Discuss Bipolar
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A variant in the 5-hydroxytryptamine (serotonin) receptor 5A (HTR5A) gene may be involved in the pathogenesis of bipolar disorder, says an international team of scientists, although they urge caution in interpreting the findings.
Despite a wealth of research into the etiology of bipolar disorder and evidence to suggest that it is the result of an interaction between genetic and environmental factors, no single gene has been identified as being definitively associated with the disorder.
Yusuke Nakamura, from the University of Tokyo in Japan, and colleagues genotyped 94 bipolar disorder patients and 184 healthy controls from Bulgaria for 191 single nucleotide polymorphisms (SNPs) in 65 candidate genes using TaqMan and/or Invader assays.
In all, 17 SNPs were significantly associated with bipolar disorder and these were further genotyped in an additional set of 78 bipolar disorder patients and 372 controls, with the results pooled with the previous analysis to give a combined set of 172 patients and 556 controls.
The most significant association with bipolar disorder was found for the rs1800883 SNP in a promoter region of the HTR5A gene, which was unaffected by sequential Bonferroni correction, the team notes in the Journal of Affective Disorders.
Analysis revealed that 56.7% of the patients were homozygous for the G risk allele, compared with 42.1% of controls, giving an odds ratio of 1.80. In addition, the risk allele was more common in patients than in controls, at 73.7% versus 62.1%.
A weak association was also found for the rs6265 SNP located in exon 2 of the brain-derived neurotrophic factor gene, with the risk C allele more frequently seen in patients than controls, while a possible association was observed for the rs5443 SNP in exon 10 of the guanine nucleotide binding protein, beta polypeptide 3 gene. However, neither survived Bonferroni correction.
“In conclusion, our findings suggest that HTR5A gene could be one of many genes of importance in the etiology of bipolar disorder in the Bulgarian population, but the effect by the genetic substitution seemed to be small even if the association is further confirmed,” the team writes.
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009
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Bipolar disorder patients do not have accelerated prefrontal gyrification index (GI) loss, but having at least one brain-derived neurotrophic factor (BDNF) gene variant may increase loss, UK scientists have found.
Brain structural abnormalities, including temporal lobe and prefrontal cortex volume reductions, have been identified in bipolar disorder patients. However, it is not clear whether the abnormalities are present at disease onset or whether they develop over time.
Noting that the BDNF valine (val)66methionine (met) variant has been linked to such brain changes, Ajay Mirakur and colleagues from the University of Edinburgh performed magnetic resonance imaging (MRI) at baseline and after 4 years in 18 bipolar I disorder patients and 18 healthy controls.
The GI was calculated as the ratio of folded inner contour to exposed outer contour. In addition, the participants underwent clinical assessment and were genotyped for BDNF val66met.
Both bipolar disorder patients and healthy controls were found to have a significant decrease in GI over 4 years in all prefrontal quadrants, and there was no significant difference in the rate of change of GI between patients and controls.
Comparing bipolar disorder patients with and without at least one BDNF val66met met allele, the team discovered that having at least one met allele was associated with a significantly increased change in GI over 4 years in all four prefrontal quadrants, but particularly in the right dorsal prefrontal cortex.
Carriers of a met allele were significantly older than val/val homozygotes, at 43.9 years versus 35.1 years. When taking age into account, there was a trend toward a significant difference in change in GI between met carriers and val/val homozygotes in the ventral quadrants, and a significant difference in dorsal quadrants.
The researchers conclude in the journal Biological Psychiatry: “We show that GI decreases significantly over time and that the rate of change in GI is not different in bipolar patients compared with control subjects but is accelerated in bipolar participants possessing at least one BDNF allele.
“These findings suggest that GI is not purely a neurodevelopmental measure and raise the possibility that GI may be a sensitive measure of morphological change with time.”
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009
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