pre- projection neurons are changed pathologically. The isocortical pyramidal cells of layers II to IV are far less inclined to develop neurofibrillary changes. In the transentorhinal cortex, the tangle-bearing neurons follow an oblique course through the superficial laminae and are finally located between the isocortical layers III and IV, findings that confirm the assumption that these neurons are constituents of the allocortical layer Pre-.Layer-specific pathology of the profound stratum as well confirms the transentorhinal region as being formed by interdigitating allocortical and isocortical layers.Supported by grants from the Deutsche Forschungsgemeinschaft     

A disease-specific psychosocial questionnaire for Parkinson’s disease caregivers

Abstract. Objective: To evaluate the Belastungsfragebogen Parkinson Angehörigen—kurzversion (BELA-A-k), a questionnaire for measuring psychosocial problems and need for help in Parkinsons disease (PD) caregivers. Methods: The Belastungsfragebogen Parkinson Angehörigen—kurzversion was translated into Dutch. It consists of 15 items with a Bothered by (Bb) and a Need for Help (NfH) score. The BELA-A-k was tested for cultural differences, relevance and feasibility in a pilot (n = 10). We determined the psychometric properties in a validation study (n = 50) and compared the BELA-A-k with the Sickness Impact Profile, the COOP/WONCA Functional Health Assessment Charts and the Loneliness Questionnaire (de Jong-Gierveld). All questionnaires were administered in person at home, in a prescribed order. Results: The BELA-A-k was completed by 60 PD-caregivers. The internal-consistency reliability coefficients for the total Bothered by (0.90) and Need for Help (0.92) scales were excellent. The internal consistency of the subscales exceeded the 0.70 standard except for the Bothered by and Need for Help Social functioning scale (Bb = 0.62; NfH = 0.65) and the Partner-bonding/Family scale (NfH = 0.69). Almost all BELA-A-k subscales correlated highly (P < 0.001) with the corresponding scales of the standard quality of life indices. Conclusion: The BELA-A-k is a relevant, reliable and valid measure for assessing psychosocial problems and need for help of PDcaregivers.     

Die Reinnervation des anheilenden freien dermoepidermalen Autotransplantates bei der Ratte

Ohne ZusammenfassungMit 22 TextabbildungenTechnische Mitarbeit:A. Beová, J. Zvára. — Photographische und mikrophotographische Arbeiten: Dr.J. paek, O. Vai. — Durchführung der Operationen: Dr.J. mahel, CSc.     

Colocalization of growth hormone (GH) and glycoprotein subunit α in GH-producing pituitary adenomas in acromegalic patients

Thirty-one consecutive cases of pituitary adenoma in acromegalic patients were studied by immunohistochemistry. All adenomas contained cells immunoreactive with the anti--subunit of gonadotropic hormones (; 0.6–53% of tumor cells) as well as with anti-growth hormone (GH; 4–74% of tumor cells). In serial section study, most cells immunoreactive with anti- were identical to cells immunoreactive with anti-GH. There was a positive correlation between the percentages of cells immunoreactive for in GH cells [(%)/GH(%)] and those for prolactin (PRL) in immunoreactive tumor cells {PRL(%)/[PRL(%)+GH(%)]} in mixed GH cell-PRL cell adenomas, suggesting that the -subunit may play a role in emergence of PRL cells.     

The effect of oxidative stress on amyloid precursor protein processing in cells engaged in β-amyloidosis is related to apolipoprotein E genotype

The reduced antioxidative defense in allele 4 carriers is suggested to contribute to -amyloidosis in Alzheimers disease and Downs syndrome. We studied the effect of oxidative stress on accumulation of amyloid- peptide (A) in vascular smooth muscle cells (SMCs) that are engaged in production of amyloid- in vivo. Previously, we found that oxidative stress caused by ferrous ions induced accumulation of A-apolipoprotein E deposits in lysosomes and was associated with a greater oxidative protein damage in 4 carriers. Here, we demonstrate that ferrous ions induce formation of A deposits also in vascular tunica media in organotypic cultures of whole brain vessels, suggesting the role of oxidative stress in development of vascular -amyloidosis. Cellular accumulation of A in SMCs treated with ferrous ions was associated with a greater accumulation of C-terminal amyloid precursor protein (APP) fragments in 4/4 than in 3/3 myocytes and reduced the amount of soluble APP in 3/3, but not 4/4, cultures. Antioxidant vitamin E prevented these effects, and, when applied alone, diminished the amount of APP C-terminal fragments and increased the amount of secreted APP in 3/3, but not 4/4, cells. C-terminal APP-immunoreactive material was accumulated in lysosomes partly with A- and N-terminal APP immunoreactivities. These results suggest that the increased accumulation of APP and its fragments in lysosomes may yield additional amounts of cellular A, particularly in 4 carriers. We hypothesize that the altered processing of APP in SMCs locally exposed to oxidative stress facilitates cellular deposition of A and contribute to the increased risk of development of -amyloidosis in 4/4 carriers.     

Psychiatric morbidity and criminality in ‘schizoid’ children grouwn-up: A records survey

A psychiatric and criminal records search was undertaken in young adult life for two groups of former child psychiatric patients: one given a diagnosis of schizoid personality in childhood and the other, matched for sex, age, IQ and socio-economic background, given other diagnoses. The prevalence of schizophrenia in the schizoid group was low but higher than in the controls and about ten times the expected population rate. The death rate from suicide was greatly raised. Adult criminality was higher than expected in bot groups but, while for men the rates were similar in schizoid and control cases, schizoid women wer more often and more seriously delinquent than their matched controls.

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Zusammenfassung Die psychiatrischen und strafrechtlichen Dokumentationsdateien junger Erwachsener, die ehemals kinder- und jugendpsychiatrische Patienten waren, wurden untersucht, wobei eine Einteilung in zwei Gruppen erfolgte: Die erste Gruppe umfaßte ehemalige kinder- und jugendpsychiatrische Patienten, dei die Diagnose einer schizoiden Persönlichkeit erhalten hatten. Die Kontrollgruppe umfaßte ehemalige kinder- und jugendpsychiatrische Patienten mit anderen Diagnosen, die für Geschlecht, Alter, IQ und sozioökonomischen Status parallelisiert wurden. Die Prävalenz von Schizophrenie in der schizoiden Gruppe war niedfrig aber höher als in der Kontrollgruppe und zehnmal häufiger als der Erwartungswert in der Allgemeinbevölkerung. Die Suizidrate war stark erhöht. Die Kriminalitätsrate war in beiden Gruppen höher als erwartet, wobei eine Geschlechtsdifferenz bestand: Bei Männern waren die Raten beider Gruppen ähnlich, hingegen hatten schizoide Frauen häufigere und schwerwiegendere Delike begangen als in der parallelisierten Kontrollgruppe.

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Résumé Une recherche concernant l'état psychiatrique et des actes criminels a été entreprise chez des jeunes adultes appartenant à deux groupes pour lesquels un diagnostic psychiatrique avait été posé dans l'enfance. L'un avait eu un diagnostic de personnalité schizoïde et l'aure apparié par le sexe. l'âge, le quotient intellectuel et l'environmennement socio-économique avait eu d'autres diagnostics Une prévalence de schizophrénes dans le groupe schizoïde était faible et plus importance que dans le groupe contrôle et environ 10 fois supérieur en taux à la population normale. Le taux de mort par suicide était fortement élevé. La criminalité adulte était plus haute que celle attendue dans les deux groupes mais, tandis que pour les hommes le taux était semblable pour le groupe schizoïde et le groupe contrôle, les femmes chizoïdes étaient plus souvent et plus sérieusement délinquantes que celles du groupe contrôle.

     

Hypofrontality on topographic EEG in schizophrenia

Summary Topographic EEG was performed in 17 DSM-III-R schizophrenic patients and in 15 sex- and agematched healthy controls. Eleven patients were firstonset (neuroleptic naive) schizophrenics. EEG band power was compared with psychopathology, neuropsychology and neurological soft signs. The EEG was recorded at 14 topographic locations monopolarly and movements of the eye and of the lid were monitored by two bipolar electro-oculogram (EOG) derivations, one vertical and one horizontal. A multivariate correction of EOG artefacts was performed based on regression analysis with respect to EOG channels. Schizophrenic patients showed higher mean and median power in most bands. These differences were most marked in the delta band, in the fast alpha and beta bands, in particular at left frontal sites. Delta power at F7 was by far the best separating variable between schizophrenics and controls in a discriminant analysis. Significant positive correlations were found between the Brief Psychiatric Rating Scale scores Anxiety-depression and Activation and power in the fast bands and negative ones between Anergia and the beta bands. Positive significant correlations emerged between the total score in the Negative Symptoms Rating Scale and the amount of delta power, predominantly over the temporal region. Impairment in the Luria-Nebraska neuropsychological scores Rhythm and Memory correlated highly significantly with EEG band power. No correlations were found between neurological soft signs and EEG band power. Our results are in line with the hypothesis of a hypofrontality in schizophrenia. It is unlikely that these findings are an artefact of prior psychiatric treatment, as they were also observed in firstonset, neuroleptic naive schizophrenics. Moreover, our data suggest that these abnormalities are of clinical and functional relevance, as they correlated significantly with psychopathological and neuropsychological parameters.     

Apolipoprotein E co-localizes with newly formed amyloid β-protein (Aβ) deposits lacking immunoreactivity against N-terminal epitopes of Aβ in a genotype-dependent manner

Different types of amyloid -protein (A)-containing plaques occur in brains of Alzheimers disease (AD) patients. Diffuse plaques seen during early stages of AD differ from neuritic plaques in later stages both with respect to the length of the A peptides and the presence of other proteins, e.g., apolipoprotein-E (apoE). Since apoE is involved in A transport and clearance, and the 4-allele of the apolipoprotein-E gene (APOE) is a major risk factor for sporadic AD, it is plausible to speculate that apoE plays a pathophysiological role in the initiation of A deposition. To address the issue of whether binding of apoE to A is involved in initial A deposition, we studied the human medial temporal lobe of 60 autopsy cases encompassing the full spectrum of AD-related pathology. In temporal lobe regions, which become involved for the first time at a given stage of -amyloidosis, all plaques represent newly formed plaques, and these were studied with immunohistochemical methods. ApoE was present in 36 cases, and was frequently co-localized with newly formed A deposits detectable with anti-A₄₂ but not with antibodies raised against N-terminal epitopes of A. In 10 additional cases, immunoreactivity against apoE was completely lacking in newly formed plaques, which, at the same time, displayed immunoreactivity against N-terminal epitopes of A. The failure of N-terminal epitopes of A to co-localize with apoE in newly formed plaques indicates that these deposits presumably contain apoE-A complexes, in which the N-terminal epitopes of A are often concealed after complexing with apoE, thus preventing subsequent binding of antibodies. Moreover, apoE-positive newly formed plaques were seen more frequently in APOE 4/4 cases than in non-APOE 4/4 individuals, thereby underlining the potentially crucial role of apoE for the development of A deposits.     

Mental illness in a cross-national perspective

Summary Findings for unselected samples of the elderly in two urban populations — one in Mannheim, Germany (n=418) and the other in Sao Paulo, Brazil (n=111)-are compared and contrasted. Each study was restricted to persons aged over 65 years living in private households, and each employed a single-stage method of psychiatric case-identification, based on the Clinical Interview Schedule (CIS). Apart from marked differences in educational standards and proportions living alone the two samples were broadly similar in their recorded socio-demographic characteristics. Comparison revealed no significant difference in total prevalence, though there was a trend towards a higher case-frequency in Sao Paulo (29.7%) than in Mannheim (23.3%). The clinical-item profiles for the two samples indicated a higher rate of symptom reporting in Sao Paulo, whereas the Mannheim sample had higher mean scores for a number of psychiatric abnormalities observed at interview. Separate cluster analyses carried out on the two data sets divided the samples into four pairs of sub-groups with similar clinical profiles, which were designated respectively as organic, depressive, neurotic and normal. While a more careful standardization of method would probably reduce the observed disparities between the samples, some of these are thought to be real and to relate to sociocultural differences, as well as to the greater stresses of daily life in Sao Paulo.     

Preliminary findings on calmodulin-stimulated Ca2+-ATPase of erythrocyte ghosts in psychotic patients

Summary Kinetic properties of the calmodulin-stimulated erythrocyte ghost Ca²⁺-ATPase seem to be altered in some sub-groups of affective and schizophrenic psychoses. The subgroup of affective disorders concerned mostly unipolar manic and bipolar psychoses with predominantly manic episodes. In the corresponding cases from schizophrenics hyper- and parakinetic basic syndromes were predominantly diagnosed. An evaluation of our preliminary results was undertaken in connection with our biochemical hypothesis on possible alterations in the regulation of Ca²⁺ concentrations and Ca²⁺-calmodulin-mediated processes under certain psychotic conditions.Our investigations were supported by the Ministerium für Hochund Fachschulwesen of the GDRParts of this paper were presented at the 5. Dresdner Symposion über Epilepsie und Antiepileptika, Dresden, November 1984. The authors wish to express their thanks to Prof. Emrich (Munich, FRG) for his assent and helpful discussions     

Diagnostic Assessment of Asperger’s Disorder: A Review of Five Third-Party Rating Scales

Five rating scales for screening and detection of Aspergers Disorder, three commercially available and two research instruments, are evaluated with reference to psychometric criteria outlined by Bracken in 1987 (Journal of Psychoeducational Assessment, 4, 313). Reliability and validity data reported in examiners manuals or published reports are reviewed. The scales included in the review are the Asperger Syndrome Diagnostic Scale (ASDS), Autism Spectrum Screening Questionnaire (ASSQ), Childhood Asperger Syndrome Test (CAST), Gilliam Aspergers Disorder Scale (GADS), and Krug Aspergers Disorder Index (KADI). All published rating scales demonstrated significant weaknesses, particularly in the use of questionable normative samples. Among the published instruments, the KADI appears to be the most sound in terms of reliability and validity. The research instruments present incomplete psychometric data to date, but hold promise as clinical instruments.     

The repetition of parasuicide in Edinburgh 1980–1981

Summary We prospectively studied all Edinburgh hospital-referred parasuicides admitted in 1980 until the end of 1981, with regard to their repetition of parasuicide. For those 259 who repeated during this time, parasuicide status at the key 1980 admission was significantly related to age group, the veterans being older than first-timers. Similarly, the total number of episodes of parasuicide in the follow-up period was significantly related to age-group and parasuicide status: those over 45 years and first-timers were less prone to repetition. Survival analysis of all 1980 admissions revealed that veterans were significantly more likely than first-timers to be admitted with a repetition from as little as 4 days after a given episode. This difference was maintained from then until the end of the follow-up period.     

Apolipoprotein E genotype and neuropathological phenotype in two members of a German family with chromosome 14-linked early onset Alzheimer's disease

Molecular genetic analysis was performed in two autopsy-confirmed cases of early-onset Alzheimer's disease belonging to a large German pedigree [FAD2, according to the nomenclature of St. George-Hyslop, et al. (1987) Science 235:885–890]. The disease in this family has been linked to chromosome 14. As gene interactions are considered to influence the age of onset and tissue pathology in Alzheimer's disease, we have studied three candidate genes that could modify disease progression. In this study a new polymerase chain reaction (PCR) assay was established for apolipoprotein E genotyping in archival neuropathological tissue, exon 17 of the amyloid precursor protein gene was directly sequenced, and a candidate mutation site at nucleotide (nt) 5460 of the mitochondrial NADH dehydrogenase subunit gene ND2 was analyzed employing PCR followed by HphI digestion. Whereas no sequence variations were detected in exon 17^APP or at nt5460 of mitochondrial DNA, the apolipoprotein E genotypes of the two cases differed. Neuropathological examination revealed a higher number of A4-positive amyloid plaques and a larger total tissue area covered by A4 deposits in the 3/3 homozygote. In contrast, the number of cortical neurofibrillary tangles and the number of plaques with tau-positive neurites appeared to be higher in the 3/4 heterozygote. Our findings support the view that the ahromosome 14 genetic defect, rather than apolipoprotein E genotype, is the preeminent factor determining Alzheimer's disease pathology in this family.     

Comparison of integrin adhesion molecules expressed by primary brain lymphomas and nodal lymphomas

The expression of 17 adhesion molecules was immunohistochemically examined in 5 primary cerebral lymphomas (PCL) and in 5 histologically similar nodal lymphomas (NL) to evaluate their possible involvement in selective targeting of lymphoma cells to the brain. PCL and NL tumor cells showed very similar expression patterns: they were consistently positive for ₃, ₄ and ₁ integrin chains; negative for ₂, ₆, ₃ and ₄ integrin chains; and heterogeneous for ₅, _L, _M, _X, ₂ and ₇ integrin chains, as well as for intercellular adhesion molecule-1 (ICAM-1) and the selectin LECAM-1. Loosely infiltrating PCL showed lower levels of the _L2 integrin than compact cell clusters. Vessels stained for ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1). We conclude that the adhesion molecules implicated in the extravasation of non-neoplastic leukocytes (₄₁/VCAM-1 and _L2/ICAM-1) are also expressed by both PCL and NL. The adhesion molecules examined are apparently not selective mediators of lymphoma cell homing to the brain, but at least _L2 integrin might be related to the infiltration pattern of PCL within the brain parenchyma.Supported by the Sander Foundation