It is known that the onset of major depressive disorder (MDD) would be associated with genetic factors. To investigate the susceptibility to psychiatric disorders, e.g. MDD, schizophrenia etc., it is necessary to compare the genetic differences of objective polymorphisms between in patients and in relative contol subjects. Recently, an increasing number of studies focused on the role of cyclic adenosine monophosphate response element binding protein 1 (CREB1) and Piccolo (PCLO) on MDD. However, there was no report about genetic characterization of polymorphisms in between MDD patients and healthy subjects in Japanese population. We analized genotype distributions and allele frequencies of CREB1 rs4675690 and PCLO rs2522833 polymorphisms in 267 Japanese subjects, respectively. In CREB1 rs4675690, C allele frequency (0.41) was lower than T allele (0.59). While in PCLO rs2522833, A allele frequency (0.45) was lower than C allele (0.55). Our findings may be useful for investigating the genetic factors concerning the susceptibility to MDD in Japanese population.Key words cAMP response element binding protein 1; Piccolo; polymorphism; Japanese; major depressive disorder Major depressive disorder (MDD) is a familial disorder and its familiarity mostly or entirely results from genetic influence.1) To investigate disease susceptibility affected by genetic polymorphism, it is often performed with comparison of genotype distributions and allele frequencies of objective polymorphism in patients with in its relative control subjects.Recently, an increasing number of studies focused on the role of transcription factor, cyclic adenosine monophosphate response element binding protein 1 (CREB1) and presynaptic cytomatrix protein, Piccolo (PCLO) on MDD. CREB1 was reported that the association with neuronal signal transduction involved in synaptic plasticity 2) and antidepressant response. 3,4) In Caucasian population, CREB1 rs4675690 polymorphism was associated with anger expression in male MDD patients 5) and suicidal behaivor in MDD patients. 6) While PCLO was localized in the presynaptic active zone 7) and involved in monoamine neurotransmission.8) PCLO polymorphism rs2522833 was related with hypothalamic-pituitary-adrenocortical (HPA) regulation during antidepressant treatment and the susceptibility to MDD in Caucasian population. 9)It was suggested that these polymorphisms may be associated with the susceptibility to MDD and therapeutic efficacy of antidepressants in Japanese population. However there was no report about CREB1 rs4675690 and PCLO rs2522833 polymorphisms in Japanese population. In this study, we examined genotype distributions and allele frequencies of CREB1 rs4675690 and PCLO rs2522833 polymorphisms in 267 Japanese healthy subjects. MATERIALS AND METHODS Japanese SubjectsThis study was performed in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines, and approved by the Ethics Committee of the University of Shizuoka, Shizuoka, Japan (approved number 18-2). A total of 267 Japanese...

To prevent recurrent depression, patients should ideally continue treatment for >6 months with the antidepressant dose that effectively suppressed acute depressive symptoms. However, there are inter-individual differences in the antidepressant doses required to achieve response and maintenance. Therefore, this study was conducted to examine the role of clinical features, including genetic polymorphisms, on the antidepressant dose required for maintenance therapy in 82 Japanese patients with depression. We calculated the antidepressant dose using the imipramine equivalent scale and the dose of concomitant anxiolytics and hypnotics using the diazepam equivalent scale. The 82 participants were classified into two groups based on the median imipramine equivalent dose, and we examined the influence of patient characteristics and the presence of genetic polymorphisms of brain-derived neurotropic factor (BDNF; rs6265) and cyclic adenosine monophosphate responsive element-binding protein 1 (CREB1; rs2253306, rs4675690, rs769963) on the antidepressant maintenance dose. Using a multivariate logistic regression analysis, we found that the concomitant diazepam equivalent dose and presence of the CREB1 rs4675690 polymorphism were significantly associated with the antidepressant maintenance dose. We concluded that these factors influenced the antidepressant dose in maintenance therapy among Japanese patients with depression. However, further research is required in large cohorts.Key words antidepressant; maintenance dose; depressive disorder; polymorphism; brain-derived neurotrophic factor; cyclic AMP responsive element binding protein 1 Depressive disorder is a common psychiatric disorder, with approximately 350 million people being affected worldwide. 1)Moreover, it is associated with a high rate of recurrence and chronicity, with 12-35% of all cases becoming chronic and 13.2% experiencing recurrence within 5 years.2-5) When starting antidepressant therapy, the dose of antidepressant is low and is slowly increased, and careful attention is paid to the development of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania, the so-called "activation syndrome." The target dose is the lowest dose that adequately suppresses depressive symptoms with tolerable side effects. After achieving remission, the therapeutic dose acutely required is continued as maintenance therapy for >6 months to prevent recurrence. 6,7)Several reports suggest that when an antidepressant is ineffective in suppressing depressive symptoms, combination therapy with another antidepressant or anxiolytic or hypnotic drugs is more effective than increasing the dose of the preexisting antidepressant. [8][9][10] In studies on Japanese patients with depression, 23.4-35.9% of cases were treated with antidepressant combination therapy and 60.3-73.0% were treated with concomitant anxiolytic or hypnotic drugs. In addition, it is known that inter-individual differences exist in the daily dosing ...