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This paper presents a case study to support the hypothesis that religiosity and spirituality (R/S), as mood balancing factors, could facilitate the recovery process for patients suffering from bipolar disorder (BD) once they have been stabilized and are receiving appropriate support (e.g., in a residential rehabilitative center). After a succinct review of BD and R/S, the patient's medical history and rehabilitation pathway are described, with a particular focus on the role played by R/S. The authors found that in this case, once the patient was stabilized, R/S helped to consolidate her feelings of well-being, increasing her positive perception of social support services and ultimately her self-confidence., (© 2024. The Author(s).)

Background: Bipolar depression accounts for most of the disease duration in type I and type II bipolar disorder (BD), with few treatment options, often poorly tolerated. Many individuals do not respond to first-line therapeutic options, resulting in treatment-resistant bipolar depression (B-TRD). Esketamine, the S-enantiomer of ketamine, has recently been approved for treatment-resistant depression (TRD), but no data are available on its use in B-TRD., Objectives: To compare the efficacy of esketamine in two samples of unipolar and bipolar TRD, providing preliminary indications of its effectiveness in B-TRD. Secondary outcomes included the evaluation of the safety and tolerability of esketamine in B-TRD, focusing on the average risk of an affective switch., Methods: Thirty-five B-TRD subjects treated with esketamine nasal spray were enrolled and compared with 35 TRD patients. Anamnestic data and psychometric assessments (Montgomery-Asberg Depression Rating Scale/MADRS, Hamilton-depression scale/HAM-D, Hamilton-anxiety scale/HAM-A) were collected at baseline (T0), at one month (T1), and three months (T2) follow up., Results: A significant reduction in depressive symptoms was found at T1 and T2 compared to T0, with no significant differences in response or remission rates between subjects with B-TRD and TRD. Esketamine showed a greater anxiolytic action in subjects with B-TRD than in those with TRD. Improvement in depressive symptoms was not associated with treatment-emergent affective switch., Conclusions: Our results supported the effectiveness and tolerability of esketamine in a real-world population of subjects with B-TRD. The low risk of manic switch in B-TRD patients confirmed the safety of this treatment., (© 2023 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Background: The pathogenetic mechanisms of Bipolar Disorder (BD) have not been totally clarified. Oxidative stress seems to be involved in the etiology of BD, and malondialdehyde (MDA) represents a candidate biomarker for monitoring this aspect in different medical conditions including mood disorders. This article has the objective to critically summarize the available data about the association between MDA and BD., Methods: A research in Pubmed, PsycINFO and Isi Web of Knowledge was fulfilled to identify studies in which MDA levels were measured in BD patients for the purpose of securing a comprehensive review concerning the issue., Results: We detected 20 articles that satisfied the inclusion criteria: most of them observed higher MDA levels (or Thiobarbituric acid-reactive substances-TBARS) in BD patients compared to healthy controls (HC), although there are some contrasting results, depending in particular on the phase of illness or the inclusion criteria or the methodological differences., Limitations: We included studies, exclusively in English, that used different laboratory methods to measure MDA., Conclusions: The analysed articles suggest that MDA or TBARS are increased in BD patients with respect to HC, thus supporting the hypothesis that MDA may be a promising and potential biomarker to monitor the course of BD, although further studies are needed to confirm this hypothesis., Competing Interests: Declaration of Conflict of Interests Prof. Buoli reports personal fees from Mylan, outside the submitted work. The other authors have no potential conflicts of interest to declare., (Copyright © 2020. Published by Elsevier B.V.)

Objective: Neutrophil-lymphocyte, monocyte-lymphocyte and platelet-lymphocyte ratio are inexpensive and reproducible biomarkers of inflammation found to be elevated in mood disorders. This study aimed to compare inflammatory ratios between bipolar disorder and major depressive disorder and between bipolar disorder manic episodes and bipolar disorder depressive episodes., Method: We included 142 Caucasian patients (major depressive disorder: n = 36; bipolar disorder manic episode: n = 66; bipolar disorder depressive episode: n = 40). We measured white blood cells, neutrophils, lymphocytes, monocytes, platelets, glucose, and total cholesterol. Neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio, and platelet-lymphocyte ratio were calculated., Results: Neutrophil-lymphocyte ratio and monocyte-lymphocyte ratio were significantly higher in bipolar disorder manic episodes when compared to bipolar disorder depressive episodes and major depressive disorder episodes after adjustment for age, sex, body mass index, and smoking., Conclusion: To our knowledge, our study is the first one to compare inflammatory ratios between different bipolar disorder phases and major depressive disorder episodes. In accord with previous studies on other inflammatory mediators, we found higher neutrophil-lymphocyte and monocyte-lymphocyte ratios in bipolar manic episodes, suggesting that inflammatory changes occur especially during acute episodes of mania., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Borderline personality disorder (BPD) has a core embodied in affective and behavioral dysregulations, impulsivity, and relational disturbance. Clinical presentation might be heterogeneous due to a combination of different symptoms listed in the DSM-5. Clinical diagnosis and assessment of the severity of manifestations might be improved through the administration of structured interviews such as the Borderline Personality Disorder Severity Index, 4th edition (BPDSI-IV). The psychometric properties of the Italian version of the BPDSI-IV were examined for the first time in 248 patients affected by BPD and 113 patients affected by bipolar disorder, proving to be a valid and accurate instrument with good internal consistency and high accuracy. The Italian version also demonstrates significant validity in the discrimination between these clinical groups (p < 5001).

Background: Randomised placebo-controlled trials investigating treatments for bipolar disorder have been hampered by wide variations of active drugs and placebo clinical response rates. It is important to estimate whether the active drug or placebo response has a greater influence in determining the relative efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood stabilisers) for bipolar depression and mania., Methods: We identified 53 randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser monotherapy ('active drugs') for bipolar depression or mania. We carried out random-effects meta-regressions, estimating the influence of active drugs and placebo response rates on treatment relative efficacy., Results: Meta-regressions showed that treatment relative efficacy for bipolar mania was influenced by the magnitude of clinical response to active drugs ( p=0.002), but not to placebo ( p=0.60). On the other hand, treatment relative efficacy for bipolar depression was influenced by response to placebo ( p=0.047), but not to active drugs ( p=0.98)., Conclusions: Despite several limitations, our unexpected findings showed that antipsychotics / mood stabilisers relative efficacy for bipolar depression seems unrelated to active drugs response rates, depending only on clinical response to placebo. Future research should explore strategies to reduce placebo-related issues in randomised, placebo-controlled trials for bipolar depression.

Evidence suggests an association between low lipid levels and suicidality in subjects with severe mental disorders. This is the first systematic review and meta-analysis aimed at exploring differences in lipid profile between suicide attempters and non-attempters with bipolar disorder. We included observational studies providing comparative cross-sectional data on total cholesterol, LDL-cholesterol and triglycerides levels. We searched main Electronic Databases, identifying 11 studies that met our inclusion criteria, including also unpublished data. Meta-analyses based on random-effects models were carried out, generating pooled standardized mean differences (SMDs). Heterogeneity among studies was estimated using the I 2 index. The meta-analyses included data on lipid profile from 11 studies based on 288 subjects with and 754 without suicide attempt, respectively. No differences in total cholesterol (SMD: -0.10; 95%CI: -0.30 to 0.10; p=0.34), LDL-cholesterol (SMD: -0.26; 95%CI: -0.65 to 0.13; p=0.19), and triglycerides (SMD: -0.06; 95%CI: -0.31 to 0.19; p=0.63) were detected. Heterogeneity across studies was low-moderate and no risk of publication bias was found. Subgroup analyses showed no differences on effect size across different study characteristics, including different time-frames of suicide attempt, except for small sample size. Therefore, the evidence for an association between serum lipid profile and suicidality in bipolar disorder cannot be claimed. More research is needed to better understand the mechanisms underlying suicidal behaviours in bipolar patients, exploring further peripheral biomarkers as this may help clinicians screen and prevent suicidality., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Borderline Personality (BPD) and Bipolar (BP) disorders stimulate an academic debate between their distinction and the inclusion of Borderline in the Bipolar spectrum. Opponents to this inclusion attribute the important differences and possible diagnostic incomprehension to overlapping symptoms. We tested 248 Borderline and 113 Bipolar patients, consecutively admitted to the Psychiatric Unit, through DSM-IV Axis I and II Disorders (SCID-I/II), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Young Mania Rating Scale (YMRS) and Borderline Personality Disorder Severity Index-IV (BPDSI-IV). All the tests statistically discriminated the disorders (p < 0.0001). Overlapping symptoms resulted significantly different (impulsivity = 5.32 in BPD vs 1.55 in BP, p < 0.0001; emotional instability = 7.11 in BPD vs 0.55 in BP, p < 0.0001) and the range of their scores gives the opportunity for an even more precise discrimination. Distinctive traits (e.g. irritability or sexual arousal) are also discussed in order to try to qualify the core of these disorders to a higher degree. Comorbidity proves to be extremely small (3.6%). However, Borderline patients with manic features offer a privileged point of view for a deeper analysis. This allows for the possibility of a more precise examination of the nature and load of each symptom. Borderline Personality and Bipolar Disorders can be distinguished with high precision using common and time-sparing tests. The importance of discriminating these clinical features may benefit from this evidence., (Copyright © 2017. Published by Elsevier Ltd.)

The aim of this systematic review and meta-analysis was testing whether low versus high doses of second-generation antipsychotics (SGAs) are associated with different clinical benefits and harms for the acute treatment of bipolar depression. We included clinical trials comparing different doses of the same SGA monotherapy for bipolar depression. SGAs defined daily doses were used to define high and low doses. Clinical benefit outcomes included improvement, response and remission rates on Montgomery-Asberg Depression Rating Scale. Clinical harm outcomes included all-cause and adverse effect-related discontinuation rates. Data from seven clinical trials testing high and low doses of quetiapine (4 trials), cariprazine, lurasidone, and ziprasidone (1 trial each), showed no differences between lower and higher doses of selected SGAs on improvement, response and remission rates, without significant heterogeneity across studies (I 2  = 0%). Subgroup analyses based on single SGAs confirmed the clinical benefit comparability between low and high doses. However, clinical harm favorable differences for low doses on all-cause (p = 0.01) and adverse effects-related discontinuation (p = 0.001) were found. In sum, this meta-analysis showed that, although no benefits were found in terms of symptoms improvement, response and remission rates, there were clear disadvantages in prescribing higher rather than lower doses of selected SGAs. The uniform methodological strength of studies increases confidence in our findings. These data need to be integrated with individual patient characteristics (e.g., clinical urgency and adverse effect sensitivity) to optimize management of acute bipolar depression., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Subjects with bipolar mania may have increased uric acid levels, based on a purinergic system dysfunction with reduced neurotransmission of adenosine. We investigated whether there were differences in uric acid levels between individuals with bipolar disorder (in manic or depressive phases) and those with major depressive disorder., Methods: We conducted a cross-sectional study recruiting 128 subjects with bipolar disorder and 118 with major depressive disorder, admitted to a psychiatric inpatient unit. Standard demographic and clinical information were retrieved from electronic charts and relevant clinical records. Fasting serum values of uric acid, as well as metabolic (total cholesterol, triglycerides, and glycaemia), oxidative stress (albumin, bilirubin), and kidney function (creatinine), parameters, were collected., Results: Subjects with bipolar mania (5.27±1.63mg/dL), but not those with bipolar depression (4.89±1.94mg/dL), had higher levels of serum uric acid (p<0.05), as compared with individuals with major depressive disorder (4.59±1.62mg/dL). Relevant linear regression analyses, controlling for metabolic profile, oxidative stress markers, kidney function, and comorbid alcohol use disorder, showed a significant association between bipolar mania (p<0.01) and increased uric acid., Conclusions: Findings of this study add evidence to the role of uric acid as state, rather than trait, marker in bipolar disorders. Explored, relevant, confounders do not seem to influence these results. The current study supports the hypothesis of a purinergic system dysfunction associated with manic phases of bipolar disorder., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Since bipolar disorder seems to be associated with purinergic system dysfunction, allopurinol might be effective in treating symptoms of mania., Aims: To estimate the efficacy and tolerability of allopurinol as adjunctive treatment for mania symptoms in people with bipolar affective disorder., Method: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the effects of adjunctive allopurinol and placebo on mania symptom changes., Results: Five RCTs were included in the meta-analysis. Participants with allopurinol augmentation had a significantly greater decrease in mania symptoms than those with placebo (SMD = -0.34, P = 0.007), especially in people with the most severe forms of mania. Remission rates, although based on only two studies (n = 177), were significantly higher among individuals receiving allopurinol, whereas for discontinuation and side-effects no difference was found., Conclusions: Our finding of a small to moderate effect size and overall low evidence for add-on allopurinol in reducing mania symptoms indicate that its use in routine practice needs further elucidation., (© The Royal College of Psychiatrists 2017.)

Previous research has hypothesised increased uric acid levels, possibly because of an amplified purinergic metabolism and a reduced adenosine activity, in subjects with bipolar disorder. This systematic review and meta-analysis aimed at estimating if individuals with bipolar disorder had uric acid levels higher than both healthy controls and subjects with major depression (trait marker hypothesis). It also tested if uric acid levels could differ in different phases of bipolar disorder (state marker hypothesis). Meta-analyses were carried out generating pooled standardized mean differences (SMDs), using random-effects models. Heterogeneity between studies was estimated using the I(2) index. Relevant sensitivity and meta-regression analyses were conducted. We searched main Electronic Databases, identifying twelve studies that met our inclusion criteria. Meta-analyses showed increased uric acid levels in individuals with bipolar disorder as compared with both healthy controls (SMD = 0.65, p < 0.001, I(2) = 82.9%) and those with major depression (SMD = 0.46, p < 0.001; I(2) = 68.7%). However, meta-regression analyses confirmed this association only as compared with healthy controls. Finally, though uric acid levels were higher in manic/mixed phases as compared with depressive ones (SMD = 0.34; p = 0.04, I(2) = 58.8%), a sensitivity analysis did not confirm the association. In sum, our meta-analysis shows that subjects with bipolar disorder have uric acid levels higher than healthy controls. The potential role of factors that might clarify the nature of this association deserves additional research., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: Recent evidence shows that bipolar disorder might be associated with a purinergic system dysfunction. This study aimed at (i) testing the association between bipolar disorder and uric acid serum levels, and (ii) clarifying whether this relationship is mediated by metabolic syndrome and other relevant metabolic parameters., Methods: Patients consecutively admitted to a Mental Health Inpatient Unit, with a diagnosis of bipolar disorder or other severe mental disorders, and an appropriate healthy control sample, were included in this cross-sectional, exploratory study. We performed linear regression analyses, to explore factors associated with uric acid levels, and formal tests of mediation to assess mediating effect of candidate variables., Results: 176 individuals with mental disorders and 89 healthy controls met inclusion criteria. Bipolar disorder was the only diagnostic subgroup significantly associated with increased uric acid levels. Furthermore, male gender, metabolic syndrome, as well as abdominal circumference and triglycerides levels, had a significant effect on uric acid. Relevant mediation analyses showed that the estimated effect between bipolar disorder and uric acid levels was only partially mediated by metabolic abnormalities., Conclusion: This study suggests a direct association between bipolar disorder and uric acid levels, only partially mediated by metabolic abnormalities. It seems consistent with results of previous studies highlighting a purinergic dysfunction in bipolar disorder and the role that purinergic modulators, lowering uric acid levels, could have in clinical practice., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Both individuals with bipolar (BD) and those with alcohol (AUD) and other substance (SUD) use disorders are likely to attempt suicide. Comorbidity of BD and AUD/SUD may increase the likelihood of suicide attempts. We conducted a meta-analysis to estimate the association of comorbid AUD/SUD and suicide attempts in subjects with BD in the literature to date., Methods: Electronic databases through January 2013 were searched. Studies reporting rates of suicide attempts in people with co-occurring BD and AUD/SUD were retrieved. Comorbid AUD and SUD and suicide attempts rates as well as demographic, clinical, and methodological variables were extracted from each publication or obtained directly from its authors., Results: Twenty-nine of 222 studies assessed for eligibility met the inclusion criteria, comprising a total of 31,294 individuals with BD, of whom 6308 (20.1%) had documented suicide attempts. There were consistent findings across the studies included. As compared to controls, subjects with BD and comorbid AUD/SUD were more likely to attempt suicide. The cross-sectional association estimates showed random-effects pooled crude ORs of 1.96 (95% CI=1.56-2.47; p<0.01), 1.72 (95% CI=1.52-1.95; p<0.01), and 1.77 (95% CI=1.49-2.10; p<0.01), for combined AUD/SUD, AUD, and SUD. There was no publication bias and sensitivity analyses based on the highest quality studies confirmed core results., Limitations: The effects of the number and the type of suicide attempts could not be investigated due to insufficient information., Conclusions: Comorbid AUD and SUD in individuals with BD are significantly associated with suicide attempts. Individuals with this comorbidity should be targeted for intensive suicide prevention efforts., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: Psychotic symptoms occur in more than half of patients affected by Bipolar Disorder (BD) and are associated with an unfavorable course of the disorder. The objective of this study is to identify the differences in the clinical and biochemical parameters between bipolar patients with or without psychotic symptoms. Methods: A total of 665 inpatients were recruited. Demographic, clinical, and biochemical data related to the first day of hospitalization were obtained via a screening of the clinical charts and intranet hospital applications. The two groups identified via the lifetime presence of psychotic symptoms were compared using t tests for quantitative variables and χ2 tests for qualitative ones; binary logistic regression models were subsequently performed. Results: Patients with psychotic BD (compared to non-psychotic ones) showed a longer duration of hospitalization (p < 0.001), higher Young Mania Rating Scale scores (p < 0.001), lower Global Assessment of Functioning scores (p = 0.002), a less frequent history of lifetime suicide attempts (p = 0.019), less achievement of remission during the current hospitalization (p = 0.028), and a higher Neutrophile to Lymphocyte Ratio (NLR) (p = 0.006), but lower total cholesterol (p = 0.018) and triglycerides (p = 0.013). Conclusions: Patients with psychotic BD have a different clinical and biochemical profile compared to their counterparts, characterized by more clinical severity, fewer metabolic alterations, and a higher grade of inflammation. Further multi-center studies have to confirm the results of this present study. [ABSTRACT FROM AUTHOR]

Treatment discontinuation is a major challenge in routine clinical settings. Despite poor adherence to antipsychotic medication, long acting injectable (LAI) formulations are an underutilized option in psychotic disorders. Recently, an earlier and broader use of LAIs has been emphasized. However, few studies have evaluated the factors associated with LAI antipsychotic discontinuation in ordinary clinical practice. The main purpose of the present study was, therefore, to identify the factors associated with LAI discontinuation in a real-world setting. Patients in treatment with LAI antipsychotics were recruited. A Cox regression analysis was applied considering a 12-month follow-up period. Moreover, a Kaplan-Meier survival analysis was applied to compare the single treatment LAI antipsychotic groups in terms of time to discontinuation. Our analysis showed an LAI discontinuation rate at 12 months, corresponding to 28.8%, with olanzapine and aripiprazole having a longer time to discontinuation compared to zuclopenthixol. The results of the present study can help clinicians with their choice of LAI antipsychotic according to patients' characteristics and in a context of precision medicine. Increasing knowledge about factors affecting discontinuation of LAI antipsychotics can improve the prescribing practices of these compounds. Individualized approaches may ameliorate long-term patients' treatment adherence, thus preventing the long-term disability caused by psychotic disorders. [ABSTRACT FROM AUTHOR]

Introduction: Bipolar Disorder (BD) is a disabling condition with suicidal behavior as one of the most common adverse outcomes. The purpose of the present research is to investigate the relationship between lifetime suicide attempts and the clinical factors/biochemical parameters in a large sample of bipolar patients. Methods: A total of 561 patients, consecutively hospitalized for BD in Milan and Monza (Italy), were recruited. Data about the demographic and clinical variables, as well as the values of blood analyses, were collected. The groups identified according to the presence/absence of lifetime suicide attempts were compared using univariate analyses. Then, three preliminary binary logistic regressions and a final logistic regression model were performed to identify the clinical and biochemical parameters associated with lifetime suicide attempts in BD. Results: Lifetime suicide attempts in BD were predicted by a longer duration of untreated illness (DUI) (p = 0.005), absence of lifetime psychotic symptoms (p = 0.025), presence of poly-substance use disorders (p = 0.033), comorbidity with obesity (p = 0.022), a last mood episode of manic polarity (p = 0.044), and lower bilirubin serum levels (p = 0.002); higher total cholesterol serum levels showed a trend toward statistical significance (p = 0.058). Conclusions: BD patients with lifetime suicide attempts present unfavorable clinical features. Some specific biochemical characteristics of bipolar patients may represent potential markers of suicidal behavior and need to be better investigated to identify new targets of treatment in the framework of personalized medicine. These preliminary findings have to be confirmed by further studies in different clinical settings. [ABSTRACT FROM AUTHOR]

Highlights • Uric acid has been hypothesized as a marker for behavioral and clinical characteristics. • We could not find an association between serum uric acid and tested behaviors. • Uric acid variations seem attributable to biochemical and metabolic parameters. • Further research on the role of purinergic system in behavioral and clinical features is needed. Abstract Previous research has hypothesized a role for serum uric acid as a marker of mental disorders and related behaviors, possibly due to its link with purinergic transmission and antioxidant activity. We tested the association of serum uric acid levels with specific behavioral and clinical characteristics in 99 individuals suffering from major affective disorders. Subjects were assessed and interviewed using the Kessler Psychological Distress Scale, the Columbia-Suicide Severity Rating Scale, the Modified Overt Aggression Scale, and the Barratt Impulsiveness Scale. We found that psychological distress and suicidal ideation severity were associated with lower uric acid serum levels. On the other hand, verbal aggression and history of violence were associated with higher levels of serum uric acid. However, according to linear regression analyses, there were no behavioral and clinical characteristics independently associated with serum uric acid. Serum uric acid levels were influenced by creatinine and BMI, as well as, possibly, by white blood cells count and gender. Despite some limitations, these results suggest that no behavioral / clinical features are associated with variations of serum uric acid, which rather seem attributable to specific biochemical and metabolic parameters. Nevertheless, the role of purinergic system in different mental disorders and behavioral abnormalities, deserves further research. [ABSTRACT FROM AUTHOR]

The immune and inflammatory system is involved in the etiology of mood disorders. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) are inexpensive and reproducible biomarkers of inflammation. This is the first meta-analysis exploring the role of NLR and PLR in mood disorder. We identified 11 studies according to our inclusion criteria from the main Electronic Databases. Meta-analyses were carried out generating pooled standardized mean differences (SMDs) between index and healthy controls (HC). Heterogeneity was estimated. Relevant sensitivity and meta-regression analyses were conducted. Subjects with bipolar disorder (BD) had higher NLR and PLR as compared with HC (respectively SMD = 0.672; p < 0.001; I 2  = 82.4% and SMD = 0.425; p = 0.048; I 2  = 86.53%). Heterogeneity-based sensitivity analyses confirmed these findings. Subgroup analysis evidenced an influence of bipolar phase on the overall estimate whit studies including subjects in manic and any bipolar phase showing a significantly higher NLR and PLR as compared with HC whereas the effect was not significant among studies including only euthymic bipolar subjects. Meta-regression showed that age and sex influenced the relationship between BD and NLR but not the relationship between BD and PLR. Meta-analysis was not carried out for MLR because our search identified only one study when comparing BD to HC, and only one study when comparing MDD to HC. Subjects with major depressive disorder (MDD) had higher NLR as compared with HC (SMD = 0.670; p = 0.028; I 2  = 89.931%). Heterogeneity-based sensitivity analyses and meta-regression confirmed these findings. Our meta-analysis supports the hypothesis that an inflammatory activation occurs in mood disorders and NLR and PLR may be useful to detect this activation. More researches including comparison of NLR, PLR and MLR between different bipolar phases and between BD and MDD are needed. [ABSTRACT FROM AUTHOR]