Plasma Concentrations of BDNF and IGF-1 in Abstinent Cocaine Users with High Prevalence of Substance Use Disorders: Relationship to Psychiatric Comorbidity

Abstract

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.

Evaluation of plasma cytokines in patients with cocaine use disorders in abstinence identifies transforming growth factor alpha (TGFα) as a potential biomarker of consumption and dual diagnosis

“…Although cocaine has been described to produce a pro-inflammatory state, the decrease in the levels of IL-17α, MIP-1α and TGFα can be interpreted as a compensatory effect that reduces the cocaine-induced inflammatory tone along the period of abstinence in comparison with control subjects. A similar phenomenon has been described for certain growth factor in our outpatient cohort of cocaine patients ( Pedraz et al, 2015 ). However, none of the proteins that were analyzed in the present study were associated with CUD severity, unlike our previously described findings with IL-1β, fractalkine or SDF-1 as severity-sensitive factors ( Araos et al, 2015 ).…”

“…In the present study, we attempted to establish potential biomarkers of cocaine consumption and/or comorbid mental disorders by identifying certain, cytokines, chemokines and growth factors in the plasma of patients with these disorders. Previous studies ( Araos et al, 2015 ; Pedraz et al, 2015 ) have revealed that the circulatory/immune system-related signal or growth factors are associated with CUD. The present results extend these observations and indicate that IL-17α, MIP-1α and TGFα are altered in subjects diagnosed with CUD during abstinence, although there was no association with the cocaine symptom severity, and that TGFα levels are also influenced by the presence of dual diagnosis.…”

“…The cocaine severity symptom was used to determine cocaine trait severity combining the seven dependence criteria and the four abuse criteria (DSM-IV-TR) ( Pavón et al, 2013 ; Araos et al, 2015 ; Pedraz et al, 2015 ).…”

Variation in chemokines plasma concentrations in primary care depressed patients associated with Internet-based cognitive-behavioral therapy

“…In previous studies, our research group has found that some of these chemokines -specifically, CCL2, CCL11, CX3CL1, and CXCL12 -are related with depressive symptoms in patients with cocaine [24][25][26] and alcohol 27 use disorders. Following those findings, this study has two main aims: Firstly, the relationship between depression and circulating plasma concentrations of CCL2, CCL11, CX3CL1, and CXCL12 will be tested.…”

Psychodermatology: a molecular link between psoriasis and anxiety disorder

“…Link to psoriasis Link to anxiety disorder BDNF (brain-derived neurotrophic factor) responsible for growth and homeostasis of brain neurons Lowered in patients with psoriasis, depression (21), chronic stress (22) Lowered in patients with anxiety disorders (23)(24)(25)(26) CCL2 (chemokine (C-C motif) ligand 2) activates chemotaxis in monocytes and basophils Significant increase in serum of patients with psoriasis (27,28) Increased in patients with anxiety disorder (29) GH1 (growth hormone) required for control of body height Increased in patients with skin diseases, including psoriasis (30) Increased in patients with stress and anxiety disorder (31) CRH (corticotropin-releasing hormone) is synthesized in response to stress and stimulates release of adrenocorticotropin Significant increase in serum of patients with psoriasis (32) Increased in patients with anxiety disorder (31,33,34) LEP (leptin) is secreted by adipocytes, regulates fat and energy metabolism, as well as some endocrine functions and an inflammatory/ immune response Increased in patients with psoriasis (35)(36)(37)(38)(39)(40)(41)(42) Increased in patients with anxiety disorder (43) TNF (tumor necrosis factor), a multifunctional proinflammatory cytokine, is involved in the regulation of a variety of cellular and physiological processes…”