P.2.d. Mood disorders and treatment − Bipolar disorders (clinical) S371

it has been suggested that lithium-responsive BD may be a distinctsubtype of the disorder and that lithium response has also a geneticcomponent, the search of a hypothetical genetic profile whichcould help clinicians to choice the proper mood stabilizer is amatter of concern. Although molecular basis underlying lithium’stherapeutic mechanism of action are still not fully elucidated,evidence supports that lithium inhibits enzymes associated to theinositol pathway [3]. In this sense, our goal was to investigate thepotential association of genetic variability at IMPA1, IMPA2 andINPP1 genes with response to lithium in bipolar patients.

Methods: For this investigation 110 unrelated Caucasian bipo-lar outpatients were studied. All patients were recruited fromthe Bipolar Disorder Unit of the Hospital Clinic of Barcelonaand from primary care settings from Oviedo. Inclusion criteriawere (a) bipolar I/II diagnosis and (b) age >18 years. Exclusioncriteria were the presence of (a) mental retardation and (b) severeorganic disease. Genomic DNA was extracted from blood samplesfrom each participant, according to standard protocols. Severalpolymorphisms at the IMPA1, IMPA2 and INPP1 genes weregenotyped. All patients were grouped and compared accordingto their level of response to lithium. Patients were classified asexcellent responders, partial responders and non-responders. Forstatistical purposes, excellent and partial responders were grouped.Patients showing no tolerability to lithium were not considered.Categorical variables were compared using Chi-square or Fisherexact tests, as appropriate. Analyses were performed using PASWv18.0 and EpiInfo. All procedures were approved by the researchethics committees in each institution.

Results: Our results showed that those BP who were cate-gorized as poor responders presented higher rates of GG geno-type of the rs630110-IMPA2 gene (OR= 2.9; 95%CI [1.05–8.19]; c2 = 4.9; p = 0.023). We found that GG genotype of thers909270-INPP1 gene also conveyed risk for a poor responseto lithium (OR= 3.19; 95%CI [1.08–9.52]; c2 = 5.66; p = 0.04).No association was found between any of the analyzed IMPA1polymorphisms and response to lithium in our sample.

Conclusions: Our findings suggest that lithium-responsivebipolar disorder’s phenotype seems to be associated with geneticvariability at IMPA2 and INPP1 genes. Therefore, these resultswould not only strengthen those studies that have suggested thepotentially significant role of genetic variability at the inositolpathway in lithium prophylactic efficacy, but also reinforce itsinvolvement in the pathophysiology of bipolar disorder.

References

[1] Nivoli AM, Murru A, Vieta E: Lithium: still a cornerstone in thelong-term treatment in bipolar disorder? Neuropsychobiology 2010;62: 27−35.

[2] Garnham J, Munro A, Slaney C, MacDougall M, Passmore M, Duffy A,O’Donovan C, Teehan A, Alda M: Prophylactic treatment response inbipolar disorder: Results of a naturalistic observation study. J AffectDisord 16−4–2007.

[3] Serretti A, Drago A: Pharmacogenetics of lithium long-term treatment:focus on initiation and adaptation mechanisms. Neuropsychobiology2010; 62: 61−71.

Disclosure statement: This abstract is financially supported by an educa-tional pre-doctoral grant from IDIBAPS.

P.2.d.015 Cognitive deficits in obese bipolar patients −the impact of body fat distribution

N. Lackner1 °, S. Bengesser1, A. Birner1, B. Reininghaus1,F. Kattnig1, F.T. Fellendorf1, A. Mitteregger1, E. Oberreither1,S.J. Wallner-Liebmann2, H.P. Kapfhammer1, E.Z. Reininghaus11Medical University of Graz, Psychiatry, Graz, Austria; 2MedicalUniversity of Graz, Institute of Pathophysiology & Immunology,Graz, Austria

Objective: Recent literature emphasizes the role of obesity inthe treatment and outcome of bipolar disorder (BD). Obesity isassociated with important clinical characteristics of BD (includingsuicidal tendency and comorbid disorders) resulting in a poorerprognosis and outcome [1]. Moreover, evidence indicates thatobesity is associated with reduced neurocognitive function in BD,even in euthymia [2].

Methods: A sample of 70 euthymic BD patients was in-vestigated with a battery of cognitive tests to assess estimatedpremorbid IQ (MWTB), concentration (d2-concentration-test),verbal learning and memory (California Verbal Learning Test),attention, psychomotor processing speech (Trail Making Test A),and executive function (Trail Making Test B, Stroop Test FWIT).Obesity was assessed using traditional anthropometric measures

(body mass index, waist circumference, waist-to-hip-ratio). Ad-ditionally, subcutaneous adipose tissue thickness was measuredby lipometer®, a non-invasive technique to provide detailed in-formation about body fat distribution [3]. Correlations betweenanthropometrics and measures of cognitive performance were gen-erated using partial correlation analyses with age and educationas covariates.

Results: The results reveal that 69% of the BD sample metthe criteria for overweight (body mass index > 25). All anthro-pometric measures were highly correlated with the total body fat(%), the subcutaneous adipose tissue, and the visceral adiposetissue. Partial correlation analyses indicate that the anthropometricvariables were associated with an impaired performance in thecognitive tasks: waist circumference was correlated with a worseperformance in the d2-concentration-test (r = −0.31, p< 0.05), inthe CVLT (trials 1−5 free recall: r = −0.34, p< 0.01; short-delayfree recall: r = −0.31, p< 0.05; short-delay cued recall: r = −0.30,p< 0.05; long-delay free recall: r = −0.36, p< 0.01; long-delaycued recall: r = −0.40, p< 0.01), and in the Stroop task (Color-bar-naming task: r = 0.27, p< 0.05; Interference task: r = 0.33,p< 0.01). Waist-to-hip-ratio was correlated with a worse perfor-mance in the CVLT (trials 1−5 free recall: r = −0.29, p< 0.05;short-delay free recall: r = −0.30, p< 0.05; short-delay cued recall:r = −0.29, p< 0.05; long-delay free recall: r = −0.31, p< 0.05) andin the Stroop Interference task (r = 0.30, p< 0.05). Furthermore,data measured by lipometer® show that higher body fat at upperabdomen was associated with a poor performance in the StroopInterference task (r = 0.26, p< 0.05). As well, total fat mass wascorrelated with the Stroop task (Color-bar-naming task: r = −0.30,p< 0.05; Interference task: r = 0.276, p< 0.05). Body mass indexwas related only to the CVLT short-delay free recall condition(r = −0.28, p< 0.05).

Conclusions: According to the literature, as well as observed inclinical practice, obesity is highly prevalent in the bipolar sample.Moreover, the findings of the present study suggest that thereis a negative association between cognitive function and obesityin bipolar patients. In addition, our study could extend existingknowledge about the relationship of obesity and cognition in

S372 P.2.d. Mood disorders and treatment − Bipolar disorders (clinical)

BD by implementing lipometer® data. It has been shown thatan impaired performance in the Stroop task, especially in theInterference task, was associated with abdominal body fat andtotal body fat. We also demonstrated that the results differ slightlydependent on the anthropometric measures that have been used.The findings strengthen the position to use more sophisticatedmethods when assessing obesity and body fat composition in BD.

References

[1] Goldstein, B.I., Liu, S.-M., Zivkovic, N., Schaffer, A., Chien, L.-C.,Blanco, C., 2011. The burden of obesity among adults with bipolardisorder in the United States. Bipolar Disorders 13, 387–395.

[2] Yim, C.Y., Soczynska, J.K., Kennedy, S.H., Woldeyohannes, H.O.,Brietzke, E., McIntyre, R.S., 2012. The effect of overweight/obesityon cognitive function in euthymic individuals with bipolar disorder.European Psychiatry 27, 223–228.

[3] Moller, R., Tafeit, E., Pieber, T.R., Sudi, K., Reibnegger, G, 2000.Measurement of Subcutaneous Adipose Tissue Topography (SAT-Top)by Means of a New Optical Device, LIPOMETER, and the Evaluationof Standard Factor Coefficients in Healthy Subjects. American Journalof Human Biology 12, 231–239.

P.2.d.016 Efficacy of olanzapine monotherapy in the

treatment of bipolar depression with varying

degrees of manic symptoms

H. Katagiri1 °, M. Tohen2, S. Fujikoshi1, H. Xue3, S. Kanba41Eli Lilly Japan K.K., Lilly Research Laboratories, Kobe, Japan;2University of New Mexico School of Medicine, Department ofPsychiatry, NM, USA; 3Lilly Suzhou Pharmaceutical Co. Ltd,Shanghai Branch Medical, Shanghai, China; 4Kyushu University,Department of Neuropsychiatry, Fukuoka, Japan

Purpose: To assess the efficacy of olanzapine monotherapy fortreatment of bipolar depression with mixed features.

Methods: Pooled data from 2 studies that examined olanzapinemonotherapy in patients with bipolar I depression (N= 1214) wereanalyzed.Study 1 was an 8-week, randomized, double-blind, placebo-

controlled clinical trial. Patients were randomized in a 4:4:1ratio to olanzapine (5−20mg/day) or placebo (or olanzapine-fluoxetine combination, which was excluded from the currentanalyses) [1]. Study 2 was a 6-week, randomized, double-blind,placebo-controlled clinical trial. Patients were randomized in a2:1 ratio to olanzapine (5−20mg/day) or placebo [2]. Patients werecategorized for mixed features by the number of concurrent manicsymptoms at baseline (0, 1 or 2, and �3, measured by an YMRSitem score �2) to evaluate efficacy. Efficacy was evaluated bychange in MADRS total score from baseline to 6 weeks, rates ofresponse and remission. Response was defined as �50% reductionin MADRS at 6 weeks. Remission was defined as a MADRStotal score �12 at 6 weeks. Missing data were imputed using lastobservation carried forward (LOCF) methodology.

Results: A total of 690 olanzapine-group and 524 placebo-group patients were included in the analysis. Percentages ofpatients in the mixed feature categories 0, 1 or 2, and �3were 31.2%, 54.6% and 14.2%, respectively. Mean changes frombaseline in MADRS total score of patients in the olanzapine-group for the 3 mixed feature categories were −13.81, −13.96and −12.90; mean changes in the placebo-group were −10.13,−10.42 and −9.23, respectively for each category. Patients in theolanzapine-group experienced a statistically significantly greatermean decrease in MADRS total score compared with those in the

placebo-group for all mixed feature categories (LSM differences:−3.68 [p< 0.001], −3.25 [p< 0.001], −3.36 [p = 0.040] for mixedfeatures 0, 1 or 2, and �3, respectively). Respective response ratesof patients in the olanzapine-group for the 3 categories of mixedfeatures were 51.0%, 49.5% and 38.0%; placebo-group responserates were 39.3%, 38.4% and 33.8%.Statistically significant treatment differences were seen in two

mixed feature categories: 0 (p = 0.029), and 1 or 2 (p = 0.006).Remission rates in the olanzapine-group were 44.0%, 39.0% and31.5%; while remission rates in the placebo-group were 32.5%,30.2% and 23.8%, respectively for each category. Statisticallysignificant differences between treatment groups were seen fortwo mixed feature categories: 0 (p = 0.026), and 1 or 2 (p = 0.021).Mean changes from baseline in MADRS total score, response rateand remission rate showed no evidence of statistically significantinteractions between baseline mixed features and olanzapine treat-ment.

Conclusions: There were statistically significant differences inMADRS mean change between olanzapine and placebo in all 3mixed feature categories. No interaction between the treatmentand mixed feature categories was found in the MADRS changeanalysis, nor was any found in the response or remission ratesanalysis. Finally, the response and remission rates of olanzapine-group in the ‘�3 mixed features’ category were lower than theother two categories, however interpretation of the results islimited due to the heterogeneous population. Further investigationsfor mixed feature are required.

References

[1] Tohen, M., Vieta, E., Calabrese, J., Ketter, T.A., Sachs, G., Bowden, C.,Mitchell, P.B., Centorrino, F., Risser, R., Baker, R.W., Evans, A.R.,Beymer, K., Dube, S., Tollefson, G.D., Breier, A., 2003. Efficacy ofolanzapine and olanzapine-fluoxetine combination in the treatment ofbipolar I depression. Arch Gen Psychiatry 60, 1079–1088.

[2] Tohen, M., McDonnell, D.P., Case, M., Kanba, S., Ha, K., Fang, Y.R.,Katagiri, H., Gomez, J.C., 2012. Randomised, double-blind, placebo-controlled study of olanzapine in patients with bipolar I depression. BrJ Psychiatry 201, 376–382.

Disclosure statement: The studies included in this abstract were fundedby Eli Lilly and Company and/or any of its subsidiaries. H. Katagiri andS. Fujikoshi are employees of Eli Lilly Japan. M. Tohen was formerlyemployed by Eli Lilly and Company (to 2008) and has received honorariafrom or consulted Eli Lilly and Company his spouse is a current employee.H. Xue is an employee of Lilly Suzhou Pharmaceutical Co., Ltd. S. Kanbareceived grants/research support from Eli Lilly and Company and he alsoreceived honoraria from Eli Lilly and Company.

P.2.d.017 Is hyperthymic temperament an alarming

sign?

P. Marinova1 °, L.G. Hranov1 1University Multiprofile Hospital“St. Naum”, Second Psychiatric Clinic, Sofia, Bulgaria

Introduction: Bipolar affective disorder (BAD) presents an il-lustration of the apparent paradox of something pleasant andcoveted by some-one being in fact a morbid phenomenon. Thedefinition of mania suggests serious problems for the affectedindividual. It is much harder for the physician to explain topatients their concerns about hypomanic states. Yet, should thehyperthymic temperament be a cause of worry? The issue remainsstill controversial. Although major depressive disorder (MDD) +hyperthymic temperament is considered by some authors to bepart of the bipolar spectrum, i.e. BAD IV [1], data on whetherthis combination is problematic or not are still scarce.