The impact of phenotypic and genetic heterogeneity on results of genome wide association studies of complex diseases.

Phenotypic misclassification (between cases) has been shown to reduce the power to detect association in genetic studies. However, it is conceivable that complex traits are heterogeneous with respect to individual genetic susceptibility and disease pathophysiology, and that the effect of heterogeneity has a larger magnitude than the effect of phenotyping errors. Although an intuitively clear concept, the effect of heterogeneity on genetic studies of common diseases has received little attention.

Brain structural signature of familial predisposition for bipolar disorder: replicable evidence for involvement of the right inferior frontal gyrus.

Background: To translate our knowledge about neuroanatomy of bipolar disorder (BD) into a diagnostic tool, it is necessary to identify the neural signature of predisposition for BD and separate it from effects of long-standing illness and treatment. Thus, we examined the associations among genetic risk, illness burden, lithium treatment, and brain structure in BD.

Methods: This is a two-center, replication-design, structural magnetic resonance imaging study.

Hippocampal volumes in bipolar disorders: opposing effects of illness burden and lithium treatment.

Objective: Hippocampal volume decrease associated with illness burden is among the most replicated findings in unipolar depression. The absence of hippocampal volume changes in most studies of individuals with bipolar disorder (BD) may reflect neuroprotective effects of lithium (Li).

Methods: We recruited 17 BD patients from specialized Li clinics, with at least two years of regularly monitored Li treatment (Li group), and compared them to 12 BD participants with < 3 months of lifetime Li exposure and no Li treatment within two years prior to the scanning (non-Li group) and 11 healthy controls.

Large positive effect of lithium on prefrontal cortex N-acetylaspartate in patients with bipolar disorder: 2-centre study.

Background: Neuroprotective effects of lithium (Li) have been well documented in tissue cultures and animal models, whereas human data continue to be limited. Previous studies investigating the association between Li treatment and brain N-acetylaspartate (NAA), a putative neuronal marker, showed mixed results because of methodological heterogeneity.

Methods: To investigate the effects of Li on prefrontal cortex NAA levels, we compared patients with bipolar disorder from specialized Li clinics in Berlin and Halifax with at least 2 years of ongoing Li treatment (Li group), patients with lifetime Li exposure of less than 3 months more than 2 years ago (non-Li group) and healthy controls.