Rodrigo B Mansur1, Juhie Ahmed2, Danielle S Cha2, Hanna O Woldeyohannes2, Mehala Subramaniapillai2, Julie Lovshin3, Jung G Lee4, Jae-Hon Lee5, Elisa Brietzke6, Eva Z Reininghaus7, Kang Sim8, Maj Vinberg9, Natalie Rasgon10, Tomas Hajek11, Roger S McIntyre2. 1. 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. 2. Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada. 3. Division of Endocrinology, Mount Sinai Hospital, University of Toronto, Toronto, Canada. 4. Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada; Paik Institute for Clinical Research, Inje University, Busan, Republic of Korea. 5. 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. 6. Research Group in Molecular and Behavioral Neuroscience of Bipolar Disorder, Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. 7. Medical University of Graz, Department of Psychiatry, Graz, Austria. 8. Research Division, Institute of Mental Health, Singapore. 9. Psychiatric Center Copenhagen, University of Copenhagen, Copenhagen, Denmark. 10. Department of Psychiatry, Stanford University, Palo Alto, CA, United States. 11. Department of Psychiatry, Dalhousie University, Halifax, Canada.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: Small sample size, open-label design, lack of a placebo group. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: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. LIMITATIONS: Small sample size, open-label design, lack of a placebo group. CONCLUSIONS: 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: Rodrigo B Mansur; Gabriel R Fries; Alisson P Trevizol; Mehala Subramaniapillai; Julie Lovshin; Kangguang Lin; Maj Vinberg; Roger C Ho; Elisa Brietzke; Roger S McIntyre Journal: Eur Neuropsychopharmacol Date: 2018-11-06 Impact factor: 4.600
Authors: Yena Lee; Mehala Subramaniapillai; Elisa Brietzke; Rodrigo B Mansur; Roger C Ho; Samantha J Yim; Roger S McIntyre Journal: Ther Adv Psychopharmacol Date: 2018-11-19
Authors: Francesco Vadini; Paola G Simeone; Andrea Boccatonda; Maria T Guagnano; Rossella Liani; Romina Tripaldi; Augusto Di Castelnuovo; Francesco Cipollone; Agostino Consoli; Francesca Santilli Journal: Int J Obes (Lond) Date: 2020-01-21 Impact factor: 5.095
Authors: Rodrigo B Mansur; Francheska Delgado-Peraza; Mehala Subramaniapillai; Yena Lee; Michelle Iacobucci; Flora Nasri; Nelson Rodrigues; Joshua D Rosenblat; Elisa Brietzke; Victoria E Cosgrove; Nicole E Kramer; Trisha Suppes; Charles L Raison; Andrea Fagiolini; Natalie Rasgon; Sahil Chawla; Carlos Nogueras-Ortiz; Dimitrios Kapogiannis; Roger S McIntyre Journal: J Psychiatr Res Date: 2020-12-04 Impact factor: 4.791
Authors: Andre F Batista; Leticia Forny-Germano; Julia R Clarke; Natalia M Lyra E Silva; Jordano Brito-Moreira; Susan E Boehnke; Andrew Winterborn; Brian C Coe; Ann Lablans; Juliana F Vital; Suelen A Marques; Ana Mb Martinez; Matthias Gralle; Christian Holscher; William L Klein; Jean-Christophe Houzel; Sergio T Ferreira; Douglas P Munoz; Fernanda G De Felice Journal: J Pathol Date: 2018-04-02 Impact factor: 7.996