Volker Arolt

Eye tracking dysfunction is a putative phenotypic susceptibility marker of schizophrenia and maps to a locus on chromosome 6p in families with multiple occurrence of the disease

The difficulties in defining the borders of the schizophrenia spectrum is one major source of variance in linkage studies of schizophrenia. The employment of biological markers may prove advantageous. Due to empirical evidence, eye tracking dysfunction (ETD) has been discussed to be the most promising marker for genetic liability to schizophrenia. With respect to the recent progress in genomic scans, which have pointed to the short arm of chromosome 6, we carried out a scan of the 6p21-23 region with 16 microsatellite markers to test for linkage between chromosomal markers and ETD as well as schizophrenia. We tested 5 models of inheritance of ETD and found maximum two-point lod scores of 3.51 for D6S271 and 3.44 for D6S282. By including these markers in a multipoint analysis, a lod score of 4.02 was obtained. In the case of schizophrenia, 7 models were tested; however, with non-significant results. Our findings, together with another recent linkage report, point to the possibility of a second susceptibility locus for schizophrenia which may be located centromeric to the HLA region. Also, the evidence of ETD being a susceptibility marker for schizophrenia receives further support.

Investigations of cytokine production in whole blood cultures of paranoid and residual schizophrenic patients

In an attempt to define potential immunological dysfunctions in schizophrenia, we determined the production of interleukin-2 (IL-2), interleukin-4 (IL-4), interferon-γ (IFN-γ), and soluble IL-2 receptor (sIL-2R) in a whole-blood assay after stimulation with phytohemagglutinin (PHA) as well as the serum concentrations of sIL-2R. Because CD4+CD45RO+T cells are the main producers of IFN-γ, we determined the percentage of these cells, as well as of pan T, CD4+T, and CD8+T cells, by flow cytometry. A whole-blood count was performed in addition. Two groups of patients were examined, paranoid-type and residual-type schizophrenics. The numbers of both monocytes and neutrophils, but not of lymphocytes, were increased significantly in the schizophrenic sample. The IFN-γ production of the schizophrenics as a whole group, and of the paranoid patients, was reduced significantly in comparison with the control group (p≤0.05). The residual patients produced less IFN-γ than the controls, but more than the paranoid patients. The latter differences did not reach statistical significance. The production of IL-4, which physiologically antagonizes the production of IFN-γ, was not significantly higher in the patient group. No changes in the lymphocyte subpopulations were observed. The production of IL-2 showed a trend toward reduction in paranoid patients, but not in residual schizophrenics. The serum sIL-2R levels were elevated slightly in schizophrenics when compared with controls. In order to rule out a possible effect of cortisol on cytokine production, 20 schizophrenic were compared with 20 age- and gendermatched controls. However, neither elevated cortisol levels were detected in the schizophrenic sample, nor significant intercorrelations between cortisol levels and cytokine production, or levels of sIL-2R, respectively. In summary, our data reinforce the possibility of immune dysfunction in schizophrenia and point to the possible relevance of disease subgroups in this respect.

Production of interferons and lymphokines in leukocyte cultures of patients with schizophrenia.

Recently, several lines of evidence have suggested the possible of immunological dysfunction in the pathogenesis of schizophrenia. We therefore investigated the ability to produce interferons and lymphokines in response to mitogenic or viral stimulation in a whole blood assay of 37 schizophrenic patients (DSM-III-R) and of 42 healthy blood donors. Phytohaemagglutinin (PHA) was used for the induction of interleukin-2 (IL-2), interferon gamma (INF gamma), interleukin-6 (IL-6) and the soluble interleukin-2 receptor (sIL-2R) and Newcastle Disease Virus (NDV) for the induction of interferon alpha 2 (INF alpha 2). All lymphokines and, in addition, the sIL-2R in the sera were determined by ELISA technique. The psychopathological status of the patients was assessed by psychiatrists according to internationally accepted standards. The patient group showed a trend to lower levels of the interferons alpha 2 and gamma and a significant decrease of IL-2 production. The sIL-2R levels were significantly increased in the sera of schizophrenic patients. The latter increase was associated with a poor assessment of prognosis (Strauss and Carpenter). This association appears to be of interest. However, its significance is not understood, since longitudinal studies could not be performed.

Major depressive disorder is associated with elevated monocyte counts

One of the most consistently reported findings in depression has been leucocytosis. In 33 in‐patients with major depressive disorder, we assessed white blood cell count (WBC) and lymphocyte subsets four times over a period of 6 weeks. The control group consisted of 44 healthy subjects. Shortly after admission, we detected significant increases in the numbers of leucocytes, granulocytes, platelets and monocytes in the depressed patients. Patients who recovered well during hospitalization showed a decrease in monocyte counts, whereas those with slower clinical improvement had significantly higher monocyte counts than the control group. This longitudinal study demonstrates that monocytes may play a role in the acute phase of depression and could provide an explanation for immunological dysfunction in depressive states.

Production of interferon-gamma in families with multiple occurrence of schizophrenia

Dysfunction of T-cell mediated immunity, which is indicated by deficient production of interleukin-2 (IL-2) and elevated levels of the soluble interleukin-2 receptor (sIL-2R), has been consistently demonstrated in schizophrenia. Recent studies on interferon-gamma (IFN-gamma), a cytokine which is also produced by T-helper cells, have indicated a lowered production in acute schizophrenia. It is not known whether this deficit is restricted to cases of acute schizophrenia or whether it is also present in residual schizophrenia and in first degree relatives, and therefore might be associated with genetic liability to the disease. We investigated 27 individuals (schizophrenics and first degree relatives) of 6 families with multiple occurrence of schizophrenia and 27 age- and sex-matched healthy controls. The production of IFN-gamma was lowered only in the acutely ill schizophrenic individuals, when compared to both controls and first degree relatives. In the context of current knowledge, this result indicates that the production of IFN-gamma can be discussed as a marker of acute exacerbation of schizophrenia, but it is not likely to represent a phenotypic marker of a genetic trait associated with the disease.

The Lübeck General Hospital Study. I: Prevalence of psychiatric disorders in medical and surgical inpatients

The aim of the Lübeck General Hospital study was to assess the prevalence rates of psychiatric disorders in medical and surgical general hospital patients, as well as treatment needs. In a cross-sectional study, a total of 400 patients were interviewed, 200 each from medical and surgical departments. We used the standardized Composite International Diagnostic Interview (CIDI) and, in addition, a clinical interview. In the first of two articles, the prevalence rates of ICD-10 diagnoses, which had to be present within seven days before the interview, are described. Of the total sample, 35.5% of the patients received a CIDI diagnosis and 46.8% a clinical diagnosis. The most prominent disorders were organic mental disorders (CIDI, 18.3%; clinical, 16.5%), alcoholism (4.5% and 8.3%), and depression (8.3% and 15.3%). With regard to the spectrum of psychiatric diagnoses, no significant differences were found between the medical and the surgical sample. When compared to surveys of the general population in Germany, the prevalence rates of organic mental disorders, alcoholism and adjustment disorders were considerably higher in general hospital patients.

Paranoid schizophrenia: non-specificity of neuropsychological vulnerability markers

During stages of remission, patients with paranoid schizophrenia seldom show severe attentional or information-processing dysfunctions, except in cases of long-term chronicity. The diagnostic specificity of four putative psychological vulnerability indicators of schizophrenia - the Span of Apprehension, the degraded stimulus Continuous Performance Test (dsCPT), the degraded stimulus visual backward masking task and the Wisconsin Card Sorting Test (WCST) - was examined in a group of patients with paranoid schizophrenia. Since no single test seems to identify all patients, the use of a combination of measures may be a useful strategy. Accordingly, the four tests were administered to 18 paranoid schizophrenic patients, 18 depressed patients and 18 normal subjects. Paranoid schizophrenic patients could be distinguished from normal subjects primarily on the basis of their performance on the backward masking task and secondarily by the dsCPT and the WCST. Paranoid schizophrenic and depressed patients could be differentiated to some extent by their performance on an information-mask condition of the backward masking task. Thus, of the four measures studied, only the degraded stimulus backward masking appeared to be a specific indicator of paranoid schizophrenia.

Eye tracking dysfunction in families with multiple cases of schizophrenia

There is increasing evidence that the genetic predisposition for schizophrenia in families affects more individuals than those fulfilling the criteria for schizophrenia. This finding is supposed to be one of the major problems in molecular genetic schizophrenia research, especially when linkage studies are employed. Eye-tracking dysfunction (ETD), which is conceived as a possible phenotypic marker for genetic liability to schizophrenia, may offer considerable advantages. However, there is only little information from families with multiple occurrence of schizophrenia. It is still unclear whether in these families ETD aggregates with diagnoses from the schizophrenia spectrum. This first report from an ongoing study presents the results of 48 individuals from 6 multiplex families. Smooth-pursuit eye movements were recorded by infrared reflectometry and assessed by quantitative measurement techniques. Along with the high degree of psychiatric morbidity in these families, in 56.3% of the individuals ETD was assessed. Reduced mean pursuit gain was present in 39.6%. The distribution of eye-tracking dysfunction resembles the distribution of schizophrenia-related psychiatry morbidity.

Psychiatric Comorbidity in Hospitalized Alcoholics after Detoxification Treatment

The aim of this study is to analyze psychiatric comorbidity of alcohol dependence with respect to prevalence rates, time of onset and indications for the course of alcoholism. 100 hospitalized alcohol

Neurobiologische Grundlagen von Psychotherapie

Trotz der in vielen Fallen unschwer zu beobachtenden „korperlichen“ Veranderungen bei Psychotherapiepatienten (z. B. der vegetativen Reaktionen oder des Ausdrucksverhaltens) wurden die psychologischen Interventionsmethoden traditionell nicht als biologische Therapien angesehen. Aus der Perspektive der kognitiven Neurowissenschaft en liegen psychischen Funktionen und Prozessen neuronale Vorgange zugrunde. Aus dieser Sicht sind und waren psychotherapeutische Behandlungen (zumindest implizit) stets Versuche, dauerhaft e Veranderungen von neuronalen Prozessen und Strukturen zu bewirken, womit sie auch eine biologische Dimension hatten. Rasante technologische Entwicklungen bei den sogenannten bildgebenden Verfahren haben neue Moglichkeiten eroff net, die funktionelle Organisation des Gehirns zu untersuchen. Die Anwendung der funktionellen Bildgebung im Bereich der Psychotherapie erscheint vielversprechend, um die zerebralen Mechanismen und Bedingungen von Wirkungen und Veranderungen im Erleben und Verhalten, aber auch von Therapieversagen zu ergrunden.