Calabrò, M.

Crisafulli, C.

Drago, A.

English

    Aalborg UniversitetGenetic underpinnings of YMRS and MADRS scores variations in a bipolar sampleCalabrò, M.; Crisafulli, C.; Drago, A.Published in:European PsychiatryDOI (link to publication from Publisher):10.1192/j.eurpsy.2023.836Creative Commons LicenseCC BY 4.0Publication date:2023Document VersionPublisher's PDF, also known as Version of recordLink to publication from Aalborg UniversityCitation for published version (APA):Calabrò, M., Crisafulli, C., & Drago, A. (2023). Genetic underpinnings of YMRS and MADRS scores variations ina bipolar sample. European Psychiatry, 66(Suppl. 1), S386-S387. Article EPP0534.https://doi.org/10.1192/j.eurpsy.2023.836General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright ownersand it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.            - Users may download and print one copy of any publication from the public portal for the purpose of private study or research.            - You may not further distribute the material or use it for any profit-making activity or commercial gain            - You may freely distribute the URL identifying the publication in the public portal -Take down policyIf you believe that this document breaches copyright please contact us at vbn@aub.aau.dk providing details, and we will remove access tothe work immediately and investigate your claim.Downloaded from vbn.aau.dk on: November 29, 202359-63). Intestinal bacterial translocation has been postulated as oneof the causes of this inflammation (Nguyen et al. J Psychiatr Res2018;99 50-61). A possible pathway is through the lipopolysacchar-ide, which is presented to CD14 through lipopolysaccharide bind-ing protein (LBP) leading to a release of systemic inflammatorymarkers like C-reactive protein (CPR) (Funda et al. Infect Immun2001;69 3772-81).Objectives: 1) Describe gut permeability in patients with BDthrough the determination of intestinal inflammatory markers(LBP, sCD14) in plasma; 2) Analyze variables associated withintestinal inflammation.Methods: Cross-sectional study of 38 patients with BD [meanage=45.50 (SD=10.93; range 23-68); males=15 (39.5%)], recruitedfrom mental health outpatient clinics in Oviedo (Spain).Assessment: Pro-inflammation biomarkers [CRP (mg/dL),Erythrocyte Sedimentation Rate (ESR) (mm/h), Neutrophil/Lymphocyte, Monocyte/Lymphocyte, Platelet/Lymphocyte andSystemic Immune Inflammation Indexes]. Indirect markers ofintestinal bacterial translocation [LBP, soluble CD14 (sCD14)].Dichotomous variables were created for LBP, considering LBP≥15 μg/dL as increased gut permeability; and for CPR, consideringCRP≥0.3 as systemic inflammation. Metabolic syndrome [ATPIIIcriteria: glucose, HDL, triglycerides (mg/dl), arterial pressure(mmHg), abdominal circumference (cm)], body mass index(BMI) (kg/m2), smoking, cannabis or alcohol use.Statistical analyses: t-Student test, multiple linear regression ana-lyses.Results: Average LBP was 14.60 μg/dL (SD=6.4) and 15 patients(39.5%) had increased gut permeability. Moreover, average CPRwas 0.40 mg/dL (SD=0.58) and 16 patients (47.1%) showed sys-temic inflammation. There were no patients with increased levels ofsCD14.Associations were found between LBP and CPR (r=0.357;p=0.032), cannabis use in the last month (t=-2.293; p=0.029),BMI (r=0.433; p=0.008) and abdominal obesity (t=3.006;p=0.005); but no with age or sex.Subsequently, a multiple linear regression model for LBP wascalculated with variables previously mentioned, and age (basedon expert criteria). The overall regression was statistically signifi-cant (R2=0.49, F=9.273, p<0.001). It was found that CPR, abdom-inal obesity, and cannabis use in the last month significantlypredicted LBP levels (table 1).Conclusions: More than one third of patients with BD hadincreased gut permeability. Almost 50% had systemic inflamma-tion. Intestinal permeability was directly related to abdominalobesity and systemic inflammation, but inversely related tocannabis use.Disclosure of Interest: None DeclaredEPP0534Genetic underpinnings of YMRS and MADRS scoresvariations in a bipolar sampleM. Calabrò1*, C. Crisafulli1 and A. Drago21Department of Biomedical and Dental Sciences andMorphofunctional Imaging, University of Messina, Messina, Italyand 2Unit for Psychiatric Research, Aalborg University Hospital,Aalborg, Denmark*Corresponding author.doi: 10.1192/j.eurpsy.2023.836Introduction: Bipolar disorder (BD) is a chronic hereditary dis-order. Trial and error principles and long period of untreateddisorder mandate further research. Relatively recent advances instatistical computing and techniques introduced Polygenic riskscores (PRS) as predictors of the genetic susceptibility to diseases.Although they provide an estimate of the risk of developing specificpathologies, they are a genome-wide measure. PRS do not providespecific information on the biological meaning of the variants. Theuse of subsets of risk variants (limited to one or few relatedbiological pathways) to calculate pathway-PRS (pPRS)may providean estimate of the functioning of specific molecular cascades.Objectives: In the present study we calculated pPRS and testedthem as potential predictive factors which, together with otherclinical/environmental features, may estimate the treatment out-come of BD individuals in a clinical realistic treatment environ-ment.Methods: 1538 BD (41.39þ/-12.66 years, 59.17% females) individ-uals from STEP-BD were included in the analysis. A latent classanalysis identified three groups of patients according to the YMRSand MADRS scores variations during ˜ 1 year (308.47þ/-293.83 days YMRS, 357.78þ/-367.76 days MADRS). A GWASanalysis with clinical covariates provided the input for pPRS cal-culation. SNPs with best nominal significance and biologic rele-vance were prioritized through GTEx. A molecular pathwayanalysis (MPA) based on the interaction network of drugs usedfor treatment provided the genetic data needed for pPRS calcula-tion. A Neural network was built using pPRS as features togetherwith other variables (including Sex, Age, Scores at baseline) topredict the 3 groups previously identified. Performance was evalu-ated through 5-fold cross-validation, Python, R and Bash served forenvironments. Gene Ontology, ReactomePA and Bioconductorwere key packages together with Cytoscape, Plink, impute andgtool.Results: Ten biological networks were retrieved from MPA: 1)GO:0016705 þ GO:0016641, 2)GO:0019585, 3)GO:003018, 4)GO:0099589 þ GO:1904014, 5)GO:0015464 þ GO:1905144, 6)GO:0004935 þ GO:0004364 þ GO:00031690, 7)GO:1903351 þGO:1903350, 8)GO:0016917 þ GO:0007214, 9)GO:0008066 þGO:0007215, 10)GO:0048016. Risk variants within the genes con-tained in each group were used to compute pPRS. The ten pPRSwere used to compute a neural network to predict treatmentoutcomes.Conclusions: BD treatment is influenced by socio-demographic,clinical and genetic factors. To tackle this complexity, we tried toimplement an approach where the multivariate analysis encom-passes clinical analysis and the biologic background of treatmentTable 1. Multiple linear regression analyses to LBPB SE β t pCPR 4.842 1.529 0.439 3.167 0.004Abdominal obesity 4.810 1.849 0.362 2.601 0.014Cannabis use -5.048 2.273 -0.296 -2.221 0.034S386 e-Poster Presentationhttps://doi.org/10.1192/j.eurpsy.2023.836 Published online by Cambridge University Pressresponse. As a result, we can infer through a hypothesis-freeapproach potential pathways whose alterations may estimate treat-ment. At the time of writing the analyses are still undergoing, thefinal results will be presented and discussed at the congress.Disclosure of Interest: None DeclaredEPP0535Organic affective disorder due to meningioma, casereportM. Garcia-Moreno1*, A. de Cós Milas2, L. Beatobe Carreño2,P. del Sol Calderón1 and Á. Izquierdo de la Puente11HOSPITAL UNIVERSITARIO PUERTA DE HIERROMAJADAHONDA and 2HOSPITAL UNIVERSITARIO DEMÓSTOLES, MADRID, Spain*Corresponding author.doi: 10.1192/j.eurpsy.2023.837Introduction: Brain tumors can be associated with psychiatricsymptoms in up to 50% of cases. The most frequent primary ismeningioma and the clinic will depend on its location. Sincesurgical treatment does not always guarantee complete resolutionof the condition, concomitant psychopharmacological treatment isusually recommended.Objectives: To review about organic mania and its differentialdiagnosis.Methods: We carry out a literature review about organic affectivedisorder accompanied by a clinical description of one patient withorganic mania.Results: A 50-year-old woman admitted due to psychotic symp-toms. She had a diagnosis of frontal and parietal meningiomatreated with surgical treatment 10 years ago. In this context shehad a diagnosis of Organic Affective Disorder and 3 previouspsychiatric admissions due to affective or psychotic symptoms.Current episode consisted in dysphoria, magalomanic ideation,delusional ideation of harm and mystical-religious content, highspeech pressure and insomnia with little awareness of the disease.Cranial magnetic resonance showed postoperative right frontalchanges and stability in parietal meningioma, with no significantdifferences compared to the previous study. Diagnosis of OrganicAffective Disorder is maintained and reintroduced treatment witharipiprazole withdrawaled by the patient weeks before. Because ofadverse effects and persistence of the symptoms described, it waschanged to olanzapine with good response and tolerability. Thebehavior was progressively adapted with improvement of the dys-phoria and without psychotic symptoms at discharge.Conclusions: Affective symptons due to organic disorders such asbrain tumors can be treated surgically and with psychopharmaco-logical treatment.Disclosure of Interest: None DeclaredEPP0536A family history of suicide in bipolar disorders:powerful, powerlessM. Sagué Vilavella1*, G. Fico1, G. Anmella1, A. Giménez1,M. Gómez Ramiro2, M. T. Pons Cabrera1, S. Madero1,A. Murru1 and E. Vieta11Deparment of Psychiatry and Psychology, Hospital Clínic, Barcelonaand 2Department of Psychiatry, Hospital Álvaro Cunqueiro, Vigo,Spain*Corresponding author.doi: 10.1192/j.eurpsy.2023.838Introduction: When completing the medical record of a patientwith bipolar disoder (BD), hardly anything is more impacting thana family history of completed suicide (FHS). In fact, FHS is a mainrisk factor for personal suicide attempts and death in this popula-tion. There are few modifiable protective factors against suicide inBD, such as lithium treatment and absence of substance abuse.Objectives: We aimed to explore the relationship between a FHSand clinical characteristics in patients with BD. Given the impactthat FHS has on the individual and on healthcare professionals, wehypothesized that it would modify behaviors towards a higherprevalence of the modifiable protective factors against suicide,namely more treatment with lithium and less drug addiction.Methods: This is a cross-sectional study that included all patientswith BD that were followed up in a specialised unit between 1998and 2020. Only subjects with complete information on FHS wereretained for the analysis. We assessed sociodemographic and clin-ical data and described it with measures of frequency, centraltendency and dispersion. Differences between subjects with andwithout FHS were calculated with χ², Fisher’s exact test and Stu-dent’s t-test as appropriate. We set the significance level at p≤0.05.All tests were two-tailed.Results: The sample consisted of 480 subjects with a mean age of45.9 years (standard deviation 14.4, range 18-88), of which 54.4%(n=261) were women. 69.2% (n=332) had a diagnosis of BD type Iand 30.8% (n=148) of BD type II. 77 subjects (16%) had a FHS.Regarding differences between groups, those with relatives who hadcommitted suicide did not show statistically significant differencesin terms of sociodemographic variables (age, gender, civil status,employment) or key clinical features (type of BD, illness duration,psychotic features, predominant polarity, rapid cycling, number oflifetime manic and depressive episodes, comorbid personality dis-order), neither did they have a higher use of lithium (55.8% vs59.3%, p=0.572) nor lower substance use disorder (10.9% vs 15.5%,p=0.34). Predictably, people with FHS had a higher prevalence offamily history of mental and affective disorders (96.1% vs 70.9%,p<0.001; 86.3% vs 56.3%, p<0.001) and of stressful life events(71.6% vs 58.9%, p=0.05). Personal lifetime suicide attempts alsotended to be higher (36.4% vs 26.7%, p=0.088).Conclusions: Contrary to our hypothesis, in our sample of subjectswith BD a FHS was not associated with a higher prevalence of themodifiable protective factors against suicide. Therefore, althoughsuicide has a major impact both in families and healthcare profes-sionals, our results suggest it does not modify attitudes towardsprevention in a real-life scenario. The main limitation of our study isits cross-sectional design, which does not allow for causal inference. Inconclusion, there is room for improvement in the fight against suicide.Disclosure of Interest: None DeclaredEuropean Psychiatry S387https://doi.org/10.1192/j.eurpsy.2023.836 Published online by Cambridge University Press

Genetic underpinnings of YMRS and MADRS scores variations in a bipolar sample

https://vbn.aau.dk/files/560972743/Calabr_Crisafulli_Drago_2023_._Genetic_underpinnings_of_YMRS_and_MADRS_scores_variations_in_a_bipolar_sample.pdf

Genetic underpinnings of YMRS and MADRS scores variations in a bipolar sample

Abstract

Similar works

Full text

Available Versions

VBN