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E Grof

Publications and source records attributed to E Grof.

At least 37 records · Page 2Linked to original sources
PubMed1994

Lithium response and genetics of affective disorders.

The authors have carried out an investigation of psychiatric morbidity in families of patients who responded and failed to respond to long-term lithium treatment. The study included 121 probands with RDC primary affective disorders and 903 first-degree relatives and spouses. Seventy-one probands were responders and 50 were nonresponders to long-term lithium treatment. Extended to 20 years, the follow-up of patients and their families provided substantial information relevant for the diagnosis and reliable assessment of lithium response. The diagnoses were based on all available information, SADS-L interviews and RDC criteria. The principal statistical methods were survival analysis and Cox regression analysis. The results revealed a significantly higher frequency of bipolar disorder in the relatives of lithium responders (3.8% vs. 0%). Schizophrenia was more common in the families of nonresponders (2.4% vs. 0.3%). There were no significant differences in the rates of other psychiatric disorders. Both family history and the proband's diagnosis contribute independently to predicting response to long-term lithium.

Adult↗
PubMed1994

Mortality during initial and during later lithium treatment. A collaborative study by the International Group for the Study of Lithium-treated Patients.

We have previously shown that the mortality of patients with recurrent affective disorders in long-term lithium treatment is not higher than that of the general population. In the present study on 471 patients from Denmark and Germany, we examined mortality during the initial year of lithium treatment and during later lithium treatment. During initial lithium treatment, the total mortality was twice as high as in the general population (difference not significant) and the mortality due to suicide 16 times higher. During later lithium treatment, the mortality rates did not differ from those in the general population. Our results indicate that patients with frequent, often severe recurrences, those chosen for prophylactic lithium treatment, are at risk of high mortality, which then diminishes as the prophylactic action of the treatment takes effect.

Adult↗
PubMed1994

Mode of inheritance in families of patients with lithium-responsive affective disorders.

A better understanding of the role of genetic factors in affective disorders is likely to result from investigating more homogeneous populations. To achieve this goal, we have systematically studied patients who are excellent responders to long-term lithium treatment and their relatives. In the families of 71 such probands, we have analyzed the mode of inheritance by comparing the observed morbidity risks with the risks expected under different genetic models. The results demonstrate major-gene effects in the transmission of primary affective disorders; the polygenic model with sex-specific thresholds could be rejected. Discrimination between the autosomal and X-chromosome models was not possible, but the autosomal recessive model predicts more realistic, gender-specific frequencies of affective disorders in the general population. These results suggest that autosomal recessive inheritance deserves serious consideration in molecular genetic investigations.

Adult↗
PubMed1993

The challenge of predicting response to stabilising lithium treatment. The importance of patient selection.

Lithium treatment, an approach with well documented efficacy, has recently been losing its treatment value. Lithium continues working, however, for those patients for whom it was proven efficacious; that is, most patients with primary episodic affective disorders. Such responders to lithium prophylaxis can be reliably identified beforehand by a comprehensive clinical assessment. The explanation for the paradox of lithium's lost efficacy lies mostly in the educational bias against a comprehensive patient assessment, and in the shift in diagnostic fashion favouring affective disorders and the treatment methods associated with them in the clinicians' minds.

Depressive Disorder↗
PubMed1992

The effect of long-term lithium treatment on the mortality of patients with manic-depressive and schizoaffective illness.

Clinical research centers in Aarhus, Berlin, Hamilton and Vienna collected mortality data for 827 manic-depressive and schizoaffective patients given lithium treatment for more than 6 months. The average duration of the treatment was 81 months and the total time on lithium 5600 patient-years. For each patient, the mortality risk was calculated by entering the appropriate national life tables for the general population. The number of observed deaths was 44; the number of expected deaths was 49.7. The standardized mortality ratio, 0.89, did not differ significantly from 1.0. The mortality of manic-depressive patients is 2-3 times that of the general population. Our data show that the mortality of manic-depressive and schizoaffective patients given long-term lithium treatment does not differ significantly from that of the general population.

Adult↗
PubMed1991

Less frequent lithium administration and lower urine volume.

OBJECTIVE: This study was designed to determine whether patients maintained on a regimen of lithium on a once-per-day schedule have lower urine volumes than do patients receiving multiple doses per day. METHOD: This was a cross-sectional study of 85 patients from a lithium clinic who received different dose schedules. Patients were admitted to the hospital for measurement of lithium level, creatinine clearance, urine volume, and maximum osmolality. RESULTS: Multiple daily doses of lithium were associated with higher urine volumes. The dosing schedule, duration of lithium treatment, and daily dose of lithium did not affect maximum osmolality or creatinine clearance. CONCLUSIONS: Urine volume can be reduced by giving lithium once daily and/or by lowering the total daily dose. Lithium-induced polyuria seems to be related to extrarenal as well as to renal effects.

Depressive Disorder↗
PubMed1990

Varieties of lithium benefit.

Over the years much effort has gone into clarifying lithium's mechanism of action. It has been well-documented, and reviewed in the present symposium, that the effects of lithium on the human body are widespread, however it remains unclear which of the many effects is the one which mediates clinical benefit. One of the obstacles to progress has probably been an incomplete integration of clinical and laboratory approaches to the problem. In this paper we briefly summarize the main observations in the clinical dimension. The best-documented clinical effects of lithium have been mood stabilization, antimanic effects and antiaggressive action. Several other effects have, however, been observed and reported, some still controversial but all deserving our attention. We conclude that one can observe not one but several distinct, qualitatively separable benefits, with different clinical characteristics. It appears important that in any future laboratory search for the relevant mechanisms of action of lithium, we keep this clinical multiplicity in mind.

Affect↗
PubMed1989

Effect of chronic lithium on sensitivity to light in male and female bipolar patients.

1. Sensitivity to white light was quantified in euthymic bipolar male and female patients maintained on long term lithium therapy and age and sex matched unmedicated controls. 2. The Dark Adaptation Threshold procedure was used to assess sensitivity of both the cone and rod photoreceptors to short pulses of light. 3. Male and female controls did not differ in sensitivity to light. 4. Male patients in comparison to both controls and female patients evidenced reduced sensitivity to light during the cone and rod portion of the dark adaptation procedure. 5. Female patients did not differ from controls on sensitivity to light. 6. Using these and other published data the results were interpreted as suggesting that lithium reduces sensitivity to light during adaptation to dark.

Adaptation, Ocular↗
PubMed1988

The effect of lithium administration on LH response in healthy volunteers.

1. As part of a systematic investigation of the effects of lithium administration on neuroendocrine function we investigated the luteinizing hormone (LH) response to luteinizing hormone releasing hormone (LHRH) of healthy males. 2. In healthy volunteers after 3 weeks of therapeutic doses of lithium the LH response to LHRH was significantly increased in comparison with the responses prior to lithium administration. 3. An attempt is made to explain these findings by underlying neurotransmitter changes.

Adult↗
PubMed1988

Bipolar patients taking lithium have increased dark adaptation threshold compared with controls.

Recent epidemiological studies of mania suggest that admissions correlate with length of day and sunlight. As well, seasonal affective disorder--a depression occurring in winter, is reported to respond to light therapy and it has been proposed that supersensitivity to light is a trait-marker of manic-depressive illness. Dark adaptation threshold (D.A.T.)--a measure of night vision--was assessed in 19 euthymic manic-depressive patients stabilized on lithium, and in 19 drug-free healthy controls. The D.A.T. was significantly raised in the patients taking lithium. It is concluded that lithium induces subsensitivity to light.

Adult↗
PubMed1987

Lithium response and the sequence of episode polarities: preliminary report on a Hamilton sample.

This is a preliminary report on a study which replicated the finding of a significant relationship between the response to long-term lithium stabilization and the sequence of episode polarities (depressive/manic) in bipolar and schizoaffective (bipolar) patients. The lithium response and the clinical course data were assessed independently, in a blind manner, utilizing a data collection which has been gathered in earlier studies. There was a significant association between lithium response (stability achieved on long-term lithium treatment) and the sequence of episode polarities. The main determinant of this association was a close link between lithium response and the MDI sequence of episode polarities. The observed association may be explained in several ways: as an artifact; due to the exclusively antimanic effect of lithium; due to true psychobiological differences between mania and depression; as a result of the differences between bipolar type one and type two patients; and finally due to bipolar heterogeneity. Considering the data available to date the explanation via bipolar heterogeneity appears to be the most likely one.

Bipolar Disorder↗
PubMed1986

Effects of lithium administration on plasma catecholamines.

The mode of action of lithium in the treatment of bipolar affective disorder is unknown. Among its actions are effects on release and response to catecholamines in experimental animals. We have therefore examined its effect on peripheral catecholamines in man. After 3 weeks of administration of therapeutic doses of lithium carbonate, healthy volunteers showed a differential response of catecholamines to insulin stimulation. Although the response of plasma norepinephrine remained unchanged, epinephrine response was dramatically reduced. These findings provide additional evidence for the separate neural regulation of the adrenal medulla and sympathetic nerve endings. Further studies are necessary to determine whether these effects on peripheral epinephrine are paralleled by changes in central epinephrine.

Adult↗
PubMed1985

Investigations of melatonin secretion in man.

Overnight melatonin secretion shows substantial and significant intraindividual stability and large interindividual variation. Melatonin concentrations obtained between 1 and 5 a.m. significantly correlate with overall melatonin secretion (expressed as the area under the curve) while a single determination of serum melatonin does not adequately reflect the entire night secretion. Secretion correlates positively with "neuroendocrine responsiveness" (rating responses in other neuroendocrine challenge tests) and there is trend for negative correlation with age. In volunteers the administration of the usual therapeutic dose of lithium did not alter the overnight melatonin secretion. However, there was an elevation of isolated secretory values at the early morning timepoints. In comparison with volunteers, lithium administration tended to reduce the overnight melatonin secretion in bipolar patients, however, the difference did not reach statistical significance.

Adolescent↗
PubMed1984

Lithium effects on neuroendocrine function.

We studied growth hormone and prolactin responses to insulin hypoglycemia and TSH response to TRH in symptom-free bipolar patients and healthy controls. There were no significant differences in prolactin and growth hormone responses to hypoglycemia between stabilized bipolar patients and healthy controls, both tested medication-free. When lithium was administered to both groups, only bipolar patients showed a dramatic reduction in prolactin and growth hormone responses. Both bipolar patients in remission and healthy controls showed an increase of TSH response to TRH when treated with lithium in comparison with the testings before lithium administration. The subjects, both patients and volunteers, showed a comparable degree of hypoglycemia on and off lithium. The observed difference in responsiveness of bipolar patients warrants further systematic investigation and offers interesting possibilities for practical utilization.

Adolescent↗
PubMed1984

Effects of lithium, nortriptyline and dexamethasone on insulin sensitivity.

The effects of lithium, dexamethasone, nortriptyline and their combinations on insulin sensitivity, expressed as a drop of plasma glucose in response to insulin challenge, were investigated in healthy volunteers. Short-term (three weeks) lithium treatment did not appear to exert any influence on the insulin sensitivity. Dexamethasone administered alone (2 mg given 57 hours prior to the test) had no effect on the insulin sensitivity of drug-free healthy subjects. However, after three weeks of lithium treatment the dexamethasone premedication resulted in slight flattening of glucose response to insulin in the same persons. Nortriptyline administered for three weeks to healthy volunteers, pretreated with dexamethasone, increased insulin sensitivity. These findings may have clinical implications regarding the treatment of depressed diabetic patients, and may provide information about the regulation of insulin sensitivity.

Adult↗
PubMed1983

Neuroendocrine strategies in affective disorders.

Neuroendocrine strategies in affective disorders have explored both resting values of hormones and hormonal responses to stimuli such as hypoglycemia, TRH, LHRH, dexamethasone, methadone and morphine. The abnormalities established to date have involved growth hormone, cortisol and TSH responses in particular. Prolactin has not been investigated to the same extent. We therefore describe several prolactin studies exemplifying selected neuroendocrine strategies. Our studies of prolactin responses included acute cases of either primary or secondary depression, stabilized bipolar patients, and healthy controls both off and on lithium. We found prolactin response to hypoglycemia significantly reduced in primary but not secondary depressions. Lithium administration led to flattened prolactin responses to hypoglycemia in stabilized bipolar patients but not in healthy controls. The flattened response in patients was observed already after 3 weeks of lithium, and remained flattened after years of treatment. The findings suggest a greater degree of prolactin response reduction in those patients showing most pronounced stability on lithium treatment.

Adjustment Disorders↗