Heritable bipolar phenotypes pinned down

By Eleanor McDermid, Senior medwireNews Reporter

A large study has pinpointed brain and behavioural traits that are genetically influenced and associated with bipolar I disorder.

Carrie Bearden (University of California, Los Angeles, USA) and team examined 169 behavioural, neurocognitive and neuroimaging traits in 181 patients with bipolar I disorder and their close relatives – 738 people in total.

They found that three-quarters of these traits were heritable, 31% were significantly associated with bipolar disorder and 24% were both heritable and associated with bipolar disorder.

Traits in this last group “are the most promising phenotypes for identifying loci contributing to disease risk, as shown for other neuropsychiatric disorders,” write the researchers in JAMA Psychiatry.

They add: “Some phenotypes in this group, such as delusion proneness, appear broadly characteristic of the major psychoses. Others, such as perceptual creativity, appear specific to [bipolar disorder] predisposition.”

Analysis of genetic loci related to these phenotypes should determine how strongly specific genes contribute to heritability, disease risk or both, says the team.

Some traits, most notably measures of working memory, affective temperament and impulsivity were associated with bipolar disorder but were not heritable, “suggesting they may be predominantly influenced by environmental or disease-specific factors.”

Overall, temperament traits were the least strongly heritable, but three measures – the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego cyclothymia scale; the Barratt Impulsiveness Scale; and Peters et al Delusions Inventory – had the strongest overall associations with bipolar disorder.

For neurocognition, the team assessed measures of executive function, working memory, processing speed, long-term memory and verbal fluency. Performance on some measures from all of these domains was heritable and many measures were also associated with bipolar disorder.

About 88% of neuroimaging traits were heritable and a large fraction were associated with bipolar disorder, predominantly measures of cortical thickness and magnetic resonance imaging volume measures. No measure of cortical surface area or axial diffusivity was related to bipolar disorder.

Of note, Bearden et al found that volume and white matter integrity of the corpus callosum were both heritable and significantly associated with bipolar disorder, which, in keeping with previous twin studies, suggests “genetically influenced alterations of this structure in [bipolar disorder].”

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