P.2.e.039 Prevalence and correlates of non-adherence with mood stabilisers in patients with bipolar I disorder

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P.2.e Affective disorders and antidepressants - Bipolar disorders (clinical)

Change from baseline to Week 3 was statistically significant in favor of cariprazine on CGI-S, CGI-I (P10% in any group) comprised extrapyramidal disorder, headache, akathisia, constipation, nausea, and dyspepsia. Conclusion: Results from this Phase II study demonstrated the efficacy of cariprazine for the treatment of acute mania associated with bipolar I disorder. Additional studies are warranted.

patients with unipolar disorder. In both groups, the obese patients showed higher median WSAS total score (20 vs. 16 and 15 vs. 11.5, respectively). Although, the median QLESQ total score was lower in the obese patients than in the normal weight patients, this difference was more evident in patients with unipolar disorder (8 vs. 39) than in patients with bipolar disorder (30 vs. 37). Conclusions:In spite of the small size of the sample, which suggested to not perform statistical analyses these preliminary results suggest that obesity causes a significant functional impairment that can add to the negative effects on working and social functioning due to the illness itself. Moreover, our results point to the relationship between obesity and poorer quality of life, which seems particularly strong in patients with unipolar disorder. Additional studies with larger number of participating subjects are undergoing.

References [1] Kiss, B., Laszlovszky, I., Horvath, A. et al. 2006 RGH-188, an atypical antipsychotic with dopamine D31D2 antagonist/partial agonist properties: in vitro characterization. Int J Neuropsychopharm 9 (suppl 1), S22l P02.213 [2] Gyertyan, I., Kiss, B., Saghy, K., et al. 2006 RGH-188, an atypical antipsychotic with dopamine D31D2 antagonist/partial agonist properties: behavioral characterization. Int J Neuropsychopharmacol 9 (suppl 1), S222. P02.2l5.

1P.2.e.0381 Mood disorders and obesity: quality of life and social functioning E. Pierantozzi 1 ., L. Bossini 1 , M. Roggi 1 , L. Padula1 , R.N. Forgione 1 , P. Castrogiovanni 1 , A. Fagiolini 1 . 1Neuroscienze, Dept. Psichiatria, Siena, Italy Purpose of the study: Patients with bipolar disorder may be at greater risk for overweight and obesity than individuals in the general population [1]. This risk may be due to the illness itself or to other factors such as unhealthy diet and life style [2] and/or medications used to treat the disorder [1]. Usually, the largest increases in weight occurred during acute treatment phase and were positively correlated with baseline scores on the Hamilton Rating Scale for Depression and negatively correlated with baseline scores on the Bech-Rafaelsen Mania Scale [1]. In Italy, a total of 40.8% of the drug-naive patients with bipolar disorder met criteria for obesity or overweight [3]. However, data regarding the prevalence of obesity in unipolar disorder are still contradictory. Moreover, several studies show that both obesity and psychiatric disorders cause a deterioration in the quality of life and in the working and social functioning. This study aims to determine the prevalence of overweight and obesity in a sample of patients with mood disorders and to evaluate whether the effects on quality of life and social functioning of obesity and mood disorder can add together. Materials and Methods:We evaluated 41 consecutive outpatients with bipolar mood disorder (N = 18, 44%) and unipolar mood disorder (N = 23, 56%). Axis I diagnosis was confirmed according to the DSM-IV using a structured interview (the Mini-International Neuropsychiatric Interview-Plus). Healthrelated quality of life was assessed using two self-reported scales, the Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ) and the Work and Social Adjustment Scale (WSAS). BMI was calculated by dividing body weight (in kg) by height (in m2). Patients were weighted in underwear, between 08:00 and 09:00 h, using a medical electronic scale (Tanita tbf300 gs). Results: The prevalence of obesity (BMI=30) was 27% (N = 11). A total of 39% of the patients with bipolar disorder met criteria for obesity, in comparison with a total of 17% of

References [1] Fagiolini, A., Frank, E., Houck, P.R., Mallinger, A., Swartz, H., Buysse, D.I, Ombao, H., Kupfer, D.I, 2002 Prevalence of obesity and weight change during treatment in patients with bipolar I disorder. J Clin Psychiatry; 63, 528-534. [2] Elmslie, IL., Silverstone, IT., Mann, II., Williams, S.M., Romans, S.E., 2000 Prevalence of overweight and obesity in bipolar patients. J Clin Psychiatry 61, 179-184. [3] Maina, G., Salvi, v., Vitalucci, A., D'Ambrosio, v., Bogetto, F., 2008 Prevalence and correlates of overweight in drug-naive patients with bipolar disorder. J Affect Disord 110(1-2), 149-55.

1p.2.e.0391 Prevalence and correlates of non-adherence with mood stabilisers in patients with bipolar I disorder A. Mechri 1 ., L. Bouzgarrou1 , A. Mrad1 , W. Douki2 , M.E Najja?, L. Gaha1 . 1 Research Laboratory "Vulnerability to Psychotic disorders ", Department of Psychiatry, Monastir, 1Unesian Republic; 2Biochemistry and Toxicology Laboratory, Department ofBiochemistry, Monastir, Tunesian Republic

Purpose: Mood stabilisers such as lithium, valproate, and carbamazepine are the mainstay of treatment of bipolar disorders. However, there is a significant efficacy-effectiveness gap. In fact, medication non-adherence and subtherapeutic plasma levels are associated with poorer clinical outcome. The reported prevalence of non-adherence with mood stabilisers is between 10% and 60%. The aims of this study were to determine the prevalence of nonadherence with mood stabilisers and to explore the correlates of non-adherence in a cohort of patients with bipolar I disorder receiving long-term treatment with mood stabilisers. Methods: A prospective two years study was carried on 117 outpatients recruited from the psychiatric department ofthe Monastir's University Hospital, from September to December 2001. We included patients meeting DSM-IV criteria for bipolar I disorder and taking mood stabilisers for long-term (one year minimum). We excluded patients whose diagnosis was revised and those who were not followed-up correctly. For the patients who changed mood stabiliser, only the period preceding this change was taken into account. The final study sample comprised 88 patients (57 male and 31 female, mean age = 38.7±11.5 years), was subdivided into three groups: patients treated with lithium carbonate (n = 38), patients treated with carbamazepine (n = 31), and patients treated with sodium valproate (n = 19). Mean dosage of prescribed mood stabilisers was about 1079±305.4 for lithium, 696.8±125.l for

P.2.g Affictive disorders and antidepressants - Other (clinical) carbamazepine, and l579±382.4 for valproate. The most commonly prescribed other medications were antipsychotic medications (51.1%), benzodiazepines (17%) and antidepressants (9%). The initial assessment consisted in a clinical evaluation, and a plasmatic dosage of different mood stabilisers. This dosage was realized using the electrodes method for lithium and the immunopolarization fluorescence technique (TDX Abbott) for carbamazepine and valproate. The follow-up was ensured by the same medical team with at least four consultations per year including the same monitoring elements. The adherence with mood stabilisers was defined by the absence of plasma levels below the therapeutic ranges during the follow-up. The therapeutic ranges were 0.61.0mmoVL for lithium, 4-l0mgIL for carbamazepine and 50100mgIL for sodium valproate. Results: Mean plasma levels of mood stabilizers were 0.68±0.22mmoVL (range, 0.25-1.18mmoVL) for lithium, 7.9±2.2mgIL (range, 0.15-l4mgIL) for carbamazepine, and 72.8±23.0mgIL (range, l7.4-135.2mgIL) for valproate. Forty nine (55.7%) of patients have met criteria for nonadherence. The rates of non-adherence were 78.9% in patients receiving lithium, 19.4% in patients receiving carbamazepine, and 62.4% in patients receiving valproate. Backward stepwise logistic regression demonstrated that non-adherence was correlated with number of recurrences during the follow-up, number of previous mood stabiliser substitutions, delay of mood stabiliser prescription and association with antipsychotic medications. Conclusions: In the follow up study, rates of mood stabiliser non-adherence are high in bipolar I patients. This finding may be related to mood stabiliser modifications and the subtherapeutic mood stabiliser levels. To improve long term treatment outcome, we should reinforce monitoring of patients and associate psychoeducational measures.

P.2.f Affective disorders and antidepressants - Bipolar disorders (basic)

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surveys suggested that some genes are contributed to the onset of this disorder. A common remedy of bipolar disorder is lithium. This drug is comparatively effective, but it has higher incidence of adverse effects, because lithium has a narrow therapeutic window. Therefore, new drugs which have both efficacy and few side effects are needed. The purpose of our present work was to investigate the involvement of DGK/3 in bipolar disorder. For this purpose, we performed some behavioral tests using DGK/3 knockout (KO) mice. Methods: We conducted 24 hours locomotor activity test and open field test to examine the activity in DGK/3 KO mice and its wild-type (WT) littermates. We also analyzed the severity of anxious and depression in DGK/3 KO mice by the behavioral methods, such as elevated plus maze test, forced swim test and tail suspension test. Furthermore, we subjected DGK/3 KO mice and its WT littermate to Y-maze test and Morris water maze test, in order to examine their cognitive function. Finally, the effect of chronic mood stabilizer, lithium treatment on the behavior was tested in DGK/3 KO mice and its WT littermates. Statistics: Statistical analysis was performed by SPSS statistics software. The data was compared using Student's t-tests or analysis of variance followed by Dunnett test. Results: In locomotor activity test (p < 0.05) and open field test (p<0.01), DGK/3 KO mice were more active than their WT littermates. In comparison with WT mice, DGK/3 KO mice stayed for long time in anxiogenic place of open field test (p < 0.05) and elevated plus maze test (p < 0.05). DGK/3 KO mice also showed lower depression like behaviors in forced swim test (p < 0.05) and tail suspension test (p < 0.001). In addition, DGK/3 KO mice exhibited cognitive impairment in Y-maze test (p < 0.01) and Morris water maze test (p < 0.05). In these abnormal behaviors DGK/3 KO mice showed, lower anxiety was improved by the chronic treatment of lithium chloride (p < 0.05). Conclusion: These profiles of DGK/3 KO mice were similar to the mania phase of bipolar I disorder patient. These findings suggested that alteration of DGK/3 function may be related to the manic symptom. Further studies will be needed to clarify the relationship between DGK/3 and bipolar disorder.

Ip.2.f.0011 Mania-like behavioural abnormalities of diacylglycerol kinase

II knockout mice

K. Kakefuda1 " A. O~agi1, K. Tsuruma1, M. Shimazawa1, K. Yokota2 , Y. Shirai , K. Horie4 , N. Sait03 , 1. Takeda4 , 1 GijU Pharmaceutical University, Biofimctional H. Hara1 . Evaluation Molecular Pharmacology, GijU, Japan; 2 Carna Biosciences Incorporated, Pharmacology, Kobe, Japan; 3 KtJbe University, Biosignal Research Center, Kobe, Japan; 4 Graduate School ofMedicine Osaka University, Department of Social and Environmental Medicine, Suita, Japan

Background and Purpose: Diacylglycerol kinase (DGK) is an enzyme which phosphorylates diacylglycerol to produce phosphatidic acid. Of 10 mammalian DGK isozymes, DGK/3 is widely distributed in the central nervous system, such regions as the olfactory bulb, cerebral cortex, striatum and hippocampus, and in mice the expression of this enzyme increases dramatically after the second week, which is coincident with the synapse formation in the brain. In addition, it has been reported that the COOHterminal of DGK/3 protein is lacking in bipolar disorder patients. Bipolar disorder is a mental illness causing unusual shifts in mood from the heights of mania to the depths of depression. The lifetime prevalence of this disease is about 1%, and epidemiological

P.2.g Affective disorders and antidepressants - Other (clinical) 1P.2.g.0011 Correlation between smoking and depression 1. Gabos Grecu1 " M. Gabos Grecu1, T. Moica1, A. Vesa 1, R. Crisan2 , M. Florea3 , G. Buicu1, C. Gabos Grecu1. 1First Clinic ofPsychiatry, Psychiatry, Targu-Mures, Romania; 2 Clinical County Hospital, Gynecology, Targu-Mures, Romania; 3 Private Health Services, General Medicine, Targu-Mures, Romania

Background: In persons with mental illness the percentage of smokers is between 50-90% compared with 24% in the general population [1,3]. Depressive patients have a probability of 40% less to give up smoking compare to a smoker who doesn't suffer of depression. Depression or depressive symptoms may be part of the clinical picture of withdrawal from nicotine (DSM IV TR), and clinical studies conducted in twins shows that severe depression occurs with greater frequency in smokers compared to non-smokers [2]. Purpose of paper: Studying the correlations between tobacco consumption and depression, to identify the effects of smoking