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Biomedical subjects

J C Krieg

Publications and source records attributed to J C Krieg.

At least 37 records · Page 2Linked to original sources
PubMed1999

Amphetamines induce apoptosis and regulation of bcl-x splice variants in neocortical neurons.

Amphetamineanalogs have emerged as popular recreational drugs of abuse. The number of reports of these substances producing severe acute toxicity and death is increasing. In 'Ecstasy' -associated deaths, focal necrosis in the liver and individual myocytic necrosis has been reported. Furthermore, serotonergic and dopaminergic neuronal cell damage has been observed in experimental amphetamine intoxication in laboratory animals. Here we demonstrate that subchronic exposure to D-amphetamine, methamphetamine, methylenedioxyamphetamine, and methylenedioxymethamphetamine ('Ecstasy') results in significant neurotoxicity in rat neocortical neurons in vitro. This neuronal cell death is accompanied by endonucleosomal DNA cleavage and differential expression of anti- and proapoptotic bcl-xL/S splice variants. In addition, we observed pronounced induction of cell stress-associated transcription factor c-jun and translation initiation inhibitor p97 after amphetamine treatment. These data support that the neurotoxic effects of different amphetamines are extended to rat neocortical neurons and that apoptotic pathways are involved in amphetamine-induced neurotoxicity.

3,4-Methylenedioxyamphetamine↗
PubMed1999

Neuroprotection by estrogens in a mouse model of focal cerebral ischemia and in cultured neurons: evidence for a receptor-independent antioxidative mechanism.

Estrogens have been suggested for the treatment of neurodegenerative disorders, including stroke, because of their neuroprotective activities against various neurotoxic stimuli such as glutamate, glucose deprivation, iron, or beta-amyloid. Here, the authors report that 17beta-estradiol (0.3 to 30 mg/kg) and 2-OH-estradiol (0.003 to 30 mg/kg) reduced brain tissue damage after permanent occlusion of the middle cerebral artery in male NMRI mice. In vitro, 17beta-estradiol (1 to 10 micromol/L) and 2-OH-estradiol (0.01 to 1 micromol/L) reduced the percentage of damaged chick embryonic neurons treated with FeSO4. In these primary neurons exposed to FeSO4, the authors also found reactive oxygen species to be diminished after treatment with 17beta-estradiol (1 to 10 micromol/L) or 2-OH-estradiol (0.01 to 10 micromol/L), suggesting a strong antioxidant activity of the estrogens that were used. Neither the neuroprotective effect nor the free radical scavenging properties of the estrogens were influenced by the estrogen receptor antagonist tamoxifen. The authors conclude that estrogens protect neurons against damage by radical scavenging rather than through estrogen receptor activation.

Animals↗
PubMed1998

Slow-wave sleep and ventricular size: a comparative study in schizophrenia and major depression.

BACKGROUND: A slow-wave sleep (SWS) deficit and a shortened rapid eye movement (REM) sleep latency are commonly described in schizophrenia and depression. In addition, a close association between ventricular system measurements and SWS are reported in both disorders; however, a comparative, combined polysomnographic and computed tomographic investigation is lacking. METHODS: In the present post hoc study we analyzed the electroencephalographic sleep pattern and the ventricular brain ratio (VBR) of 14 drug-naive schizophrenic patients and of 14 depressed patients who were drug-free for a sufficient time period. RESULTS: Whereas the depressives showed the often described SWS and REM sleep changes, these measurements were quite normal in the schizophrenics. The VBR values were similar in both patient groups and exceeded in 71% of the schizophrenics and in 50% of the depressives the cutoff point of a "normal" VBR value. A close association between SWS and VBR was found in the depressives but not in the schizophrenics. CONCLUSIONS: The results of the present study of drug-naive schizophrenic patients and of depressed patients indicate only a minor overlap between the pathophysiological changes observed in both disorders. Therefore, the present investigation adds evidence for the assumption that schizophrenia and depression are etiopathogenetically distinct entities, rather than representing points on a continuum of liability.

Adult↗
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↗
PubMed1998

Serum leptin levels increase rapidly after initiation of clozapine therapy.

Weight gain is a major side-effect of treatment with clozapine. In order to investigate the influence of the atypical neuroleptic clozapine on leptin secretion, serum leptin levels were measured in 12 patients at baseline and for a 10-week period after initiation of treatment. Serum clozapine levels and levels of its metabolites were simultaneously assessed. Alterations of body weight and body composition were determined. During the 10-week observation period leptin levels differed significantly from the levels determined at baseline (P < 0.0001). During the first 2 weeks of treatment serum leptin levels at least doubled in eight of the 12 patients. The maximal relative increase over baseline was 536%. Low doses of clozapine were sufficient to induce this effect. Within a 10-week period mean body weight, mean body mass index, mean fat mass and mean lean body mass all increased. Based on the results we suggest that in predisposed individuals clozapine induces an increased appetite; overeating and weight gain can ensue, which in turn underlie elevated leptin secretion.

Adipose Tissue↗
PubMed1997

Platelet serotonin and interleukin-1 beta after sleep deprivation and recovery sleep in humans.

Sleep deprivation (SD) represents a well-established therapy for major depression. Recent findings suggest that the antidepressive effects of sleep deprivation are mediated at least in part by pro-serotoninergic mechanisms. Furthermore, SD has been demonstrated to modify different host defense activities. We therefore investigated the serotonin (5-HT) content in platelets, platelet density distribution and 5-HT-induced IL-1 beta release from platelets in 10 healthy men before and after total SD (TSD) as well as after recovery sleep. Blood samples were drawn on 3 consecutive days at 7.00 h, 13.00 h, and 19.00 h, respectively. In addition, the psychophysiological parameters tiredness and wakefulness were assessed. After TSD the normal daily variation of IL-1 beta release with high morning levels and low evening levels was found to be significantly inverted. The release of IL-1 beta corresponded positively to the subjectively experienced tiredness of the probands. Analysis of platelet density distribution indicated a significant daily variation of low density platelets with low levels in the morning and high levels in the evening, which was absent after TSD. Our findings favour an increased pro-serotoninergic effect after TSD, which comprises respective variations of the host defense system, but is abolished by consecutive recovery sleep.

Adult↗
PubMed1997

Sleep in schizophrenia: a polysomnographic study on drug-naive patients.

A slow wave sleep (SWS) deficit and a shortened rapid eye movement (REM) sleep latency are commonly reported in schizophrenic patients. However, most of these patients have been off neuroleptic medication for only a short period of time. Therefore, the reported sleep alterations may be due to residual drug effects. We polysomnographically investigated 22 drug-naive patients with a schizophrenic disorder, paranoid type, and 20 normal controls. In addition, we assessed the ventricular brain ratio (VBR) by means of computed assisted tomography. Except for a prolonged sleep onset latency, increased wake time and decreased stage 2 sleep, the patients showed a sleep pattern, i.e., of SWS and REM sleep, comparable with that of controls. The VBR was increased in 71% of the patients but was not associated with the patients' clinical characteristics or their SWS and REM sleep patterns. Our results indicate that the commonly reported SWS and REM sleep changes in schizophrenia reflect the remnant of prior neuroleptic treatment rather than the pathophysiology of the disorder itself.

Adult↗
PubMed1997

Pre-morbid psychometric profile of subjects at high familial risk for affective disorder.

BACKGROUND: Recent observations indicate that a certain pre-morbid personality profile ('autonomic lability', i.e. elevated neuroticism, frequent somatic complaints and increased interpersonal sensitivity) appears to be a valid antecedent of major depression. However, most of these prospective studies used samples drawn from the general population, which limits the power of any observed differences between subjects who developed a depressive disorder during the follow-up period and those who did not. METHODS: We investigated the psychometric profile of 54 high-risk probands (aged between 18 years and 45 years) without a current or lifetime diagnosis of any psychiatric disorder, but who had first-degree relatives with an affective disorder according to DSM-III-R criteria. Twenty-two control probands, matched for age and gender and without any personal or family history of psychiatric disorders, served as the reference group. RESULTS: As a group, the high-risk probands scored higher than the controls on scales that assessed neuroticism, rigidity, depressive cognitions, vegetative lability and stress. With an individual-orientated approach (cluster analysis), 30 high-risk probands were identified as conspicuous, characterized by elevated rigidity and increased 'autonomic lability'. The remaining 24 high-risk probands showed a psychometric profile very similar to that of the controls. CONCLUSIONS: The present findings in 54 probands at high risk for affective disorders not only strongly underline the assumption that the personality trait 'autonomic lability' is a valid antecedent of at least major depression, but also add the personality trait 'rigidity' as a further and potential candidate for a true vulnerability marker for affective disorders.

Adolescent↗
PubMed1997

Perception of body size and body satisfaction in recovered anorexic women: comparison with restrained and unrestrained eaters.

The perception of body size, measured by three different methods, and body satisfaction were assessed in 23 formerly anorexic inpatients with an "intermediate" (n = 9) or a "good" outcome (n = 14) and compared with the data obtained from 21 restrained and 20 unrestrained eaters. Using the Kinaesthetic Size Estimation Apparatus, overestimation and uncertainty in the perception of body size became apparent in both groups of former patients. The other two methods, Video Distortion Technique and Image Marking Procedure, did not produce comparable results. There was only a trend towards higher scores on body dissatisfaction, as measured by the Body Shape Questionnaire, in the patients' groups in comparison with the group of unrestrained eaters, whereas the patients' scores on body dissatisfaction were quite similar to those of the restrained eaters. None of these measures discriminated between the two outcome categories of "intermediate" and "good.". These findings suggest that restoration of body weight, by itself, obviously does not cause a normalization of body experience in all its components in patients with anorexia nervosa.

Adolescent↗
PubMed1996

Dysregulation of the hypothalamic-pituitary-adrenocortical system in panic disorder.

The responsiveness of the hypothalamic-pituitary-adrenocortical (HPA) system was investigated with the combined dexamethasone-corticotropin-releasing hormone (DEX-CRH) challenge test in 13 patients with "pure" panic disorder. After DEX pretreatment, this group of patients had higher CRH-induced adrenocorticotrophic hormone (ACTH) and cortisol levels than the control group, but lower than a reference group of depressed patients. The panic disorder patients were also in a middle position in the ratio of suppressors to nonsuppressors on the dexamethasone suppression test (DST) and in the ratio of normal to abnormal results on the DEX-CRH test. Our results using the combined DEX-CRH test, which is known to be much more sensitive than the original DST, support the hypothesis that HPA system functioning is altered in panic disorder patients and that this dysregulation is directly involved in the pathogenesis of the disorder.

Adrenal Glands↗
PubMed1995

In quest of identifying vulnerability markers for psychiatric disorders by all-night polysomnography.

BACKGROUND: The persistence of a depressionlike sleep pattern in fully remitted depressed patients suggests that the pattern is a trait characteristic of sleep measurements. However, in the past, subjects have undergone investigation only after the onset of the disorder, and, therefore, the altered sleep pattern may merely represent a biological scar. METHODS: We polysomnographically investigated 54 healthy subjects who had no lifetime or current diagnosis of a psychiatric disorder but had at least one first-degree relative with major depression or a bipolar disorder and at least one further close relative with major depression, a bipolar disorder, or a schizophrenic disorder. Twenty unrelated control probands without a personal and family history of psychiatric disorders and 18 unrelated inpatients with major depression served as reference groups. Prior to investigation, all healthy subjects had been free of any prescription and nonprescription drug for at least 3 months. The depressed patients were free of drugs for at least 1 week. All subjects slept for 2 nights in the sleep research unit. The sleep of the second night was recorded and visually scored. RESULTS: Analysis of the individual sleep cycles in these subjects revealed both a reduced amount of slow wave sleep and increased rapid eye movement density in the first sleep cycle. Discriminant analysis showed that 10 subjects (18%) had sleep patterns similar to those of depressed patients. CONCLUSIONS: According to our observations, one fifth of the healthy subjects with a high genetic load for psychiatric disorders showed a conspicuous (depression-like) sleep pattern. The follow-up will determine whether this sleep pattern indeed represents a trait marker indicating vulnerability.

Adult↗
PubMed1995

Altered hypothalamic-pituitary-adrenocortical regulation in healthy subjects at high familial risk for affective disorders.

Altered negative feedback control of the hypothalamic-pituitary-adrenocortical (HPA) system is a frequent laboratory sign of major depression. It coincides with depressive episodes and partially reverses after recovery from psychopathology. Such an HPA disturbance in feedback control can be acquired as a result of stressful life experiences and be compounded by age or it can be genetically predetermined at all levels involved in fine-tuned neuroendocrine regulation. Major psychiatric disorders run in families and a high familial load for an affective illness therefore increases an individual's risk of becoming affected. We investigated whether the HPA feedback disturbance observed among patients with depression is present in otherwise healthy individuals who are at high risk for psychiatric disorders because they have a first-degree relative with an affective illness. Using rigid psychodiagnostic techniques, we screened 431 consecutively admitted patients with depression and identified 35 families with one or more high-risk probands (HRPs). The results of a combined dexamethasone/human corticotropin-releasing hormone (DEX-CRH) test showed that the group of dexamethasone-pretreated (1.5 mg; 23.00 h) HRPs released more cortisol after stimulation with human CRH (100 micrograms; 15.00 h the next day) than a control group (CPs), but less than a group of patients with an acute major depressive episode (DPs). The peak cortisol values were 146.1 +/- 147.7 nmol/l (mean +/- SD) (HRPs), 75.3 +/- 47.9 nmol/l (CPs) and 278.2 +/- 199.2 nmol/l (DPs), yielding significant (F = 9.66, p < 0.001) group differences, with values for HRPs vs. CPs and HRPs vs. DPs being significant at the 1% level (t test).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗