title: Depression, marijuana use and early-onset marijuana use conferred unique effects on neural connectivity and cognition.
abstract: Marijuana (MJ) use is common. Research shows risks for psychiatric illnesses, including major depressive disorder (MDD) and cognitive deficits with MJ use, particularly early-onset use. We investigated cognitive function, functional connectivity, and genetic risk with MDD alone and combined with MJ use, and differences between early-vs. late-onset/non-MJ use in youth.
  
  
  
  A total of 74 youth in four groups were studied: healthy control, MDD, frequent MJ use and current/past MDD plus frequent MJ use. Psychiatric symptoms, cognitive performance and demographics were measured. Default mode network (DMN) brain connectivity was determined. Risk alleles in six genes of interest were evaluated.
  
  
  
  DMN differences among groups in reward-processing and motor control regions were found; the effects of MJ use and MDD were distinct. Early-onset MJ use was associated with lower IQ and hyperconnectivity within areas of the DMN. Early-onset MJ use was associated with the BDNF risk allele.
  
  
  
  Cognitive deficits linked with early-onset MJ use were present within several years after MJ use began and may result from, predispose to, or share a common cause with early-onset MJ use. The DMN was affected by MDD, MJ and their combination, as well as by early-onset MJ use. BDNF carrier state may predispose to early-onset MJ use.
authors: Department of Psychiatry, University of Western Ontario, London, ON, Canada. Elizabeth.Osuch@lhsc.on.ca.|Department of Medical Biophysics, University of Western Ontario, London, ON, Canada. Elizabeth.Osuch@lhsc.on.ca.|Program in Neuroscience, University of Western Ontario, London, ON, Canada. Elizabeth.Osuch@lhsc.on.ca.|Lawson Health Research Institute, London, ON, Canada. Elizabeth.Osuch@lhsc.on.ca.
authors: E A
authors: EA
authors: Osuch
authors: Robarts Research Institute, London, ON, Canada.
authors: K
authors: K
authors: Manning
authors: Robarts Research Institute, London, ON, Canada.
authors: R A
authors: RA
authors: Hegele
authors: Department of Psychiatry, University of Western Ontario, London, ON, Canada.|Department of Medical Biophysics, University of Western Ontario, London, ON, Canada.|Lawson Health Research Institute, London, ON, Canada.|Department of Medical Imaging, University of Western Ontario, London, ON, Canada.|Department of Diagnostic Imaging, St. Joseph's Hospital, London, ON, Canada.
authors: J
authors: J
authors: Théberge
authors: Department of Psychiatry, University of Western Ontario, London, ON, Canada.|Program in Neuroscience, University of Western Ontario, London, ON, Canada.|Department of Psychology, University of Western Ontario, London, ON, Canada.
authors: R
authors: R
authors: Neufeld
authors: Department of Psychiatry, University of Western Ontario, London, ON, Canada.|Department of Psychology, University of Western Ontario, London, ON, Canada.|Brain and Mind Institute, London, ON, Canada.
authors: D
authors: D
authors: Mitchell
authors: Department of Psychiatry, University of Western Ontario, London, ON, Canada.|Department of Medical Biophysics, University of Western Ontario, London, ON, Canada.|Program in Neuroscience, University of Western Ontario, London, ON, Canada.
authors: P
authors: P
authors: Williamson
authors: Department of Psychology, University of Western Ontario, London, ON, Canada.
authors: R C
authors: RC
authors: Gardner
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001931:Brain Mapping / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000235:genetics; D003865:Major Depressive Disorder / Q000235:genetics / Q000503:physiopathology*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000235:genetics / Q000503:physiopathology* / Q000523:psychology; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: cognitive function; default mode network; major depressive disorder; marijuana; young adult; youth