CRY1 Variations Impacts on the Depressive Relapse Rate in a Sample of Bipolar Patients

Antonio Drago,Barbara Monti,Diana De Ronchi,Alessandro Serretti 대한신경정신의학회 2015 PSYCHIATRY INVESTIGATION Vol.12 No.1

ObjectiveaaA relevant part of the social and personal burden caused by Bipolar Disorder (BD) is related to depressive phases. Authors investigated the genetic impact of a set of variations located in CRY1, a gene involved in the control of the circadian rhythms, towards depressive episodes in a sample of bipolar patients from the STEP-BD sample. As a secondary analysis, CYR1 variations were analyzed as predictors of sleep disruption. Methodsaa654 bipolar patients were included in the analysis. Data were available genome-wide. The part of the genome coding for the CRY1 was imputed and pruned according to standards in the field. 7 SNPs were available for the analysis. A correction for multitesting was applied and we had sufficient power (0.80) to detect a small-medium effect size (0.22) between two allelic frequencies each one represented by at least 300 subjects. ResultsaaIntronic rs10861688 was associated with the number of depressive events corrected for the times patients were assessed during the period of observation. In particular, AA subjects (n=21) had 4.46±3.15 events, AG (n=141) had 3.08±3.17 and GG (n=342) 2.65±2.97 (p=0.0048, beta=-0.22). No other significant associations were reported. ConclusionaaWe bring further evidence that genes involved in the regulation of circadian rhythms may be relevant to depressive bipolar phases. Independent confirmation analyses are mandatory.

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.

Dysbindin gene (DTNBP1) and schizophrenia in Korean population

Pae, Chi-Un,Mandelli, Laura,De Ronchi, Diana,Kim, Jung-Jin,Jun, Tae-Youn,Patkar, Ashwin A.,Serretti, Alessandro Springer-Verlag 2009 European archives of psychiatry and clinical neuro Vol.259 No.3

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>

Effect of the Dysbindin Gene on Antimanic Agents in Patients with Bipolar I Disorder

Dong-Hwan Yun,Chi-Un Pae,Antonio Drago,Laura Mandelli,Diana De Ronchi,Ashwin A. Patkar,In Ho Paik,Alessandro Serretti,Jung-Jin Kim 대한신경정신의학회 2008 PSYCHIATRY INVESTIGATION Vol.5 No.2

Objective: We previously reported an association between dysbindin gene (DTNBP1) variants and bipolar I disorder (BID). This paper expands upon previous findings suggesting that DTNBP1 variants may play a role in the response to acute mood stabilizer treatment. Methods: A total of 45 BID patients were treated with antimanic agents (lithium, valproate, or carbamazepine) for an average of 36.52 (±19.87) days. After treatment, the patients were evaluated using the Clinical Global Impression (CGI) scale and the Young Mania Rating Scale (YMRS) and genotyped for their DTNBP1 variants (rs3213207 A/G, rs1011313 C/T, rs2005976 G/A, rs760761 C/T and rs2619522 A/C). Results: There was no association between the variants investigated and response to mood stabilizer treatment, even after considering possible stratification factors. Conclusion: Although the small number of subjects is an important limitation in our study, DTNBP1 does not seem to be involved in acute antimanic efficacy. Objective: We previously reported an association between dysbindin gene (DTNBP1) variants and bipolar I disorder (BID). This paper expands upon previous findings suggesting that DTNBP1 variants may play a role in the response to acute mood stabilizer treatment. Methods: A total of 45 BID patients were treated with antimanic agents (lithium, valproate, or carbamazepine) for an average of 36.52 (±19.87) days. After treatment, the patients were evaluated using the Clinical Global Impression (CGI) scale and the Young Mania Rating Scale (YMRS) and genotyped for their DTNBP1 variants (rs3213207 A/G, rs1011313 C/T, rs2005976 G/A, rs760761 C/T and rs2619522 A/C). Results: There was no association between the variants investigated and response to mood stabilizer treatment, even after considering possible stratification factors. Conclusion: Although the small number of subjects is an important limitation in our study, DTNBP1 does not seem to be involved in acute antimanic efficacy.

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.

Dimensions of Delusions in Major Depression: Socio-demographic and Clinical Correlates in an Unipolar-Bipolar Sample

Leonardo Zaninotto,Daniel Souery,Raffaella Calati,Giovanni Camardese,Luigi Janiri,Stuart Montgomery,Siegfried Kasper,Joseph Zohar,Diana De Ronchi,Julien Mendlewicz,Alessandro Serretti 대한정신약물학회 2015 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.13 No.1

Objective: The present study aims at exploring associations between a continuous measure of distorted thought contents and a set of demographic and clinical features in a sample of unipolar/bipolar depressed patients. Methods: Our sample included 1,833 depressed subjects. Severity of mood symptoms was assessed by the 21 items Hamilton Depression Rating Scale (HAM-D). The continuous outcome measure was represented by a delusion (DEL) factor, extracted from HAM-D items and including items: 2 (“Feelings of guilt”), 15 (“Hypochondriasis”), and 20 (“Paranoid symptoms”). Each socio-demographic and clinical variable was tested by a generalized linear model test, having depressive severity (HAM-D score−DEL score) as the covariate. Results: A family history of major depressive disorder (MDD; p=0.0006), a diagnosis of bipolar disorder, type I ( p=0.0003), a comorbid general anxiety disorder (p<0.0001), and a higher number of manic episodes during lifetime (p<0.0001), were all associated to higher DEL scores. Conversely, an older age at onset (p<0.0001) and a longer duration of hospitalization for depression over lifetime (p=0.0003) had a negative impact over DEL scores. On secondary analyses, only the presence of psychotic features (p<0.0001) and depressive severity (p<0.0001) were found to be independently associated to higher DEL scores. Conclusion: The retrospective design and a non validated continuous measure for distorted thought contents were the main limitations of our study. Excluding the presence of psychotic features and depressive severity, no socio-demographic or clinical variable was found to be associated to our continuous measure of distorted thinking in depression.

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>

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>