Cannabis use in adolescence linked to schizophrenia
Psychoactive compound in cannabis may trigger the brain disorder, researchers say
April 26, 2017
Science Daily/American Friends of Tel Aviv University
Scientists believe that schizophrenia, a disorder caused by an imbalance in the brain's chemical reactions, is triggered by a genetic interaction with environmental factors. A new Tel Aviv University study published in Human Molecular Genetics now points to cannabis as a trigger for schizophrenia.
The research, conducted by Dr. Ran Barzilay and led by Prof. Dani Offen, both of TAU's Sackler School of Medicine, finds that smoking pot or using cannabis in other ways during adolescence may serve as a catalyst for schizophrenia in individuals already susceptible to the disorder.
"Our research demonstrates that cannabis has a differential risk on susceptible versus non-susceptible individuals," said Dr. Barzilay, principal investigator of the study. "In other words, young people with a genetic susceptibility to schizophrenia -- those who have psychiatric disorders in their families -- should bear in mind that they're playing with fire if they smoke pot during adolescence."
The research team included Prof. Inna Slutsky and Hadar Segal-Gavish, both of TAU's Sackler School of Medicine, and Prof. Abraham Weizman of Geha Medical Health Center and Prof. Akira Sawa of Johns Hopkins Medical Center.
Clinical picture of mouse models mimics human adolescence
Researchers exposed mouse models with a genetic susceptibility to schizophrenia -- the mutant DISC-1 gene -- to THC, the psychoactive compound in cannabis. During a time period similar to that of human adolescence, the susceptible mice were found to be at a far higher risk for lasting brain defects associated with the onset of schizophrenia.
Four categories of mice were used in the experiment: Genetically susceptible and exposed to cannabis; genetically susceptible and not exposed to cannabis; genetically intact and exposed to cannabis; and, finally, genetically intact and not exposed to cannabis. Only the genetically susceptible mice developed behavioral and biochemical brain pathologies related to schizophrenia after being exposed to cannabis, behavioral tests and neurological biochemical analyses revealed.
"The study was conducted on mice but it mimics a clinical picture of 'first episode' schizophrenia, which presents during adolescence in proximity to robust cannabis use," said Dr. Barzilay, a child and adolescent psychiatrist.
The researchers also discovered the mechanism through which the cannabis and the specific gene interact.
"A protective mechanism was observed in the non-susceptible mice," said Prof. Offen. "This mechanism involves the upregulation of a protective neurotrophic factor, BDNF, in the hippocampus. We showed in the study that if we artificially deliver BDNF to the genetically susceptible mice, they could be protected from the deleterious effect of THC during adolescence.
"This research clearly has implications in terms of public health," Prof. Offen concluded. "The novel protective mechanism identified in the study may serve as a basis for the future development of compounds capable of attenuating the deleterious effect of cannabis on brain development. However, until that time, it is important that young people at risk for psychiatric disorders (i.e., have psychiatric disorders in their family or have reacted strongly to drugs in the past) should be particularly cautious with cannabis use during adolescence."
https://www.sciencedaily.com/releases/2017/04/170426124305.htm
How cannabis use during adolescence affects brain regions associated with schizophrenia
May 8, 2012
Science Daily/Royal College of Surgeons in Ireland (RCSI)
New research from the Royal College of Surgeons in Ireland (RCSI) published in Nature's Neuropsychopharmacology has shown physical changes to exist in specific brain areas implicated in schizophrenia following the use of cannabis during adolescence. The research has shown how cannabis use during adolescence can interact with a gene, called the COMT gene, to cause physical changes in the brain.
The COMT gene provides instructions for making enzymes which breakdown a specific chemical messenger called dopamine. Dopamine is a neurotransmitter that helps conduct signals from one nerve cell to another, particularly in the brains reward and pleasure centres. Adolescent cannabis use and its interaction with particular forms of the COMT gene have been shown to cause physical changes in the brain as well as increasing the risk of developing schizophrenia.
Dr Áine Behan, Department of Physiology, RCSI and lead author on the study said 'This is the first study to show that the combined effects of the COMT gene with adolescent cannabis use cause physical changes in the brain regions associated with schizophrenia. It demonstrates how genetic, developmental and environmental factors interact to modulate brain function in schizophrenia and supports previous behavioural research which has shown the COMT gene to influence the effects of adolescent cannabis use on schizophrenia-related behaviours.
The three areas of the brain assessed in this study were found to show changes in cell size, density and protein levels.
'Increased knowledge on the effects of cannabis on the brain is critical to understanding youth mental health both in terms of psychological and psychiatric well-being,' Dr Behan continued.
The research was funded by the Health Research Board and Science Foundation Ireland.
Senior authors include Professor David Cotter and Professor Mary Cannon, Department of Psychiatry and Professor John Waddington, Department of Molecular and Cellular Therapeutics, RCSI. Additional authors in the study included Magdalena Hryniewiecka,
Department of Psychiatry, RCSI, Dr Colm O'Tuathaigh and Dr Anthony Kinsella, Department of Molecular and Cellular Therapeutics, RCSI as well as collaborators Professor Maria Karayiorgou and Professor Joseph Gogos from the Department of Neuroscience, Columbia University, New York.
https://www.sciencedaily.com/releases/2012/05/120508112748.htm