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Monoamine oxidase A (MAOA) gene hypomethylation in panic disorder − an epigenetic risk pattern reversed by psychotherapy?
S166
P.1.a. Basic and clinical neuroscience − Genetics and epigenetics
P.1.a.006 Hot genes in schizophrenia: case-control, pharmacogenetics and exploratory analyses in two independent samples S. Porcelli1 ° , S.J. Lee2 , C. Han3 , A.A. Patkar4 , D. De Ronchi5 , A.R. Atti5 , A. Serretti5 , C.U. Pae2 1 Universit`a di Bologna, Department of Biomedical and NeuroMotor Sciences, Bologna, Italy; 2 The Catholic University of Korea College of Medicine, Department of Psychiatry, Seoul, South-Korea; 3 College of Medicine, Department of Psychiatry, Seoul, South-Korea; 4 Duke University Medical Center, Department of Psychiatry and Behavioural Sciences, Durham, USA; 5 University of Bologna, Department of Biomedical and NeuroMotor Sciences, Bologna, Italy Introduction: Although environmental factors play a relevant role in schizophrenia (SCZ) pathogenesis, high heritability points to a major role for inherited genetic variants in the etiology of SCZ. Similarly, a genetic contribution for antipsychotic response (AR) has been suggested. Recently, a set of genes was detected through a genome-wide association study (GWAS) approach in the largest sample of SCZ patients and controls even investigated. Thus, currently they are considered as the most promising genes in SCZ pathogenesis [1]. Aims: We investigated the effects of genetic variants within five of these promising genes − i.e. PPP3CC, RORA, SP4, ST8SIA2 and ZNF804A − in two independent samples in order to confirm GWAS results in two well-phenotyped samples and to better elucidate their specific role through a number of exploratory analyses. Methods: We recruited a Korean sample of 176 SCZ patients and 326 healthy controls and an Italian sample of 83 SCZ patients and 194 healthy controls. The PANSS was used to assess psychopathological severity and antipsychotic response (AR). Several clinical features were recorded in both samples. Differences in the allelic and genotype frequencies were calculated using the c2 statistics. Traditional statistical analyses were performed using “Statistica” package while test for association using multimarker haplotypes were performed using the statistic environment “R cran”, package “haplo.score”. Differences in the genotype frequencies were calculated using the c2 statistics. Repeated measure Analysis of Variance was used to investigate the AR. The main outcome measures were: (1) differences among genotypic frequencies between cases and controls and (2) influence of the SNPs on clinical improvement, as measured by PANSS scale. Furthermore, we performed a number of exploratory analyses in order to better dissect the role of these genes in psychopathological features. Results: In the Korean sample RORA rs10438338 was associated with SCZ (p = 0.03) as well as haplotype rs2282888rs2237304-rs10272006-rs12673091 within SP4 gene (p = 0.02). In the Italian sample 3 PPP3CC variants (rs11780915 p = 0.006; rs10108011 p = 0.01; rs2249098 p = 0.0004), ZNF804A rs1344706 (p = 0.02) and SP4 rs12673091 (p = 0.02) were associated with SCZ. The haplotype rs11780915-rs10108011-rs2249098 within PPP3CC gene and the haplotype rs7603001-rs1344706 within ZNF804A gene were associated with SCZ as well (respectively p = 0.03 and p = 0.02). Further, several RORA variants were associated with AR (Korean sample: rs1871858 p = 0.02; rs12900122 p = 0.06, rs17204440 p = 0.02, haplotype rs1020729-rs1871858 p = 0.01; Italian sample: rs12900122 p = 0.003). In the Italian sample also 2 SP4 variants (rs2282888 p = 0.02; rs10272006 p = 0.02) and ST8SIA2 rs4777989 (p = 0.04) were associated with AR. Exploratory analyses suggested that: (1) PPP3CC, ST8SIA2
and SP4 genes may be implicated in the develop and severity of psychotic symptoms, (2) RORA gene may play a role in AR, particularly of negative symptomatology, as well as ZNF804A gene. Conclusions: Considering limitations linked to the sample size and candidate genes approach, our results further support a role for these gene in SCZ, as well as in AR. Analyses in well phenotyped samples could help researchers to refine the role of these genes for further, focused investigations. References [1] Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 511, 421–427.
P.1.a.007 Monoamine oxidase A (MAOA) gene hypomethylation in panic disorder − an epigenetic risk pattern reversed by psychotherapy? C. Ziegler1 ° , J. Richter2 , M. Mahr1 , A. Gajewska1 , M.A. Schiele1 , T. Lang3 , P. Pauli4 , A. Reif5 , W. Rief6 , T. Kircher7 , V. Arolt8 , A.O. Hamm2 , J. Deckert1 , K. Domschke1 1 University Hospital of W¨urzburg, Department of Psychiatry Psychosomatics and Psychotherapy, W¨urzburg, Germany; 2 University of Greifswald, Institute of Psychology, Greifswald, Germany; 3 University of Bremen, Outpatient Psychotherapy Treatment Center, Bremen, Germany; 4 University of W¨urzburg, Department of Biological Psychology- Clinical Psychology and Psychotherapy, W¨urzburg, Germany; 5 Goethe-University Frankfurt, Department of Psychiatry Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany; 6 University of Marburg, Section for Clinical Psychology and Psychotherapy, Marburg, Germany; 7 University of Marburg, Department of Psychiatry, Marburg, Germany; 8 University of M¨unster, Department of Psychiatry and Psychotherapy, M¨unster, Germany Panic disorder (PD) is an anxiety disorder with a lifetime prevalence of 1−3% characterized by recurring panic attacks. Cognitive behavioral therapy (CBT) is a highly effective therapy option for many patients with PD. Nevertheless, treatment resistance in 20−40% of all patients goes along with a high individual and socioeconomic burden. This accentuates the need for a better understanding of the mechanisms of action of therapeutic interventions. Epigenetic patterns like methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD) and are hypothesized to mediate treatment success and resistance, respectively. Plasticity of epigenetic patterns might constitute a key mechanism of successful fear extinction. The present psychotherapy-epigenetic study for the first time investigated MAOA gene methylation changes during the course of a psychotherapeutic intervention in PD patients as a possible correlate of treatment success. First, DNA methylation at 13 CpG sites in the exonI/intronI region of the MAOA gene was analyzed and compared between female Caucasian PD patients (N = 28; age (mean ± s.d.): 34.57±8.51 years; discovery sample) and age- and sex-matched healthy controls (N = 28, age (mean ± s.d.): 34.96±9.02 years) via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. Furthermore, MAOA methylation was analyzed at baseline (T0) and after (T1) a standardized 6-week cognitive behavioral therapy (CBT) in PD patients of the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent replication sample of patients with PD undergoing an intensified CBT (N = 20; age: 33.55±11.15 years).
P.1.a. Basic and clinical neuroscience − Genetics and epigenetics
S167
In the discovery sample, PD patients showed lower MAOA methylation than healthy controls (P < 0.001) and baseline PD severity correlated negatively with MAOA methylation at T0 (P = 0.01). Additionally, PD patients were grouped into responders and non-responders to CBT with responders decreasing in the number of panic attacks at T1 and non-responders not differing or even increasing in the number of experienced attacks after CBT. Responders displayed a significant increase in average MAOA methylation (mean change: +3.4%), while in nonresponders average methylation decreased (−2.0%) (P = 0.001). Remarkably, responders reached average MAOA methylation level of healthy controls after CBT. Convergingly, in the replication sample symptom reduction after CBT correlated significantly with an increase in MAOA methylation (average methylation: r = 0.42, single CpG sites: r = 0.01–0.57), reaching statistical significance for methylation at 5 out of 12 CpG sites (P = 0.020–0.030). The present psychotherapy-epigenetic study supports and replicates previous evidence for MAOA DNA hypomethylation as a risk marker of PD. Additionally, the results for the first time suggest restitution of altered MAOA methylation patterns as a potential epigenetic correlate of treatment response to CBT in PD. Further replication is warranted to confirm MAOA methylation patterns and their plasticity as a peripheral biomarker of disease risk and treatment response in PD. The developing idea of epigenetic signatures as a mechanism of action of psychotherapeutic response is hoped to contribute to a more effective treatment of anxiety disorders, e.g. by promoting psychotherapeutic or pharmacological options inducing epigenetic changes for longterm extinction effects.
InfinitiTM Analyzer, using also the the 24-item Italian version of the Brief Psychiatric Rating Scale (BPRS-24) Ver. 4.0 to measure treatment response or failure. Response to treatment was defined by a change in BPRS-24 score 25% as evaluated at baseline (T0) and at stable treatment (Tdays) under 100% of medications adherence. DeltaBPRS-24 score <25% identified a TF. BPRS was evaluated by at least two 6-years experienced treating psychiatrists in blinded fashion. Results: Ten revolving door patients were valuated after their admission in psychiatric clinical unit and, according to variation of BPRS after 14 days, showed treatment failure. The revolving-door (RD) condition is a periodical patients readmission without symptoms improvement raising costs in psychiatric settings. Their CYP2D6 polymorphism was: patient 1 (*2A/*5), 2 (*1/*2A), 3 (*2A/*4), 4 (*4/*17), 5 (*2A/*4), 6 (*9/*41), 7 (*2/*4/*10/*41/*XN), 8 (*2A/*2A), 9 (*2A/*4), 10 (*2A/*2A). 3 of these mutations involve 100% enzyme activity, 4 involve 50% enzyme activity, 2 involve <50% enzyme activity, and 1 is a new type of mutation under investigation. Conclusions: In the present study we demonstrate that the knowledge of CYP2D6 genotype is useful for both the reduction of therapeutic attempt during patient clinical history, and a guide toward a better patient management. We personalized patients’ therapy, according to the specific CYP2D6 polymorphism, with subsequent clinical improvement of all patients. In presence of a Poor Metabolizer phenotype, i.e. mutations strongly reducing CYP2D6 EA (50% < EA 0), the choice of non-CYP2D6 metabolized drugs is strongly suggested. Conversely, in presence of a Rapid /Ultra rapid Metabolizer phenotype, i.e., mutations inducing CYP2D6 EA (EA >100, a reduction of drug dosage is needed.
P.1.a.008 CYP2D6 genotype polymorphism: tailored treatments in psychiatric patients
References [1] Ravyn, D., Ravyn, V., Lowney, R., Nasrallah, H.A., 2013. CYP450 pharmacogenetic treatment strategies for antipsychotics: a review of the evidence. Schizophr Res 149, 1−14. [2] Savino, M., Seripa, D., Gallo, A.P., Garrubba, M., D’Onofrio, G., Bizzarro, A., et al., 2011. Effectiveness of ahigh-throughput genetic analysis in the identification of responders/non-responders to CYP2D6metabolized drugs. Clin Lab 57, 887–893. [3] Stingl, J., Viviani, R., 2015. Polymorphism in CYP2D6 and CYP2C19, members of the cytochrome P450 mixed-function oxidase system, in the metabolism of psychotropic drugs. J Intern Med 277, 167–177.
M. La Montagna1 ° , E. Stella1 , D. Seripa2 , G. Miscio2 , A. Rinaldi1 , A. Bellomo1 , M. Lozupone1 1 University of Foggia, Department of Mental Health - Psychiatric Unit, Foggia, Italy; 2 IRCCS Casa Sollievo della Sofferenza, Department of Medical Sciences, San Giovanni Rotondo, Italy Introduction: Psychiatric disorders, mainly bipolar disorders (Bds), are chronic diseases characterized by repeated and severe changes in mood, leading to significant mental and social impairments with an increased risk for suicide, and thus among the most important causes of death and disability worldwide. Another very important characteristic is the presence of recurrent therapeutic failures (TFs), regardless of the initial choice of psychiatric medication. Many patients didn’t respond sufficiently to the treatments chosen, according to international guidelines. These medications are frequently CYP2D6 substrates. Cytochrome P450 (CYP) 2D6 may partially explain this clinical difficulties, thanks to interindividual variations in drug-metabolizing enzyme [1−3]. Some commonly used drugs CYP2D6 inhibitors can dramatically lower a patient’s enzymatic activity (EA) and thereby shift the patient metabolic capacity toward the low end of the activity distribution. CYP2D6 genotype has been shown to be associated with antidepressant, antipsychotic and mood stabilizers outcomes across several dimensions. Aims: To assess the specific CYP2D6 polymorphism of the enrolled patients and, according to these results, to tailor psychiatric medication choice and dose. Methods: We analyzed 16 clinical relevant polymorphisms CYP2D6 genotype in Psychiatric Unit of Foggia, by means of the
P.1.a.009 Nine differentially expressed genes from a post mortem study and their association with suicidal status in a sample of suicide completers, attempters and controls M. Balestri1 ° , C. Crisafulli2 , L. Donato2 , I. Giegling3 , R. Calati4 , N. Antypa1 , B. Schneider5 , D. Marusic6 , M.E. Tarozzi1 , M. Paragi7 , A.M. Hartmann3 , B. Konte3 , A. Marsano1 , A. Serretti1 , D. Rujescu3 1 University of Bologna, Department of Biomedical and NeuroMotor Sciences, Bologna, Italy; 2 University of Messina, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Messina, Italy; 3 University of Halle, Department of Psychiatry, Halle, Germany; 4 IRCCS Brescia, Centro S. Giovanni di Dio- Fatebenefratelli, Brescia, Italy; 5 LVR-Clinic- Cologne, Department of Addiction- LVR-ClinicCologne, Cologne, Germany; 6 University of Primorska, Mental Health Department- PINT, Primorska, Slovenia; 7 Institute of Public Health of the Republic of Slovenia, Institute of Public Health, Slovenia, Slovenia Background: Several lines of evidence indicate that suicidal behaviour is partly heritable, with multiple genes implicated in its
P.1.a. Basic and clinical neuroscience − Genetics and epigenetics
P.1.a.006 Hot genes in schizophrenia: case-control, pharmacogenetics and exploratory analyses in two independent samples S. Porcelli1 ° , S.J. Lee2 , C. Han3 , A.A. Patkar4 , D. De Ronchi5 , A.R. Atti5 , A. Serretti5 , C.U. Pae2 1 Universit`a di Bologna, Department of Biomedical and NeuroMotor Sciences, Bologna, Italy; 2 The Catholic University of Korea College of Medicine, Department of Psychiatry, Seoul, South-Korea; 3 College of Medicine, Department of Psychiatry, Seoul, South-Korea; 4 Duke University Medical Center, Department of Psychiatry and Behavioural Sciences, Durham, USA; 5 University of Bologna, Department of Biomedical and NeuroMotor Sciences, Bologna, Italy Introduction: Although environmental factors play a relevant role in schizophrenia (SCZ) pathogenesis, high heritability points to a major role for inherited genetic variants in the etiology of SCZ. Similarly, a genetic contribution for antipsychotic response (AR) has been suggested. Recently, a set of genes was detected through a genome-wide association study (GWAS) approach in the largest sample of SCZ patients and controls even investigated. Thus, currently they are considered as the most promising genes in SCZ pathogenesis [1]. Aims: We investigated the effects of genetic variants within five of these promising genes − i.e. PPP3CC, RORA, SP4, ST8SIA2 and ZNF804A − in two independent samples in order to confirm GWAS results in two well-phenotyped samples and to better elucidate their specific role through a number of exploratory analyses. Methods: We recruited a Korean sample of 176 SCZ patients and 326 healthy controls and an Italian sample of 83 SCZ patients and 194 healthy controls. The PANSS was used to assess psychopathological severity and antipsychotic response (AR). Several clinical features were recorded in both samples. Differences in the allelic and genotype frequencies were calculated using the c2 statistics. Traditional statistical analyses were performed using “Statistica” package while test for association using multimarker haplotypes were performed using the statistic environment “R cran”, package “haplo.score”. Differences in the genotype frequencies were calculated using the c2 statistics. Repeated measure Analysis of Variance was used to investigate the AR. The main outcome measures were: (1) differences among genotypic frequencies between cases and controls and (2) influence of the SNPs on clinical improvement, as measured by PANSS scale. Furthermore, we performed a number of exploratory analyses in order to better dissect the role of these genes in psychopathological features. Results: In the Korean sample RORA rs10438338 was associated with SCZ (p = 0.03) as well as haplotype rs2282888rs2237304-rs10272006-rs12673091 within SP4 gene (p = 0.02). In the Italian sample 3 PPP3CC variants (rs11780915 p = 0.006; rs10108011 p = 0.01; rs2249098 p = 0.0004), ZNF804A rs1344706 (p = 0.02) and SP4 rs12673091 (p = 0.02) were associated with SCZ. The haplotype rs11780915-rs10108011-rs2249098 within PPP3CC gene and the haplotype rs7603001-rs1344706 within ZNF804A gene were associated with SCZ as well (respectively p = 0.03 and p = 0.02). Further, several RORA variants were associated with AR (Korean sample: rs1871858 p = 0.02; rs12900122 p = 0.06, rs17204440 p = 0.02, haplotype rs1020729-rs1871858 p = 0.01; Italian sample: rs12900122 p = 0.003). In the Italian sample also 2 SP4 variants (rs2282888 p = 0.02; rs10272006 p = 0.02) and ST8SIA2 rs4777989 (p = 0.04) were associated with AR. Exploratory analyses suggested that: (1) PPP3CC, ST8SIA2
and SP4 genes may be implicated in the develop and severity of psychotic symptoms, (2) RORA gene may play a role in AR, particularly of negative symptomatology, as well as ZNF804A gene. Conclusions: Considering limitations linked to the sample size and candidate genes approach, our results further support a role for these gene in SCZ, as well as in AR. Analyses in well phenotyped samples could help researchers to refine the role of these genes for further, focused investigations. References [1] Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 511, 421–427.
P.1.a.007 Monoamine oxidase A (MAOA) gene hypomethylation in panic disorder − an epigenetic risk pattern reversed by psychotherapy? C. Ziegler1 ° , J. Richter2 , M. Mahr1 , A. Gajewska1 , M.A. Schiele1 , T. Lang3 , P. Pauli4 , A. Reif5 , W. Rief6 , T. Kircher7 , V. Arolt8 , A.O. Hamm2 , J. Deckert1 , K. Domschke1 1 University Hospital of W¨urzburg, Department of Psychiatry Psychosomatics and Psychotherapy, W¨urzburg, Germany; 2 University of Greifswald, Institute of Psychology, Greifswald, Germany; 3 University of Bremen, Outpatient Psychotherapy Treatment Center, Bremen, Germany; 4 University of W¨urzburg, Department of Biological Psychology- Clinical Psychology and Psychotherapy, W¨urzburg, Germany; 5 Goethe-University Frankfurt, Department of Psychiatry Psychosomatic Medicine and Psychotherapy, Frankfurt, Germany; 6 University of Marburg, Section for Clinical Psychology and Psychotherapy, Marburg, Germany; 7 University of Marburg, Department of Psychiatry, Marburg, Germany; 8 University of M¨unster, Department of Psychiatry and Psychotherapy, M¨unster, Germany Panic disorder (PD) is an anxiety disorder with a lifetime prevalence of 1−3% characterized by recurring panic attacks. Cognitive behavioral therapy (CBT) is a highly effective therapy option for many patients with PD. Nevertheless, treatment resistance in 20−40% of all patients goes along with a high individual and socioeconomic burden. This accentuates the need for a better understanding of the mechanisms of action of therapeutic interventions. Epigenetic patterns like methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD) and are hypothesized to mediate treatment success and resistance, respectively. Plasticity of epigenetic patterns might constitute a key mechanism of successful fear extinction. The present psychotherapy-epigenetic study for the first time investigated MAOA gene methylation changes during the course of a psychotherapeutic intervention in PD patients as a possible correlate of treatment success. First, DNA methylation at 13 CpG sites in the exonI/intronI region of the MAOA gene was analyzed and compared between female Caucasian PD patients (N = 28; age (mean ± s.d.): 34.57±8.51 years; discovery sample) and age- and sex-matched healthy controls (N = 28, age (mean ± s.d.): 34.96±9.02 years) via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. Furthermore, MAOA methylation was analyzed at baseline (T0) and after (T1) a standardized 6-week cognitive behavioral therapy (CBT) in PD patients of the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent replication sample of patients with PD undergoing an intensified CBT (N = 20; age: 33.55±11.15 years).
P.1.a. Basic and clinical neuroscience − Genetics and epigenetics
S167
In the discovery sample, PD patients showed lower MAOA methylation than healthy controls (P < 0.001) and baseline PD severity correlated negatively with MAOA methylation at T0 (P = 0.01). Additionally, PD patients were grouped into responders and non-responders to CBT with responders decreasing in the number of panic attacks at T1 and non-responders not differing or even increasing in the number of experienced attacks after CBT. Responders displayed a significant increase in average MAOA methylation (mean change: +3.4%), while in nonresponders average methylation decreased (−2.0%) (P = 0.001). Remarkably, responders reached average MAOA methylation level of healthy controls after CBT. Convergingly, in the replication sample symptom reduction after CBT correlated significantly with an increase in MAOA methylation (average methylation: r = 0.42, single CpG sites: r = 0.01–0.57), reaching statistical significance for methylation at 5 out of 12 CpG sites (P = 0.020–0.030). The present psychotherapy-epigenetic study supports and replicates previous evidence for MAOA DNA hypomethylation as a risk marker of PD. Additionally, the results for the first time suggest restitution of altered MAOA methylation patterns as a potential epigenetic correlate of treatment response to CBT in PD. Further replication is warranted to confirm MAOA methylation patterns and their plasticity as a peripheral biomarker of disease risk and treatment response in PD. The developing idea of epigenetic signatures as a mechanism of action of psychotherapeutic response is hoped to contribute to a more effective treatment of anxiety disorders, e.g. by promoting psychotherapeutic or pharmacological options inducing epigenetic changes for longterm extinction effects.
InfinitiTM Analyzer, using also the the 24-item Italian version of the Brief Psychiatric Rating Scale (BPRS-24) Ver. 4.0 to measure treatment response or failure. Response to treatment was defined by a change in BPRS-24 score 25% as evaluated at baseline (T0) and at stable treatment (Tdays) under 100% of medications adherence. DeltaBPRS-24 score <25% identified a TF. BPRS was evaluated by at least two 6-years experienced treating psychiatrists in blinded fashion. Results: Ten revolving door patients were valuated after their admission in psychiatric clinical unit and, according to variation of BPRS after 14 days, showed treatment failure. The revolving-door (RD) condition is a periodical patients readmission without symptoms improvement raising costs in psychiatric settings. Their CYP2D6 polymorphism was: patient 1 (*2A/*5), 2 (*1/*2A), 3 (*2A/*4), 4 (*4/*17), 5 (*2A/*4), 6 (*9/*41), 7 (*2/*4/*10/*41/*XN), 8 (*2A/*2A), 9 (*2A/*4), 10 (*2A/*2A). 3 of these mutations involve 100% enzyme activity, 4 involve 50% enzyme activity, 2 involve <50% enzyme activity, and 1 is a new type of mutation under investigation. Conclusions: In the present study we demonstrate that the knowledge of CYP2D6 genotype is useful for both the reduction of therapeutic attempt during patient clinical history, and a guide toward a better patient management. We personalized patients’ therapy, according to the specific CYP2D6 polymorphism, with subsequent clinical improvement of all patients. In presence of a Poor Metabolizer phenotype, i.e. mutations strongly reducing CYP2D6 EA (50% < EA 0), the choice of non-CYP2D6 metabolized drugs is strongly suggested. Conversely, in presence of a Rapid /Ultra rapid Metabolizer phenotype, i.e., mutations inducing CYP2D6 EA (EA >100, a reduction of drug dosage is needed.
P.1.a.008 CYP2D6 genotype polymorphism: tailored treatments in psychiatric patients
References [1] Ravyn, D., Ravyn, V., Lowney, R., Nasrallah, H.A., 2013. CYP450 pharmacogenetic treatment strategies for antipsychotics: a review of the evidence. Schizophr Res 149, 1−14. [2] Savino, M., Seripa, D., Gallo, A.P., Garrubba, M., D’Onofrio, G., Bizzarro, A., et al., 2011. Effectiveness of ahigh-throughput genetic analysis in the identification of responders/non-responders to CYP2D6metabolized drugs. Clin Lab 57, 887–893. [3] Stingl, J., Viviani, R., 2015. Polymorphism in CYP2D6 and CYP2C19, members of the cytochrome P450 mixed-function oxidase system, in the metabolism of psychotropic drugs. J Intern Med 277, 167–177.
M. La Montagna1 ° , E. Stella1 , D. Seripa2 , G. Miscio2 , A. Rinaldi1 , A. Bellomo1 , M. Lozupone1 1 University of Foggia, Department of Mental Health - Psychiatric Unit, Foggia, Italy; 2 IRCCS Casa Sollievo della Sofferenza, Department of Medical Sciences, San Giovanni Rotondo, Italy Introduction: Psychiatric disorders, mainly bipolar disorders (Bds), are chronic diseases characterized by repeated and severe changes in mood, leading to significant mental and social impairments with an increased risk for suicide, and thus among the most important causes of death and disability worldwide. Another very important characteristic is the presence of recurrent therapeutic failures (TFs), regardless of the initial choice of psychiatric medication. Many patients didn’t respond sufficiently to the treatments chosen, according to international guidelines. These medications are frequently CYP2D6 substrates. Cytochrome P450 (CYP) 2D6 may partially explain this clinical difficulties, thanks to interindividual variations in drug-metabolizing enzyme [1−3]. Some commonly used drugs CYP2D6 inhibitors can dramatically lower a patient’s enzymatic activity (EA) and thereby shift the patient metabolic capacity toward the low end of the activity distribution. CYP2D6 genotype has been shown to be associated with antidepressant, antipsychotic and mood stabilizers outcomes across several dimensions. Aims: To assess the specific CYP2D6 polymorphism of the enrolled patients and, according to these results, to tailor psychiatric medication choice and dose. Methods: We analyzed 16 clinical relevant polymorphisms CYP2D6 genotype in Psychiatric Unit of Foggia, by means of the
P.1.a.009 Nine differentially expressed genes from a post mortem study and their association with suicidal status in a sample of suicide completers, attempters and controls M. Balestri1 ° , C. Crisafulli2 , L. Donato2 , I. Giegling3 , R. Calati4 , N. Antypa1 , B. Schneider5 , D. Marusic6 , M.E. Tarozzi1 , M. Paragi7 , A.M. Hartmann3 , B. Konte3 , A. Marsano1 , A. Serretti1 , D. Rujescu3 1 University of Bologna, Department of Biomedical and NeuroMotor Sciences, Bologna, Italy; 2 University of Messina, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Messina, Italy; 3 University of Halle, Department of Psychiatry, Halle, Germany; 4 IRCCS Brescia, Centro S. Giovanni di Dio- Fatebenefratelli, Brescia, Italy; 5 LVR-Clinic- Cologne, Department of Addiction- LVR-ClinicCologne, Cologne, Germany; 6 University of Primorska, Mental Health Department- PINT, Primorska, Slovenia; 7 Institute of Public Health of the Republic of Slovenia, Institute of Public Health, Slovenia, Slovenia Background: Several lines of evidence indicate that suicidal behaviour is partly heritable, with multiple genes implicated in its