Accelerated loss of prefrontal gyrification in bipolar disorder is linked to having at least one brain-derived neurotropgic factor (BDNF) variant, although the overall rate is no higher in such patients, say UK researchers.

Studies have shown that there are structural cerebral abnormalities in bipolar disorder patients, but it is not clear whether they are present at disease-onset or develop over time. As a measure of brain morphology, the gyrification index (GI) of cortical folding has been found to be increased in patients with acute schizophrenia and decreased in those with chronic schizophrenia.

To examine GI changes in bipolar disorder, Ajay Mirakhur and colleagues, from the University of Edinburgh, performed magnetic resonance imaging at baseline and after 4 years in 18 bipolar I disorder patients and 18 healthy controls. They calculated prefrontal GI as the ratio of folded inner contour to exposed outer contour.

Both bipolar disorder patients and healthy controls had a significant decrease in GI over 4 years for dorsal and ventral prefrontal quadrants bilaterally, with no significant difference in the rate of change between patients and controls.

The team also found that bipolar disorder patients with at least one BDNF val⁶⁶met met allele experienced a significantly increased change in GI, particularly in the right dorsal prefrontal cortex, compared with patients with no copies of the BDNF val⁶⁶met met allele, with, GIs at baseline and at follow-up of 2.48 versus 2.31 and 2.47 versus 2.42, respectively.

Interestingly, the team notes in the journal Biological Psychiatry that carriers of the met allele were significantly older than non-carriers, at 43.9 years versus 35.1 years. After taking age into account, the associations between the met allele and change in GI were significant only in the dorsal quadrants. Taking into account medications had no effect on the findings.

“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,” the researchers conclude.

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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Variation in the melatonin-related G protein-coupled receptor 50 (GPR50) gene appears to play a role in affective disorder, particularly in women, say UK researchers.

G protein-coupled receptors mediate transmembrane signal transduction in response to ligand binding, and are involved in many diseases including depression and anxiety, Douglas Blackwood (University of Edinburgh) and colleagues explain.

Indeed, “they are the therapeutic targets for approximately 50% of all recently released drugs, including 5-hydroxytryptamine 2C antagonists which are used to treat depression,” they add.

A recent study detected an association between the GPR50 gene and bipolar disorder in a Scottish population. Blackwood et al replicated this study in a second sample from the same population, consisting of 338 patients with bipolar disorder, 359 with major depressive disorder (MDD), and 913 mentally healthy individuals.

They also investigated the effects of the GPR50 genotype on the clinical phenotype and treatment response of a subset of 56 patients with early-onset MDD.

As reported in the journal Neuroscience Letters, an intronic single nucleotide polymorphism of the GPR50 gene ??” rs1202874 ??” was significantly associated, albeit relatively weakly, with bipolar disorder in women, at an odds ratio of 1.9. This association remained significant after correction for multiple testing.

The association was strengthened when women with MDD fulfilling Ghaemi’s criteria for bipolar spectrum disorder were also included.

The researchers say that the association between the GPR50 gene and bipolar disorder may be restricted to women “because gene expression level may be influenced by hormonal factors, particularly given that GPR50 is expressed in the hypothalamic??”pituitary axis.”

The investigators failed to find a significant association between the ?”502-505 deletion polymorphism, which was associated with bipolar disorder in women in the original study, and any disorder regardless of gender.

Even after combining the original data with the current data to give a total sample of 336 women with bipolar disorder and 542 female mentally healthy controls, the association was only just significant and the effects size was reduced compared with the original findings, at an odds ratio of 1.41.

However, detailed study of patients with early-onset MDD showed that men who were homozygous for the ?”502-505 deletion polymorphism were more likely to have a family history of depression, while homozygous women had an earlier age of illness onset, a greater number of depressive episodes, higher scores on the hypomania checklist, and lower initial thinking time on the Stockings of Cambridge test than other patients.

“This suggests carriers of the deletion may have an illness of greater severity [and] be more likely to develop a bipolar type illness in later life,” Blackwood and team write.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

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