Heart rate variability in patients with fully remitted major depressive disorder.

OBJECTIVE: Cardiac autonomic dysregulation has been reported in major depressive disorder (MDD), but scarce studies investigated that in fully remitted MDD. METHODS: To examine cardiac autonomic function in remitted MDD, 470 unmedicated individuals with a diagnosis of MDD earlier in life and 462 healthy volunteers, aged 18-65 years, were recruited for a case-control analysis. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV) parameters. Frequency-domain indices of HRV were obtained. The obtained results were evaluated in association with personality traits assessed by the Tridimensional Personality Questionnaire. RESULTS: In patients with remitted MDD, no differences in RR intervals and all frequency-domain indices of HRV could be detected as compared with controls. Stratified analyses by the presence of a history of suicide ideation (the SI+ vs. the SI-subgroup) revealed decreased cardiac vagal control in the SI+ subgroup. The correlation analysis revealed an inverse relation between HRV levels and the harm avoidance score (which has been suggested to be associated with serotonergic activity), mainly attributable to the robust association in the SI+ subgroup. CONCLUSION: Our study shows that cardiac autonomic dysregulation is not shown in remitted MDD patients as a whole but is limited to the subgroup of remitted MDD patients with a history of suicidal ideation. In view of the higher risk for cardiac complications in these vulnerable individuals, one might consider the treatment to restore their autonomic function.

Developing consensus 3D-QSAR and pharmacophore models for several beta-secretase, farnesyl transferase and histone deacetylase inhibitors.

Three consensus 3D-QSAR (c-3D-QSAR) models were built for 38, 34, and 78 inhibitors of ß-secretase, histone deacetylase, and farnesyltransferase, respectively. To build an individual 3D-QSAR model, the structures of an inhibitor series are aligned through docking of a protein receptor into the active site using the program GOLD. CoMFA, CoMSIA, and Catalyst are then performed for the training set of each structurally aligned inhibitor series to obtain a 3D-QSAR model. Since the consensus in features identified is high for the same pharmacophore features selected for building a 3D-QSAR model by a 3D-QSAR method, a c-3D-QSAR model for each inhibitor series is constructed by combining the pharmacophore features selected for building the 3D-QSAR model using the SYBYL spread sheet and PLS module. Each c-3D-QSAR pharmacophore model built was examined visually and compared with that obtained by simultaneous mapping of the corresponding 3D-QSAR pharmacophores built onto a selected inhibitor structure. It was found that the c-3D-QSAR model built for an inhibitor series improves not only the overall prediction statistics for both training and test sets but also the prediction accuracy for some less active inhibitors of the series.

Repeated angioedema following administration of venlafaxine and mirtazapine.

We report a rare case of a 48-year-old female who presented with bilateral lower-leg swelling due to a medication-induced angioedema resulting from the use of two common classes of antidepressants, venlafaxine and mirtazapine. Although the mechanisms by which the antidepressants achieve these effects are not understood, the recent recognition of a novel antidepressant-dependent form of angioedema may offer important insights into the mechanisms by which the antidepressants exert their effects.

Association study of the norepinephrine transporter gene polymorphisms and bipolar disorder in Han Chinese population.

Many studies have indicated that the norepinephrine transporter (NET) may play an important role in the mechanisms underlying affective disorders. Thus, the genes of the NET (SLC6A2) are good candidates for research on bipolar disorder (BPD). This study examined whether the NET gene is a susceptibility factor for the BPD in Han Chinese. A promoter -182 T/C polymorphism (rs 2242446) and the exonic polymorphism 1287 G/A (rs 5569) of the NET gene were analysed using a polymerase chain reaction (PCR)-based method in 261 BPD patients and 245 unrelated, age- and gender-matched controls. Furthermore, to reduce the clinical heterogeneity, we also carried out analysis in clinical subgroups of bipolar patients defined according to type I and type II BPD, presence or absence of family history of major affective disorders and the age at onset of BPD. No significant difference was found between either bipolar patients or its more homogeneous subgroups and healthy controls in the genotype and allele frequencies for the investigated NET polymorphisms. Our results suggest that the investigated polymorphisms of NET are not major risk factors responsible for predisposition to BPD or its clinical subtypes in Han Chinese. However, replication studies with larger different ethnic samples are needed.

Lack of association between the norepinephrine transporter gene and major depression in a Han Chinese population.

OBJECTIVE: Although the physiological mechanisms contributing to the development of major depression remain unclear, several lines of evidence suggest that the catecholaminergic system involving the norepinephrine transporter (NET) is implicated in the etiology of major depression. This study aims to determine whether major depression is associated with the NET gene in a Han Chinese population. METHODS: We analyzed the NET promoter T-182C polymorphism and another silent polymorphism G1287A in exon 9 of the NET gene with a polymerase chain reaction (PCR)-based method in 216 patients with major depression and 210 unrelated, age-and sex-matched healthy control subjects. We interviewed all subjects with the Chinese Version of the Modified Schedule of Affective Disorders and Schizophrenia-Lifetime; major depressive disorder was diagnosed according to DSM-IV criteria. In addition, to reduce the clinical heterogeneity, we performed a subtype analysis with clinically important variables, such as family history of major affective disorder and age at onset of major depression. RESULTS: No significant difference was observed between the patients and healthy control subjects in the genotype distributions and allele frequencies for the investigated NET polymorphisms. Similarly, no significant differences were found between more homogeneous subgroups of patients and normal control subjects. CONCLUSIONS: This study suggests that the investigated polymorphisms in the NET gene are not major risk factors in increasing susceptibility to either major depression or its clinical subtypes in a Han Chinese population. However, larger replication studies with different ethnic samples are needed.

Lack of association between dopamine D3 receptor Ser9Gly polymorphism and schizophrenia in Han Chinese population.

BACKGROUND: The Ser9Gly polymorphism in dopamine D3 receptor gene (DRD3) was considered an important factor in the pathogenesis of schizophrenia. Allele and genotype frequencies of this polymorphism were studied in different ethnic groups of schizophrenic patients. However, the results have been inconclusive. OBJECTIVE: To determine whether the DRD3 Ser9Gly polymorphism is associated with schizophrenia or influences its psychopathological symptoms in Han Chinese population. METHOD: We recruited 256 schizophrenic patients and 285 normal controls matched for gender, age and ethnicity. Pretreatment psychotic symptoms were evaluated with the Positive and Negative Symptom Scale (PANSS) in 128 acutely exacerbated schizophrenic in-patients. Genotyping of Ser9Gly polymorphism was performed with a polymerase chain reaction restriction fragment length polymorphism method and reconfirmed by a direct sequencing technique. RESULTS: No significant difference was found between either patients with schizophrenia or with more homogeneous schizophrenic subgroups and healthy controls in genotype distributions and allele frequencies for the DRD3 Ser9Gly polymorphism. Similarly, DRD3 Ser9Gly genotype differences failed to reach significance in PANSS global, positive, negative and general symptoms scores. There is a trend (P = 0.064) towards higher PANSS positive symptoms scores in subjects carrying the Gly/Gly genotype. CONCLUSION: This study does not support the role of DRD3 Ser9Gly polymorphism in increasing genetic risk for schizophrenia in Han Chinese population. Still, there is a possibility that the DRD3 Ser9Gly variant may reflect genetic variation of severity of positive symptoms in acutely exacerbated schizophrenia. Further studies are warranted to investigate the effect of the DRD3 Ser9Gly polymorphism in relation to longer time course of schizophrenia, including treatment response to antipsychotics.