The Influence of AHI1 Variants on the Diagnosis and Treatment Outcome in Schizophrenia

Porcelli, Stefano,Pae, Chi-Un,Han, Changsu,Lee, Soo-Jung,Patkar, Ashwin A.,Masand, Prakash S.,Balzarro, Beatrice,Alberti, Siegfried,De Ronchi, Diana,Serretti, Alessandro MDPI 2015 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.16 No.2

<P>The present study aimed to explore whether four single nucleotide polymorphisms (SNPs) within the AHI1 gene could be associated with schizophrenia (SCZ) and whether they could predict the clinical outcomes in SCZ patients treated with antipsychotics. Four hundred twenty-six (426) in-patients with SCZ and 345 controls were genotyped for four AHI1 SNPs (rs11154801, rs7750586, rs9647635 and rs9321501). Baseline and clinical measures for SCZ patients were assessed through the Positive and Negative Syndrome Scale (PANSS). Allelic and genotypic frequencies in SCZ subjects were compared with those of controls using the χ<SUP>2</SUP> statistics. The repeated-measure ANOVA was used for the assessment of treatment outcomes measured by PANSS changes. The case-control analysis did not show any difference in the genotypic distribution of the SNPs, while in the allelic analysis, a weak association was found between the rs9647635 A allele and SCZ. Furthermore, in the haplotype analysis, three haplotypes resulted in being associated with SCZ. On the other hand, two SNPs (rs7750586 and rs9647635) were associated with clinical improvement of negative symptoms in the allelic analysis, although in the genotypic analysis, only trends of association were found for the same SNPs. Our findings suggest a possible influence of AHI1 variants on SCZ susceptibility and antipsychotic response, particularly concerning negative symptomatology. Subsequent well-designed studies would be mandatory to confirm our results due to the methodological shortcomings of the present study.</P>

CACNA1C gene and schizophrenia: a case–control and pharmacogenetic study

Porcelli, Stefano,Lee, Soo-Jung,Han, Changsu,Patkar, Ashwin A.,Serretti, Alessandro,Pae, Chi-Un Wolters Kluwer Health, Inc. All rights reserved. 2015 PSYCHIATRIC GENETICS Vol.25 No.4

AIM: The present study aimed to explore whether 24 single nucleotide polymorphisms (SNPs) within the CACNA1C gene were associated with schizophrenia (SCZ) and antipsychotic response. METHODS: A sample of 176 SCZ inpatients and 326 healthy controls of Korean ethnicity was collected for this purpose. Psychopathological status was evaluated at baseline and at discharge using the Positive and Negative Syndrome Scale (PANSS). RESULTS: In the case–control study, rs1006737 (P=0.05) and rs2239104 (P=0.03) were associated with SCZ. Further, the rs10848635–rs1016388–rs1006737 haplotype was also associated with SCZ (P=0.03, simulate P=0.02). In the pharmacogenetic analyses, we did not find any association among the investigated SNPs and improvement in the PANSS total score. However, rs723672 and rs1034936 were associated with improvement in the PANSS positive subscale (respectively, P=0.02 and 0.05), rs2283271 in the negative subscale (P=0.01), rs10848635 and rs1016388 in the general subscale (respectively, P=0.03 and 0.04), and the rs3819536–rs2238062 haplotype (global statistics, P=0.1; simulate P=0.04). CONCLUSIONS: Our findings further support a role for the CACNA1C gene, particularly for the rs1006737, in SCZ. Further, five SNPs were associated with improvement in PANSS subscales, suggesting a role for this gene in antipsychotic response as well. However, taking into account the limitations of the present study, further research is needed to confirm our findings.

Abelson Helper Integration Site-1 Gene Variants on Major Depressive Disorder and Bipolar Disorder

Stefano Porcelli,배치운,한창수,이수정,Ashwin A Patkar,Prakash S. Masand,Beatrice Balzarro,Siegfried Alberti,Diana De Ronchi,Alessandro Serretti 대한신경정신의학회 2014 PSYCHIATRY INVESTIGATION Vol.11 No.4

Objective The present study aimed to explore whether 4 single nucleotide polymorphisms (SNPs) within the AHI1 gene could be associated with major depressive disorder (MD) and bipolar disorder (BD), and whether they could predict clinical outcomes in mood disorders. Methods One hundred and eighty-four (184) patients with MD, 170 patients with BD and 170 healthy controls were genotyped for 4 AHI1 SNPs (rs11154801, rs7750586, rs9647635 and rs9321501). Baseline and final clinical measures for MD patients were assessed through the Hamilton Rating Scale for Depression (HAM-D). Allelic and genotypic frequencies in MD and BD subjects were compared with those of each disorder and healthy group using the χ2 statistics. Repeated measures ANOVA was used to test possible influences of SNPs on treatment efficacy. Results The rs9647635 A/A was more represented in subjects with BD as compared with MD and healthy subjects together. The rs9647635 A/A was also more presented in patients with MD than in healthy subjects. With regard to the allelic analysis, rs9647635 A allele was more represented in subjects with BD compared with healthy subjects, while it was not observed between patients with MD and healthy subjects. Conclusion Our findings provide potential evidence of an association between some variants of AHI1 and mood disorders susceptibility but not with clinical outcomes. However, we will need to do more adequately-powered and advanced association studies to draw any conclusion due to clear limitations.

Age of Onset in Schizophrenia Spectrum Disorders: Complex Interactions between Genetic and Environmental Factors

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.

Influence of GRIA1, GRIA2 and GRIA4 polymorphisms on diagnosis and response to treatment in patients with major depressive disorder.

Chiesa, Alberto,Crisafulli, Concetta,Porcelli, Stefano,Han, Changsu,Patkar, Ashwin A,Lee, Soo-Jung,Park, Moon Ho,Jun, Tae-Youn,Serretti, Alessandro,Pae, Chi-Un Springer International 2012 European archives of psychiatry and clinical neuro Vol.262 No.4

<P>The present study is aimed to exploring whether some single nucleotide polymorphisms (SNPs) within GRIA1, GRIA2 and GRIA4 could be associated with major depressive disorder (MDD) and whether they could predict clinical outcomes in Korean in-patients, respectively, treated with antidepressants. One hundred forty-five (145) patients with MDD and 170 healthy controls were genotyped for 17 SNPs within GRIA1, GRIA2 and GRIA4. Baseline and final clinical measures, including the Montgomery-Asberg Depression Rating Scale (MADRS) for patients with MDD, were recorded. No association was observed between alleles, genotypes and haplotypes under investigation and clinical and demographical variables. As a secondary finding, a marginal association was observed between rs4302506 and rs4403097 alleles within GRIA2 and age of onset in patients with MDD. Our findings provide evidence for a possible association between rs4302506 and rs4403097 SNPs and age of onset in patients with MDD. However, taking into account that the several limitations of our study including the moderately small sample size of our study, our findings should be considered with caution and further research is needed to draw more definitive conclusions.</P>

No Effect of Serotoninergic Gene Variants on Response to Interpersonal Counseling and Antidepressants in Major Depression

Alessandro Serretti,Chiara Fabbri,Silvia Pellegrini,Stefano Porcelli,Pierluigi Politi,Silvio Bellino,Marco Menchetti,Veronica Mariotti,Cristina Demi,Valentina Martinelli,Marco Cappucciati,Paola Bozzat 대한신경정신의학회 2013 PSYCHIATRY INVESTIGATION Vol.10 No.2

Objective-Gene variants within the serotonin pathway have been associated with major depressive disorder (MDD) treatment outcomes, however a possible different modulation on pharmacological or psychological treatments has never been investigated. Methods-One hundred sixty MDD patients were partially randomized to either inter-personal counseling (IPC) or antidepressants. The primary outcome was remission at week 8. Five serotonergic polymorphisms were investigated (COMT rs4680, HTR1A rs6295, HTR2A rs2224721, HTR2A rs7997012 and SLC6A4 rs421417). Results-IPC (n=43) and antidepressant (n=117) treated patients did not show any difference in remission rates at week 8 (corrected for baseline severity, age and center). None of the studied gene variants impacted on response and remission rates at week 8 neither in the IPC nor in the antidepressant group. An analysis of the whole sample showed a trend of association between rs7997012 AA genotype and a better treatment outcome. Conclusion-Our study confirms that IPC is an effective psychological intervention comparable to antidepressants in mild-moderate MDD. Polymorphisms related to the serotonin system did not exert a major effect on clinical outcomes in none of the treatment groups.

Influence of <i>BDNF</i> Variants on Diagnosis and Response to Treatment in Patients with Major Depression, Bipolar Disorder and Schizophrenia

Pae, Chi-Un,Chiesa, Alberto,Porcelli, Stefano,Han, Changsu,Patkar, Ashwin A.,Lee, Soo-Jung,Park, Moon Ho,Serretti, Alessandro,De Ronchi, Diana S. Karger AG 2011 Neuropsychobiology Vol.65 No.1

<P><I>Aim:</I> The present study aimed to explore whether some single nucleotide polymorphisms (SNPs) within the <I>BDNF</I> gene could be associated with major depression (MD), bipolar disorder (BD) and schizophrenia, and whether they could predict clinical outcomes in Korean inpatients treated with antidepressants, mood stabilizers and antipsychotics, respectively. <I>Methods:</I> One hundred and forty-five patients with MD, 132 patients with BD, 221 patients with schizophrenia and 170 psychiatrically healthy controls were genotyped for 5 <I>BDNF</I> SNPs (rs2030324, rs7103873, rs10835210, rs11030101 and rs6265). Baseline and final clinical measures - including the Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale and Positive and Negative Symptoms Scale for patients with MD, BD and schizophrenia, respectively - were recorded. <I>Results:</I> rs10835210 CA and rs11030101 AT genotype frequencies were higher in BD and schizophrenia patients than in healthy and MD subjects. No significant association was found with clinical improvement. <I>Discussion:</I> Our findings provide evidence of an association between BDNF and BD and schizophrenia. However, taking into account the several limitations of our study, including the moderately small sample size, further research is needed to draw more definitive conclusions.</P><P>Copyright © 2011 S. Karger AG, Basel</P>