Serum epidermal growth factor, clinical illness course, and limbic brain volumes in early-stage bipolar disorder

Background: Epidermal growth factor (EGF) belongs to a family of growth factors implicated in the etiology of psychiatric illnesses. We conducted this cross-sectional case-control study to determine whether (1) serum EGF levels differ between bipolar disorder (BD) patients and non-BD comparison subjects, (2) EGF levels in patients are influenced by mood illness related factors (number of past mood episodes, medication treatment) and non-mood illness related factors (body mass index), and (3) lower EGF levels predict lower limbic brain volumes in BD. Methods: We measured serum EGF in 51 early-stage BD patients and 22 healthy comparison subjects (HS). A subset of 25 patients underwent cerebral magnetic resonance imaging (MRI). Participants were assessed at the University of British Columbia Mood Disorders Centre between June 2004 and June 2012. Results: A general linear model with diagnosis and BMI category (overweight/obese vs normal weight) as factors showed that patients had lower mean log(e)-transformed EGF (LnEGF) than HS (4.99 vs 5.47, p = .011). There was no effect of BMI and no diagnosis x BMI interaction. Multiple linear regression models showed that in patients, more past mood episodes predicted lower LnEGF (β = −0.358, t = −2.585, p = .013) and lower LnEGF predicted lower bilateral temporal lobe volumes (left: β = 0.560, p = .011; right: β = 0.543, p = .009). Limitations: Our cross-sectional study design limits our ability to make inferences about the causal directions of the relationships between EGF, diagnosis, mood episodes, and brain volumes. Conclusions: These findings provide preliminary evidence that EGF is a novel biomarker that may play a role in the pathophysiology of BD.