Brain-derived neurotrophic factor, impaired glucose metabolism, and bipolar disorder course.
The neurotrophin brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker in bipolar disorder (BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism (IGM) on plasma levels of BDNF in individuals with BD, and on the relationship between BDNF and variables of illness course.



We measured and compared the plasma levels of BDNF in individuals with BD (n=57) and healthy controls (n=26). IGM was operationalized as pre-diabetes or type 2 diabetes mellitus. Information related to current and past psychiatric/medical history, as well as prescription of pharmacological treatments was also captured.



Individuals with BD had lower levels of BDNF, relative to healthy controls, after adjustment for age, gender, current medications, smoking, alcohol use, and IGM (P=.046). There was no effect of IGM (P=.860) and no interaction between BD diagnosis and IGM (P=.893). Peripheral BDNF levels were positively correlated with lifetime depressive episodes (P<.001), psychiatric hospitalizations (P=.001) and suicide attempts (P=.021). IGM moderated the association between BDNF and the number of previous mood episodes (P<.001), wherein there was a positive correlation in euglycemic participants and a negative correlation in individuals with IGM.



BD is independently associated with lower levels of BDNF; IGM may modify the relationship between BDNF and BD course, suggesting an interactive effect of BDNF with metabolic status on illness progression.
Department of Psychiatry, Research Group in Behavioral Neuroscience of Bipolar Disorder (GP-TB), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.|Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada.
Rodrigo B
RB
Mansur
Department of Psychiatry, Research Group in Behavioral Neuroscience of Bipolar Disorder (GP-TB), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
Camila M
CM
Santos
Department of Psychiatry, Research Group in Behavioral Neuroscience of Bipolar Disorder (GP-TB), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.|Department of Psychiatry, Clinic for Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.
Lucas B
LB
Rizzo
Department of Psychiatry, Research Group in Behavioral Neuroscience of Bipolar Disorder (GP-TB), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
Elson
E
Asevedo
Department of Psychiatry, Research Group in Behavioral Neuroscience of Bipolar Disorder (GP-TB), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
Graccielle R
GR
Cunha
Department of Psychiatry, Research Group in Behavioral Neuroscience of Bipolar Disorder (GP-TB), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.|Vila Maria Outpatient Clinic, São Paulo, Brazil.
Mariane N
MN
Noto
Department of Psychiatry, Research Group in Behavioral Neuroscience of Bipolar Disorder (GP-TB), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
Mariana
M
Pedrini
Department of Psychiatry, Research Group in Behavioral Neuroscience of Bipolar Disorder (GP-TB), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
Maiara
M
Zeni-Graiff
Department of Psychiatry, Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), São Paulo, Brazil.
Quirino
Q
Cordeiro
Psychiatric Center Copenhagen, University of Copenhagen, Copenhagen, Denmark.
Maj
M
Vinberg
Bipolar Disorder Program and Laboratory of Molecular Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Flavio
F
Kapczinski
Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada.
Roger S
RS
McIntyre
Department of Psychiatry, Research Group in Behavioral Neuroscience of Bipolar Disorder (GP-TB), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
Elisa
E
Brietzke
D000328:Adult; D000428:Alcohol Drinking / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D001938:Brazil; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D018450:Disease Progression; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000378:metabolism / Q000523:psychology; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D013223:Statistics as Topic
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D005947:Glucose
bipolar disorder; brain-derived neurotrophic factor; diabetes; impaired glucose metabolism