Association study of the INPP1, 5HTT, BDNF, AP-2beta and GSK-3beta GENE variants and restrospectively scored response to lithium prophylaxis in bipolar disorder.

In the present study we investigated the influence of a series variants in genes (the serotonin transporter, glycogen synthase kinase-3beta, inositol polyphosphatase 1-phosphate, brain-derived neurotrophic factor and activator protein 2beta) related to the action of lithium carbonate, a drug used for prophylaxis in mood disorders. We used a sample of unrelated patients with bipolar disorder type I on lithium therapy for at least 2 years who met the proposed response criteria for prophylactic response. Of the 134 patients, 61 patients were considered full responders, 49 non-responders and 24 partial responders.

Allelic association analysis of the functional insertion/deletion polymorphism in the promoter region of the serotonin transporter gene in bipolar affective disorder.

The human serotonin transporter gene (5-HTT) is a candidate for the pathogenesis of mood disorders, including bipolar disorder (BPD). The 5-HTT gene has a 44-bp insertion/deletion polymorphism within the promoter region (5-HTTLPR) with 2 allelic forms, the long (l) and the short (s) variants, which affect transcriptional rates of the 5-HTT gene. Association between the low-activity s variant and BPD has been suggested but remains controversial, as replication has not been consistent.

Association study of dopamine D2 and D3 receptor gene polymorphisms with cocaine dependence.

Genetic factors play a role in the vulnerability to cocaine dependence. The reinforcing properties of cocaine are related to the dopaminergic system, and, in particular, the dopamine receptors have been linked to the reward mechanisms. The present study examines the role of the variants TaqI A of the dopamine D2 receptor gene and BalI of the dopamine D3 receptor gene in a Brazilian sample consisting of 730 cocaine dependents and 782 healthy controls.

Allelic association analysis of phospholipase A2 genes with schizophrenia.

Several studies suggest increased activity of phospholipase A2 in schizophrenic patients. In the present study, variants of four genes coding for phospholipase A2 enzyme groups (sPLA2, cPLA2, iPLA2 and PAFAH) were analysed in a case-control sample using 240 schizophrenic patients and 312 healthy controls. No difference was observed on the allelic and genotypic distribution of cPLA2 and sPLA2 gene polymorphisms among the groups.

[Genes related to phospholipid metabolism as risk factors related to bipolar affective disorder].

The studies of genetic epidemiology provides consistent evidence of genetic factors having a major role on the risk for the bipolar affective disorder, although, vulnerability genes have not yet been identified in unequivocal form. The authors show that phospholipids play an important role in the cellular signalling processes, besides this, some studies with mood-stabilisers neurochemistry suggest that these drugs act in the phospholipase regulated signalling views. They conclude that analysis of gene variants that code enzymes of the phospholipids metabolism as potential susceptibility genes can extend the knowledge concerning the risk factors and the physiopatological mechanisms underling this mood disturbance.

Allelic association study between phospholipase A2 genes and bipolar affective disorder.

Objectives: In vivo studies demonstrating that lithium is a powerful phospholipase A2 (PLA2) inhibitor suggest that PLA2 activation, and subsequent cell signaling overactivation by increased fatty acid release may be the primary abnormality in bipolar affective disorder (BPAD), thus making PLA2 genes attractive candidates for the susceptibility to BPAD. The present study investigates polymorphisms in cytosolic phospholipase A2 (cPLA2), calcium-independent phospholipase A2 (iPLA2), and secretory phospholipase (sPLA2) genes in a Brazilian sample.

Methods: A cross-sectional study was performed with 181 unrelated DSM-IIIR BPAD subjects and 312 controls.