Genome-wide association study on bipolar disorder in the Bulgarian population.

Bipolar disorder is a severe psychiatric disorder influenced by environmental and genetic factors. Genetic studies have implicated many variants in the disease's etiology but only few have been successfully replicated. We conducted a genome-wide association study (GWAS) on bipolar disorder in the Bulgarian population followed by a replication study of the top 100 single nucleotide polymorphisms (SNPs) showing the smallest P values. The GWAS was performed on 188 bipolar disorder patients and 376 control subjects genotyped on the Illumina 550 platform. The replication study was conducted on 122 patients and 328 controls. Although our study did not show any association P value that achieved genome-wide significance, and none of the top 100 SNPs reached the Bonferroni-corrected P value in the replication study, the plausible involvement of some variants cannot be entirely discarded. Three polymorphisms, rs8099939 [P = 2.12 × 10(-6), odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.43-2.67] in GRIK5, rs6122972 (P = 3.11 × 10(-6), OR = 2.02, 95% CI = 1.46-2.80) in PARD6B and rs2289700 (P = 9.14 × 10(-6), OR = 2.13, 95% CI = 1.53-2.95) in CTSH remained associated at a similar level after Mantel-Haenszel test for combining the results from the genome-wide and replication studies. A modest association was also detected for SNP rs1012053 (GWAS P = 4.50 × 10(-2)) in DGKH, which has already been reported as the most significant variant in a previous genome-wide scan on bipolar disorder. However, further studies using larger datasets are needed to identify variants with smaller effects that contribute to the risk of bipolar disorder.

Temperature and pulse chronomes in patients with neurotic and affective disorders treated with some antidepressants and tranquillizers.

The axillary temperature and the pulse rate for 1 minute were taken hourly from 7:00 a.m. to 11:00 p.m. in 65 physically and mentally healthy individuals and in 365 inpatients with neuroses and affective disorders. In approximately one fifth of the sample these measures were taken in the night hours too. Some of them were examined before and after treatment with antidepressants (imipramine, amitriptyline, maprotiline, trimipramine, clomipramine, viloxazine) and tranquillizers (benzodiazepines). The total number of cases adds up to 615 patients. The data were analyzed with the method of F. Halberg for cosinor-analysis (cosinor-rhythmometry). Our findings indicate that the temperature and pulse mesors in patients with neuroses and affective disorders before treatment are higher than in healthy individuals. In both patients groups (neuroses and affective disorders) these psychotropic drugs produce desynchronosis between pulse and temperature. The distribution by diagnoses show that the same antidepressant can transform the pulse and temperature chronome in different ways. This is due, on the one hand, to the different etiology of the disease process in each patient and, on the other hand, to the external agent (the drug).

Interrelationship between cortisol levels in plasma and the circadian rhythm of temperature, pulse and blood pressure in depressed patients with good and disturbed sleep.

Cortisol levels in plasma were measured in 122 depressed patients at 8:00 a.m. and 11:00 p.m. on the first day and at 8:00 a.m., 4:00 p.m. and 11:00 p.m. on the second day after oral administration of dexamethasone. Some of the patients were studied before and after medication so the total number of plasma cortisol level examinations came to 173. All patients had to describe the state of their sleep with the help of a questionnaire. The temperature and pulse of 92 patients were taken hourly from 7:00 a.m. to 11:11 p.m. for two consecutive days where the total measurements came to 34. 27 patients out of these had their blood pressure taken. A control group of 65 healthy persons without somatic and psychic disorders was tested at the same time. We found out that plasma cortisol levels in patients with disturbed sleep were higher compared to the group with good sleep. It was also noticed that younger patients and males had higher plasma cortisol level. Patients with disturbed sleep had higher Mesors (midline-estimating statistic of rhythm, 'Mesor') of temperature, pulse and systolic blood pressure. Healthy persons had significantly lower pulse Mesors compared to patients with good and disturbed sleep. The percentage distribution of suppressors and nonsuppressors showed no differences by sex, age and sleep disturbances.

The blood pressure and heart rate chronome of centenarians.

Rhythm characteristics of blood pressure (BP) and heart rate (Hr) of 11 healthy centenarians and 66 medical students are described. Each subject ambulatorily monitored measured BP and HR around the clock at 15-min intervals for 48 hours. Least-squares spectra were obtained by the fit of cosine curves (cosinor) and compared between the two populations. Confounding by geographic differences seems to be ruled out by comparisons with results from international data bases. A shift in prominence from the circadian domain to higher frequency harmonics was found for the BP but not for the HR of centenarians. In clinically mostly healthy centenarians, markers of primary aging may consist of a relatively low circadian BP and HR amplitude and a tendency toward internal and external desynchronization. Whether these chronobiologic changes with age are desirable, indifferent or undesirable can now be elucidated by outcome studies, in the light of the reference standards provided herein.