title: Liraglutide promotes improvements in objective measures of cognitive dysfunction in individuals with mood disorders: A pilot, open-label study.
abstract: There is a paucity of treatments that are capable of reliably and robustly improving cognitive function in adults with mood disorders. Glucagon-like peptide-1 is synthesized centrally and its receptors are abundantly expressed in neural circuits subserving cognitive function. We aimed to determine the effects of liraglutide, a GLP-1 receptor (GLP-1R) agonist, on objective measures of cognition in adults with a depressive or bipolar disorder.
  
  
  
  In this 4-week, pilot, open-label, domain-based study (e.g. cognition), we recruited 19 individuals with major depressive disorder (MDD) or bipolar disorder (BD) and an impairment in executive function, defined as a below-average performance in the Trail Making Test-B (TMTB). Liraglutide 1.8mg/day was added as an adjunct to existing pharmacotherapy.
  
  
  
  Participants had significant increases from baseline to week 4 in the TMTB standard score (age and education corrected) (Cohen's d=0.64, p=0.009) and in a composite Z-score comprising multiple cognitive tests (i.e. Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Stroop test) (Cohen's d=0.77, p<0.001). Neither changes in mood rating scales nor metabolic parameters were associated with changes in cognitive performance (all p>0.05); however baseline insulin resistance (IR) and body mass index (BMI) moderated the changes in the composite Z-score (p=0.021 and p=0.046, respectively), indicating larger responses in individuals with higher IR and BMI at baseline. There was a significant increase in lipase (p<0.001), but individual values were above the upper limit of normality.
  
  
  
  Small sample size, open-label design, lack of a placebo group.
  
  
  
  Liraglutide was safe and well tolerated by a sample of non-diabetic individuals with mood disorders and had beneficial effects on objective measures of cognitive function. Larger studies with controlled trial designs are necessary to confirm and expand the results described herein.
authors.affiliation: Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada; Research Group in Molecular and Behavioral Neuroscience of Bipolar Disorder, Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. Electronic address: rodrigomansur71@uol.com.br.
authors.forename: Rodrigo B
authors.initials: RB
authors.lastname: Mansur
authors.affiliation: Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Juhie
authors.initials: J
authors.lastname: Ahmed
authors.affiliation: Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Danielle S
authors.initials: DS
authors.lastname: Cha
authors.affiliation: Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Hanna O
authors.initials: HO
authors.lastname: Woldeyohannes
authors.affiliation: Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Mehala
authors.initials: M
authors.lastname: Subramaniapillai
authors.affiliation: Division of Endocrinology, Mount Sinai Hospital, University of Toronto, Toronto, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Lovshin
authors.affiliation: Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada; Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea.
authors.forename: Jung G
authors.initials: JG
authors.lastname: Lee
authors.affiliation: Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada; Department of Psychiatry, Samsung Seoul Hospital, Sungkyunkwan University, School of Medicine, Seoul, Republic of Korea.
authors.forename: Jae-Hon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Research Group in Molecular and Behavioral Neuroscience of Bipolar Disorder, Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Elisa
authors.initials: E
authors.lastname: Brietzke
authors.affiliation: Medical University of Graz, Department of Psychiatry, Graz, Austria.
authors.forename: Eva Z
authors.initials: EZ
authors.lastname: Reininghaus
authors.affiliation: Research Division, Institute of Mental Health, Singapore.
authors.forename: Kang
authors.initials: K
authors.lastname: Sim
authors.affiliation: Psychiatric Center Copenhagen, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Maj
authors.initials: M
authors.lastname: Vinberg
authors.affiliation: Department of Psychiatry, Stanford University, Palo Alto, CA, United States.
authors.forename: Natalie
authors.initials: N
authors.lastname: Rasgon
authors.affiliation: Department of Psychiatry, Dalhousie University, Halifax, Canada.
authors.forename: Tomas
authors.initials: T
authors.lastname: Hajek
authors.affiliation: Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada.
authors.forename: Roger S
authors.initials: RS
authors.lastname: McIntyre
mesh_terms: D000328:Adult; D000339:Affect; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D003071:Cognition; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000523:psychology; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D056344:Executive Function; D005260:Female; D006801:Humans; D054795:Incretins / Q000627:therapeutic use*; D000069450:Liraglutide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000188:drug therapy / Q000523:psychology; D009325:Nausea / Q000139:chemically induced; D010865:Pilot Projects; D057190:Stroop Test; D016896:Treatment Outcome; D014706:Verbal Learning
chemical_list: D054795:Incretins; D000069450:Liraglutide
keywords: Bipolar disorder; Cognition; Glucagon-like peptide-1; Insulin resistance; Liraglutide; Major depressive disorder