R B Mansur1,2,3, E Brietzke3,4, R S McIntyre1,2,3,5, B Cao1,6, Y Lee3,5, L Japiassú2, K Chen1,7, R Lu1, W Lu1, T Li1, G Xu1,7, K Lin1,7,8. 1. Department of Affective Disorders, the Affiliated Hospital of Guangzhou Medical University, (Guangzhou Huiai Hospital), Guangzhou Medical University, Guangzhou, China. 2. Department of Psychiatry, University of Toronto, Toronto, ON, Canada. 3. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada. 4. Department of Psychiatry, Universidade Federal de Sao Paulo, Sao Paulo, Brazil. 5. Institute of Medical Science, University of Toronto, Toronto, ON, Canada. 6. Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA. 7. Laboratory of Emotion and Cognition, the Affiliated Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou Medical University, Guangzhou, China. 8. Laboratory of Neuropsychology, University of Hong Kong, Hong Kong, Hong Kong.
Abstract
OBJECTIVE: To compare brain-derived neurotrophic factor (BDNF) levels between offspring of individuals with bipolar disorders (BD) and healthy controls (HCs) and investigate the effects of BDNF levels and body mass index (BMI) on brain structures. METHOD: Sixty-seven bipolar offspring and 45 HCs were included (ages 8-28). Structural images were acquired using 3.0 Tesla magnetic resonance imaging. Serum BDNF levels were measured using enzyme-linked immunosorbent assay. Multivariate and univariate analyses of covariance were conducted. RESULTS: Significantly higher BDNF levels were observed among bipolar offspring, relative to HCs (P > 0.025). Offspring status moderated the association between BDNF and BMI (F1 =4.636, P = 0.034). After adjustment for relevant covariates, there was a trend for a significant interaction of group and BDNF on neuroimaging parameters (Wilks'λ F56,94 =1.463, P = 0.052), with significant effects on cerebellar white matter and superior and middle frontal regions. Brain volume and BDNF were positively correlated among HCs and negatively correlated among bipolar offspring. Interactions between BDNF and BMI on brain volumes were non-significant among HCs (Wilks'λ F28,2 =2.229, P = 0.357), but significant among bipolar offspring (Wilks'λ F28,12 =2.899, P = 0.028). CONCLUSION: Offspring status and BMI moderate the association between BDNF levels and brain structures among bipolar offspring, underscoring BDNF regulation and overweight/obesity as key moderators of BD pathogenesis.
OBJECTIVE: To compare brain-derived neurotrophic factor (BDNF) levels between offspring of individuals with bipolar disorders (BD) and healthy controls (HCs) and investigate the effects of BDNF levels and body mass index (BMI) on brain structures. METHOD: Sixty-seven bipolar offspring and 45 HCs were included (ages 8-28). Structural images were acquired using 3.0 Tesla magnetic resonance imaging. Serum BDNF levels were measured using enzyme-linked immunosorbent assay. Multivariate and univariate analyses of covariance were conducted. RESULTS: Significantly higher BDNF levels were observed among bipolar offspring, relative to HCs (P > 0.025). Offspring status moderated the association between BDNF and BMI (F1 =4.636, P = 0.034). After adjustment for relevant covariates, there was a trend for a significant interaction of group and BDNF on neuroimaging parameters (Wilks'λ F56,94 =1.463, P = 0.052), with significant effects on cerebellar white matter and superior and middle frontal regions. Brain volume and BDNF were positively correlated among HCs and negatively correlated among bipolar offspring. Interactions between BDNF and BMI on brain volumes were non-significant among HCs (Wilks'λ F28,2 =2.229, P = 0.357), but significant among bipolar offspring (Wilks'λ F28,12 =2.899, P = 0.028). CONCLUSION: Offspring status and BMI moderate the association between BDNF levels and brain structures among bipolar offspring, underscoring BDNF regulation and overweight/obesity as key moderators of BD pathogenesis.
Authors: Xueyi Shen; Doretta Caramaschi; Mark J Adams; Rosie M Walker; Josine L Min; Alex Kwong; Gibran Hemani; Miruna C Barbu; Heather C Whalley; Sarah E Harris; Ian J Deary; Stewart W Morris; Simon R Cox; Caroline L Relton; Riccardo E Marioni; Kathryn L Evans; Andrew M McIntosh Journal: Genome Med Date: 2022-03-31 Impact factor: 15.266