Search PubMed⌕ Search

Biomedical subjects

M Ackenheil

Publications and source records attributed to M Ackenheil.

At least 55 records · Page 3Linked to original sources
PubMed1996

A multicentre inter-rater reliability study using the OPCRIT computerized diagnostic system.

We examined the reliability of the OPCRIT system from ratings produced by 30 USA and European clinicians involved in molecular genetic research. The OPCRIT system facilitates a polydiagnostic approach to research on severe psychiatric disorders. OPCRIT comprises a 90-item checklist of signs and symptoms and a suite of computer programs, which together generate diagnoses according to the operational criteria of 12 major classificatory systems (e.g. DSM-III, DSM-III-R, RDC, ICD-10). Thirty summaries of actual cases ranging in signs and symptoms, taken from independent sources, were rated by participants from research centres across Europe and the USA using the OPCRIT system. Each rating was then compared to a standard rating using a kappa statistic. Good levels of reliability were observed within all classifications (e.g. DSM-III-R, kappa = 0.73, RDC, kappa = 0.71; ICD-10, kappa = 0.70) and a similar pattern of ratings was found in both the European and USA samples. We conclude that the OPCRIT system, is both flexible and practicable retaining the 'top-down' advantage of operational definitions as well as the 'bottom-up' potential offered by well defined signs, symptoms and other component items. Within the limitations of an international, multicentre design this study shows that the OPCRIT system affords good reliability with raters from a variety of geographical and theoretical backgrounds.

Diagnosis, Computer-Assisted↗
PubMed1995

Linkage analysis between pericentrometric markers on chromosome 18 and bipolar disorder: a replication test.

Replication was attempted of a recent report on linkage between bipolar affective disorder and pericentrometric loci on chromosome 18. Linkage to these markers was excluded in a sample of five extended multiplex families using lod-score and affected-pedigree-member methods. In one family, however, the lod score exceeded 1.0. Although the proposed susceptibility genes are unlikely to have a major impact on the occurrence of bipolar disorder, they might modify the genetic risk in a minority of familial cases.

Adult↗
PubMed1995

Potential linkage for schizophrenia on chromosome 22q12-q13: a replication study.

In an attempt to replicate a potential linkage on chromosome 22q12-q13.1 reported by Pulver et al. [1994: Am J Med Genet 54:36-43], we have analyzed 4 microsatellite markers which span this chromosomal region, including the IL2RB locus, for linkage with schizophrenia in 30 families from Israel and Germany. Linkage analysis by pairwise lod score analysis as well as by multipoint analysis did not provide evidence for a single major gene locus. However, a lod score of Zmax = 0.612 was obtained for a dominant model of inheritance with the marker D22S304 at recombination fraction 0.2 by pairwise analysis. In addition, using a nonparametric method, sib pair analysis, a P value of 0.068 corresponding to a lod score of 0.48 was obtained for this marker. This finding, together with those of Pulver et al. [1994: Am J Med Genet 54:36-43] and Coon et al. [1994: Am J Med Genet 54:72-79], is suggestive of a genetic factor in this region, predisposing for schizophrenia in a subset of families. Further studies using nonparametric methods should be conducted in order to clarify this point.

Chromosomes, Human, Pair 22↗
PubMed1995

Immunoglobulin and albumin content of cerebrospinal fluid in schizophrenic patients: relationship to negative symptomatology.

Alterations of the cerebrospinal fluid (CSF) protein contents and the blood brain barrier (BBB) in schizophrenia have been observed by several authors but no relationship to clinical characteristics like psychopathology, the course or the duration of the disease could be described until now. We have studied 27 schizophrenic patients upon each of whom a lumbar punction had been carried out for clinical reasons. The average values of the patients were within the normal range. Nine patients (33%) showed the total protein content to be > 45 mg% and 6 (22%) > 50 mg%. In the latter 6 patients an impaired BBB (raised albumin CSF/serum quotient) and in 4 patients (15%) a raised CSF immunoglobulin (IgG) were observed. No relation to the patient's age and the duration of the disease was found but correlations with the Scale for the Assessment of Negative Symptoms (SANS) showed significant results in the subscores "affective flattening/affective blunting", "alogia/paralogia" as well as in the total score with respect to the CSF contents of albumin and IgG (p = 0.009-0.02). These correlations suggest that the CSF albumin and the CSF IgG are related to the negative symptomatology in schizophrenia and that patients with these CSF alterations may have a higher risk of developing negative symptoms.

Adolescent↗
PubMed1995

Evaluation of a susceptibility gene for schizophrenia on chromosome 6p by multipoint affected sib-pair linkage analysis.

The influence of genetic factors in schizophrenia has been convincingly demonstrated by family, twin and adoption studies, but the mode of transmission remains uncertain. The reported pattern of recurrence risks suggests a set of interacting loci. Based on prior evidence for linkage on chromosome 6p (K. Kendler, pers. comm.), we have scanned the short arm of chromosome 6 in 54 families for loci predisposing to schizophrenia, using 25 microsatellite markers spanning 60 centiMorgans (cM). Allele sharing identity by descent was examined in affected sib-pairs from these families, followed by multipoint sib-pair linkage analysis. Positive lod scores were obtained over a wide region (D6S470 to D6S271), with a maximum lod score of 2.2 occurring near D6S274, located in 6p22. However, we obtained a lod score of -2 at D6S296, the locus found by others to provide the greatest linkage evidence. At D6S274, we report a positive lod score as do Straub et al. (individually non-significant). A combined total lod of 3.6-4.0 suggests the possibility of a susceptibility locus in this region. However, methodological differences between our studies makes a firm conclusion difficult.

Chromosome Mapping↗
PubMed1994

Expression of human heat-shock protein 70 antigens and gamma/delta T-cell receptor antigens in human central nervous tissue.

The human gamma delta T cell receptor is normally expressed on lymphoid tissue. Because expression of different molecules of the T-cell system has been described on human brain cells, we examined the expression of T-cell receptor gamma delta antigens with a panel of various anti-gamma/delta TCR mAbs using immunohistochemistry on different regions of frozen human postmortem tissue of five different brains. We found expression of gamma/delta TCR antigens on brain tissue in different regions of the brain, probably on neurons. Using mAbs against the 70-kd human heat-shock-protein (hsp 70), immunohistochemistry showed staining of microglia. A polymerase chain reaction analysis using a highly sensitive primer sequence against the constant region delta sequence supports the notion that the gamma/delta TCR is expressed in human brain; however, the sequence cannot be assigned to a specific tissue with this method. Both heat shock proteins and the gamma/delta TCR seem to be involved in autoimmune processes, and their expression on colocalizing structures in human CNS may play a role in triggering neuropsychiatric autoimmune disorders.

Base Sequence↗
PubMed1994

Absence of linkage between schizophrenia and the dopamine D4 receptor gene.

The dopamine D4 receptor gene and the closely placed tyrosine hydroxylase (TH) receptor gene are important candidate genes for schizophrenia; both are located on the short arm of chromosome 11. Multipoint linkage analyses excluded linkage of schizophrenia/schizoaffective disorder to both candidate genes in a sample of 15 multiplex and systematically recruited families. This result was not dependent on the definition of the affection status and on the specification of the mode of transmission (insofar as it is monogenic) of the disease. There was no evidence for a subgroup of families being linked. This result does not preclude the possibility that the D4 receptor gene or the TH gene has only a nonmajor effect on the genetic etiology of schizophrenia or that families in other populations are linked.

Genes, Dominant↗
PubMed1994

No evidence of linkage between the dopamine D2 receptor gene and schizophrenia.

The antipsychotic effects of dopamine D2 receptor antagonists (neuroleptics) and the psychotomimetic effects of dopamine agonists suggest that a defect of the D2 receptor gene might be a factor in the etiology of schizophrenia. Fifteen families that contained several members suffering from schizophrenia were tested for linkage between the D2 receptor gene and schizophrenia. In addition, four flanking markers were tested. The mode of inheritance was assumed to be dominant. Five different models of the affection status, which ranged from a narrow to a broad definition of the affection status, were studied. Linkage analysis was carried out with dominant, recessive, and intermediate modes of transmission. Two-point and multipoint analyses between schizophrenia and the D2 receptor gene resulted in log-likelihood differences < -2 for all five models, and linkage between this candidate gene and schizophrenia was excluded. A mutation in the D2 receptor gene itself is therefore extremely unlikely to be related to a higher susceptibility to schizophrenia, at least in the present group of families.

Bipolar Disorder↗
PubMed1994

Blunted growth hormone response to clonidine in Gilles de la Tourette syndrome.

Noradrenergic mechanisms have been involved in the pathogenesis of Gilles de la Tourette Syndrome (GTS). Since the central alpha 2 adrenergic agonist clonidine is widely used as a therapeutic agent in GTS, the present study aimed at assessing whether GH release after clonidine, representing central alpha 2-adrenergic receptor sensitivity, was altered in GTS. After administration of 2 micrograms/kg body weight clonidine, the GH response was examined in nine drug-free, alcohol-abstinent GTS patients (eight men, one woman) and in nine age- and sex-matched abstinent healthy controls. A blunted response of GH release (< 5 ng/ml) was observed in seven patients and the area under the curve (AUC) of the GH-release was significantly reduced (p < .01) compared to controls. This finding indicates an involvement of the noradrenergic system in GTS.

Adult↗
PubMed1994

Spiperone binding capacity in lymphocytes of patients with alcohol- and drug-induced psychosis: preliminary results.

An increased spiperone binding capacity in lymphocytes has been proposed as a possible biological marker for schizophrenia while in previous studies patients with alcohol dependence were shown to have a normal binding capacity. In a pilot study the spiperone binding capacity was studied in 8 patients with alcohol hallucinosis, 11 patients with acute drug-induced psychosis and 12 patients with other organic psychosis. An increased binding capacity, defined as > 4 fmol/l E6 cells, was found in only 1 patient with alcohol hallucinosis, 3 patients with drug-induced psychosis and 2 patients with other organic psychosis. Possible implications of these findings for future research are discussed.

Adult↗
PubMed1993

Cellular immunity, HLA-class I antigens, and family history of psychiatric disorder in endogenous psychoses.

We found an increased lymphocyte proliferation after stimulation with an antigen "cocktail" in 49 schizophrenic patients and 37 patients suffering from affective psychosis, compared with 45 healthy control subjects. On the basis of this and other findings such as increased numbers of CD3+ and CD4+ cells, an increased ratio of CD4+/CD8+ cells, and a reduced level of suppressor cell activity in schizophrenia and endogenous depression, we investigated the influence of the human leukocyte antigen-Class I (HLA-A, HLA-B, HLA-C) system on the altered immune function and evaluated the relationship to immune function of a family history of psychiatric disorders. A cluster analysis of cases with regard to the HLA-Class I antigens was first performed in a group of 133 healthy control subjects, and two immunogenetically different clusters were found; then 86 patients (49 schizophrenics, 37 affective psychoses) for whom immune functional data were available were assigned to the two HLA-I clusters that had been determined in the control subjects. Analyses of variance (ANOVAs) showed no differences in immune function between the two clusters. With respect to the cluster assignment and the family history of psychiatric diseases, a two-way ANOVA revealed significant differences in the lymphocyte response to the antigen cocktail, in the number of CD8+ cells, and in one suppressor cell assay. When patients were compared by ANOVA on the basis of family history of psychiatric disorder, patients with a positive family history showed a significantly higher number of CD4+ cells and a higher CD4+/CD8+ ratio. Moreover, certain HLA genes, especially HLA-A1, HLA-B8, HLA-B16, and HLA-C2 seemed to be related to the immune function and/or to the immune function and the family history.

Adolescent↗
PubMed1993

Investigations of the cellular immunity during depression and the free interval: evidence for an immune activation in affective psychosis.

1. Results of investigations of the immune function in affective disorders are conflicting. Some authors described an immune suppression, others an immune activation in major depression. The authors performed a study of cellular immunity in the MDD subtype endogenous depression. 23 patients suffering from endogenous depression were investigated during the depressive state, the results were compared with a group of 14 patients during the free interval and 51 healthy controls. 2. The lymphocyte proliferation after incubation with diphtheria- and tetanus toxoid, mainly stimulating T-cells, was reduced but after incubation with an antigen-cocktail, stimulating both, T- and B-cells, was increased in patients during depression and during the free interval compared to controls. 3. The CD3(+)- and CD4(+)-cells were significantly enhanced in both groups of patients while the CD8(+)-cells showed no differences to the controls. The ratio CD4+/CD8+ was increased in patients, too, as described in some autoimmune disorders. 4. The suppressor cell activity was significantly reduced in the PWM-assay and in the PHA-assay. The mixed lymphocyte culture showed a tendency to reduced suppressor cell activity as well. 5. The results point to an immune activation and to a disturbed control of the proliferative activity in affective psychosis. A T-cell related defect, not compensated by an increased number of CD3+- and CD4+ -cells is discussed. 6. From our point of view, the conflicting results of psychoneuroimmunological investigations in depressive disorders may be related to etiologically different subgroups of depression. The diagnostic category of MDD is possibly one of the traps in psychoneuroimmunology.

Adult↗
PubMed1993

3H-spiperone binding capacity in mononuclear cells: a family study.

1. A family study was carried out using a putative biological vulnerability trait in families of schizophrenics and schizoaffective indexprobands to investigate, if the clinical phenotype and a biological marker for schizophrenia are cosegregating within families. 2. The binding capacity of the dopamine antagonist spiperone to mononuclear cells was investigated in 21 indexprobands and a total of 147 first and second degree relatives. 3. Increased binding capacity could be found in 17 indexprobands and in their affected relatives, independently from clinical diagnosis and in 22% of their normal relatives. 4. No increased binding capacity was found in 4 indexprobands and in their affected relatives and not n any of the unaffected relatives. These results indicate, that increased spiperone binding may cosegregate with the risk for functional psychoses and that families, loaded with psychiatric disturbances may be distinguished on a biological basis.

Adult↗
PubMed1993

T-cells and psychopathology in schizophrenia: relationship to the outcome of neuroleptic therapy.

Until recently, attention has been focused on the pathogenetic aspects of immunological findings in schizophrenic patients. There has been no mention of the relationship between such findings and schizophrenic symptoms. To study the probable relationship between T-cells and T-cell subgroups in the course and prognosis of schizophrenia, immunological and psychopathological parameters were correlated in 55 patients suffering from schizophrenia (ICD-9: 295.0-295.6) or schizoaffective psychosis (ICD-9: 257.7) before neuroleptic treatment. The correlations were performed for a second time in 24 of these patients after clinical improvement at a reinvestigation. Positive correlations of the Brief Psychiatric Rating Scale and the Scale for Assessment of Negative Symptoms with the numbers of CD3+ and CD4+ T-cells (total T- and T-helper cells), which were enhanced compared with controls, were found at the reinvestigation after clinical improvement, whereas no significant correlation could be detected at the pretreatment investigation. These results show that the cellular immune parameters are related to the course of the psychopathological symptoms in schizophrenia and, possibly, are a marker of the therapeutic outcome or neuroleptic treatment.

Adolescent↗
PubMed1992

Evidence against linkage of schizophrenia to chromosome 5q11-q13 markers in systematically ascertained families.

Ten pedigrees systematically ascertained in Germany were tested for linkage to chromosome 5q11-q13. In order to replicate the previous report by Sherrington et al (1988), families with a bipolar family member were omitted from the lod score calculations, all diagnoses were based upon Research Diagnostic Criteria, and four different models of the affection status were calculated, including the model for which Sherrington et al calculated the highest lod scores. None of the families investigated showed a positive lod score. Using multipoint linkage analyses, we were able to exclude the region for which a positive linkage has been reported.

Chromosomes, Human, Pair 5↗