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Biomedical subjects

E Mellerup

Publications and source records attributed to E Mellerup.

16 recordsLinked to original sources

No association between the -399 C > T polymorphism of the neuropeptide Y gene and schizophrenia, unipolar depression or panic disorder in a Danish population.

OBJECTIVE: A polymorphism in the promoter region of the NPY gene at position -399 C > T was recently reported to be associated with schizophrenia in a Japanese population and with treatment refractory unipolar depression in a Swedish population. The objective of this study was to investigate potential associations between the polymorphism and three psychiatric disorders in a Danish population. METHOD: We investigated the occurrence of the polymorphism in patients with schizophrenia (n = 291), unipolar depression (n = 256) and panic disorder (n = 142) compared with controls (n = 716). RESULTS: We detected the polymorphism -399 C > T at a frequency of 48% in controls. No significant differences were found between genotype or allele frequencies in controls vs. the patient groups. CONCLUSION: The lack of association between the -399 C > T polymorphism and schizophrenia, unipolar depression or panic disorder, respectively, suggests that the polymorphism is not involved in the etiology of these disorders in the Danish population.

Adult↗

Platelet serotonin transporter in stroke patients.

OBJECTIVES: Post-stroke depression can be treated with serotonin transport inhibitors suggesting a role for the serotonin system in these patients. The number of platelet serotonin transporters in stroke patients and in control subjects have been measured in this study. MATERIAL AND METHODS: Newly admitted stroke patients who did develop or who did not develop a post-stroke depression, non-acute patients who previously had had a stroke and control subjects were compared. The number of platelet serotonin transporters was analysed by ligand binding methodology. RESULTS: The number of platelet serotonin transporters was low shortly after a stroke compared with normal subjects; no difference was found between the stroke patients who developed a post-stroke depression and those who did not. CONCLUSION: A low number of platelet serotonin transporters may be a non-specific state marker for a condition as acute stroke.

Acute Disease↗

Platelet serotonin transporters and the transporter gene in control subjects, unipolar patients and bipolar patients.

OBJECTIVE: The purpose of the present study was to relate the number of platelet serotonin transporters in unipolar and bipolar patients and in control subjects to two polymorphisms in the serotonin transporter gene: a VNTR in intron 2 and a deletion/insertion in the promoter region. METHOD: Density of platelet serotonin transporters was determined by radioligand binding analysis. Genotyping was performed by PCR amplification of polymorphic regions followed by size determination of the obtained fragments. RESULTS: The control subjects and the two groups of patients were similar with respect to the genotype and allele distribution belonging to the two polymorphisms in the serotonin transporter gene for. An interaction between status (control, unipolar- or bipolar patient) and VNTR genotype regarding the number of platelet serotonin transporters was observed; unipolar patients with the genotype 12/10 had more platelet serotonin transporters than bipolar patients and controls with this genotype. No association related to the polymorphism was found in the promoter region of the serotonin transporter gene. CONCLUSION: An association was observed between the polymorphism in intron 2 of the serotonin transporter gene and the number of platelet serotonin transporters. Unipolar patients with a particular genotype had more platelet serotonin transporters than the corresponding controls and bipolar patients.

Adult↗

Prophylactic efficacy of lithium administered every second day: a WHO multicentre study.

OBJECTIVES: To study the prophylactic efficacy of lithium administered every second day to patients with bipolar disorder or recurrent unipolar depressive disorder. METHODS: The study was carried out as a WHO multicentre study in five different psychiatric clinics: Russia (Moscow), Canada (Montreal), India (Lucknow), Germany (Munich) and South Korea (Pusan), with the lithium tablets being supplied from Denmark (Copenhagen). Participation in the study was conditional on the patient having been in prophylactic lithium treatment for the preceding 2-year period and having been free of depressive or manic phases during the preceding 6 months. After a 2-month baseline period during which lithium was administered every day, the treatment was changed to lithium intake every second day, this regimen in most cases being continued for 22 months. RESULTS: Forty-seven patients, 42 with a diagnosis of bipolar disorder and five with a diagnosis of recurrent unipolar depressive disorder, participated in the study. The number of patients from each centre ranged from six to 11. The mean lithium dose every second day was 36 mmol lithium, leading to a mean 12-h standard serum lithium concentration during the last month of treatment at 0.78+/-0.16 mmol/L. Lithium intake every second day was effective in 38 out of 47 patients. The remaining nine patients had recurrences, a number not differing from the 16 patients in the same group of 47 patients who, during the 2-year period preceding the study, had recurrences. The mean 12-h standard serum lithium concentration was lower in the patients who had recurrences than in those who stayed euthymic. The results suggest that to be effective when administered every second day, lithium must be given in a dose leading to a 12-h standard serum lithium concentration at 0.8 mmol/L or above. CONCLUSIONS: In the dose administered, lithium intake every second day was as effective as lithium intake every day. The amount and severity of lithium-related side effects were apparently not influenced by the change to lithium intake every second day.

Adult↗

Non-acetylcholine displaceable 3[H]epibatidine binding in the rat brain.

Using autoradiography two types of 3[H]epibatidine binding in rat brain was found, the by far most widespread was nicotine displaceable, and represented nicotinic cholinergic receptors, probably the two subtypes alpha4beta2 and alpha3beta4. Using acetylcholine and nicotine in concentrations able to displace 3[H]epibatidine from the alpha4beta2 and alpha3beta4 subunits, in a few brain structures a non-acetylcholine and non-nicotine displaceable 3[H]epibatidine binding was found. The binding was almost exclusively localised to the medial and lateral habenula, interpeduncular nucleus and pineal gland; at 0.1 nM 3[H]epibatidine it represented about 40% of the total 3[H]epibatidine binding. A literature search directed at neurotransmitters in habenula did not demonstrate any neurotransmitter with this anatomical distribution in the brain, suggesting that the non-acetylcholine displaceable 3[H]epibatidine binding represents a binding site, not previously described.

Acetylcholine↗

Prevalence of winter depression in Denmark.

An unselected cohort of 3556 subjects in Copenhagen was asked to complete the Seasonal Pattern Assessment Questionnaire (SPAQ) for estimating the presence of seasonal affective disorders (SAD or winter depression). Completed questionnaires were received from 1794 subjects in total. About 12% of the respondents had a Global Seasonality Score (GSS) high enough to indicate the presence of SAD. Among those respondents without SAD, women and younger people were found to be much more sensitive to seasonal and weather changes than men and older people, respectively.

Adult↗

The influence of climate on development of winter depression.

126 patients suffering from winter depression participated in the study. Every second week patients completed the 13 item Beck Depression Inventory (BDI) in the period September to May in the years 1991 to 1994. Local weather data from this period were obtained from the Meteorological Institute, Copenhagen. No significant correlation was found between score on BDI and cloud cover, rainfall or atmospheric pressure. A significant correlation was found between score on BDI and minutes of sunshine, global radiation, length of daylight and temperature. This is in accordance with the theory, that lack of light is a contributing factor for development of winter depression.

Adult↗

Brain 5-HT1A, 5-HT1D, and 5-HT2 receptors in suicide victims.

We report on 5-HT1A, 5-HT1D, and 5-HT2 binding sites in 23 control subjects and 18 suicide victims subdivided according to the method of death and the previous existence of depressive symptoms. No difference in maximum binding (Bmax) or binding affinity (Kd) was found between the control and overall suicide groups for the binding sites studied. The drug overdose subgroup showed, however, a significant decrease in the 5-HT1A binding affinity, probably explained by the higher sensitivity of this binding site to the acute administration of tricyclic antidepressants. A significant decrease in 5-HT1D binding affinity was also found in the depressed suicides, together with a significant decrease in the number of 5-HT1D binding sites in the nondepressed suicides. Further studies should be carried out on the 5-HT1D binding site as it might represent a new tool in the understanding of the depressive illness.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Effect of aging in human cortical pre- and postsynaptic serotonin binding sites.

5-HT1A, 5-HT1D, 5-HT2 binding sites and affinity and 5-HT uptake sites were simultaneously determined in frontal cortex samples from 23 control subjects, aged 16-75 years. A significant reduction in the number of 5-HT1D and 5-HT2 binding sites was found with regard to age, together with a significant decrease in the 5-HT2 binding affinity. It is suggested that the total 5-HT1 age-related loss described in previous studies could be ascribed to the 5-HT2 subtype. Furthermore, aging does not seem to be associated with a reduced cortical serotonergic innervation, as indicated by the stability of the [3H]paroxetine-labeled 5-HT uptake sites.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Serotonin receptors in the brain of rats treated chronically with imipramine or RU24969: support for the 5-HT1B receptor being a 5-HT autoreceptor.

Rats were treated by intraperitoneal injection for four weeks with either RU24969, a 5-HT1B and 5-HT1A agonist or imipramine, a 5-HT uptake inhibitor. Pre- and postsynaptic 5-HT receptors were measured to compare the effect of direct or indirect stimulation of the 5-HT autoreceptor (5-HT1B receptor). The 5-HT transport protein (5-HT uptake site), labelled with [3H]paroxetine, was unaffected after treatment with either one of the drugs. The density of 5-HT2 receptors, labelled with [3H]ketanserin, we found increased after treatment with RU24969 (Bmax = 161 fmol/mg protein) and decreased after treatment with imipramine (Bmax = 109 fmol/mg protein) as compared with control rats (Bmax = 134 fmol/mg protein). The 5-HT1B receptor was found decreased both by the imipramine treatment (Bmax = 106 fmol/mg protein) and the treatment with RU24969 (Bmax = 105 fmol/mg protein), compared with control rats (Bmax = 130 fmol/mg protein). The 5-HT1A receptor was found to be decreased after treatment with RU24969 (control: Bmax = 62 fmol/mg protein; RU24969-treated: 49 fmol/mg protein), but unchanged after treatment with imipramine (Bmax = 58 fmol/mg protein). These results correspond to what could be expected, if the 5-HT1B receptor is the 5-HT autoreceptor.

Animals↗

Evaluation of disability, incapacity and environmental status scales in multiple sclerosis.

From the Danish Multiple Sclerosis (MS) population a representative sample of 249 patients with a clinically definite diagnosis of MS has been tested by use of the Functional System Scale and Disability Status Scale of Kurtzke and the Incapacity and Environmental Status Scales of the IFMSS. Validity and reliability of the items and the properties of summed scales have been estimated. A statistical evaluation showed that generally the Incapacity and the Environmental Status Scales worked well. Problems encountered with the use of the Incapacity scale are mentioned and on statistical grounds a proposal of an incapacity scale with fewer items is presented.

Activities of Daily Living↗

Long-term transfer-factor treatment for multiple sclerosis.

In groups of 16 patients with multiple sclerosis, 13 months' double-blind treatment with transfer factor from random normal donors differed from placebo treatment only in producing a temporary restoration of lymphocyte reactivity to measles virus antigen, and did not arrest the degeneration of nerve tissue.

Adult↗