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Biomedical subjects

C J Lauer

Publications and source records attributed to C J Lauer.

At least 19 recordsLinked to original sources
PubMed2005

The Munich vulnerability study on affective disorders: premorbid neuroendocrine profile of affected high-risk probands.

One of the most characteristic alterations in depression is a disturbed regulation of the hypothalamic-pituitary-adrenocortical (HPA) system. A function test combining the pre-treatment of 1.5 mg dexamethasone (DEX) with a challenge of 100 microg corticotropin-releasing hormone (CRH) reveals a pathological increase in the adrenocorticotropin and cortisol release in patients with major depression. These changes partially persist after successful treatment with remission and therefore, might represent trait or vulnerability markers. To further address this question, we were investigating the premorbid neuroendocrine profile of 74 healthy high-risk probands (HRPs) with a positive family history for affective disorders. The aim was to identify premorbid vulnerability factors. During the observation period, 19 HRPs developed an affective disorder. Their premorbid DEX/CRH test results were compared with 19 age- and sex matched controls. No significant differences could be observed between these two groups. Our results suggest that a dysregulated HPA system indicated by this function test can rather be regarded as a neurobiological scar developing during the course of affective disorders.

Adult↗
PubMed2004

The Munich vulnerability study on affective disorders: premorbid psychometric profile of affected individuals.

OBJECTIVE: We conducted a longitudinal high-risk study to identify psychometric vulnerability markers for affective disorders. METHOD: We examined 82 healthy subjects [high-risk probands (HRPs)] with at least one first-degree relative suffering from an affective disorder. The premorbid psychometric profile of 20 HRPs who developed a psychiatric disorder during follow-up was compared with the profile of control subjects without personal and family history of psychiatric disorders matched for age and gender. RESULTS: Somatization, complaints (vegetative lability), and perception of strain are increased in HRPs who developed a psychiatric disorder. These alterations were not influenced by the time interval until the onset of the disorder. CONCLUSION: The premorbid psychometric profile in subjects at high risk for affective disorders is characterized by somatization, complaints, and elevated perception of strain. Together with previous findings our results suggest that these alterations can be regarded as potential vulnerability markers for affective disorders.

Adaptation, Psychological↗
PubMed2001

Patterns of response to repeated total sleep deprivations in depression.

BACKGROUND: Patterns of response and nonresponse in repeated sleep deprivation (SD) are of both clinical and scientific interest; as yet, studies have yielded inconsistent results. METHODS: Eighteen inpatients suffering from a major depression were subjected to a series of six scheduled total sleep deprivations within 3 weeks; 12 of them completed the whole protocol. All were under a constant antidepressant medication with amitriptyline. SD effects were measured using observer and self rating scales. RESULTS: Each single SD led to a significant improvement. Of the 12 patients who completed the protocol, seven were classified as responders at endpoint (i.e., 1 week after the sixth TSD). The majority of patients exhibited a pattern of responses and nonresponses randomly distributed over time. There was no temporal trend. The initial effect did not predict the average response to the following SDs. LIMITATIONS: One third of patients dropped out before completing the protocol which limits the scope of the study. CONCLUSIONS: Response to a single SD is not generalizable on a series of following SDs in an individual. The mechanism of action of SD does probably not involve mechanisms subjected to habituation or sensitization.

Amitriptyline↗
PubMed2001

Neuroendocrine, polysomnographic and psychometric observations in healthy subjects at high familial risk for affective disorders: the current state of the 'Munich vulnerability study'.

The present article summarizes the main results of the cross-sectional part of the 'Munich Vulnerability Study' in which healthy first-degree relatives of patients with an affective disorder were investigated by assessing their neuroendocrine, polysomnographic and psychometric status. As patients with an acute episode of a major depression, the group of the healthy relatives exhibited signs of a hyperactive hypothalamic-pituitary-adrenocortical system verified by the combined dexamethasone corticotropin-releasing hormone (DEX/CRH) test, as well as a slow wave sleep deficit in the first sleep cycle and an increased amount of rapid eye movements during REM sleep. The psychometric profile of the healthy relatives was characterised by elevated scores on the scales measuring 'Rigidity' and 'Autonomic Lability'. On a single-case level, 32% of the healthy first-degree relatives of patients with an affective disorder exhibited 'depression-like' features or conspicuous findings in at least two of the three (i.e. neuroendocrine, polysomnographic, psychometric) areas assessed. Whether the relatives with the neurobiological and psychometric abnormalities we identified have a higher risk for developing an affective disorder than those without has to be answered by the still ongoing prospective part of the study.

Adolescent↗
PubMed2000

Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo.

Schizophrenia is a major psychiatric disease, which affects the centre of the personality, with severe problems of perception, cognition as well as affective and social behaviour. In cerebrospinal fluid of drug-free schizophrenic patients, a significant decrease in the level of total glutathione (GSH) by 27% (P<0.05) was observed as compared to controls, in keeping with the reported reduced level of its metabolite gamma-glutamylglutamine. With a new non-invasive proton magnetic resonance spectroscopy methodology, GSH level in medial prefrontal cortex of schizophrenic patients was found to be 52% (P = 0.0012) lower than in controls. GSH plays a fundamental role in protecting cells from damage by reactive oxygen species generated among others by the metabolism of dopamine. A deficit in GSH would lead to degenerative processes in the surrounding of dopaminergic terminals resulting in loss of connectivity. GSH also potentiates the N-methyl-D-aspartate (NMDA) receptor response to glutamate, an effect presumably reduced by a GSH deficit, leading to a situation similar to the application of phencyclidine (PCP). Thus, a GSH hypothesis might integrate many established biological aspects of schizophrenia.

Adolescent↗
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

Sleep-endocrine effects of mifepristone and megestrol acetate in healthy men.

Administration of steroid hormones was demonstrated to modulate the sleep electroencephalogram (EEG) and sleep-associated hormonal secretion in specific ways. The present study was conducted to compare the effects of mifepristone (Mif), a mixed glucocorticoid (GR) and progesterone receptor (PR) antagonist, and megestrol acetate (Meg), a PR agonist. Nine healthy men were pretreated with either placebo or 200 mg Mif or 320 mg Meg, or a combination of both. Changes in plasma adrenocorticotropic hormone (ACTH), cortisol, and growth hormone concentrations were registered every 30 min; sleep EEG recordings were obtained continuously. Administration of Mif increased the morning plasma ACTH and cortisol surges, whereas Meg had the opposite effect. Growth hormone secretion was lowered by Mif pretreatment and enhanced by Meg. Simultaneous administration of both compounds led to largely compensated effects. The sleep EEG changes induced by Mif were a slight increase in the time awake and a delayed onset of slow-wave sleep. Meg led to a reduction of rapid-eye-movement sleep. Simultaneous administration of Mif and Meg showed a synergism in increasing time awake and shallow sleep: it therefore may be concluded that the sleep EEG effects are mediated by an interaction of GR and PR in unknown mechanisms.

Adrenocorticotropic Hormone↗
PubMed1997

REM sleep disinhibition at sleep onset: a comparison between narcolepsy and depression.

Shortened REM latency and increased REM density are frequently observed in both narcolepsy and depression, suggesting a common mechanism of REM sleep disinhibition in these disorders. We compared night sleep recordings of 24 depressive and 24 narcoleptic patients. The amount of REM sleep and REM density did not differ between the patient groups; however, REM latency distributions differed significantly. Whereas in narcoleptic patients REM episodes started either immediately at sleep onset or following at least 60 min of non-REM sleep, in depressives two thirds of REM latencies were in the range from 1 to 60 min. In narcoleptic patients, short as compared to long REM latencies were associated with longer total sleep time, greater sleep efficiency, reduced amounts of wakefulness, and increased amounts of slow-wave sleep. In depressive subjects the reverse pattern was seen. We conclude that a common mechanism of REM sleep disinhibition in narcolepsy and depression is very unlikely.

Adult↗
PubMed1997

Effects of clozapine on sleep: a longitudinal study.

Polysomnographic studies on the effects of clozapine, an atypical antipsychotic agent with strong sedative properties, on night sleep report inconsistent results. Most of these studies did not include baseline recordings and were not controlled for clozapine-induced fever, which is known to alter nocturnal sleep. We conducted a 2-week longitudinal polysomnographic investigation in 10 long-term drug-free schizophrenic patients prior to and at the end of the first and second weeks of clozapine treatment. Rectal temperature was measured daily and patients with fever (> 37.9 degrees C) were excluded. Clozapine significantly improved sleep continuity. In addition, non-rapid eye movement (NREM) sleep and in particular stage 2 sleep increased significantly, while the amounts of stage 4 and slow-wave sleep decreased significantly. Clozapine increased significantly REM density, but it did not affect the amount of REM sleep. We conclude that in patients who do not experience clozapine-induced fever, clozapine has strong sleep consolidating effects resulting from an increase in stage 2 NREM 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↗
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

[Sleep disorders in chronic pain and generalized tendomyopathy].

Patients with a chronic pain syndrome often suffer from sleep disturbance. As both symptoms are frequent in the fibromyalgia syndrome, these patients in particular have been examined in this regard. No clear polysomnographic evaluation of the subjectively experienced sleep disturbance in these patients has been done so far. Therefore, we recorded the sleep EEG of 13 patients with a fibromyalgia syndrome in order to objectively characterize their sleep. Furthermore, we were interested in the relationship between the sleep alterations and pain intensity. In a subsequent placebo-controlled study based on pathophysiological considerations, we attempted to beneficially influence the sleep disturbance and the pain syndrome with the 5-HT2-receptor antagonist ketanserine, as this system has been proved to play a major role in the regulation of both sleep and pain. The results of our studies in patients with fibromyalgia show that the alteration of sleep is mainly characterized by a disturbance of sleep continuity associated with the experience of pain intensity. The application of 5-HT-receptor-antagonists may be a new strategy for the common treatment of sleep disturbance and the pain syndrome which needs to be evaluated in further studies. Duration of the patients' illness seems to be a predictive value in relation to intensity of the symptoms and the therapeutic outcome.

Adult↗
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↗