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ABSTRACT: Gender differences in various clinical features of schizophrenia have been noted and estrogen has been regarded to play important roles. A few previous studies on the association between estrogen receptor (ER) genotypes and schizophrenia focused mainly on ER α gene but failed to report consistent results. The present study was designed to analyze the differences in the frequencies of both ERα and ERβ gene polymorphisms in subjects with schizophrenia compared to healthy controls among Korean population. Moreover, we investigate the association between different genotypes of ER genes and various clinical variables of schizophrenia. We observed that PvuII and XbaI polymorphisms of ERα gene showed significant differences between patients with schizophrenia and control groups (p=0.006). Among clinical variables, only the age of onset was related to RsaI genotype of ERβ gene (p=0.039). In conclusion, the present study suggests that ERα gene polymorphisms may be associated with the pathogenesis of schizophrenia and RsaI AA genotype of ERβ might have protective effect on age at onset of schizophrenia in Korean patients with schizophrenia.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 01/2012; 36(1):1-4. · 3.25 Impact Factor
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Seong-Su Lee,
Jeong-Seok Seo,
Sung-Rae Kim,
Jo-Eun Jeong,
Beom-Woo Nam,
Ju-Yul Lee,
Hee-Jin Lee,
Chul Lee,
Chang-Uk Lee, In-Ho Paik,
Jeong-Ho Chae,
Sook-Hee Chai,
Soon-Jib Yoo,
Wang-Youn Won,
Dai-Jin Kim
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ABSTRACT: Our aim was to evaluate the changes in blood glucose control and lipid profiles after 2-months of smoking cessation in healthy males.
Smoking abstinence was evaluated through self-report and urine cotinine levels. 12 individuals who succeeded in quitting smoking were analyzed. Fasting values of glucose and insulin were used to estimate the β-cell activity and insulin resistance was evaluated using the Homeostasis Model Assessment (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI).
The data showed that the subjects had a significant increase in weight, body mass index and fasting plasma glucose levels after smoking cessation. The HOMA-Insulin Resistance and the HOMA β-cell function increased significantly (p=0.005, p=0.047 respectively). The QUICKI showed a significant decrease (p=0.005). In addition, the low-density lipoprotein cholesterol levels decreased significantly (p=0.028); however, changes in the high-density lipoprotein cholesterol, the triglyceride and total cholesterol levels were not significant (p=0.284, p=0.445 respectively).
During the initial stage of smoking abstinence, insulin resistance increased and insulin sensitivity decreased due to elevated body weight and fat composition. Therefore, it is important to educate individuals that stop smoking about the necessity of weight control during smoking cessation programs.
Psychiatry investigation 06/2011; 8(2):149-54. · 0.99 Impact Factor
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ABSTRACT: Post-menopausal women experience variable biological and psychological changes. The effect of reduced levels of estrogen can effect on post-menopausal depression. Estrogen triggers physiological responses by binding to the estrogen receptor (ER). Two subtypes of ER, ERa and ERb are now known. We investigated the significance of ERa and ERb polymorphisms and post-menopasal depression in this study. Forty three women with post-menopausal depression and 63 post-menopausal women without depression as normal controls were recruited. Polymerase chain reaction-restriction fragment length polymorphism method was used to investigate genotypes of ERa and ERb polymorphisms. Genotypes of PvuII and XbaI polymorphism of ERa receptor were significantly different in patients with post-menopausal depression comparing with controls. Genotypes of ERb did not show association with post-menopausal depression. Our study showed that ERa receptor polymorphism had an association with depression in post-menopausal women. It suggests that investigation of ER genes and their functions might be important for understanding pathophysilogical mechanism of post-menopausal depression.
Psychiatry investigation 09/2010; 7(3):224-7. · 0.99 Impact Factor
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ABSTRACT: Psychotic agitation of psychiatric patients is a common manifestation that needs emergent management. Traditionally, parenteral or intramuscular injection of antipsychotics was conducted for treatment of psychotic agitation. Considering that the rapidly absorbed form of risperidone (risperidone orodispersible tablet) could be used for the agitated patient, comparison of oral risperidone and intramuscular haloperidol was performed in emergency treatment of psychotic agitation in this study.
124 patients with psychotic agitation were recruited at the emergency room or inpatient ward. They were randomly assigned to either the group of oral risperidone or intramuscular haloperidol. Efficacy of both treatments was measured and compared using the 5-item acute agitation cluster from the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) and the Clinical Global Impression-Severity of Illness Scale (CGI-S). Tolerability and safety were also compared between the two groups.
The PANSS-EC and CGI-S scores were significantly decreased over time in both treatment groups without any significant group difference and time by group interaction effect (F = 459.7, p < 0.0001). There were no serious adverse events in both groups.
For the emergency treatment of psychotic agitation, risperidone orodispersible tablet was as effective and tolerable as intramuscular administration of haloperidol. Therefore, we might choose oral medication instead of intramuscular injection for treatment of patients with acute psychotic agitation.
Neuropsychobiology 01/2010; 62(2):81-6. · 2.67 Impact Factor
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ABSTRACT: The aim of the present work was to investigate possible differences in terms of efficacy and tolerability between different switching options to aripiprazole. 77 subjects were randomly assigned to (1) administration of aripiprazole (10 mg) with simultaneous discontinuation of current antipsychotic; (2) administration of aripiprazole (10 mg) and tapering off current antipsychotic over 4 weeks with half dose after the first 2 weeks; (3) administration of aripiprazole (10 mg) and tapering off current antipsychotic over 6 weeks with half dose after the first 2 weeks. Efficacy assessments included CGI-S, CGI-I, BPRS and SANS. Safety assessments included SAS, BAS and AIMS. Severity of symptoms significantly decreased from baseline over the 12 weeks of treatment. Patients switched to aripiprazole with immediate discontinuation of the previous antipsychotic showed an increase of symptoms' severity at week 1. However, severity of side effects did not overall change significantly during the 12-weeks follow-up. Previous treatment's tapering off strategy for switching patients to aripiprazole could be preferable as compared to abrupt discontinuation, in order to prevent early worsening of symptoms and premature discontinuation of treatment, though this results has to be considered with caution given the limitations of the study.
European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 06/2009; 19(8):562-70. · 3.68 Impact Factor
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ABSTRACT: Impaired processing of working memory information is one of the cognitive deficits seen in patients with schizophrenia. This study aims at corroborating the differences in the brain activities involved in the process of working memory between patients with schizophrenia and the controls. Twelve patients with schizophrenia and 11 controls participated in the study. Functional magnetic resonance imaging (fMRI) was used to assess cortical activities during the performance of a two-back verbal working memory paradigm using the Korean alphabet as mnemonic content. Group analysis revealed that inferior fontal, middle frontal, and superior temporal region showed decreased cortical activities in the patient group compared to those of the controls. This study showed a decreased activation in inferior fontal (BA 47), middle frontal (BA 6), and superior temporal (BA 22/38) neural networks from the patient group and confirmed the earlier findings on the impaired working memory of schizophrenic patients in the fMRI investigation.
The International journal of neuroscience 11/2008; 118(10):1467-87. · 0.86 Impact Factor
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ABSTRACT: Dysbindin gene (DTNBP1) has been associated with schizophrenia, but literature findings are inconsistent, and further analyses are required. This study is aimed to investigate if a set of DTNBP1 variations might influence clinic psychotic phenotype or treatment response in a sample of 240 Korean schizophrenic in-patients. Four variants have been selected (rs3213207; rs1011313; rs16876759; rs2619522) on the basis of previous findings of association with schizophrenia, bipolar disorder and antidepressant response. Single marker analysis gave marginal results. Haplotype analysis identified a significant association between A-A (rs3213207(A/G), rs1011313(A/G)) haplotype and lower PANSS total and positive scores at baseline (p=0.01; 0.02) and at discharge (p=0.008; 0.005). Covariate analysis revealed a more stable significant association between A-A haplotype and baseline scores. These results suggest a protective effect of A-A haplotype on psychotic positive symptoms at baseline.
Neuroscience Letters 09/2008; 440(2):150-4. · 2.11 Impact Factor
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ABSTRACT: We recently reported an association between TAAR6 (trace amine associated receptor 6 gene) variations and schizophrenia (SZ). We now report an association of a set of TAAR6 variations and clinical presentation and outcome in a sample of 240 SZ Korean patients. Patients were selected by a Structured Clinical Interview, DSM-IV Axis I disorders - Clinical Version (SCID-CV). Other psychiatric or neurologic disorders, as well as medical diseases, were exclusion criteria. To assess symptom severity, patients were administered the CGI scale and the PANSS at baseline and at the moment of discharge, 1 month later on average. TAAR6 variations rs6903874, rs7452939, rs8192625 and rs4305745 were investigated; rs6903874, rs7452939 and rs8192625 entered the statistical investigation after LD analysis. Rs8192625 G/G homozygosis was found to be significantly associated both with a worse clinical presentation at PANSS total and positive scores and with a shorter period of illness before hospitalization. No haplotype significant findings were found. The present study stands for a role of the TAAR6 in the clinical presentation of SZ. Moreover, our results show that this genetic effect may be counteracted by a correct treatment. Haplotype analysis was not informative in our sample, probably also because of the incomplete SNPs' coverage of the gene we performed. Further studies in this direction are warranted.
European Psychiatry 07/2008; 23(6):390-5. · 2.77 Impact Factor
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ABSTRACT: 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.
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).
There was no association between the variants investigated and response to mood stabilizer treatment, even after considering possible stratification factors.
Although the small number of subjects is an important limitation in our study, DTNBP1 does not seem to be involved in acute antimanic efficacy.
Psychiatry investigation 06/2008; 5(2):102-5. · 0.99 Impact Factor
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ABSTRACT: Heat shock proteins (HSPs) are a promising candidate gene in schizophrenia as they are believed to play a protective role in the central nervous system. An alteration in the titers of antibodies to the HSPs in schizophrenia patients has been suggested. Association between the three polymorphisms of HSP70-1 (HSPA1A), HSP70-hom (HSPA1L) and HSP70-2 (HSPA1B) and schizophrenia has been reported. Therefore, this study investigated the association between an enlarged set of SNPs at HSP70 gene and schizophrenia.
Two hundred and ninety-four patients with schizophrenia and 287 controls were enrolled in the study. Genotypings of 5 SNPs of HSP70 were performed using pyrosequencing method. Haploview 3.2 was used to generate a linkage disequilibrium map and to test for Hardy-Weinberg equilibrium. Single locus and haplotype-based associations were tested. Tests for associations using and multi-marker haplotypes were performed by using a COCAPHASE v2.403. Association of SNP markers and clinical variables were analyzed by analysis of variance.
Significant association was detected at rs2075799 (allele A, X2 = 8.03, df = 1, P = 0.0046), but not at rs2227956 (P = 0.28), rs1043618 (P = 0.88), rs562047 (P = 0.47) or rs539689 (P = 0.32). In fact, the rs2075799*G/A genotype was more represented in patients with schizophrenia than in controls (X2 = 8.23, df= 1, P = 0.0041). Haplotype based associations were also detected (global P value 0.000003); the T-A-C-C-G haplotype was more prevalent among the patients (odds ratio, OR 5.95). Sliding windows analysis revealed a major contribution from rs2227956 and rs2075799 (global-P value 0.0075), with T-A haplotype significantly associated with schizophrenia. There was no evidence of an association between the clinical variables and schizophrenia across the genotypes.
Our results raise the possibility that HSP70 gene (i.e., haplotypes of rs2075799) might be implicated in the development of schizophrenia, although limited by rare haplotypic association with the disease. Hence further studies from different ethnics should be performed to confirm these results.
European Archives of Psychiatry and Clinical Neuroscience 03/2008; 258(4):239-44. · 3.49 Impact Factor
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Jung-Jin Kim,
Laura Mandelli,
Chi-Un Pae,
Diana De Ronchi,
Tae-Youn Jun,
Chul Lee, In-Ho Paik,
Ashwin A Patkar,
David Steffens,
Alessandro Serretti,
Changsu Han
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ABSTRACT: Dysbindin gene has been repeatedly associated with psychiatric disorders and schizophrenia in particular. This study aimed to investigate the variants of dysbindin gene in major depressive disorder (MDD). One hundred and eighty eight patients with MDD and 350 controls were investigated for 4 variants within the dysbindin gene (rs3213207 A/G, rs1011313 C/T, rs760761 C/T, and rs2619522 A/C). Haplotype analyses revealed a significant association with MDD (p=0.0007, protective A-C-T-A and A-C-C-C haplotypes), in particular the effect was due to the rs760761 (C/T) and rs2619522 (A/C) haplotype (p=0.000026). These results suggest a protective effect of some dysbindin gene haplotypes on the development of MDD. Coupled with previous findings on schizophrenia, our finding suggests that dysbindin gene variants may have a role in the susceptibility to MDD. Adequately powered further studies in different ethnic groups are warranted.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 03/2008; 32(2):375-9. · 3.25 Impact Factor
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Chi-Un Pae,
Hye-Sook Yu,
Daniela Amann,
Jung-Jin Kim,
Chang-Uk Lee,
Soo-Jung Lee,
Tae-Youn Jun,
Chul Lee, In-Ho Paik,
Ashwin A Patkar,
Bernard Lerer
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ABSTRACT: Trace amines and their receptors may be implicated in the pathogenesis of psychiatric disorders. Previous studies have reported association of the trace amine associated receptor 6 (TAAR6) gene with susceptibility to schizophrenia and bipolar disorder but results have not been consistent. The purpose of this study was to examine these associations in Korean patients and also to test for association of TAAR6 with susceptibility to major depressive disorder (MDD). A case control sample consisting of 281 patients with schizophrenia, 190 patients with bipolar disorder, 187 patients with MDD and 288 psychiatrically healthy control subjects, was examined. Patients with schizoaffective disorder were not included in any of the psychiatric samples. Five single nucleotide polymorphisms (SNPs: rs4305745; rs8192625; rs7452939; rs6903874 and rs6937506) were genotyped in the TAAR6 gene and in the 3' regulatory region, using pyrosequencing. SNP rs6903874 was significantly associated with schizophrenia (p = 0.012) and bipolar disorder (p = 0.004). A three SNP haplotype consisting of alleles GCT from SNPs rs7452939, rs6903874 and rs6937506, respectively, was significantly over-represented in patients with schizophrenia (p = 0.0003) and bipolar disorder (p = 0.00002). A second three SNP haplotype (GTT) derived from the same SNPs was significantly under-represented in patients with bipolar disorder (p = 0.001). The GTT haplotype associations withstand the most rigorous corrections for multiple testing. These findings strongly support association of the TAAR6 gene with susceptibility to both schizophrenia and bipolar disorder in Korean patients. Further studies are needed to confirm these findings in this and other populations and to identify functional variants in TAAR6 that may be implicated in pathogenesis.
Journal of Psychiatric Research 02/2008; 42(1):35-40. · 4.66 Impact Factor
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ABSTRACT: Quinone oxidoreductase (NQO1) plays a key role in the cellular antioxidant defense by detoxifying quinine derivatives. Case-control association study of the possible relationship between the NQO1 gene polymorphism and mood disorders (patients with major depressive disorder, n=61; patients with bipolar I disorder, n=80; control, n=106) was carried out using PCR-based techniques. These preliminary results showed that the NQO1 gene polymorphism was not related to a susceptibility to mood disorders.
Psychiatry Research 10/2007; 153(1):83-6. · 2.52 Impact Factor
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ABSTRACT: There has been increasing evidence that the alteration of antioxidant enzymes such as manganese superoxide dismutase (MnSOD) might be implicated in the development of schizophrenia and/or tardive dyskinesia (TD). This study investigated the association of a MnSOD gene (MnSOD) polymorphism (Ala-9Val) with schizophrenia as well as its involvement in TD. Patients with schizophrenia (n=262) and healthy controls (n=263) were enrolled in this study and genotyped by a polymerase chain reaction-based method. The distribution of the MnSOD genotypes and alleles was not significantly different between patients and controls. Logistic regression analysis also failed to reveal any association between MnSOD genotypes and TD. Taken together, these results suggest that the MnSOD polymorphism does not contribute to the development of schizophrenia and/or TD, at least in the Korean population.
Psychiatry Research 10/2007; 153(1):77-81. · 2.52 Impact Factor
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Chi-Un Pae,
Alessandro Serretti,
Laura Mandelli,
Hye-Sook Yu,
Ashwin A Patkar,
Chang-Uk Lee,
Soo-Jung Lee,
Tae-Youn Jun,
Chul Lee, In-Ho Paik,
Jung-Jin Kim
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ABSTRACT: We investigated a possible association between dysbindin gene (DTNBP1) variants and bipolar I disorder (BID). Five SNPs within DTNBP1 (rs3213207, rs1011313, rs2005976, rs760761, and rs2619522) were genotyped for 151 patients with BID and 478 controls. We observed a significant protective association of the haplotype A-C-G-T-A (all SNPs, P = 0.00016) and particularly G-T-A (the last three SNP, P = 0.00007) within DTNBP1 variants investigated. Single marker and subgroup (e.g., psychotic features, age at onset, family history, etc.) analyses showed no significant association. Although the association was due to a small number of subjects, specific DTNBP1 haplotypes, previously associated with schizophrenia, may be also associated with BID. Adequately powered studies from different ethnicities will be necessary to confirm our findings.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 08/2007; 144B(5):701-3. · 3.70 Impact Factor
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ABSTRACT: In the search of predictors of antidepressant efficacy, much interest has recently focused on pro-inflammatory proteins, as they were found to be elevated during major depressives states and decreased by antidepressant drugs. In the present paper we investigated the role of the genes coding for heat-shock-70 family proteins, recently hypothesized to be activated by antidepressants and thus mediate the reduction of pro-inflammatory cytosines. One hundred and forty two hospitalised patients, affected by major depression and treated with antidepressants drugs for a major depressive episode were evaluated for depressive severity at the baseline and at the discharge and genotyped for five SNPs within the genes HSPA1L, HSPA1A and HSPA1B. Markers were not individually associated with symptom severity after treatment. Instead, we found a three markers haplotype, including SNPs within HSPA1L and HSPA1A, associated with a poorer response to antidepressant treatment (p=0.005). Single markers as well as haplotypes were not associated with other clinical features. In conclusion, genetic variants within the genes coding for HSP-70 family proteins may affect the action of antidepressants and thus their therapeutic efficacy.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 07/2007; 31(5):1006-11. · 3.25 Impact Factor
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ABSTRACT: The primary objective of this study was to compare the safety and tolerability of a rapid initiation of quetiapine with the conventional initiation approved by the U.S. Food and Drug Administration (FDA). The secondary objectives included assessment of the efficacy of a rapid initiation of quetiapine compared with a conventional initiation approved by the FDA.
Patients with acute schizophrenia were randomly assigned in a 3:1 ratio to the rapid-initiation group (200 mg on day 1, 400 mg on day 2, 600 mg on day 3, and 800 mg on day 4) or to the conventional-initiation group (50 mg on day 1, 100 mg on day 2, and increased in 100 mg/day increments to reach 400 mg on day 5). The tolerability measures were Barnes Akathisia Scale (BAS) and Simpson-Angus Scale (SAS) as well as all adverse events at day 1, 2, 3, 4, 5, 6, and 7 and at day 14. Standard efficacy measures were administered at baseline, day 1, day 4, day 5, day 7, and day 14. These measures consisted of the Positive and Negative Syndrome Scale (PANSS), PANSS-Excited Component (EC), and Clinical Global Impressions-Severity of Illness (CGI-S) scale.
Forty patients were randomly assigned to treatment. The mean (SD) dose of quetiapine at study end point was 763.3 (106.6) and 600.0 (249.4) mg/day in the rapid-initiation group and conventional-initiation group, respectively. The most common side effects were sedation and dizziness, with no significant differences in frequency between groups. Only 2/30 patients from the rapid-initiation group discontinued treatment due to an adverse event (both for sedation), and 1/10 patients from the conventional-initiation group discontinued before receiving quetiapine. Neither serious adverse events nor differences between groups in vital signs, laboratory assessments, ECG measures, or weight changes were reported. Rapid initiation of quetiapine was generally well-tolerated and was associated with a faster onset of action than conventional initiation as measured by improvement in psychotic symptoms at days 4 and 5.
This study may offer preliminary evidence for tolerability and effectiveness in rapid dose initiation of quetiapine in the treatment of schizophrenia.
The Journal of Clinical Psychiatry 04/2007; 68(3):399-405. · 5.80 Impact Factor
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ABSTRACT: Schizophrenia has complicated pathogeneses that is not able to be explained by any one supposed hypothesis, although alterations in dopamine neurotransmission have been widely accepted as the most plausible mechanism. A transition from traditional typical antipsychotics to contemporary atypical antipsychotics which have significantly improved tolerability and enhanced specific efficacy has been also made based on this dopamine hypothesis. Cysteamine is a natural product of mammalian cells and found to be useful pharmacological alternative. A number of evidence suggests that cysteamine may control directly or indirectly dopamine neurotransmission in nucleus accumbens and other schizophrenia-related brain regions. Systemic cysteamine injection mitigated the apomorphine-induced stereotypy as well as decreasing motor stimulant effects of amphetamine, which favor cysteamine over animal models of schizophrenia relative to hyperactivity of dopaminergic pathway. In addition, cysteamine showed neuroprotective effects by way of enhancing central and serum brain derived neurotrophic factor (BDNF) that has been proved to be altered in patients with schizophrenia. Antipsychotic drugs exert their effect partly by modifying the synthesis and distribution of BDNF in selected brain region. Cysteamine was effective to reverse a disruption in prepulse inhibition, an endophenotypic marker of schizophrenia. Cysteamine can also stimulate the release of cortical dopamine, which is interesting in that decreased dopaminergic function in the cerebral cortex has been repeatedly demonstrated in patients with schizophrenia and associated with prominent depressive and negative symptoms. Cysteamine can also increase an important antioxidant, glutathione. Finally, cysteamine treatment was found to decrease weight gain, cataleptic behavior, and serum prolactin levels, which are the major beneficial properties of contemporary atypical antipsychotics. Hence, further explorations of therapeutic implication of cysteamine for schizophrenia in preclinical studies should be warranted in future.
Medical Hypotheses 02/2007; 69(1):199-202. · 1.39 Impact Factor
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Chi-Un Pae,
Alessandro Serretti,
Laura Mandelli,
Diana De Ronchi,
Ashwin A Patkar,
Tae-Youn Jun,
Jung-Jin Kim,
Chang-Uk Lee,
Soo-Jung Lee,
Chul Lee, In-Ho Paik
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ABSTRACT: 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).
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-Asberg 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.
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.
Despite limitations due to the sample size and the mild antidepressant response, we observed a significant association between DTNBP1 variants and antidepressant response.
Pharmacogenetics and Genomics 02/2007; 17(1):69-75. · 3.48 Impact Factor
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ABSTRACT: Despite the fact that antidepressants represent the gold standard for the treatment of depression, not all patients treated with an antidepressant monotherapy achieve complete remission of depressive symptoms and functional recovery. Therefore, further examination of the components that may be involved in the action mechanism of antidepressants will benefit patients who show either no response or partial response by identifying their hidden functions and key roles in the therapeutic mechanism of antidepressants. The cocaine- and amphetamine-regulated transcript (CART), which is a brain-enriched mRNA with a protein product(s) is an interesting neuropeptide in relation to the treatment of depression. CART mRNA is strongly expressed in the major limbic structures that modulate affect and anxiety as well as being a possible key target for the action of antidepressants. A bidirectional relationship between CART and the hypothalamic-pituitary-adrenal (HPA) axis activity has been accepted to date, which suggests that CART might efficiently bridge the interaction between the stress-related events and the neurobehavioral response. The regulation of the signal transduction pathways by CART by modulating neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), kinases (trkB), and neurotransmitters (5-HT), can also contribute to the treatment of depression. It might have an augmenting effect in the treatment of depression because it acts as a putative and potential neurotransmitter/cotransmitter that is involved in psychostimulant action as well. Finally, preliminary results suggest that CART directly controls the expression of major neurotransmitters such as serotonin, noradrenaline, and dopamine. Hence, further studies on therapeutic implications of CART for depression are warranted and will contribute to the development of newer selective antidepressants.
Medical Hypotheses 02/2007; 69(1):132-5. · 1.39 Impact Factor
