Biomedical subjects

S Modell

Publications and source records attributed to S Modell.

11 recordsLinked to original sources

PubMed1998

[The Munich Vulnerability Study of Affective Disorders. Overview of the results at index study].

The neurobiological alterations commonly found in affective disorders (e.g., alterations in the nocturnal sleep profile, dysfunction of the hypothalamic-pituitary-adrenocortical system) gradually recover with improvement of the depressive syndrome. Their persistence during full clinical remission, however, is associated with an increased risk for relapse and, thus may represent trait markers for affective disorders. In order to test this hypothesis, we designed a prospective study in which healthy first-degree relatives (high-risk probands; HRPs; n = 54) of patients with an affective disorder are investigated by means of polysomnography, the combined dexamethasone and corticotropine-releasing hormone (DEX-CRH) test and a variety of psychometric scales. In the present part of the study (index assessment), these HRPs, as a group, showed depression-like alterations in both the sleep pattern and the DEX-CRH-test outcome; furthermore, their psychometric profile was characterized by elevated scores on the scales assessing "rigidity" and "autonomic lability". On a single-case level, 35% of the HRPs were identified as conspicuous (depression-like) in at least two of the three areas investigated. A decision of whether or not this "conspicuousness" indeed represents a trait marker for affective disorders can be reached when the follow-up part of the study has identified those HRPs with their respective premorbide status who have developed an affective disorder in the meantime.

Adolescent↗

PubMed1998

The pre-morbid psychometric profile is stable over time in subjects at high familial risk for affective disorders.

BACKGROUND: The pre-morbid personality profile 'autonomic lability' (e.g. elevated neuroticism, frequent somatic complaints and increased interpersonal sensitivity) is suggested to be an antecedent of major depression. Recently, we reported that the psychometric profile of healthy first-degree relatives of patients with an affective disorder (so-called high-risk probands; HRPs) was characterized by the personality trait 'rigidity' in association with 'autonomic lability' and speculated that such a profile might be a potential candidate for a true vulnerability marker for affective disorders. Because one major prerequisite for any valid vulnerability marker is its stability over time, we re-examined our HRPs about four years after index assessment. METHODS: Sixteen HRPs from the initial sample (n=54) participated in the follow-up investigation which, on average, took place 47 months after index assessment. All these HRPs had remained mentally healthy during the follow-up period. RESULTS: The psychometric profile was remarkably stable over the four-year period when considering the total group of the 16 HRPs. On an individual level, similar findings were obtained. Allowing a fluctuation within a narrowly defined 'band width', a constancy of the self-ratings was found in 75% of the HRPs, within a broader 'band width' this was the case in 88% of the HRPs. LIMITATIONS: The power of the present observations appears to be somewhat limited due to the still small sample size of HRPs re-investigated and the fact that the control probands were not yet re-examined. CONCLUSIONS: The present follow-up findings in 16 probands at high risk for an affective disorder indicate a sufficient stability of the psychometric profile over time, so that this requirement for a true vulnerability marker is fulfilled.

Adult↗

PubMed1998

Hormonal response pattern in the combined DEX-CRH test is stable over time in subjects at high familial risk for affective disorders.

One of the major neurobiological alterations in depressive disorders consists in a disturbed regulation of the hypothalamic-pituitary-adrenocortical (HPA) system. This is reflected by a pathological increase in the adrenocorticotropin (ACTH) and cortisol release after pretreatment with 1.5 mg dexamethasone (DEX) the previous night and a challenge with 100 micrograms corticotropin-releasing hormone (CRH) the next day. The changes evoked by this combined DEX-CRH test recede partially with an improvement of the psychopathological symptoms of depressed patients. It is still unclear, however, whether this long-lasting disturbance of the HPA system is due to acquired changes in the acute illness or whether it plays a causal role and could be considered as a trait or vulnerability marker for depression. In a previous study we have examined the HPA function of healthy probands with a high genetic load for affective disorders. We found that this group of high-risk probands (HRPs) showed abnormal DEX-CRH test results with a cortisol release that was between that of a control group and a group of patients with depression. In a follow-up study we now reexamined 14 of the 47 HRPs about 4 years after the index investigation and found surprisingly constant DEX-CRH test results, so that one of the requirements for a vulnerability marker is fulfilled.

Adrenocorticotropic Hormone↗

PubMed1997

Corticosteroid receptor function is decreased in depressed patients.

Decreased feedback control of the hypothalamic-pituitary-adrenocortical (HPA) system as revealed by the combined dexamethasone and corticotropin-releasing hormone (DEX-CRH) test has been documented in the vast majority of patients with affective disorders. This finding was interpreted as a failure at the level of the glucocorticoid receptor (GR)-mediated feedback action, which apparently fails to restrain HPA activity in the presence of elevated plasma corticosteroid levels. To test this hypothesis we conducted the DEX/CRH test using increasing doses of DEX in order to establish a dose-response relationship. We used three different DEX doses (0.75, 1.5, 3.0 mg) in three groups of depressed patients and controls. As expected, increasing DEX doses were associated with decreasing amounts of adrenocorticotropin (ACTH) and cortisol being released after CRH injection. However, dose-response curves for both plasma ACTH and cortisol concentrations were shifted to higher area under the curve (AUC) values among patients compared to controls. Pretreatment with 0.75 and 1.5 mg DEX produced significantly higher AUC values for both plasma ACTH and cortisol values among patients. These differences became less obvious with the higher DEX doses, indicating that the dose of 1.5 mg used in the majority of clinical studies so far is well suited to differentiate between healthy controls and patients. The reported data here are consistent with the hypothesis that an altered GR capacity or function underlies the exaggerated HPA activity in depression.

Adrenocorticotropic Hormone↗

PubMed1996

Efficacy and safety of an opiate sigma-receptor antagonist (SL 82.0715) in schizophrenic patients with negative symptoms: an open dose-range study.

The psychotomimetic effects of opiate agonists/antagonists led to the hypothesis that opiate sigma receptors could be involved in the etiology of schizophrenia. This assumption is supported by animal trials with selective sigma-receptor antagonists. SL 82.0715 is a substance with a highly selective affinity for sigma receptors. To clarify the question whether it improves negative symptoms of schizophrenia, ten chronic schizophrenic patients with a predominant negative symptomatology were examined and treated with increasing doses (2.5 - 10.0 mg/d). Psychopathology was evaluated weekly using the PANSS, BPRS, and CGI, side-effects were assessed by the HAS and the S/A scale. Four patients showed improvement of negative symptoms (two slight, two marked improvement), two patients deteriorated as regards the positive symptomatology, psychopathology in the other patients did not change. The tolerability of SL 82.0715 was very good, no extrapyramidal side-effects occurred. To further evaluate the therapeutic efficacy, open studies with a larger number of patients and/or double-blind studies are necessary.

Adult↗

PubMed1996

Dysmorphophobia: differential-diagnostic aspects.

The case of a patient presenting with a depressive-suicidal syndrome and dysmorphophobia, which also showed a delusional character, is discussed concerning the differential-diagnostic difficulties. The nosology of the disorder is discussed especially regarding the variants in the new classification systems.

Adult↗

PubMed1994

[Rhabdomyolysis in neuroleptic therapy: an abortive malignant neuroleptic syndrome?].

We report on the case of a 24 year old female patient, who, at first developed during 8 weeks of neuroleptic therapy parkinsonism and then, after improvement of psychopathology an acute rhabdomyolysis. Hyper-Ck-aemia up to 11,340 U/l was observed. Laboratory parameters normalized shortly after neuroleptics had been withdrawn and no further complications followed. Symptomatology is discussed with special reference to the possibility of an abortive malignant neuroleptic syndrome.

Adult↗

PubMed1993

[Paranoid psychosis in a patient with hypothyroidism and vitamin B12 deficiency].

The case of a 39 year old in-patient with a paranoid syndrome is presented. During the course of examination, a vitamin B12 deficiency as well as a hypothyreosis were found, which seemed to have a common cause in an autoimmune disease. The paranoid symptoms disappeared completely under treatment with vitamin B12 and thyroid hormones. Moreover, the neuropsychological deficit improved markedly. The relationship between psychiatric symptoms and organic disease, and also the differential diagnosis, is discussed.

Adult↗

PubMed1992

[New aspects in the diagnosis, pathogenesis and therapy of schizophrenic negative symptoms].

The treatment of negative symptoms requires a thorough diagnostic assessment. Their lack of homogeneity has important clinical implications. Negative symptoms are unspecific for schizophrenia, differ in cause and manifestation, and may appear at all stages of the illness. There is much evidence for the responsivity of negative symptoms to pharmacological and psychosocial treatment. This paper gives a short survey of the historical development of the concept of negative symptoms, the development of scales specifically measuring both negative and positive symptoms, and various recently discussed hypotheses concerning pathogenesis and treatment strategies. Important is a therapeutic concept individually adjusted to the patient's needs, including pharmacological, psychotherapeutic and social measures.

Antipsychotic Agents↗

PubMedDate not supplied

Elevated response of growth hormone to graded doses of apomorphine in schizophrenic patients.

Three different dosages of apomorphine (0.003 mg/kg, 0.006 mg/kg, 0.012 mg/kg) were administered to stimulate the release of growth hormone (GH) in 16 male schizophrenic patients (age: 30.6, SD: 8.1 years) and 12 healthy male controls (age: 29, SD: 3.2 years). Results showed a significantly higher GH response (P < 0.01) after stimulation with 0.006 mg/kg apomorphine (APO). In contrast, stimulation with 0.012 apomorphine was unable to distinguish patients from normal controls. The results support the hypothesis of an increased dopaminergic receptor sensitivity in the hypothalamic-pituitary system of acute schizophrenic patients. This disturbance of dopaminergic neurotransmission could be observed only after a stimulation with low doses of apomorphine.

Acute Disease↗

PubMedDate not supplied

The Munich vulnerability study on affective disorders: overview of the cross-sectional observations at index investigation.

BACKGROUND: An altered nocturnal sleep pattern and a dysfunction of the hypothalamic-pituitary-adrenocortical system are neurobiological abnormalities typical for depression. A persistence of these neurobiological alterations during remission has been shown to be associated with an increased risk for a relapse. However, it remains unclear whether these persisting abnormalities are trait markers indicative of an increased vulnerability for affective disorders or only represent 'biological scars' acquired during past episodes. Thus, respective examinations need to be performed in the premorbid state in order to answer this open question. METHODS: In the present article we have summarized the various results of the index investigation of a prospectively designed study in which we investigated 54 healthy first-degree relatives (high-risk probands; HRPs) of patients with an affective disorder using polysomnography, the combined dexamethasone corticotropine-releasing hormone (DEX-CRH) test and psychometric measurements. RESULTS: In the cross-sectional part of this study the HRPs, as a group, exhibited a 'depression-like' sleep EEG profile and DEX-CRH test result, while their psychometric profile was characterized by elevated scores on the measures 'Rigidity' and 'Autonomic lability'. On an individual level, 35% of the HRPs were identified as conspicuous in at least two of the three areas under investigation. CONCLUSIONS: The question of whether these abnormalities do indeed reflect trait markers indicative of an increased vulnerability for depression will be answered by the longitudinal part of the study that allows for the retrospective identification of the premorbid status of those HRPs who develop an affective disorder during the follow-up period.

Adolescent↗