Agnieszka Permoda-Osip

Single ketamine infusion in bipolar depression resistant to antidepressants: are neurotrophins involved?

We investigated serum brain‐derived neurotrophin factor (BDNF), nerve growth factor (NGF), neurotrophin‐3 (NTF3), neurotrophin‐4 (NTF4) and the glial‐derived neurotrophic factor (GDNF), in relation to ketamine efficacy, in bipolar depressed patients resistant to treatment with antidepressants.

Response to prophylactic lithium in bipolar disorder may be associated with a preservation of executive cognitive functions

We assessed performance on the Wisconsin Card Sorting Test (WCST), measuring executive functions, in 30 patients showing different prophylactic effect of lithium (excellent lithium responders-ER, partial responders-PR and non-responders-NR), and in fifty persons of their offspring (12 of ER, 26 of PR, and 12 of NR). Age- and gender head-to-head matched population consisted of 30 subjects for lithium group and 50 subjects for the offspring of lithium patients. In lithium patients, NR had significantly worse results compared to the remaining groups and to control subjects on perseverative errors (WCST-P) and conceptual responses (WCST-%conc). No differences were observed in the offspring of patients with different effect of lithium, however, they showed an impairment on WCST-P and WCST-%conc compared to matched healthy controls. Therefore, the favorable effect of lithium prophylaxis may be associated with a preservation of executive cognitive functions and the offspring of bipolar patients shows an impairment of such functions.

Clinical and pathogenic aspects of candidate genes for lithium prophylactic efficacy

A number of candidate genes for lithium prophylactic efficacy have been proposed, some of them being also associated with a predisposition to bipolar illness. The aim of the present study was to investigate a possible association between polymorphisms of 14 common genes with the quality of prophylactic lithium response in patients with bipolar mood disorder, in relation to the putative role of these genes in the pathogenesis of this disorder. Some association with lithium prophylactic efficacy was found for the polymorphisms of 5HTT, DRD1, COMT, BDNF and FYN genes, but not for 5HT2A, 5HT2C, DRD2, DRD3, DRD4, GSK-3, NTRK2, GRIN2B and MMP-9. Possible aspects of these genes with regard to the mechanism of lithium activity and pathogenesis of bipolar mood disorder are discussed.

Hyperhomocysteinemia in bipolar depression: clinical and biochemical correlates.

Background: Depression may be associated with elevated homocysteine (HCY) levels. Procedures aiming at its decrease, i.e. supplementation with folic acid or vitamin B12, have antidepressant effect. Both depression and elevated HCY can increase cardiovascular risk. In this study, clinical and biochemical factors, including markers of endothelial function, in relation to hyperhomocysteinemia, in patients with bipolar depression during acute episode were studied. Method: One hundred and twelve patients (24 male, 88 female), aged 20-78 (mean 51 ± 14 years), with depressive episode in the course of bipolar mood disorder have been included. The assays were made of serum concentrations of HCY, vitamin B12, folic acid as well as markers of endothelial function such as E-selectin and intracellular adhesion molecule-1 (ICAM-1). Results: Hyperhomocysteinemia (>15 mM) was found in 50 patients (45%), significantly more frequently in male (67%) than in female subjects (39%). Female patients with hyperhomocysteinemia were significantly older than the remaining ones. A significant inverse correlation between HCY level and concentration of folic acid and vitamin B12 as well as with E-selectin and ICAM-1 was observed. Conclusion: The results point to a significant prevalence of hyperhomocysteinemia in bipolar depressed patients during an acute episode. They also corroborate the correlation between increased concentration of HCY and lower level of vitamin B12 and folic acid. An unexpected finding of negative correlation of HCY level with markers of endothelial functions in such patients is discussed in view of current concepts of the role of HCY in various conditions.

Single ketamine infusion and neurocognitive performance in bipolar depression.

We estimated neurocognitive performance using the trail making test (TMT) and the Stroop color-word interference test before, and on the 3(rd) day after a single infusion of ketamine, in 18 bipolar depressed patients receiving mood-stabilizing drugs. The performance on all tests significantly improved on the 3(rd) day after ketamine infusion which correlated positively with baseline intensity of neuropsychological impairment and was not associated either with baseline intensity of depression or reduction of depressive symptoms after 3 or 7 days. The results suggest that in such population of patients, single ketamine infusion may improve neuropsychological performance independently of antidepressant effect.

Homocysteine and cognitive functions in bipolar depression

AIM The aim of the study was to evaluate a relationship between concentrations of hoocysteine (HCY), vitamin B12 and folic acid and disturbances of cognitive functions during acute episode of bipolar depression. METHODS 116 patients were studied (93 women, 23 men), aged 20-78 (mean 51±13) years during acute episode of bipolar depression. Depression was evaluated by the 17-item Hamiltons Depression Rating Scale (HDRS). The following tests measuring cognitive functions were applied: Trail Making Test, Wisconsin Card Sorting Test, Stroop Test and Wechsler Adult Intelligence Scale-Revised. In all patients, the measurements of serum homocysteine, vitamin B12 and folic acid were carried out. RESULTS Hyperhomocystemia (HCY>15μM/l) was detected in 41 patients (35%), more frequently in men (52%) than in women (31%). Patients with hyperhomocysteinemia achieved worse results in sub-tests of WAIS-R (verbal understanding and perceptional organization). In men, negative correlation was found between HCY concentration and number of errors in Stroop Test, and WCST (total errors and non-perseverative errors). In women with bipolar disorder, type II, negative correlation between HCY concentration and time of Stroop Test, and between vitamin B12 concentration and number of errors in Stroop Test, were demonstrated. In the whole group and in men, there was positive correlation between higher folic acid concentration and the number of errors in Stroop Test. CONCLUSIONS The results obtained show higher HCY concentration in considerable proportion of patients with bipolar depression, especially in men. They also confirm a connect between high homocysteine concentration and worse performance in some neuropsychological tests. Such relationship was more marked in men.

Kidney, thyroid and other organ functions after 40 years or more of lithium therapy: a case series of five patients.

We present the cases of five patients (two men aged 64 years and 79 years) and three women (aged 64 years, 65 years and 75 years) who have received lithium treatment for 40–45 years, with particular regard to kidney and thyroid functions, hypercalcaemia and cognition, in the context of disease course and overall functioning. Lithium was initiated in the early phase of the illness (in three patients within the first 2 years). In four patients, lithium concentration was between 0.60 and 0.65 mmol/l and in one patient, between 0.7 and 0.8 mmol/l. Four were very good lithium responders. One man had stage 3 chronic kidney disease, and the other stage 2/3 chronic kidney disease. All three women had asymptomatic stage 2 chronic kidney disease. One woman had severe thyroid dysfunction (Hashimoto’s disease) with extremely high levels of antithyroid peroxidase antibodies and antithyroglobulin antibodies and was receiving thyroxine. Serum calcium levels were normal or borderline in all five patients, and most cognitive functions were comparable to healthy persons of similar gender, age and years of education. All the patients were professionally active until 55–65 years and their family and social functioning were satisfactory. It was concluded that, in good lithium responders, ultra-long-term treatment with lithium enables good professional and psychosocial functioning, and the possible somatic side effects are manageable.

Are genes connected with homocysteine metabolism associated with bipolar disorder

Background: Increased levels of homocysteine have been observed in various psychiatric disorders, among them in schizophrenia, depression and bipolar mood disorder. Of the genes connected with homocysteine metabolism, some studies have found an association between polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene and bipolar disorder. The aim of this study was to investigate a possible association between 5 polymorphisms of 4 genes coding enzymes of homocysteine metabolism and bipolar disorder. Method: A total of 120 patients with bipolar disorder (24 male, 96 female) and 167 subjects from the general population (81 male, 86 female) were included in the study. Genotyping was performed for the C677T (rs1801133) and A1298C (rs1801131) polymorphisms of the MTHFR gene, for the T833C polymorphism (rs5742905) of the cystathionine-β-synthase (CBS) gene, for the A2756G polymorphism (rs1805087) of the homocysteine methyltransferase gene, and for the A66G polymorphism (rs1801394) of the methionine synthase reductase (MTRR) gene. Results: An association with bipolar disorder was found for the T833C polymorphism (rs5742905) of the CBS gene. However, in the patient sample, the genotypes of this polymorphism were not in Hardy-Weinberg equilibrium. No relationship to bipolar disorder was obtained for the remaining polymorphisms studied. Conclusions: These results are the first suggesting a possible association between T833C polymorphism (rs5742905) of the CBS gene and bipolar disorder. We were unable to confirm an association between bipolar disorder and C677T polymorphism (rs1801133) of the MTHFR gene, as suggested in some previous studies.

Family-based association study of interleukin 6 (IL6) and its receptor (IL6R) functional polymorphisms in schizophrenia in the Polish population.

Schizophrenia is a heterogeneous disorder and its etiology remains incompletely elucidated. Among possible causes, immunological factors have been implicated in its pathogenesis and course. The inflammatory system may trigger or modulate the course of schizophrenia through complex mechanisms influencing neurodevelopment, neuroplasticity and neurotransmission. Recent studies indicate a role of excessive interleukin-6 (IL6) signaling in the pathogenesis of schizophrenia. Findings regarding changes in the circulating levels of soluble interleukin-6 receptor (sIL6R) in schizophrenia have been equivocal. The study was performed on a group of 147 trio (patients diagnosed with schizophrenia and their healthy parents). Polymorphisms of IL6 (rs1800795, rs1800797) and IL6R (rs4537545, rs4845617, rs2228145) genes were genotyped with the use of TaqMan SNP Genotyping Assays. No association of the polymorphisms from IL6 and IL6R genes with schizophrenia was found. We also investigated haplotypes in IL6 gene (consisting of rs1800795 and rs1800797) and in IL6R gene (consisting of rs4537545, rs2228145). We also found no preference in transmission of any haplotype. Our results do not support the theory that polymorphisms of IL6 and IL6R genes are involved in the pathogenesis of schizophrenia. It seems advisable to carry out further examinations of the role of these polymorphisms in schizophrenia by means of TDT method and classical (case-control) association method.

P.2.e.019 Efficacy of single ketamine infusion in bipolar depression: relationship with serum BDNF

B. Yoon1 °, W. Bahk2, K. Min3, D. Jon4, Y. Shin5, S. Lee6. 1Naju National Hospital, Department of Psychiatry, Naju, South-Korea; 2College of Medicine The Catholic University of Korea, Department of Psychiatry, Seoul, South-Korea; 3College of Medicine Chung-Ang University Hospital, Department of Psychiatry, Seoul, South-Korea; 4Hallym University Hospital, Department of Psychiatry, Anyang, South-Korea; 5Kangbuk Samsung Hospital, Department of Psychiatry, Seoul, SouthKorea; 6Wonkang University Hospital, Department of Psychiatry, Iksan, South-Korea