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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.

Background: High levels of inflammation and oxidative stress are observed in bipolar disorder (BD) being further associated with mood symptoms and cognitive dysfunction. Due to the crosstalk between the periphery and central nervous system, the blood-brain barrier (BBB) disruption has been considered a key mechanism of the BD pathophysiology. This study aimed to evaluate claudin-5 expression in the brain of a model of mania induced by D-amphetamine (AMPH). Methods: Wistar rats were injected with AMPH (2 mg/kg i.p.) and treated with lithium (47.5 mg/kg i.p.). Locomotor behavior was assessed, followed by euthanasia, blood collection, and brain removal. Tumor necrosis factor (TNF) α and thiobarbituric acid reactive substances (TBARS) were quantified in the serum and brain tissue, and claudin-5 was quantified in the brain. Results: AMPH-injected animals exhibited increased locomotor activity. In the serum, TBARS levels were augmented in lithium-treated groups, while TNFα was not detected. In the brain, TBARS and TNFα did not differ between groups but were positively andstrongly correlated in the striatum of AMPH-injected rats. Contrary to our hypothesis, AMPH and lithium injections did not affect claudin-5 levels in the brain. Limitations: The main limitations include the lack of a dynamic marker of BBB integrity and limited number of biomarkers analyzed. Conclusions: This is one of the first attempts to investigate the effects of AMPH on BBB integrity, and no disruption was observed. Still, we provide rationale for future research to elucidate the importance of BBB disruption in BD, recently proposed as a marker of illness progression.

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.

Background: It has been reported that patients with bipolar disorder (BD) present changes in peripheral levels of the inflammatory cytokine CCL11, particularly at latestages. The aim of this study is to evaluate CCL11 levels in a population-based sample of drug-naive young adults. Methods: This is a cross-sectional study nested to a large population-based study. 29 drug-naive young adults with BD and 29 controls selected from this cohort were matched for sex, age, and years of education. The diagnosis of psychiatric disorders was performed using the Mini International Neuropsychiatric Interview PLUS. Serum levels of CCL11 were measured using sandwich-ELISA. Independent samples T-test was used to assess differences between groups regarding CCL11 levels. Multivariate linear regression analyses were used to evaluate the effect of independent factors on CCL11 levels. Results: There were no demographic differences between individuals with BD and controls. No significant differences were found regarding CCL11 levels between groups. The final multivariate model showed that the variables that remained independently associated with higher CCL11 levels were male sex (B:41.41 [CI95%: 15.66 - 67.15], p = 0.002) and tobacco use (B:22.71 [CI95%: 1.28 - 44.15], p = 0.038). Conclusions: The present study suggests that there is a possible influence of sex and tobacco use on CCL11 levels, as male sex and smoking status were associated with higher CCL11 levels in our sample. It also suggests that peripheral levels of CCL11 may not be involved in the pathophysiology of BD at early stages of the disorder.

There is evidence suggesting clinical progression in a subset of patients with bipolar disorder (BD). This progression is associated with worse clinical outcomes and biological changes. Molecular pathways and biological markers of clinical progression have been identified and may explain the progressive changes associated with this disorder. The biological basis for clinical progression in BD is called neuroprogression. We propose that the following intertwined pathways provide the biological basis of neuroprogression: inflammation, oxidative stress, impaired calcium signaling, endoplasmic reticulum and mitochondrial dysfunction, and impaired neuroplasticity and cellular resilience. The nonlinear interaction of these pathways may worsen clinical outcomes, cognition, and functioning. Understanding neuroprogression in BD is crucial for identifying novel therapeutic targets, preventing illness progression, and ultimately promoting better outcomes.

Mesenchymal stem cells (MSCs) are multipotent progenitor cells that have the capacity to differentiate into all lineages of mesodermal origin, e.g., cartilage, bone, and adipocytes. MSCs have been identified at different stages of development, including adulthood, and in different tissues, such as bone marrow, adipose tissue and umbilical cord. Recent studies have shown that MSCs have the ability to migrate to injured sites. In this regard, an important characteristic of MSCs is their immunomodulatory and anti-inflammatory effects. For instance, there is evidence that MSCs can regulate the immune system by inhibiting proliferation of T and B cells. Clinical interest in the use of MSCs has increased considerably over the past few years, especially because of the ideal characteristics of these cells for regenerative medicine. Therapies with MSCs have shown promising results neurodegenerative diseases, in addition to regulating inflammation, they can promote other beneficial effects, such as neuronal growth, decrease free radicals, and reduce apoptosis. Notwithstanding, despite the vast amount of research into MSCs in neurodegenerative diseases, the mechanism of action of MSCs are still not completely clarified, hindering the development of effective treatments. Conversely, studies in models of psychiatric disorders are scarce, despite the promising results of MSCs therapies in this field as well.

BACKGROUND: Bipolar disorder (BD) is a significant cause of functional, cognitive, and social impairment. However, classic studies of functioning and social skills have not investigated how BD may impact behavior on the Internet. Given that the digital age has been changing the way people communicate, this study aims to investigate the pattern of Internet use in patients with BD. METHODS: This cross-sectional study assessed 30 patients with BD I or II and 30 matched controls. Patients were not in an acute mood episode, according to DSM-IV. A standard protocol examined sociodemographic variables and social behavior on the Internet, assessed by Facebook number of friends (FBN) and lifetime estimated number of offline contacts (social network number, SNN). RESULTS: SNN (p

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.