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Biomedical subjects

M Ackenheil

Publications and source records attributed to M Ackenheil.

At least 19 recordsLinked to original sources
PubMed2000

Serotonin transporter (5-HTT) gene polymorphism in psychogeriatric patients.

Several studies have attempted to confirm an association between a deletion/insertion polymorphism within the promoter region of the serotonin transporter gene (5-HTT) and Alzheimer's disease independent from the apolipoprotein E (APOE) varepsilon4 status. We examined this deletion/insertion polymorphism of the serotonin transporter gene in a sample of 222 consecutively recruited gerontopsychiatric patients which was divided into four different diagnostic groups: Alzheimer's disease (N=84), mild cognitive impairment (N=29), subjective cognitive complaints (N=49), depression/other psychiatric disorders (N=56) and 118 healthy, non-demented controls. The aim of this approach was to test whether the investigated polymorphism has a high enough selectivity and specificity to distinguish between the different gerontopsychiatric disorders or to differentiate genetically AD from other forms of dementia, respectively. We could not detect any significant differences in the allelic distribution of the deletion/insertion polymorphism of the 5-HTT gene between the four patient subgroups and the control group. This finding indicates that the serotonin transporter does not appear to be a major susceptibility factor in the pathophysiology of Alzheimer's disease and other psychogeriatric disorders.

Aged↗
PubMed2000

Decreased levels of soluble intercellular adhesion molecule-1 (sICAM-1) in unmedicated and medicated schizophrenic patients.

BACKGROUND: The soluble intercellular adhesion molecule-1 (sICAM-1) is a marker for the activation of the cellular immune system. Since an activation of the immune system has been observed in a part of the schizophrenic patients, we measured the serum levels of soluble ICAM-1 (sICAM-1) in schizophrenic patients and correlated them to the patient's psychopathology. METHODS: To monitor a possible effect of antipsychotic therapy, 36 schizophrenic patients were examined twice: first without antipsychotic medication immediately after admission to the hospital and then, after clinical improvement before discharge. The results were compared with those of 36 age- and gender-related healthy individuals. RESULTS: The schizophrenic patients showed significantly decreased serum levels of sICAM-1 at the first examination (248 +/- 95 ng/mL) and at re-examination (266 +/- 95 ng/mL) compared with the comparison group (323 +/- 74 ng/mL). Patients with more pronounced negative symptoms showed higher levels of sICAM-1 at the first examination. CONCLUSIONS: We conclude that reduced sICAM-1 levels in schizophrenia indicate a reduced activity of the cellular immune system in at least a subgroup of schizophrenic patients.

Acute Disease↗
PubMed2000

Linkage of mood disorders with D2, D3 and TH genes: a multicenter study.

BACKGROUND: It has been suggested that the dopaminergic system is involved in the pathophysiology of mood disorders. We conducted a multicenter study of families with mood disorders, to investigate a possible linkage with genes coding for dopamine receptor D2, dopamine receptor D3 and tyrosine hydroxylase (TH). METHODS: Twenty three mood disorder pedigrees collected within the framework of the European Collaborative Project on Affective Disorders were analyzed with parametric and non-parametric linkage methods. Various potential phenotypes were considered, from a narrow (only bipolar as affected) to a broad (bipolar+major depressive+schizoaffective disorders) definition of affection status. RESULTS: Parametric analyses excluded linkage for all the candidate genes, even though small positive LOD (Limit of Detection) scores were observed for TH in three families. Non-parametric analyses yielded negative results for all markers. CONCLUSION: The D2 and D3 dopamine receptors were, therefore, not a major liability factor for mood disorders in our sample, whereas TH may play a role in a subgroup of patients.

Bipolar Disorder↗
PubMed1999

Tyrosine hydroxylase polymorphism and phenotypic heterogeneity in bipolar affective disorder: a multicenter association study.

Tyrosine hydroxylase (TH), the rate-limiting enzyme in the metabolism of catecholamines, is considered a candidate gene in bipolar affective disorder (BPAD) and has been the subject of numerous linkage and association studies. Taken together, most results do not support a major gene effect for the TH gene in BPAD. Genetic and phenotypic heterogeneity may partially explain the difficulty of confirming the exact role of this gene using both association and linkage methods. Four hundred one BPAD patients and 401 unrelated matched controls were recruited within a European collaborative project (BIOMED1 project in the area of brain research, European Community grant number CT 92-1217, project leader: J. Mendlewicz) involving 14 centers for a case-control association study with a tetranucleotide polymorphism in the TH gene. Patients and controls were carefully matched for geographical origin. Phenotypic heterogeneity was considered and subgroup analyses were performed with relevant variables: age at onset, family history, and diagnostic stability. No association was observed in the total sample or for subgroups according to age at onset (n = 172), family history alone (n = 159), or high degree of diagnostic stability and a positive family history (n = 131). The results of this association study do not confirm the possible implication of TH polymorphism in the susceptibility to BPAD.

Adult↗
PubMed1999

Relationship of substance P, 5-hydroxyindole acetic acid and tryptophan in serum of fibromyalgia patients.

The serotonergic system has repeatedly been discussed to be involved in the pathophysiology of fibromyalgia (FM), which is a syndrome of widespread pain and sleep disturbance. Elevated levels of substance P (SP), a mediator of nociception, have been described in FM. In this study the possible relationship between SP and serotonin (5-HT) together with its precursor tryptophan (TRP) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) was evaluated in 51 serum samples of fibromyalgia patients. These parameters were compared with clinical data such as pain intensity or sleep quality. A strong negative correlation between SP and 5-HIAA (P = .000) as well as between SP and TRP (P = .009) could be demonstrated. High serum concentrations of 5-HIAA and TRP showed a significant relation to low pain scores (5-HIAA: P = .030; TRP: P = .014). Moreover, 5-HIAA was strongly related to good quality of sleep (P = .000), while SP was related to sleep disturbance (P = .005). These data are valid to support the hypothesis of a systemic involvement of 5-HT and SP in fibromyalgia.

Adult↗
PubMed1999

Possible association of fibromyalgia with a polymorphism in the serotonin transporter gene regulatory region.

OBJECTIVE: To analyze the genotypes of the promoter region of the serotonin transporter gene (5-HTT) in patients with fibromyalgia (FM). METHODS: Genomic DNA from 62 patients meeting the American College of Rheumatology 1990 criteria for FM and 110 healthy controls was analyzed by polymerase chain reaction. Additionally, the psychopathologic state of 52 of the FM patients was evaluated using the Beck Depression Inventory (BDI) and the Symptom Checklist-90-Revised (SCL-90-R). RESULTS: The 5-HTTLPR genotypes in FM patients versus controls were distributed as follows: L/L 27% versus 34%, L/S 42% versus 50%, and S/S 31% versus 16%. FM patients with the S/S genotype had higher mean scores on the BDI and the SCL-90-R compared with those in the L/L and L/S groups. CONCLUSION: A higher frequency of the S/S genotype of 5-HTT was found in FM patients compared with healthy controls. The S/S subgroup exhibited higher mean levels of depression and psychological distress. These results support the notion of altered serotonin metabolism in at least a subgroup of patients with FM.

Adult↗
PubMed1999

The T102C polymorphism of the 5-HT2A-receptor gene in fibromyalgia.

Based on a possible involvement of serotonergic dysfunction in the pathophysiology of fibromyalgia (FM) and on preliminary reports of a possible genetically driven vulnerability for this disorder we investigated the silent T102C polymorphism of the 5-HT2A-receptor gene in 168 FM patients and 115 healthy controls. Our results showed a significantly different genotype distribution in FM patients with a decrease in T/T and an increase in both T/C and C/C genotypes as compared to the control population (Fisher's Exact test, two-sided, P = 0.008). However, the increase in allele-C102 frequency felt short of significance (P = 0.07). Correlation of genotypes to clinical parameters revealed no influences on age of onset, duration of disease or psychopathological symptoms, measured with the Beck Depression Inventory and the symptom checklist SCL-90-R. In contrast to that the pain score, being a self reported information on pain severity, was significantly higher in patients of the T/T genotype (Mann-Whitney U test, P = 0.028). This suggests that the T102-allele might be involved in the complex circuits of nociception. However, the T102C polymorphism is not directly involved in the aetiology of FM but might be in linkage dysequilibrium with the true functional variant, which has to be unravelled.

Adult↗
PubMed1999

The role of immune function in schizophrenia: an overview.

Immune alterations in schizophrenia have been described for decades. However, modern immunological methods and new insights into the highly developed and functionally differentiated immune system allows an integrative view of both, the older and also recent findings of immunological abnormalities in schizophrenia. Both, the unspecific and the specific arm of the immune system seem to be involved in the dysfunction of the immune system in schizophrenia. The unspecific "innate" immune system shows signs of an overactivation in unmedicated schizophrenic patients, as increased monocytes and gamma delta-cells point to. Increased levels of Interleukin-6 (IL-6) and the activation of the IL-6 system in schizophrenia might also be the result of the activation of monocytes/macrophages. On the contrary, several parameters of the specific cellular immune system are blunted, e.g. the decreased T-helper-1 (TH-1) related immune parameters in schizophrenic patients both, in vitro and in vivo. It seems that a TH-1-TH-2 imbalance with a shift to the TH-2 system is associated with schizophrenia. During antipsychotic therapy with neuroleptics, the specific TH-1 related immune answer becomes activated, but also the B-cell system and the antibody production increases.

Antipsychotic Agents↗
PubMed1999

Antibodies to heat shock proteins in schizophrenic patients: implications for the mechanism of the disease.

OBJECTIVE: The involvement of heat shock proteins has been determined in the pathophysiology of several disorders of the central nervous system, including multiple sclerosis. To elucidate their role in schizophrenia, the authors investigated antibody titers to heat shock proteins in unmedicated and medicated patients with schizophrenia. METHOD: Using the enzyme-linked immunosorbent assay technique, the authors measured titers of antibodies to 60 kilodaltons (kD) heat shock proteins (HSP60) and 70 kD heat shock proteins (HSP70) in 30 patients with schizophrenia before and during neuroleptic treatment and compared the titers with those of 31 healthy individuals. RESULTS: Ten (33%) of 30 patients with schizophrenia but only one (3%) of 31 healthy individuals showed immunoreactivity to HSP60 or HSP70. The authors found especially high anti-HSP70 titers in never-medicated patients. High anti-HSP60 titers were mainly found in patients who were being treated with neuroleptics. CONCLUSIONS: Since heat shock proteins are involved in diverse neuroprotective mechanisms, antibodies against heat shock proteins may inhibit neuroprotection. The authors discuss the implications of these findings for schizophrenia.

Adult↗
PubMed1999

Increase in expression of adhesion molecule receptors on T helper cells during antipsychotic treatment and relationship to blood-brain barrier permeability in schizophrenia.

OBJECTIVE: The authors estimated the expression of adhesion molecule receptors (VLA-4 and LFA-1) on T helper (CD4+) and T suppressor/cytotoxic (CD8+) lymphocytes in schizophrenic patients before and during antipsychotic treatment and studied the relationship of these subpopulations to CSF measures and blood-brain barrier permeability. METHOD: Blood was drawn from hospitalized patients with schizophrenia before (N = 45) and after (N = 22) neuroleptic treatment and from an age-matched comparison group (N = 41). Lumbar punctures were performed on 32 of the schizophrenic patients. RESULTS: During antipsychotic treatment there were significant increases in the percentage of VLA-4+/CD4+ and VLA-4+/CD8+ cells. VLA-4+/CD4+ and LFA-1+/CD4+ cells were both closely related to disturbance of the blood-brain barrier. Higher values for VLA-4+/CD4+ and LFA-1+/CD4+ cells were found in patients with a disturbed blood-brain barrier. CONCLUSIONS: The findings suggest that adhesion molecules are involved in immunoregulation between the central nervous system and the peripheral immune system in schizophrenia.

Adult↗
PubMed1998

Blood-cerebrospinal fluid barrier impairment as indicator for an immune process in schizophrenia.

An impairment of the blood-cerebrospinal fluid barrier (BCB) has repeatedly been described in schizophrenic patients. A BCB impairment can be due to vascular leakage during an inflammatory process, or to neuroleptic treatment. The soluble intercellular adhesion molecule-1 (sICAM-1) has been demonstrated to be a reliable marker for an inflammatory process causing an BCB impairment. To clarify the basis of a BCB impairment in schizophrenic patients, we measured the sICAM-1 levels in CSF of 40 schizophrenic patients. High concentrations of sICAM-1 were found to be related to high concentrations of albumin, IgG and total protein in CSF. A BCB impairment was associated with high levels of sICAM-1. Our data indicate an inflammatory mechanism of BCB impairment in schizophrenics and should enrich the discussion on an expanded immunological diagnosis in schizophrenia.

Adult↗
PubMed1998

Genetics and pathophysiology of affective disorders: relationship to fibromyalgia.

Depression and fibromyalgia (FM) share common symptoms, indicating a close relationship between both disorders. FM patients frequently present symptoms of major depression. Genetic epidemiological studies show that genetic transmission is one important component. Molecular genetic studies are on the way; the serotonin transporter promoter gene seems to be associated with neurotic anxiety and FM. Biochemical studies related to the serotonin and norepinephrine neurotransmission are disturbed in both disorders. This view is supported by the response to treatment with antidepressants.

Diagnosis, Differential↗
PubMed1998

Self-reported depression, familial history of depression and fibromyalgia (FM), and psychological distress in patients with FM.

The prevalence of FM in the general population is estimated at 2%. FM is among the three most common diagnoses in ambulatory adult rheumatology practice. To study the degree of depression, the familial history of depression and FM, as well as the psychological distress in our FM population, we mailed a standardized questionnaire to 304 FM patients. The response rate was 33%. We found BDI scores higher than 21 in 27% of the patients indicating clinical relevant depression. The patients had high levels of global distress measured with the SCL-90-R as well as elevated scores in the subscales. Twenty three percent had a familial history of depression, 46% a familial history of FM, and 46% had been diagnosed with depression in the past.

Adult↗
PubMed1998

The serotonin syndrome scale: first results on validity.

As a modification of the diagnostic criteria of the serotonin syndrome proposed by Sternbach, we developed the Serotonin syndrome scale for the operationalized assessment of both the presence and the severity of the core symptoms of the serotonin syndrome. In a first study on the validity of this scale, the relationships between the serotonin syndrome score (SSS) and both the paroxetine plasma levels (n = 42) and the loudness dependence of the auditory evoked potentials (LDAEP; n = 24) were investigated in depressed patients treated with paroxetine. A strong LDAEP is supposed to indicate low central serotonergic neurotransmission, and vice versa. The SSS was positively related to paroxetine plasma levels and negatively to the LDAEP. Both results support the validity of the serotonin syndrome scale. Using a SSS > 6 as diagnostic criterion, mild serotonin syndromes were diagnosed in 5 of our 42 patients. The Serotonin syndrome scale may become a useful tool for clinicians and scientists dealing with the serotonin syndrome.

Adult↗
PubMed1998

Autoantibodies against 60-kDa heat shock protein in schizophrenia.

Immunological abnormalities in schizophrenic patients have been reported for many years. However, the question of whether these parameters are involved in the pathophysiology of the disorder or represent treatment effects is still not answered. We investigated a combination of humoral and soluble immune parameters in 30 unmedicated schizophrenic patients before and during antipsychotic treatment and in 31 healthy controls. The aim of our study was to unravel an underlying immune process, to elucidate the influence of neuroleptic treatment and to identify a subgroup of schizophrenics. Antibodies against human 60-kDa heat-shock protein (HSP60), serum levels of soluble ICAM-1 and IL-2R were determined and correlated with parameters of blood-brain barrier and of psychopathology. In 10% of the drug-free but in 20% of the medicated schizophrenics, especially in females, we observed immunoreactivity against HSP60, high levels of IgG in CSF and a blood-brain barrier impairment. The high HSP antibody titres correlated with high levels of sIL-2R and sICAM-1. Only one of the controls showed antibodies against HSP60. Our results suggest that the observed immunological alterations are more pronounced during neuroleptic treatment than in the drug-free state. Whether or not this differential response to treatment with altered antibody production represents a subgroup of patients has yet to be determined.

Adolescent↗
PubMed1998

Psychoneuroimmunology and the cytokine action in the CNS: implications for psychiatric disorders.

1. Parallel to the current rapid development of new immunological methods, immune mechanisms are gaining more importance for our understanding of psychiatric disorders. The purpose of this article is to review basic and clinical investigations that elucidate the relationship between the CNS and the immune system. 2. The topical literature dealing with the interactions of immune system, neurotransmitters, psychological processes, and psychiatric disorders, especially in relation to cytokines, is reviewed. 3. An activation of the immune system in schizophrenia and depressive disorders has repeatedly been described. Cytokines, actively transported into the CNS, play a key role in this immune activation. It was recently observed that cytokines activate astrocytes and microglia cells, which in turn produce cytokines by a feedback mechanism. Moreover, they strongly influence the dopaminergic, noradrenergic, and serotonergic neurotransmission. 4. There are indications that the cascade of cytokines can be activated by neuronal processes. These findings close a theoretical gap between stress and its influence on immunity. Psychomotor, sickness behavior and sleep are related to IL-1; disturbances of memory and cognitive impairment are to IL-2, in part also to TNF-alpha. The hypersecretion of IL-2 is assumed to have a prominent influence on schizophrenia, and IL-6, on depressive disorders. 5. Although single cytokines most likely do not have a specificity for certain psychiatric disorders, a characteristic pattern of cytokine actions in the CNS, including influences of the cytokines on the blood-brain barrier, seems to play a role in psychiatric disorders. This may have therapeutic implications for the future.

Animals↗
PubMed1998

European Collaborative Project on Affective Disorders: interactions between genetic and psychosocial vulnerability factors.

Despite strong evidence provided by genetic epidemiology of genetic involvement in the aetiology of bipolar and unipolar affective disorders, the exact nature of the predisposing gene(s) is still being investigated through linkage and association studies. The interaction of susceptibility genes and environmental factors in these diseases is also of fundamental importance and requires proper investigation. Interesting theories have recently been proposed examining the possible role of various chromosomal regions, candidate genes and mutations in affective disorders. Reliable multicentre-based methodology is currently being employed to examine these theories, with attention given to statistical analysis and the statistical power of the sample. The present article describes the European Collaborative Project on Affective Disorders (ECPAD) 'Interactions between genetic and psychosocial vulnerability factors', involving 15 European centres. A description is given of the association and family samples collected for the project and also the methodology used to analyse interactions in the gene-psychosocial environment. This material provides a powerful tool in the search for susceptibility genes in affective disorders and takes into account non-genetic aetiological factors.

Adolescent↗