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.
Bibliographical noteFunding Information:
Dr. Bond has received consulting fees and/or research grants from: Pfizer, Alkermes, Myriad Genetics, the Canadian Institutes of Health Research (CIHR), and the University of Minnesota Foundation. Dr. Torres has received speaking/consulting fees from Lundbeck, Sumitomo Dainippon, and Community Living British Columbia. Dr. Lam has received speaking/consulting fees and/or research grants from Akili, Allergan, Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, Brain Canada, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments (CANMAT), Canadian Psychiatric Association, CME Institute, Hansoh, Janssen, Lundbeck, Lundbeck Institute, Medscape, Mind Mental Health Technologies, Otsuka, Pfizer, St. Jude Medical, University Health Network Foundation, and Vancouver General Hospital Foundation. Dr. Yatham has received speaking/consulting fees and/or research grants from Alkermes, Allergan, AstraZeneca, Bristol Myers Squibb, CANMAT, CIHR, Dainippon Sumitomo Pharma, Janssen, Lundbeck, Otsuka, Sunovion, and Teva.
The data for this manuscript were generated from the Systematic Treatment Optimization Program for Early Mania (STOP-EM), which was supported by an unrestricted grant to LNY from AstraZeneca Canada. The analysis of serum epidermal growth factor was supported by an investigator-initiated grant ( WS1952848 ) to DJB from Pfizer Canada. The sponsors had no input into the design or conduct of the study, the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to submit the manuscript for publication.
The data for this manuscript were generated from the Systematic Treatment Optimization Program for Early Mania (STOP-EM), which was supported by an unrestricted grant to LNY from AstraZeneca Canada. The analysis of serum epidermal growth factor was supported by an investigator-initiated grant (WS1952848) to DJB from Pfizer Canada. The sponsors had no input into the design or conduct of the study, the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to submit the manuscript for publication.The authors wish to acknowledge Dr Ana C. Andreazza, PhD, University of Toronto who conducted the assay of serum EGF. These data were presented in part at the 18th Annual Conference of the International Society for Bipolar Disorders, July 13-16, 2016, Amsterdam, the Netherlands.
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- Bipolar disorder
- Body mass index
- Epidermal growth factor
- Magnetic resonance imaging