Alma Mihaljević Peleš

Association between C-reactive protein and homocysteine with the subcomponents of metabolic syndrome in stable patients with bipolar disorder and schizophrenia.

Abstract Vuksan-Cusa B, Sagud M, Jakovljevic M, Mihaljevic Peles A, Jaksic N, Mihaljevic S, Zivkovic M, Kudlek Mikulic S, Jevtovic S. Association between C-reactive protein and homocysteine with the subcomponents of metabolic syndrome in stable patients with bipolar disorder and schizophrenia. Nord J Psychiatry 2012;Early Online:1–6. Background: Previous studies revealed high prevalence of metabolic syndrome (MetS) in patients with bipolar disorder and schizophrenia. C-Reactive protein (CRP) and homocysteine have also both emerged as independent risk factors for the development of cardiovascular disease (CVD) but are less investigated in psychiatric disorders. Aims: The aim of this study was to ascertain which specific subcomponents of MetS are associated with levels of CRP and homocysteine in patients with bipolar disorder and schizophrenia. Methods: Our sample consisted of patient group (n = 122) (60 bipolar and 62 schizophrenic patients) treated with second-generation antipsychotics (SGA) and healthy controls (n = 59). MetS was defined according to NCEP ATP-III criteria; the cut-off point for elevated CRP was set up at 5 mg/l and for hyperhomocysteinemia at 15 μmol/l. Results: In the patient group, homocysteine was correlated with waist circumference, systolic and diastolic blood pressure, triglycerides and blood glucose, while CRP was correlated with waist circumference and diastolic blood pressure. Patients with hyperhomocysteinemia had an 8.442 times higher chance to have met the criteria for MetS while elevated CRP was not a significant predictor of MetS. Conclusions: There is a complex association between CRP and homocysteine with specific subcomponents of MetS in patients with bipolar disorder and schizophrenia. Given the high risk of cardiovascular disorders in psychiatric patients, these relationships deserve further investigation. Clinically, it could be useful to include the measurement of homocysteine and CRP levels in routine psychiatric diagnostic procedures.

Association study of paroxetine therapeutic response with SERT gene polymorphisms in patients with major depressive disorder.

We investigated the relationships between LS promoter (SERTPR) and ls intron2 (SERTin2) genetic variants of serotonin transporter (SERT) polymorphisms with treatment response in 130 patients with major depressive disorder (MDD) treated with paroxetine (20 mg/day) for 6 weeks. To assess and evaluate therapeutic response to paroxetine all patients were rated weekly using the HAMD-17 scale. Responders were defined as those subjects with a decrease in HAMD scale by≥50% at week 6 of treatment. Comparison of genotypes and alleles frequency of the SERTPR between responders and non-responders revealed significant differences among genotypes and overrepresentation of the S allele in the group of non-responders (P=0.0004). SERTin2-ss genotype bearing subjects showed better treatment response compared to ls and ll genotype from the fourth week of treatment (P=0.035). Statistical differences were also found in distributions of the estimated haplotypes between responders and non-responders, while subsequent analysis revealed overrepresentation of S/l haplotype (P=0.006) in the group of non-responders. SERTPR and SERTin2 were found to be in linkage disequilibrium in studied population. These findings identify genetic factors associated with paroxetine treatment response in MDD patients.

Metabolic syndrome and serum homocysteine in patients with bipolar disorder and schizophrenia treated with second generation antipsychotics

There is accumulating evidence for an increased prevalence of metabolic syndrome (MetS) in bipolar patients, which is comparable to the prevalence of MetS in patients with schizophrenia. Hyperhomocysteinaemia has emerged as an independent and graded risk factor for the development of cardiovascular disease (CVD), which is, at the same time, the primary clinical outcome of MetS. The aim of this study was to ascertain if the presence of MetS was associated with hyperhomocysteinaemia in patients with bipolar disorder (N=36) and schizophrenia (N=46) treated with second-generation antipsychotics (SGA). MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP-III) criteria and the cut-off point for hyperhomocysteinaemia was set up at 15 μmoll(-1). Results of the study indicated that the presence of the MetS is statistically significantly associated with the elevated serum homocysteine in all participants. As hyperhomocysteinaemia has emerged as an independent risk factor for psychiatric disorder and CVD, it could be useful to include fasting homocysteine serum determination in the diagnostic panels of psychiatric patients to obtain a better assessment of their metabolic risk profile.

Diagnostic accuracy of serum brain derived neurotrophic factor concentration in antidepressant naïve patients with first major depression episode.

Diagnosing major depressive disorder (MDD) continues to be based on meeting phenomenological and descriptive criteria. As of yet, there is still no non-invasive, peripheral biomarker that would allow for a certain diagnosis of MDD. The objective of this paper is to use the receiver operating characteristic (ROC) analysis to test the diagnostic value of serum concentrations of brain derived neurotrophic factor (BDNF) in diagnosing the first episode of MDD. Among 1014 patients admitted for an initial psychiatric evaluation, antidepressant naïve patients diagnosed with first episode MDD were separated into the test group. Only patients signing an informed consent form were included in the study. Using DSM-IV-TR diagnostic criteria, those patients meeting the MDD criteria (N = 122) and patients not meeting MDD or other psychiatric disorder criteria (N = 142) were differentiated. Subjects with repeated episode MDD (N = 121) and other psychiatric comorbid illnesses (N = 138) in the MDD group were excluded from the study. In the group without MDD or other psychiatric illnesses, patients with physical comorbidities (N = 59) were excluded. The serum concentration of BDNF was determined in all patients using the ELISA assay. Subjects with first episode MDD showed differences in serum BDNF concentrations (ng/mL) in comparison to the control group of patients not meeting the criteria for first episode MDD (mean ± SD; 37.5 ± 13.3 vs. 56.8 ± 6.3; t = 1.372; df = 262; p < 0.01). The ROC analysis established a discriminant diagnostic value of serum BDNF in diagnosing MDD. The area under the curve (AUC) was 0.892 with a 95% confidence level (0.826-0.939), which was statistically significant at p < 0.01. The serum BDNF had a high diagnostic sensitivity of 83.9% and a specificity of 93%. Serum BDNF concentrations appear to be a promising tool in discriminating subjects with MDD from those without MDD.

The effect of lamotrigine on platelet monoamine oxidase type B activity in patients with bipolar depression

Lamotrigine is an anticonvulsant drug effective in the treatment of epilepsy and bipolar depression. Preclinical data showed that lamotrigine inhibited monoamine oxidase (MAO) activity in vitro. The aim of the study was to determine the effects of 6-weeks lamotrigine treatment on platelet MAO type B (MAO-B) activity in patient with bipolar depression. The study included 26 female patients with bipolar I disorder in depressive episode (DSM-IV criteria, Hamilton Depression Rating Scale (HAMD) and Young Mania Rating Scale). Platelet MAO-B activity was determined spectrofluorimetrically before and after 6 weeks of the treatment with a relatively low dose of lamotrigine (100 mg/day). Six weeks of treatment with lamotrigine significantly decreased platelet MAO-B activity in bipolar depressed patients. This inhibitory effect was not related to smoking status and was independent of the treatment combinations (lamotrigine alone or in combination with either lithium or antipsychotics). Lamotrigine treatment induced a decrease in total HAMD scores in bipolar depressed patients, which was not significantly correlated with reduction of platelet MAO-B activity. These findings provide in vivo insight of lamotrigine effect on platelet MAO-B activity in patients with bipolar depression. Its in vivo MAO-B inhibiting effect might have contributed in part to its antidepressant activity.

The effect of lamotrigine on platelet serotonin concentration in patients with bipolar depression

Antiepileptic drug lamotrigine, similarly to selective serotonin reuptake inhibitor paroxetine in patients with MDD, decreased platelet 5-HT concentration in patients with bipolar depression. The results suggest that lamotrigine possesses in vivo 5-HT uptake inhibiting property, and this effect might have contributed to its antidepressant activity.