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Mandelli, L.,Wang, S. M.,Han, C.,Lee, S. J.,Patkar, A. A.,Masand, P. S.,Pae, C. U.,Serretti, A. Springer Science + Business Media 2017 ADVANCES IN THERAPY Vol.34 No.3
<P>Introduction: Ample evidence suggested a role of sigma-1 receptor in affective disorders since the interaction of numerous antidepressants with sigma receptors was discovered. A recent study on Japanese subjects found a genetic variant within the encoding gene SIGMAR1 (rs1800866A>C) associated with major depressive disorder (MDD). We aimed to evaluate the same polymorphism in both MDD and bipolar disorder (BD) as well as its relationship to response to treatment with antidepressants and mood stabilizers. Methods: A total of 238 MDD patients treated for an acute episode of depression, 132 BD patients in treatment with mood stabilizers for a manic or mixed episode, and 324 controls were genotyped for rs1800866. At discharge, response to treatments was evaluated in MDD and BD patients by the Hamilton Rating Scale for Depression (HRSD) and the Young Mania Rating Score (YMRS), respectively. Results: In our Korean sample, allele frequencies were different from those reported in other Asian and non-Asian populations. The CC genotype was associated with BD and, as a trend, with MDD. No significant effect was observed on response to antidepressants in MDD or mood stabilizers in BD, although the CC genotype was more frequent among BD patients experiencing a mixed episode. Conclusion: The present findings are the first to propose the putative role of genetic variants within SIGMAR1 and sigma-1 receptor in BD. Sigma-1 receptor can modulate a number of central neurotransmitter systems as well as some other signaling pathways (e.g., neurotrophin and growth factor signaling) which are seemingly involved in BD and other mood disorders.</P>
Laura Mandelli,Elena Toscano,Stefano Porcelli,Chiara Fabbri,Alessandro Serretti 대한신경정신의학회 2016 PSYCHIATRY INVESTIGATION Vol.13 No.2
In this study we evaluated the role of a candidate gene for major psychosis, Sialyltransferase (ST8SIA2), in the risk to develop a schizophrenia spectrum disorders, taking into account exposure to stressful life events (SLEs). Eight polymorphisms (SNPs) were tested in 94 Schizophreniainpatients and 176 healthy controls. Schizophrenia patients were also evaluated for SLEs in different life periods. None of the SNPs showed association with schizophrenia. Nevertheless, when crossing genetic variants with childhood SLEs, we could observe trends of interaction with age of onset. Though several limitations, our results support a protective role of ST8SIA2 in individuals exposed to moderate childhood stress.
Marco Calabrò,Laura Mandelli,Concetta Crisafulli,Soo-Jung Lee,Tae-Youn Jun,Sheng Min Wang,Ashwin A Patkar,Prakash S Masand,Changsu Han,Chi-Un Pae,Alessandro Serretti 대한정신약물학회 2019 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.17 No.3
Objective: Genetics factors are likely to play a role in the risk, clinical presentation and treatment outcome in major depressive disorder (MDD). In this study, we investigated the role of three candidate genes for MDD; calcium voltagegated channel subunit alpha1 C (CACNA1C ), cholinergic receptor nicotinic alpha 7 subunit (CHRNA7 ), and mitogenactivated protein kinase 1 (MAPK1 ). Methods: Two-hundred forty-two MDD patients and 326 healthy controls of Korean ancestry served as samples for the analyses. Thirty-nine single nucleotide polymorphisms (SNPs) within CACNA1C, CHRNA7, and MAPK1 genes were genotyped and subsequently tested for association with MDD (primary analysis) and other clinical features (symptoms’ severity, age of onset, history of suicide attempt, treatment outcome) (secondary analyses). Single SNPs, haplotypes and epistatic analyses were performed. Results: Single SNPs were not associated with disease risk and clinical features. However, a combination of alleles (haplotype) within MAPK1 was found associated with MDD-status. Secondary analyses detected a possible involvement of CACNA1C haplotype in resistance to antidepressant treatment. Conclusion: These data suggest a role for MAPK1 and CACNA1C in MDD risk and treatment resistance, respectively. However, since many limitations characterize the analysis, the results must be considered with great caution and verified.
Marco Calabrò,Laura Mandelli,Concetta Crisafulli,Marco Di Nicola,Roberto Colombo,Luigi Janiri,Soo-Jung Lee,Tae-Youn Jun,Sheng Min Wang,Prakash S Masand,Ashwin A Patkar,Changsu Han,Chi-Un Pae,Alessandr 대한정신약물학회 2020 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.18 No.2
Objective: Genetic variations in the gene encoding zinc finger protein 804A gene (ZNF804A) have been associated with major depression and bipolar disorder. In this work we focused on the potential influence of ZNF804A variations on the risk of developing specific sub-phenotypes as well as the individual response to available treatments. Methods: We used two samples of different ethnic origin: a Korean sample, composed by 242 patients diagnosed with major depression and 132 patients diagnosed with bipolar disorder and 326 healthy controls; an Italian sample composed 151 major depression subjects, 189 bipolar disorder subjects and 38 outpatients diagnosed for a primary anxiety disorder. Results: Our analyses reported an association of rs1344706 with psychotic phenotype in the cross-diagnostic pooled sample (geno p = 4.15 × 10−4, allelic p = 1.06 × 10−4). In the cross-diagnosis Italian sample but not in the Korean one, rs7597593 was involved with depressive symptoms improvement after treatment (geno p = 0.025, allelic p = 0.007). Conclusion: The present study evidenced the role of ZNF804A alterations in symptoms improvement after treatment. Both manic and depressive symptoms seem to be modulated by ZNF804A, though the latter was observed in the bipolar pooled sample only. The role of this factor is likely related to synaptic development and maintenance; however, further analyses will be needed to better understand the molecular mechanics involved with ZNF804A.
Dysbindin associated with selective serotonin reuptake inhibitor antidepressant efficacy
Pae, Chi-Un,Serretti, Alessandro,Mandelli, Laura,De Ronchi, Diana,Patkar, Ashwin A.,Jun, Tae-Youn,Kim, Jung-Jin,Lee, Chang-Uk,Lee, Soo-Jung,Lee, Chul,Paik, In-Ho Lippincott Williams Wilkins, Inc. 2007 PHARMACOGENETICS AND GENOMICS Vol.17 No.1
OBJECTIVE: Antidepressant drug efficacy is partially under genetic control and a number of gene variants have been associated with antidepressants efficacy over the last few years. In the search for further genes influencing antidepressant response we focused on the dysbindin gene (dystrobrevin-binding-protein 1, DTNBP1). BASIC METHODS: One hundred and four Korean inpatients affected by major depressive disorder were treated with various antidepressants at standard therapeutic daily doses and rated with the 10-items Montgomery–Åsberg Depression rating scale (MADRS) at baseline and discharge. Five DTNBP1 variants (rs3213207 A/G, rs1011313 C/T, rs2005976 G/A, rs760761 C/T and rs2619522 A/C) were analysed for all patients. RESULTS: Rs2005976 was found to be significantly associated with final MADRS scores, with the rarest A allele associated with higher final scores (P=0.00055), rs760761 also showed a significant association (P=0.0058) and rs2619522 showed a positive trend (P=0.025). Markers were not significantly associated with Clinical Global Impression Scale scores. Five marker haplotypes were mildly associated with MADRS final scores but when considering the block composed of the three single nucleotide polymorphisms individually associated with response (rs2005976, rs760761 and rs2619522), results were more marked (P=0.0096), with the more frequent G–C–A haplotype associated with a positive outcome. CONCLUSIONS: Despite limitations due to the sample size and the mild antidepressant response, we observed a significant association between DTNBP1 variants and antidepressant response.
No influence of FAT polymorphisms in response to aripiprazole.
Pae, Chi-Un,Chiesa, Alberto,Mandelli, Laura,De Ronchi, Diana,Serretti, Alessandro Springer-Verlag 2010 Journal of human genetics Vol.55 No.1
<P>The aim of this study was to investigate possible influences of a set of markers in the FAT gene (rs2306987, rs2306990, rs2637777 and rs2304865) on efficacy and tolerability of aripiprazole in the treatment of schizophrenic patients. Efficacy was assessed at baseline and weeks 1, 2, 4, 6, 8 and 12 using the Clinical Global Impression Severity and Improvement scale (CGI-S; CGI-I), the Brief Psychiatric Rating Scale and the Schedule for the Assessment of Negative Symptoms scale. Side effects were evaluated by means of the Simpson-Angus Scale for Extrapyramidal Symptoms, the Barnes Akathisia Scale and the Abnormal Involuntary Movement Scale. Multivariate analyses were employed to test possible influences of single nucleotide polymorphisms on clinical and safety variables. Analysis of haplotypes was also performed. No relevant association between FAT variants and clinical or safety scores was observed. Haplotype analysis did not reveal any significant association with clinical and safety scores at any time as well. Our data suggest no association between investigated alleles and genotypes in FAT and response to aripiprazole. However, because several limitations characterize the present study, further investigations on larger studies are required.</P>
Possible Modulatory Role of ARC Gene Variants in Mood Disorders
Concetta Crisafulli,Marco Calabrò,Laura Mandelli,Sheng Min Wang,Soo-Jung Lee,Changsu Han,Ashwin Patkar,Prakash Masand,Chi Un Pae,Daniel Souery,Julien Mendlewicz,Alessandro Serretti 대한정신약물학회 2021 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.19 No.1
Objective: The genetic background of mood disorders is gradually emerging through the use of large multicenter samples but a detailed phenotyping is complementary in elucidating the role of modulating variants. Methods: In the present paper we focused on the possible modulatory effects of ARC gene variants on two independent mood disorder samples of European (n = 246 bipolar disorder) and Korean (n = 132 bipolar disorder; n = 242 major depressive disorder [MDD]) ancestry. Results: No result survived Bonferroni correction, however we evidenced promising trend toward possible association between ARC gene variants and mood disorder phenotypes. In particular, we evidenced weak correlations of ARC single nucleotide polymorphisms with depressive symptoms severity (evaluated through Hamilton depression rating scale scores) in the MDD Korean (rs7465272) and European (rs11167152) samples. Additionally rs10110456 was found to be related to Family History, while rs7465272 was related to suicide risk in the Korean sample. Finally, rs7465272 was associated with body mass index in the European sample. Conclusion: Overall, ARC gene variants may have a partial role in modulatory effect on treatment efficacy or phenotypes of mood disorders. Further studies, on larger samples may provide a better understanding on the role of ARC gene variants in the symptom severity and treatment outcomes in patients with mood disorders.
Linda Sangalli,Domenico Dalessandri,Stefano Bonetti,Gualtiero Mandelli,Luca Visconti,Fabio Savoldi 대한치과교정학회 2022 대한치과교정학회지 Vol.52 No.1
Objective: Planning of incisal position is crucial for optimal orthodontic treatment outcomes due to its consequences on facial esthetics and occlusion. A systematic summary of the proposed parameters is presented. Methods: Studies on Google Scholar©, PubMed©, and Cochrane Library, providing quantitative information on optimal central incisor position were included. Results: Upper incisors supero-inferior position (4–5 mm to upper lip, 67–73 mm to axial plane through pupils), antero-posterior position (3–4 mm to Nasion-A, 3–6 mm to A-Pogonion, 9–12 mm to true vertical line, 5 mm to A-projection, 9–10 mm to coronal plane through pupils), bucco-lingual angulation (4–7° to occlusal plane perpendicular on models, 20–22° to Nasion-A, 57–58° to upper occlusal plane, 16–20° to coronal plane through pupils, 108–110° to anterior-posterior nasal spine), mesio-distal angulation (5° to occlusal plane perpendicular on models). Lower incisors supero-inferior position (41–48 mm to soft-tissue mandibular plane), antero-posterior position (3–4 mm to Nasion-B, 1–3 mm to A-Pogonion, 12–15 mm to true vertical line, 6–8 mm to coronal plane through pupils), bucco-lingual angulation (1-4° to occlusal plane perpendicular on models, 87–94° to mandibular plane, 68° to Frankfurt plane, 22–25° to Nasion-B, 105° to occlusal plane, 64° to lower occlusal plane, 21° to A-Pogonion), mesiodistal angulation (2° to occlusal plane perpendicular on models). Conclusions: Although these findings can provide clinical guideline, they derive from heterogeneous studies in terms of subject characteristics and reference methods. Therefore, the optimal incisal position remains debatable.
Pae, Chi-Un,Chiesa, Alberto,Mandelli, Laura,Patkar, Ashwin A.,Gibiino, Sara,Serretti, Alessandro Springer-Verlag 2010 Clinical drug investigation Vol.30 No.3
<P>Despite the increasing evidence relating to strategies for switching between different antipsychotics, little evidence is available about predictors of improvement or worsening while switching. In a previous study, we compared different options for switching to aripiprazole and found that patients with schizophrenia switched to aripiprazole with immediate discontinuation of the previous antipsychotic showed an increase in symptom severity after 1 week.</P>