Bipolar pedigree endophenotypes found

By Lucy Piper, Senior medwireNews Reporter

Researchers have found cognitive endophenotypes in a single extended family showing linkage of bipolar disorder to a risk locus on chromosome 4.

"This family provided a rare opportunity to characterize a neuropsychological endophenotype in a homogenous sample of relatives with a common genetic risk factor," say Douglas Blackwood (University of Edinburgh, UK) and colleagues.

The study showed that verbal learning and semantic verbal fluency impairments may represent a cognitive endophenotype for both bipolar disorder and major depression in relatives of bipolar disorder patients, because impairments were present in high-risk relatives irrespective of whether they had affective disorder symptoms.

The study participants included 15 family members carrying the risk haplotype, of whom eight were diagnosed with bipolar disorder or depression and seven with no psychiatric diagnosis. These were compared with 36 unrelated patients with bipolar disorder, 40 with major depressive disorder, and 33 mentally healthy individuals.

Cognitive function tests showed that family members carrying the risk haplotype were significantly impaired in indices of memory and executive function compared with mentally healthy individuals. And there was no significant difference in these impairments between those with and without psychiatric diagnoses.

Significant deficits were seen for verbal learning and verbal fluency, as measured on the California Verbal Learning Test and Verbal Fluency Test. Moreover, the researchers note that high-risk relatives irrespective of whether or not they had a psychiatric diagnosis had similar deficits in these two measures to those of the bipolar disorder group.

"This suggests that these tests are closely linked to the genetic aetiology of bipolar disorder and can be considered as part of a neuropsychological endophenotype," the researchers report in BipolarDisorders.

"The study also supports the view that major depression in a close relative of a patient with bipolar disorder may be considered 'bipolar spectrum' sharing endophenotypes with bipolar disorder but not depression in the absence of bipolar family history."

For example, average scores for the semantic aspect of verbal fluency were 50.9 for mentally healthy individuals versus 46.1 for the major depression group, 41.1 for the bipolar disorder group, and 39. 9 and 39.7 for the high-risk family members with and without a psychiatric diagnosis, respectively.

The researchers note that "semantic organization may also be relevant to learning in declarative verbal tasks."

They explain: "For example, the learning of words in a list may be performed by clustering words by semantic features and thereby relying on networks of semantic associations.

"Therefore, the integrity and organization of a semantic store may, when disrupted, produce deficits in declarative memory encoding and semantic fluency measures common to our findings."

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