Jasmina Grubišin

Association study of MDR1 and 5-HT2C genetic polymorphisms and antipsychotic-induced metabolic disturbances in female patients with schizophrenia

The objective of this study was to determine the association of 5-HT2C (serotonin 2C receptor) and MDR1 (multidrug resistant protein) genetic polymorphisms and antipsychotic-induced metabolic abnormalities among female patients with DSM IV schizophrenia spectrum disorders. We have previously reported the associations of −759CT 5-HT2C and G2677T and C3435T MDR1 genetic polymorphisms and olanzapine/risperidone-induced weight gain in a similar sample of patients. Here, we included a total of 101 previously non-medicated female patients treated with olanzapine/risperidone over a 3-month period. The variables analyzed included fasting glucose, total cholesterol, low-density lipoprotein, high-density lipoprotein and triglyceride levels in blood, blood pressure and waist circumferences. We observed significant association of −759T 5-HT2C genetic variant and greater increase in waist circumference (P=0.03), fasting glucose level (P=0.046) and triglyceride level (P=0.045) in blood after a 3-month period. The 2677T and 3435T MDR1 genetic variants were significantly associated with the greater increase in fasting glucose level in blood when patients were using olanzapine (P<0.001 and P=0.028, respectively). Our data indicate a possible influence of −759CT 5-HT2C and MDR1 G2677T and C3435T MDR1 genetic polymorphisms on the development of metabolic abnormalities among female patients treated with olanzapine/risperidone.

Metabolic syndrome in female patients with schizophrenia treated with second generation antipsychotics: a 3-month follow-up.

The objective of this study was to determine the occurrence of metabolic abnormalities among previously unmedicated female patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition schizophrenia spectrum disorders and their associations with olanzapine and risperidone treatment. We analysed 94 female patients who were treated with olanzapine or risperidone in the period of 3 months. Analysed variables included fasting glucose, total cholesterol, low-density lipoprotein (LDL), high-density lipoproteins and triglycerides in blood, blood pressure (BP), waist and hip circumferences and body mass index (BMI). At baseline, 14 patients (15%) fulfilled criteria for metabolic syndrome. After 3 months of treatment, 25 patients (27%) fulfilled criteria for metabolic syndrome, and their baseline BMI was the only predictor for its development. Treatment with both antipsychotics was associated with significant increase in waist circumference. Positive family history of diabetes mellitus contributed to a significant greater increase in abdominal obesity, significant higher baseline levels and a borderline significant increase in fasting glucose among olanzapine-treated patients. Olanzapine admission was associated with a significant increase in LDL and risperidone with a significant increase in triglycerides. Metabolic abnormalities seem to be more prevalent in unmedicated female patients with schizophrenia spectrum disorders than expected based on results in general population (adjusted for age and sex). Olanzapine treatment might induce significant alterations in metabolic profiles, especially among patients with positive family history of diabetes, mostly by inducing abdominal obesity. The association of risperidone application and increase in triglyceride level still needs to be determined.

Association between psychopathology and suicidal behavior in schizophrenia. A cross-sectional study of 509 participants.

BACKGROUND Suicide in schizophrenia is a serious problem--ideation rates go up to 40%, and approximately one half of patients attempt suicide at least once. The distinction between attempters and ideators is vital in everyday clinical practice. AIM To explore the association between psychopathology and suicidal behavior in a comparative study of three groups of patients with schizophrenia: suicide ideators, suicide attempters, and subjects without suicide ideation and behavior. METHOD The study included 509 patients: suicide attempters (n = 159), ideators (n = 180), and a comparative group (n = 170). The clinical assessment consisted of a structured psychiatric interview and an evaluation of sociodemographics, suicidality (SIBQ), psychopathology (PANSS), and depression (CDSS). RESULTS Suicide attempters were more depressed than ideators, and both groups had higher CDSS scores than the comparative group. The overall contribution of positive, negative, and general PANSS symptoms was not statistically significant enough to differentiate ideators from attempters. A principal component analysis of the PANSS items revealed five components: disinhibition, withdrawal, anxiety and guilt, reality distortion, and disorganization. Two logistic regression analyses showed that suicide ideation or attempt was significantly related to depression, anxiety, guilt, gender, age, and number of previous hospitalizations. Compared to suicide ideators, attempters were more depressed, had a higher number of previous hospitalizations, and lower education. CONCLUSION The results indicate that clinicians should look for depression, anxiety, and guilt feelings, while positive and negative symptoms seem to be less relevant for suicide assessment in schizophrenia.

Psychometric properties and factor structure of the Temperament and Character Inventory-Revised (TCI-R) in a Croatian psychiatric outpatient sample

OBJECTIVE The goal of this study was to investigate psychometric properties and factorial structure of the Croatian adaptation of the Temperament and Character Inventory-Revised (TCI-R) in a sample of psychiatric outpatients (n=328). METHOD The participants filled out the TCI-R, as well as self-report measures of the Big-Five personality traits (IPIP-50), trait impulsivity (BIS-11), depression (BDI-II), suicidality (SBQ-R), and life satisfaction (SWLS). We explored the internal consistency of 7 domains and 29 subscales and compared it with the Croatian version of the original TCI used in prior studies. Principal component analysis with promax rotation was conducted on temperament and character subscales separately, while concurrent validity was examined through the TCI-Rs relations with the abovementioned psychological measures. RESULTS The TCI-R scales showed adequate internal consistencies, with Cronbachs alpha values ranging from 0.77 to 0.93. The internal consistency showed to be higher in comparison with the Croatian version of the original TCI. The postulated four-factor structure of temperament and the three-factor structure of character were confirmed. The meaningful associations with other measures supported the concurrent validity of the TCI-R. CONCLUSION The Croatian adaptation of the TCI-R exhibited satisfactory reliability and validity in a sample of psychiatric outpatients. These findings support the use of the TCI-R in Croatian clinical settings over its predecessor (TCI).

Brain-derived neurotrophic factor serum and plasma levels in the treatment of acute schizophrenia with olanzapine or risperidone: 6-week prospective study

Abstract Antipsychotics have been the mainstay of the treatment of schizophrenia, and their potential role in neuroprotection could be related to brain-derived neurotrophic factor (BDNF). So far different effects on both serum and plasma levels of BDNF were reported related to the various antipsychotic treatments. Aim of this study was to investigate the influence of olanzapine or risperidone on both plasma and serum levels of BDNF in patients with acute schizophrenia. For 50 participants with acute episode of schizophrenia both plasma and serum BDNF, along with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression scale, were assessed pretreatment and post treatment – after 6 weeks of either risperidone or olanzapine. Results show that a weak correlation between pretreatment plasma and serum levels of BNDF was found no longer significant after 6 weeks of treatment. Antipsychotics, olanzapine and risperidone showed no significant effect on post treatment plasma and serum levels of BDNF. Pretreatment plasma level of BDNF and PANSS positive subscale were positively correlated. Post treatment serum level of BDNF and Clinical Global Impression were negatively correlated. In conclusion, plasma and serum BDNF levels could be different markers to some extent with regard to clinical symptoms, response to therapy and outcome. The interrelation between serum and plasma BDNF should be established in further studies.