The association of blood biomarkers with cerebral white matter and myelin content in bipolar disorder: a systematic review

Objectives: Evidence from diffusion tensor imaging (DTI) and postmortem studies has demonstrated white-matter (WM) deficits in bipolar disorder (BD). Changes in peripheral blood biomarkers have also been observed; however, studies evaluating the potential relationship between brain alterations and the periphery are scarce. The objective of this systematic review is to investigate the relationship between blood-based biomarkers and WM in BD. Methods: PubMed, Embase, and PsycINFO were used to conduct literature searches. Cross-sectional or longitudinal studies reporting original data which investigated both a blood-based biomarker and WM (by neuroimaging) in BD were included. Results: Of 3,750 studies retrieved, 23 were included. Several classes of biomarkers were found to have a significant relationship with WM in BD. These included cytokines and growth factors (interleukin-8 [IL-8], tumor necrosis factor alpha [TNF-α], and insulin-like growth factor binding protein 3 [IGFBP-3]), innate immune system (natural killer cells [NK]), metabolic markers (lipid hydroperoxidase, cholesterol, triglycerides), the kynurenine (Kyn) pathway (5-hydroxyindoleacetic acid, kynurenic acid [Kyna]), and various gene polymorphisms (serotonin-transporter-linked promoter region). Conclusion: This systematic review revealed that blood-based biomarkers are associated with markers of WM deficits observed in BD. Longitudinal studies investigating the potential clinical utility of these specific biomarkers are encouraged. Systematic review registration: PROSPERO CRD42021279246.

Effects of childhood trauma on BDNF and TBARS during crack-cocaine withdrawal

Objective: To evaluate the association between childhood trauma (CT) and serum levels of brain-derived neurotrophic factor (BDNF) and thiobarbituric acid-reactive substances (TBARS) during crack-cocaine withdrawal. Method: Thirty-three male crack-cocaine users were recruited at admission to a public addiction treatment unit. Serum BDNF and TBARS levels were evaluated at intake and discharge. Information about drug use was assessed by the Addiction Severity Index-6th Version (ASI-6); CT was reported throughout the Childhood Trauma Questionnaire (CTQ). CTQ scores were calculated based on a latent analysis model that divided the sample into low-, medium-, and high-level trauma groups. Results: There was a significant increase in BDNF levels from admission to discharge, which did not differ across CT subgroups. For TBARS levels, we found a significant time vs. trauma interaction (F2,28 = 6.357, p = 0.005,ηp 2 = 0.312). In participants with low trauma level, TBARS decreased, while in those with a high trauma level, TBARS increased during early withdrawal. Conclusion: TBARS levels showed opposite patterns of change in crack-cocaine withdrawal according to baseline CT. These results suggest that CT could be associated with more severe neurological impairment during withdrawal.

Evaluation of BDNF levels in patients hospitalized for physical trauma at an emergency hospital in Porto Alegre, southern Brazil / Avaliação dos níveis de BDNF em pacientes hospitalizados por trauma físico em um hospital de emergência de Porto Alegre, sul do Brasil

Abstract Objective To assess the association between brain-derived neurotrophic factor (BDNF) levels and acute stress disorder (ASD) in patients who have suffered physical trauma. Methods Data were collected at an emergency hospital in Porto Alegre, state of Rio Grande do Sul, southern Brazil. Participants were over 18 years of age, victims of physical trauma, and had been hospitalized for a minimum of 48 hours. A total of 117 hospitalized patients who agreed to participate in the research were grouped according to the shift in which blood was collected (38 subjects from the morning shift and 79 from the afternoon shift), had their BDNF levels measured and responded to other questionnaires. Respondents were further grouped by age into three ranges: 18-30, 31-50 and 51-70 years. Results We found a significant difference in the distribution of BDNF between the two shifts in which blood samples were collected, with the afternoon group having higher BDNF levels (U = 1906.5, p = 0.018). A difference was observed only between the 18-30 group and the 51-70 group in the afternoon shift (Umorning = 1107, pmorning = 0.575; Uafternoon = 7175, pafternoon = 0.028). Conclusions The population whose blood samples were collected in the afternoon showed significantly higher values of BDNF compared to those of the morning shift. This same population presented lower BDNF levels when associated with ASD subtypes A1, A2, and A. We hypothesize that the lower values of BDNF measured in the morning shift were due to a response to the circadian cycle of cortisol, whose action inhibits the expression of serum neurotrophins.

Resumo Objetivo Verificar a associação entre os níveis de fator neurotrófico derivado do cérebro (brain-derived neurotrophic factor [BDNF]) e transtorno de estresse agudo (TEA) em pacientes que sofreram trauma físico. Métodos Os dados foram coletados em um hospital de emergência de Porto Alegre, Rio Grande do Sul, Brasil. Os participantes eram maiores de 18 anos, vítimas de trauma físico e estavam hospitalizados por um período mínimo de 48 horas. Um total de 117 pacientes hospitalizados que concordaram em participar da pesquisa foram agrupados de acordo com o turno de realização da coleta de sangue (38 sujeitos no turno da manhã e 79 sujeitos no turno da tarde), tiveram seus níveis de BDNF medidos e responderam a outros questionários. Os entrevistados também foram agrupados por idade em três faixas etárias: 18-30, 31-50 e 51-70 anos. Resultados Encontramos uma diferença significativa na distribuição de BDNF entre os turnos, sendo que o grupo da tarde apresentou níveis maiores de BDNF (U = 1906,5, p = 0,018). Houve diferença entre o grupo de 18-30 anos e o de 51-70 anos no turno da tarde (Umanhã = 1107, pmanhã = 0,575; Utarde = 7175, ptarde = 0,028). Conclusões A população cuja coleta ocorreu à tarde apresentou valores significativamente maiores de BDNF em relação à coleta do turno da manhã. Esta mesma população apresentou menores níveis dessa neurotrofina quando associada com os subtipos A1, A2 e A de TEA. É possível hipotetizar que os menores valores de BDNF aferidos na coleta do turno da manhã se devam a uma resposta ao ciclo circadiano do cortisol, cuja ação inibe a expressão de neurotrofinas séricas.