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The aim of our study was to investigate the association between lifestyle behaviors and symptoms of depression and anxiety during the COVID-19 pandemic in Canada. A web survey was conducted between July 3–August 3, 2020, across Canada. The main outcomes considered were a positive screening for depression, as evaluated by the PHQ-2 and positive screening for anxiety, as evaluated by the GAD-7. Lifestyle behaviors were assessed using the Short Multidimensional Lifestyle Inventory Evaluation—Confinement (SMILE-C), an instrument adapted for lifestyle behaviors during the COVID-19 pandemic. The total sample size included 404 participants, of which 24.3% had a positive screen for depression, 20.5% for anxiety, and 15.5% for both. We found significant differences in SMILE-C scores between individuals with a positive and individuals with a negative screen for depression ( P < .001). Likewise, there were significant differences in SMILE-C scores between individuals with a positive and individuals with a negative screen for anxiety ( P < .001). We found an association between unhealthy lifestyle behaviors and symptoms of depression and anxiety during the COVID-19 lockdown in Canada. The findings highlight the importance of lifestyle medicine (LM) education and targeted lifestyle interventions to promote healthy behaviors and help reduce the burden of mental disorders.

Purpose: Women with premenstrual dysphoric disorder (PMDD) and premenstrual syndrome (PMS) experience substantial functional impairment and decreased quality of life. While previous research has highlighted a relationship between premenstrual disturbances and suicide risk, no meta-analysis has been conducted to quantitatively assess the findings. Methods: A systematic review and meta-analysis was conducted by searching the literature in three databases (Pubmed, PsycINFO, and EMBASE) on July 15, 2020. Studies that assessed the relationship between suicidality (attempt, ideation, and/or plan) and premenstrual disturbance (PMDD, PMS, and/or premenstrual symptoms) were included. Results: Thirteen studies were included in the qualitative review (n = 10 included in meta-analysis). Results revealed that women with PMDD are almost seven times at higher risk of suicide attempt (OR: 6.97; 95% CI: 2.98–16.29, p

Background: Bipolar disorder may undertake a progressive course in a subset of patients, and research efforts have been made to understand the biological basis underlying this process. This systematic review examined the literature available on biological markers associated with illness progression in bipolar disorder. Methods: Peer-reviewed articles were assessed using Embase, PsycINFO and PubMed, as well as from external sources. After initial screening, a total of 871 citations from databases and other sources were identified. Participants with a diagnosis of bipolar disorder were included in our systematic review; however, studies with participants younger than 15 or older than 65 were excluded. All studies were assessed using the Newcastle-Ottawa Scale assessment tool, and data pertaining to the results were extracted into tabular form using Google Sheets and Google Documents. The systematic review was registered on PROSPERO international prospective register of systematic reviews (ID Number: CRD42020154305). Results: A total of 35 studies were included in the systematic review. Increased ventricular size and reduction of grey matter volume were the most common brain changes associated with illness progression in bipolar disorder. Among the several biomarkers evaluated in this systematic review, findings also indicate a role of peripheral inflammatory markers in this process. Discussion: The studies evaluating the biological basis of the illness progression in bipolar disorder are still scarce and heterogeneous. However, current evidence supports the notion of neuroprogression, the pathophysiological process related to progressive brain changes associated with clinical progression in patients with bipolar disorder. The increase in peripheral inflammatory biomarkers and the neuroanatomical changes in bipolar disorder suggest progressive systemic and structural brain alterations, respectively.

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: Bipolar disorder (BD) is a recurrent chronic psychiatric disorder. Evidence indicates that many individuals with BD exhibit high serum levels of inflammation and oxidative stress markers, which are further associated with mood symptoms and cognitive dysfunction. Due to the crosstalk between the periphery and central nervous system in BD, the disruption of the blood-brain barrier (BBB) has been proposed as a key mechanism of the pathophysiology of the disorder. This study aimed to investigate claudin-5 expression – a major protein of the BBB – in the brain of an animal model of mania induced by d-amphetamine (AMPH) and evaluate the effects of treatment with lithium. Results: AMPH-injected animals exhibited increased overall activity in the open field test. In the serum, TBARS levels were augmented in the lithium-treated groups, regardless of AMPH injection, while TNFα was not detected. In the brain, TBARS and TNFα did not differ between groups but were positively and strongly correlated in the ST of AMPH-injected rats. Contrary to the primary hypothesis, AMPH and lithium injections did not affect brain claudin-5 protein levels.Conclusions: This is one of the first attempts to investigate the effects of AMPH on BBB integrity. Although no evidence of BBB disruption was found in the current study, our results provide evidence and rationale for future research to elucidate the importance of such alteration in BD.

Cholinergic transmission is critical to high-order brain functions such as memory, learning, and attention. Alzheimer's disease (AD) is characterized by cognitive decline associated with a specific degeneration of cholinergic neurons. No effective treatment to prevent or reverse the symptoms is known. Part of this might be due to the lack of in vitro models that effectively mimic the relevant features of AD. Here, we describe the characterization of an AD in vitro model using the SH-SY5Y cell line. Exponentially growing cells were maintained in DMEM/F12 medium and differentiation was triggered by the combination of retinoic acid (RA) and BDNF. Both acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) enzymatic activities and immunocontent were determined. For mimicking tau and amyloid-β pathology, RA + BDNF-differentiated cells were challenged with okadaic acid (OA) or soluble oligomers of amyloid-β (AβOs) and neurotoxicity was evaluated. RA + BDNF-induced differentiation resulted in remarkable neuronal morphology alterations characterized by increased neurite density. Enhanced expression and enzymatic activities of cholinergic markers were observed compared to RA-differentiation only. Combination of sublethal doses of AβOs and OA resulted in decreased neurite densities, an in vitro marker of synaptopathy. Challenging RA + BDNF-differentiated SH-SY5Y cells with the combination of sublethal doses of OA and AβO, without causing considerable decrease of cell viability, provides an in vitro model which mimics the early-stage pathophysiology of cholinergic neurons affected by AD.

Objective: The purpose of this study was to assess the efficacy and tolerability of tianeptine as an adjunctive maintenance treatment for bipolar depression. Methods: This is a multicenter double-blind randomized placebo-controlled maintenance trial of adjunctive tianeptine 37.5 mg/day. Participants ( n=161) had a Montgomery-Asberg Depression Rating Scale ⩾12 at entry. After eight weeks of open-label tianeptine treatment, those who responded to tianeptine ( n=69) were randomized to adjunctive tianeptine ( n=36) or placebo ( n=33) in addition to usual treatment. Kaplan-Meier estimates and the Mantel-Cox log-rank test were used to evaluate differences in time to intervention for a mood episode between the tianeptine and placebo groups. We also assessed overall functioning, biological rhythms, quality of life, rates of manic switch and serum brain-derived neurotrophic factor levels. Results: There were no differences between adjunctive tianeptine or placebo regarding time to intervention or depression scores in the 24-week double-blind controlled phase. Patients in the tianeptine group showed better performance in the letter-number sequencing subtest from the Wechsler Adult Intelligence Scale at the endpoint ( p=0.014). Tianeptine was well tolerated and not associated with higher risk for manic switch compared to placebo. Conclusion: Tianeptine was not more effective than placebo in the maintenance treatment of bipolar depression. There is preliminary evidence suggesting a pro-cognitive effect of tianeptine in working memory compared to placebo.

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.

Objective: This study used machine learning techniques combined with peripheral biomarker measurements to build signatures to help differentiating (1) patients with bipolar depression from patients with unipolar depression, and (2) patients with bipolar depression or unipolar depression from healthy controls. Methods: We assessed serum levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, tumor necrosis factor-α, interferon-γ, interleukin-17A, brain-derived neurotrophic factor, lipid peroxidation and oxidative protein damage in 54 outpatients with bipolar depression, 54 outpatients with unipolar depression and 54 healthy controls, matched by sex and age. Depressive symptoms were assessed using the Hamilton Depression Rating Scale. Variable selection was performed with recursive feature elimination with a linear support vector machine kernel, and the leave-one-out cross-validation method was used to test and validate our model. Results: Bipolar vs unipolar depression classification achieved an area under the receiver operating characteristics (ROC) curve (AUC) of 0.69, with 0.62 sensitivity and 0.66 specificity using three selected biomarkers (interleukin-4, thiobarbituric acid reactive substances and interleukin-10). For the comparison of bipolar depression vs healthy controls, the model retained five variables (interleukin-6, interleukin-4, thiobarbituric acid reactive substances, carbonyl and interleukin-17A), with an AUC of 0.70, 0.62 sensitivity and 0.7 specificity. Finally, unipolar depression vs healthy controls comparison retained seven variables (interleukin-6, Carbonyl, brain-derived neurotrophic factor, interleukin-10, interleukin-17A, interleukin-4 and tumor necrosis factor-α), with an AUC of 0.74, a sensitivity of 0.68 and 0.70 specificity. Conclusion: Our findings show the potential of machine learning models to aid in clinical practice, leading to more objective assessment. Future studies will examine the possibility of combining peripheral blood biomarker data with other biological data to develop more accurate signatures.

Present antidepressant treatments are only helpful in a quarter of patients with bipolar depression, and new strategies are warranted. Increasing evidence suggests that accelerated polyamine metabolism is associated with the pathophysiology of depression. Polyamines regulate stress responses, inflammation, and neuronal signaling in the central and enteric nervous system. Agmatine is a promising target of altered polyamine metabolism considering its unique ability to regulate intracellular polyamine content and neuroprotective effects. Areas covered: This review discusses the polyamine system and its relationship to the central and enteric nervous system, focusing on results from preclinical studies supporting the relationship between agmatine and the pathophysiology of depression. We also discussed the main mechanisms underlying the antidepressant and neuroprotective effects of agmatine. Expert opinion: Our review points out the possible relationship between polyamines and the pathophysiology of depression. It discusses the efficacy of agmatine in several models of depressive-like behaviour, and suggests that it may prove to be an efficacious adjunctive treatment in bipolar depression. Furthermore, it discusses a proposed pathway linking systemic inflammation, observed in a subset of bipolar disorder patients, to abnormal polyamine metabolism and associated changes in the epithelial gut barrier and blood-brain barrier.

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.

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.

Objectives Previous studies measuring serum levels of biomarkers of inflammation/oxidative stress and neurotrophins levels in fibromyalgia (FM) have rendered inconsistent results. In the present study, our aim was to explore the levels of interleukins, oxidative stress markers and brain-derived neurotrophic factor (BDNF) in patients with FM in relation to depression and severity of disease. Methods In a prospective controlled cross-sectional study, serum concentrations of IL-6, IL-8, IL-10, TNF-α, thiobarbituric acid reactive substances (TBARS), protein carbonyl and BDNF were measured in 69 FM patients and 61 healthy controls (all women). In the FM group, the Fibromyalgia Impact Questionnaire (FIQ), the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS) were applied. Mann Whitney’s and Spearman correlation tests were used for statistical analysis. Results The FM patients demonstrated a significant impact of the disease on quality of life (FIQ 70.2 ± 17.8) and most of them had depression at some level (82.6% and 87.0% as assessed by BDI and HDRS, respectively). Most biomarkers (IL-6, IL-8, TNF-α, TBARS and protein carbonyl) and BDNF did not differ significantly between patients and controls, but the IL-10 levels were higher in FM patients (adjusted p = 0.041). Among FM patients, there was no correlation of HDRS, FIQ, and BDI scores with any biomarker tested here. Conclusion We observed no significant differences in biomarkers between FM patients and controls, except for higher levels of IL-10 (an anti-inflammatory cytokine) in patients. The levels of biomarkers were not correlated with parameters of disease and depression severity.

Acute exercise increases brain-derived neurotrophic factor (BDNF) serum levels in majorly depressed and anxious patients. However, to the best of our knowledge, no study has evaluated the acute effects of exercise on BDNF serum levels in Bipolar Disorder (BD). The objective of the present study was to evaluate the peripheral BDNF serum response to a single maximum session of exercise in BD participants and age- and gender-matched healthy participants. BD participants (n=18) and age- and gender-matched healthy participants (n=18) were recruited to perform a single bout of maximal exercise on a cycle ergometer. Blood samples were collected prior to and immediately after the exercise protocol. There was a significant group effect and a significant group x time x gender interaction. BD participants presented significantly higher BDNF serum levels when compared to their healthy control counterparts. Exercise increases the BDNF levels of BD women, but not men.

Background Numerous studies have reported reduced peripheral brain-derived neurotrophic factor (BDNF) in major depression (MD). However, most of these studies used multidimensional depression rating scales, and failed to identify a relationship between BDNF levels and depression severity. Unidimensional scales are a more valid measure of syndrome severity. In these scales, items are ordered in increasing severity, so that as scores increase, syndrome severity increases; thus, each item adds unique information, and items can be totaled to a meaningful sum. The current study used the HAM-D6, a unidimensional measure of depression, to examine if it could identify a correlation between serum BDNF and depression severity. Methods Serum BDNF levels and symptom severity were assessed in 163 depressed patients, including those with both unipolar (84.0%) and bipolar (16.0%) depression. The evaluation of depression severity included the total HAM-D17 and 3 subscales, including the HAM-D6. Results On average, patients presented moderate to severe depression (HAM-D17=21.2±5.5). Overall BDNF levels were 60.4±22.6ng/mL. The correlation between serum BDNF and depression severity was modest and not different when assessed by the HAM-D6 subscale or the HAM-D17 as a whole ( z =0.951; p =0.341), despite being statistically significant for the HAM-D6 ( r =−0.185; p =0.019; 95% CI: −0.335 to −0.033), but not for the entire HAM-D17 ( r =−0.127; p =0.108; 95% CI: −0.272 to 0.027). Conclusion We could not identify a strong relationship between serum BDNF levels and depression severity using the HAM-D6. This is in concordance with results of previous studies that reported no correlation between these variables, and indicates that the properties of the clinical measures used cannot explain the results these studies.

Objectives: Recent studies have pointed to neuroinflammation, oxidative stress and neurotrophic factors as key mediators in the pathophysiology of mood disorders. Little is however known about the cascade of biological episodes underlying the cognitive deficits observed during the acute and euthymic phases of bipolar disorder (BD). The aim of this review is to assess the potential association between cognitive impairment and biomarkers of inflammation, oxidative stress and neurotrophic activity in BD. Methods: Scopus (all databases), Pubmed and Ovid Medline were systematically searched with no language or year restrictions, up to November 2013, for human studies that collected both inflammatory markers and cognitive data in BD. Selected search terms were bipolar disorder, depression, mania, psychosis, inflammatory, cognitive and neurotrophic. Results: Ten human studies satisfied the criteria for consideration. The findings showed that high levels of peripheral inflammatory-cytokine, oxidative stress and reduced brain derived neurotrophic factor (BDNF) levels were associated with poor cognitive performance. The BDNF val66met polymorphism is a potential vulnerability factor for cognitive impairment in BD. Conclusions: Current data provide preliminary evidence of a link between the cognitive decline observed in BD and mechanisms of neuroinflammation and neuroprotection. The identification of BD specific inflammatory markers and polymorphisms in inflammatory response genes may be of assistance for therapeutic intervention.

Exercise can be an effective treatment for depression. Although the efficacy of exercise is well established, little is known concerning the biological changes associated with the antidepressant effects of exercise. A randomized, controlled trial was conducted to evaluate the effects of adding exercise to the usual treat- ment on the thiobarbituric acid-reactive substances (TBARS) and brain-derived neurotrophic factor (BDNF) serum levels of severely depressed inpatients. Twenty-six participants were randomized to an exercise group (n = 15, exercise ? treatment as usual) or a control group (n = 11, treatment as usual). The participants in the exer- cise group completed a targeted dose of 16.5 kcal/kg/week of aerobic exercise, three times per week, throughout their hospitalizations. The control group did not exercise during their hospitalizations. The mean hospitalization length was of 21.63 (4.5) 9 23.82 (5.7) days for exercise and control groups, respectively. The exercise group performed a median of nine sessions. After adjusting for previous tobacco use, a significant group 9 time interaction was found for TBARS serum levels (p = 0.02). A post hoc Bonferroni test revealed differences between the exercise and control groups at discharge. A significant time effect (p \ 0.001) but no group 9 time interaction was found (p = 0.13) for BDNF serum levels. Adding exercise to the usual treatment of severely depressed inpatients decreases the TBARS serum levels of severely depressed inpatients after 3 weeks. Adding exercise had no additional effects on BDNF serum levels.

Background: Increased inflammatory markers and oxidative stress have been reported in serum among patients with bipolar disorder (BD). The aim of this study is to assess whether biochemical changes in the serum of patients induces neurotoxicity in neuronal cell cultures. Methods: We challenged the retinoic acid-differentiated human neuroblastoma SH-SY5Y cells with the serum of BD patients at early and late stages of illness and assessed neurite density and cell viability as neurotoxic endpoints. Results: Decreased neurite density was found in neurons treated with the serum of patients, mostly patients at late stages of illness. Also, neurons challenged with the serum of late-stage patients showed a significant decrease in cell viability. Conclusions: Our findings showed that the serum of patients with bipolar disorder induced a decrease in neurite density and cell viability in neuronal cultures.

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. Células tronco mesenquimais (CTMs) são células progenitoras multipotentes que têm a capacidade de se diferenciar em todas as linhagens de origem mesodérmica, como, cartilagem, ossos, e adipócitos. CTMs têm sido identificadas em diferentes fases do desenvolvimento, incluindo a idade adulta e em diferentes tecidos, tais como medula óssea, tecido adipose e cordão umbilical. Estudos recentes têm mostrado que as CTMs possuem a capacidade de migrar para locais de lesões. Nesse sentido, uma característica importante das CTMs são os seus efeitos imunomodulatórios e anti-inflamatórios. Por exemplo, há evidências que as CTMs podem regular o sistema imune por inibição da proliferação de células T e B. O interesse clínico no uso das CTMs tem aumentado consideravelmente nos últimos anos, especialmente devido às características ideais destas células para a medicina regenerativa. Terapias com CTMs têm mostrado resultados promissores em doenças neurodegenerativas, além de regular a inflamação, elas podem promover outros efeitos benéficos, tais como, crescimento neuronal, diminuição de radicais livres e reduzir a apoptose. No entanto, apesar de muitas pesquisas das CTMs em doenças neurodegenerativas, o mecanismo de ação das CTMs ainda não estão completamente esclarecidos, o que dificulta o desenvolvimento de tratamentos eficazes. Por outro lado, estudos em modelos de doenças psiquiátricas são escassos, apesar dos resultados promissores utilizando terapias com CTMs nesta área.

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

Recent studies highlight the presence of systemic toxicity as an integral dimension of bipolar disorder pathophysiology, possibly linking this mood disorder with other medical conditions and comorbidities. This review summarizes recent findings on possible peripheral biomarkers of illness activity, with a focus on neurotrophins, inflammation and oxidative stress. The possible mechanisms underlying the systemic toxicity associated with acute episodes in bipolar disorder are also discussed. Finally, the authors outline novel therapies that emerge from this new research and the assessment of multiple biomarkers as a potential approach to improving management strategies in bipolar disorder.

Bipolar disorder (BD) is a severe chronic psychiatric disorder that has been associated with cellular dysfunctions related to mitochondria, neurotrophin levels, and oxidative stress. Evidence has shown that endoplasmic reticulum (ER) stress may be a common pathway of the cellular changes described in BD. In the present study we assessed unfolded protein response (UPR) and the effects of this cellular process on lymphocytes from patients with BD. We also evaluated whether the stage of chronicity of BD was associated with changes in UPR parameters. Cultured lymphocytes from 30 patients with BD and 32 age- and sex-matched controls were treated with tunicamycin, an ER stressor, for 12 or 24 h to measure levels of UPR-related proteins (GRP78, eIF2α-P, and CHOP) using flow cytometry, and for 48 h to analyse ER stress-induced cell death. In healthy controls but not in patients we found an increase in levels of GRP78, eIF2α-P, and CHOP after ER stress induction. In addition, tunicamycin-induced cell death was significantly higher in patients compared to controls. More importantly, early-stage patients did not differ from controls while the late-stage patients showed an impaired ER stress response. Thus, dysfunction in ER-related stress response may be associated with decreased cellular resilience in BD and illness progression.