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Modulation of brain structure by catechol-O-methyltransferase Val158Met polymorphism in chronic cannabis users

Authors

  • Albert Batalla,

    1. Department of Psychiatry, Clinical Institute of Neuroscience, Hospital Clínic, IDIBAPS, CIBERSAM, Spain
    2. Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Spain
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  • Carles Soriano-Mas,

    1. CRC Mar, Hospital del Mar, Spain
    2. Department of Psychiatry, Bellvitge University Hospital-IDIBELL, CIBERSAM, Spain
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  • Marina López-Solà,

    1. CRC Mar, Hospital del Mar, Spain
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  • Marta Torrens,

    1. Neuroscience Program, IMIM (Hospital del Mar Medical Research Institute)-INAD-Parc de Salut Mar, Autonomous University of Barcelona and Pompeu Fabra University, Spain
    2. Red de Trastornos Adictivos (RETIC), IMIM-INAD-Parc de Salut Mar, Spain
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  • José A. Crippa,

    1. Neuroscience and Cognitive Behavior Department, University of Sao Paulo, Brazil
    2. INCT Translational Medicine (INCT-TM, CNPq), Brazil
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  • Sagnik Bhattacharyya,

    1. Department of Psychosis Studies, King's College London, Institute of Psychiatry, UK
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  • Laura Blanco-Hinojo,

    1. CRC Mar, Hospital del Mar, Spain
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  • Ana B. Fagundo,

    1. Neuroscience Program, IMIM (Hospital del Mar Medical Research Institute)-INAD-Parc de Salut Mar, Autonomous University of Barcelona and Pompeu Fabra University, Spain
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  • Ben J. Harrison,

    1. CRC Mar, Hospital del Mar, Spain
    2. Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Australia
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  • Santiago Nogué,

    1. Clinical Toxicology Unit, Emergency Department, Hospital Clínic, IDIBAPS, University of Barcelona, Spain
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  • Rafael de la Torre,

    1. Neuroscience Program, IMIM (Hospital del Mar Medical Research Institute)-INAD-Parc de Salut Mar, Autonomous University of Barcelona and Pompeu Fabra University, Spain
    2. CIBEROBN, Spain
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  • Magí Farré,

    1. Neuroscience Program, IMIM (Hospital del Mar Medical Research Institute)-INAD-Parc de Salut Mar, Autonomous University of Barcelona and Pompeu Fabra University, Spain
    2. Red de Trastornos Adictivos (RETIC), IMIM-INAD-Parc de Salut Mar, Spain
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  • Jesús Pujol,

    1. CRC Mar, Hospital del Mar, Spain
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  • Rocío Martín-Santos

    Corresponding author
    1. Department of Psychiatry, Clinical Institute of Neuroscience, Hospital Clínic, IDIBAPS, CIBERSAM, Spain
    2. Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Spain
    3. Neuroscience Program, IMIM (Hospital del Mar Medical Research Institute)-INAD-Parc de Salut Mar, Autonomous University of Barcelona and Pompeu Fabra University, Spain
    4. Neuroscience and Cognitive Behavior Department, University of Sao Paulo, Brazil
    • Correspondence to: Rocío Martín-Santos, Department of Psychiatry, Instituto Clínico de Neurociencias, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Calle Villarroel, 170; 08036 Barcelona, Spain. E-mail: rmsantos@clinic.ub.es

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Abstract

Neuroimaging studies have shown that chronic consumption of cannabis may result in alterations in brain morphology. Recent work focusing on the relationship between brain structure and the catechol-O-methyltransferase (COMT) gene polymorphism suggests that functional COMT variants may affect brain volume in healthy individuals and in schizophrenia patients. We measured the influence of COMT genotype on the volume of four key regions: the prefrontal cortex, neostriatum (caudate-putamen), anterior cingulate cortex and hippocampus-amygdala complex, in chronic early-onset cannabis users and healthy control subjects. We selected 29 chronic cannabis users who began using cannabis before 16 years of age and matched them to 28 healthy volunteers in terms of age, educational level and IQ. Participants were male, Caucasians aged between 18 and 30 years. All were assessed by a structured psychiatric interview (PRISM) to exclude any lifetime Axis-I disorder according to Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition. COMT genotyping was performed and structural magnetic resonance imaging data was analyzed by voxel-based morphometry. The results showed that the COMT polymorphism influenced the volume of the bilateral ventral caudate nucleus in both groups, but in an opposite direction: more copies of val allele led to lesser volume in chronic cannabis users and more volume in controls. The opposite pattern was found in left amygdala. There were no effects of COMT genotype on volumes of the whole brain or the other selected regions. Our findings support recent reports of neuroanatomical changes associated with cannabis use and, for the first time, reveal that these changes may be influenced by the COMT genotype.

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