Plasma concentrations of BDNF and IGF-1 in abstinent cocaine users with high prevalence of substance use disorders: relationship to psychiatric comorbidity.
Recent studies have identified biomarkers related to the severity and pathogenesis of cocaine addiction and common comorbid psychiatric disorders. Monitoring these plasma mediators may improve the stratification of cocaine users seeking treatment. Because the neurotrophic factors are involved in neural plasticity, neurogenesis and neuronal survival, we have determined plasma concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1) and IGF-1 binding protein 3 (IGFBP-3) in a cross-sectional study with abstinent cocaine users who sought outpatient treatment for cocaine (n = 100) and age/body mass matched controls (n = 85). Participants were assessed with the diagnostic interview 'Psychiatric Research Interview for Substance and Mental Disorders'. Plasma concentrations of these peptides were not different in cocaine users and controls. They were not associated with length of abstinence, duration of cocaine use or cocaine symptom severity. The pathological use of cocaine did not influence the association of IGF-1 with age observed in healthy subjects, but the correlation between IGF-1 and IGFBP-3 was not significantly detected. Correlation analyses were performed between these peptides and other molecules sensitive to addiction: BDNF concentrations were not associated with inflammatory mediators, lipid derivatives or IGF-1 in cocaine users, but correlated with chemokines (fractalkine/CX3CL1 and SDF-1/CXCL12) and N-acyl-ethanolamines (N-palmitoyl-, N-oleoyl-, N-arachidonoyl-, N-linoleoyl- and N-dihomo-γ-linolenoyl-ethanolamine) in controls; IGF-1 concentrations only showed association with IGFBP-3 concentrations in controls; and IGFBP-3 was only correlated with N-stearoyl-ethanolamine concentrations in cocaine users. Multiple substance use disorders and life-time comorbid psychopathologies were common in abstinent cocaine users. Interestingly, plasma BDNF concentrations were exclusively found to be decreased in users diagnosed with both primary and cocaine-induced disorders for mood and anxiety disorders. In summary, BDNF, IGF-1 and IGFBP-3 were not affected by a history of pathological use of cocaine supported by the absence of associations with other molecules sensitive to cocaine addiction. However, BDNF was affected by comorbid mood disorders. Further research is necessary to elucidate the role of BDNF and IGF-1 in the transition to cocaine addiction and associated psychiatric comorbidity.
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
María
M
Pedraz
Department of Physiology, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain.
Ana Isabel
AI
Martín-Velasco
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
Nuria
N
García-Marchena
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
Pedro
P
Araos
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
Antonia
A
Serrano
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
Pablo
P
Romero-Sanchiz
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
Juan
J
Suárez
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
Estela
E
Castilla-Ortega
Department of Pediatrics & Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain; Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
Vicente
V
Barrios
Centro de Tratamiento Ambulatorio Mijas Costa-Diputación de Málaga, Mijas, Spain.
Rafael
R
Campos-Cloute
Centro Provincial de Drogodependencia-Diputación de Málaga, Málaga, Spain.
Juan Jesús
JJ
Ruiz
Neurosciences Program, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain; Institut de Neuropsiquiatria i Addiccions (INAD) del Parc de Salut MAR, Barcelona, Spain; Department of Psychiatry. Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
Marta
M
Torrens
Department of Pediatrics & Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain; Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
Julie Ann
JA
Chowen
Department of Pediatrics & Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain; Department of Pediatrics, Universidad Autónoma de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
Jesús
J
Argente
Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain; Neurosciences Program, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain; Facultat de Ciencies de la Salut i de la Vida, Universitat Pompeu Fabra (CEXS-UPF), Barcelona, Spain.
Rafael
R
de la Torre
Departamento de Psicobiología y Metodología de las Ciencias del Comportamiento, Facultad de Psicología, Universidad de Málaga, Málaga, Spain.
Luis Javier
LJ
Santín
Department of Physiology, Faculty of Medicine, Complutense University of Madrid, Madrid, Spain.
María Ángeles
MÁ
Villanúa
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
Fernando
F
Rodríguez de Fonseca
Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga-Universidad de Málaga, Málaga, Spain.
Francisco Javier
FJ
Pavón
D000293:Adolescent; D000328:Adult; D000368:Aged; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D018925:Chemokines / Q000097:blood; D019970:Cocaine-Related Disorders / Q000150:complications / Q000175:diagnosis* / Q000453:epidemiology; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007118:Immunoassay; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007407:Interviews as Topic; D008297:Male; D001523:Mental Disorders / Q000150:complications / Q000175:diagnosis; D008875:Middle Aged; D015995:Prevalence; D011863:Radioimmunoassay; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor; D018925:Chemokines; D016207:Cytokines; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; C579455:BDNF protein, human