Addiction; Attention; DNMT1; DNMT3A; Global methylation; DNA (Cytosine-5-)-Methyltransferase 1; DNMT1 protein, human; DNA Methyltransferase 3A; DNA (Cytosine-5-)-Methyltransferases; DNMT3A protein, human; Cocaine; NF-kappa B; Tumor Necrosis Factor-alpha; Humans; Adolescent; Male; Female; DNA (Cytosine-5-)-Methyltransferase 1/metabolism; DNA Methylation; DNA (Cytosine-5-)-Methyltransferases/metabolism; Pilot Projects; NF-kappa B/metabolism; Tumor Necrosis Factor-alpha/metabolism; Epigenesis, Genetic; Cocaine-Related Disorders/complications; Cocaine-Related Disorders/genetics; Cocaine-Related Disorders/metabolism; Inflammation/metabolism; Cocaine/adverse effects; Attention Deficit Disorder with Hyperactivity/genetics; Attention Deficit Disorder with Hyperactivity/etiology; Attention Deficit Disorder with Hyperactivity; Cocaine-Related Disorders; Inflammation; Psychiatry and Mental Health; Biological Psychiatry
Abstract :
[en] Cocaine base paste (CBP) is an intermediate product in the process of obtaining cocaine (COC), known for its low cost, high toxicity, and poor quality. Its use became widespread in Argentina during the socioeconomic crisis of 2001-2002 and is more prevalent among individuals under 25 and those from low socioeconomic backgrounds. This pilot study aimed to characterize inflammatory and epigenetic mechanisms involved in CBP and COC addiction, and their relationship to attention deficits. We analyzed adolescents with CBP dependence (n = 25), COC dependence (n = 22), and non-dependent controls (CTR, n = 25). Gene expression analysis revealed decreased levels of NF-κB and TNF-α in both drug-dependent groups. The CBP group also showed reduced expression of DNMT1 and DNMT3A, while only DNMT1 was decreased in the COC group. These changes were consistent with lower global DNA methylation levels in both groups compared to controls. We observed that DNMT1 expression was related to top-down attention. While higher DNMT1 levels were associated with better attention performance in the CTR and COC groups, the CBP group showed the opposite pattern. These findings support the presence of distinct molecular adaptations in CBP and COC abusers and may help identify potential targets linked to cognitive deficits in addiction.
Disciplines :
Psychiatry
Author, co-author :
Sonzogni, Silvina V; Neuroepigenetics Laboratory, Institute of Biological Chemistry (IQUIBICEN-CONICET), Department of Biological Chemistry, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina. Electronic address: silvinasonzogni@gmail.com
de la Fuente, Laura A; National Scientific and Technical Research Council (CONICET), Argentina, Institute of Cognitive and Translational Neuroscience, INECO Foundation, Favaloro University (INCyT), Argentina, Department of Physics, University of Buenos Aires (UBA), Argentina, Uruguayan Centre of Molecular Imaging (CUDIM), Av. Dr. Américo Ricaldoni 2010, Montevideo, 11600, Argentina
Mimura, Camila; Neuroepigenetics Laboratory, Institute of Biological Chemistry (IQUIBICEN-CONICET), Department of Biological Chemistry, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina
Aragón Daud, Agustina ; Université de Liège - ULiège > Département des sciences cliniques ; Institute of Cognitive and Translational Neuroscience, INECO Foundation, Favaloro University (INCyT), Argentina
Vignaga, Sofía Schurmann; Institute of Cognitive and Translational Neuroscience, INECO Foundation, Favaloro University (INCyT), Argentina
Vota, Daiana; Institute of Biological Chemistry (IQUIBICEN-CONICET), Department of Biological Chemistry, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina
Manes, Facundo; National Scientific and Technical Research Council (CONICET), Argentina, Institute of Cognitive and Translational Neuroscience, INECO Foundation, Favaloro University (INCyT), Argentina
Cetkovich, Marcelo; Institute of Cognitive and Translational Neuroscience, INECO Foundation, Favaloro University (INCyT), Argentina
Torralva, Teresa; Institute of Cognitive and Translational Neuroscience, INECO Foundation, Favaloro University (INCyT), Argentina
Ibañez, Agustin; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibañez, Santiago de Chile, Chile, Cognitive Neuroscience Center (CNC), Universidad de San Andrés, Buenos Aires, Argentina, Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland
Cánepa, Eduardo T; Neuroepigenetics Laboratory, Institute of Biological Chemistry (IQUIBICEN-CONICET), Department of Biological Chemistry, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina
Language :
English
Title :
Inflammatory and epigenetic alterations associated with attention deficits in adolescents with cocaine base paste addiction.
Florencio Fiorini Foundation CONICET - National Scientific and Technical Research Council
Funding text :
This work was supported by the Florencio Fiorini Foundation , Rommers Foundation, and Consejo Nacional de Investigaciones Cient\u00EDficas y T\u00E9cnicas ( CONICET )
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