State-dependent decrease in levels of brain-derived neurotrophic factor in bipolar disorder: A meta-analytic study

Evidence has suggested a role of brain-derived neurotrophic factor (BDNF) in the pathogenesis of bipolar disorder (BD). Recent studies have examined BDNF levels in BD patients, but showed inconsistent results. In current study, meta-analyses by random-effects model were performed to compare blood BDNF levels between BD patients and healthy controls, and examine patients based on different affective status (manic, depressed, or euthymic state). Fifteen studies from 10 citations were included into the analysis. Pooling of results from all studies indicated that, overall, patients with BD had a lower level of BDNF than healthy controls (p = 1 × 10⁻⁴). But when separating these studies based on different affective status, it showed that the significance existed only when comparing patients in manic (p = 0.0008) or depressed (p = 0.02) state with controls, but not in euthymic state (p = 0.25). In addition, BDNF level was significantly increased after pharmacological treatment of manic state (p = 0.01). These findings indicate that BDNF levels are abnormally reduced in manic and depressed states of BD, and the reduced level in manic state increases after treatment. They suggest a role of blood BDNF level as a state-dependent biomarker of bipolar disorder.     

Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes

Genetic and pharmacological studies have suggested that brain-derived neurotrophic factor (BDNF) may be associated with the pathophysiology of bipolar disorder (BD). The present study investigated serum BDNF levels in manic, depressed, euthymic BD patients and in matched healthy controls, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum BDNF levels were decreased in manic (p = 0.019) and depressed (p = 0.027) BD patients, as compared with euthymic patients and controls. Serum BDNF levels were negatively correlated with the severity of manic (r = −0.37, p = 0.005) and depressive (r = −0.30, p = 0.033) symptoms. These findings further support the hypothesis that the BDNF signaling system may play a role in the pathophysiology of BD.     

Increased serum glial cell line-derived neurotrophic factor immunocontent during manic and depressive episodes in individuals with bipolar disorder

Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor from the transforming growth factor β family, which plays a role in the development and function of hippocampal cells. Preclinical studies suggest that changes in neurotrophic growth factor systems might be involved in the pathophysiology of mood disorders including bipolar disorder (BD) [E.J. Nestler, M. Barrot, R.J. DiLeone, A.J. Eisch, S.J. Gold, L.M. Monteggia, Neurobiology of depression, Neuron 34 (2002) 13–25]. This is the first study to analyze GDNF immunocontent in BD subjects across different mood states, including mania, depression, and remission (euthymia). Fourty-four bipolar patients (14 depressed, 15 manic, and 15 euthymic) and 14 healthy controls, diagnosed according to the Structural Clinical Interview for DSM-IV were studied. Serum GDNF immunocontent was measured using Western blotting. Serum GDNF immunocontent was increased in manic (F = 42.31; p = 0.001; one-way ANOVA) and depressed (F = 42.31; p = 0.004; one-way ANOVA) bipolar patients, but not in euthymic patients as compared with controls. Our results indicate that changes in GDNF immunocontent occur during acute major affective episodes in bipolar subjects. These results further support the role of neurotrophins in the pathophysiology of bipolar disorder. Whether the observed increase in GDNF immunocontent correspond to a pathological or an adaptive response remains to be determined.     

A double-blind,randomized, placebo-controlled trial of adjunctive ramelteon for the treatment of insomnia and mood stability in patients with euthymic bipolar disorder

BackgroundAbnormalities in circadian rhythms are prominent features of bipolar disorder. Disrupted circadian rhythms are associated with an increased risk of relapse in bipolar disorder. Normalizing the circadian rhythm pattern of bipolar patients may improve their sleep and lead to fewer mood exacerbations. This study evaluated adjunctive ramelteon for the treatment of insomnia and mood stability in euthymic bipolar patients.MethodsParticipants with euthymic bipolar disorder and sleep disturbances were randomized to receive adjunctive ramelteon or placebo in addition to their regular psychiatric medications for up to 24 weeks or until they experienced a relapse (defined as a depressed or manic event).Results83 participants were randomized to receive ramelteon (n=42) or placebo (n=41). Forty participants relapsed (48.2%). Cox regression analyses indicated that participants who received ramelteon (odds ratio 0.48, p=.024) were less likely to relapse. Kaplan Meier curves also indicated longer median survival times in the ramelteon group (Mdn=188 days) versus the placebo group (Mdn=84 days) X2(1)=5.33, p=.02. There were no serious adverse events in this study.LimitationsThis was a small study with only 83 participants. The one-week window of confirmed stability is shorter than time intervals used in other studies.ConclusionsThe present study shows that ramelteon was effective in maintaining stability for individuals with bipolar disorder. Patients treated with ramelteon were approximately half as likely to relapse as patients treated with placebo throughout the 24-week treatment period.     

Impulsivity and phase of illness in bipolar disorder

BACKGROUND: Impulsivity is prominent in bipolar disorder, but there is little quantitative information relating it to phase of illness. METHODS: We measured impulsivity in patients with bipolar disorder who had not met episode criteria for at least 6 months, patients who were manic, and healthy control subjects. Impulsivity was measured using the Barratt Impulsiveness Scale (BIS) and performance on the computerized Immediate Memory-Remote Memory Task (IMT-DMT), based on the Continuous Performance Test, which has been shown to reflect risk of impulsivity in other populations. RESULTS: BIS scores in euthymic and manic bipolar subjects were identical, and were significantly elevated compared to controls. Commission errors (impulsive responses) on the IMT-DMT were elevated in manic subjects but were identical to controls in euthymic subjects. Measures of impulsivity did not appear related to depressive symptoms. LIMITATIONS: The number of subjects was too small for detailed investigation of the role of comorbidities; subjects were receiving pharmacological treatments. CONCLUSIONS: Impulsivity has state- and trait-related aspects in bipolar disorder.     

Adult attachment in bipolar 1 disorder

Objectives. To determine how security of adult attachment style is related to the mania, major depression and euthymic mood states in bipolar 1 (BP1) disorder. Design. An observational cross‐sectional study. Method. One hundred and seven BP1 patients (34 in a manic type episode, 30 in major depressive episode, and 43 in remission) and 41 healthy controls similar in age, gender, reading age, and education were recruited. The groups were compared on self‐reported mean and preferred attachment style controlling for psychiatric comorbidity. Results. Preferred attachment style was insecure in 84 (78%) BP1 patients but only 13 (32%) healthy controls (χ²=34.3, df=3, and p<.001). Healthy controls reported higher secure attachment, lower anxious, and lower preoccupied attachment scores than all groups of patients with bipolar disorder, although the scores for secure attachment in mania and preoccupied attachment in euthymic patients were not significantly different from healthy controls. Overall, within the bipolar groups, anxious attachment style varied little with mood but mania was associated with higher secure and preoccupied attachment style, and depression with higher preoccupied and lower dismissing attachment style scores. Conclusions. Insecure attachment is found in most patients with BP1 disorder. Attachment style is affected by mood episodes so it should be assessed when a patient with bipolar disorder is in remission with minimal residual depressive or manic symptoms.     

Cognitive–linguistic deficits in euthymic elderly patients with bipolar disorder

Background

There is increasing evidence that bipolar disorder is also associated with neuropsychological impairments persisting during euthymia, thus representing a trait-like feature of the disease. Language and speech abnormalities are also present in bipolar disorder, especially in verbal fluency and verbal memory. However, there is a lack of studies in the literature investigating different levels of linguistic processing (phonological, syntactical, and semantic) in a single cohort of euthymic bipolar patients. Based on previous findings of pervasive language impairment in euthymic elderly bipolar patients, the aim of this study was to comprise a more thorough investigation on the subject.

Methods

We studied 19 euthymic bipolar patients aged 60 and above, and 20 cognitively healthy subjects using the Arizona Battery for Communication Disorders of Dementia (ABCD) and the Test for Reception of Grammar Version 2 (TROG-2) in order to assess the phonological, syntactic, and semantic domains of language.

Results

Bipolar patients performed poorer than controls in Linguistic Expression (p=0.011), in Linguistic Comprehension (Following Commands; p=0.025 and Reading Comprehension of Sentences; p=0.007), and in the TROG-2 (p=0.006).

Limitations

The small sample comprising only elderly patients; the lack of statistical power to analyze the potential effect of individual medications on the cognitive performance.

Conclusions

Our data demonstrate that linguistic impairment is present in euthymic bipolar patients, affecting mostly syntactic and lexical–semantic abilities, both in comprehension and production of language. These deficits are interrelated with other cognitive skills also known to be affected in bipolar disorder, such as executive functions and episodic memory.     

Serum neurotrophin-3 is increased during manic and depressive episodes in bipolar disorder

Accumulating evidence suggest that neural changes and cognitive impairment may accompany the course of bipolar disorder. Such detrimental effects of cumulative mood episodes may be related to changes in neurotrophins that take place during mood episodes but not during euthymic phases. The present study investigated serum neurotrophin-3 (NT-3) levels in patients with bipolar disorder during manic, depressed, and euthymic states, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum NT-3 levels were increased in manic (p<0.001) and depressed (p<0.001) BD patients, as compared with euthymic patients and normal controls. These findings suggest that the NT-3 signaling system may play a role in the pathophysiology of BD.     

Trait impulsivity in patients with mood disorders

BACKGROUND: Impulsivity is a key component of the manic behavior of bipolar disorder and is reported to occur in bipolar patients as a stable characteristic, i.e. a trait. Nevertheless, impulsivity has not been widely studied in depressed bipolar patients. We assessed impulsivity in depressed and euthymic bipolar and unipolar patients and healthy controls. We hypothesized that bipolar subjects would have higher levels of trait impulsivity than the comparison groups. METHODS: Twenty-four depressed bipolar, 24 depressed unipolar, 12 euthymic bipolar, and 10 euthymic unipolar patients, as well as 51 healthy subjects were evaluated with the Barratt Impulsiveness Scale (BIS). Analysis of covariance with age and sex as covariates was used to compare mean group differences. RESULTS: Depressed bipolar, euthymic bipolar, and depressed unipolar patients did not differ, and showed greater impulsivity than healthy controls on all of the BIS scales. Euthymic unipolar patients scored higher than healthy controls only on motor impulsivity. LIMITATIONS: Higher number of past substance abusers in the bipolar groups, and no control for anxiety and personality disorders, as well as small sample sizes, limit the reach of this study. CONCLUSIONS: This study replicates prior findings of stable trait impulsivity in bipolar disorder patients, and extends them, confirming that this trait can be demonstrated in depressed patients, as well as manic and euthymic ones. Trait impulsivity may be the result of repeated mood episodes or be present prior to their onset, either way it would influence the clinical presentation of bipolar disorder.     

Serum levels of brain-derived neurotrophic factor in patients with schizophrenia and bipolar disorder

There is evidence that major psychiatric discords such as schizophrenia (SZ) and bipolar disorder (BD) are associated with dysregulation of synaptic plasticity with downstream alterations of neurotrophins. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system (CNS), and performs many biological functions such as promoting the survival, differentiation, and plasticity of neurons. Variants in the BDNF gene increase the risk of SZ and bipolar disorder. Chronic administration of drugs used to treat SZ and BD, such as lithium, valproate, quetiapine, clozapine, and olanzapine, increases BDNF expression in rat brain. To examine serum BDNF, three groups of chronically medicated DSM-IV SZ patients, on treatment with clozapine (n = 27), typical (n = 14), and other atypical antipsychotics (n = 19), 30 euthymic BD patients, and 26 healthy control had 5 ml blood samples collected by venipuncture. Serum BDNF levels were significantly higher in SZ patients (p < 0.001) when compared to either controls or euthymic BD patients. Increased BDNF in SZ patients might be related to the course of illness or to treatment variables. Prospective studies are warranted.     

Attention orienting and inhibitory control across the different mood states in bipolar disorder: An emotional antisaccade task

An antisaccade experiment, using happy, sad, and neutral faces, was conducted to examine the effect of mood-congruent information on inhibitory control (antisaccade task) and attentional orienting (prosaccade task) during the different episodes of bipolar disorder (BD) – manic (n = 22), depressive (n = 25), and euthymic (n = 24). A group of 28 healthy controls was also included. Results revealed that symptomatic patients committed more antisaccade errors than healthy individuals, especially with mood-congruent faces. The manic group committed more antisaccade errors in response to happy faces, while the depressed group tended to commit more antisaccade errors in response to sad faces. Additionally, antisaccade latencies were slower in BD patients than in healthy individuals, whereas prosaccade latencies were slower in symptomatic patients. Taken together, these findings revealed the following: (a) slow inhibitory control in BD patients, regardless of their episode (i.e., a trait), and (b) impaired inhibitory control restricted to symptomatic patients (i.e., a state)     

Systematic review and voxel-based meta-analysis of diffusion tensor imaging studies in bipolar disorder

Background

Diffusion tensor imaging (DTI) studies have shown changes in the microstructure of white matter in bipolar disorder. Studies suggest both localised, predominantly fronto-limbic, as well as more widespread changes in white matter, but with some apparent inconsistency. A meta-analysis of white matter alterations in adults with bipolar disorder was undertaken.

Method

Whole-brain DTI studies comparing adults with bipolar disorder to healthy controls on fractional anisotropy (FA) were retrieved using searches of MEDLINE and EMBASE from between 2003 and December 2012. White-matter tract involvement was collated and quantified. Clusters of significantly altered FA were meta-analysed using effect-size signed differential mapping (ES-SDM).

Results

Ten VBA studies (252 patients and 256 controls) and five TBSS studies (138 patients and 98 controls) met inclusion criteria. Sixty-one clusters of significantly different FA between bipolar disorder and healthy controls were identified. Analysis of white-matter tracts indicated that all major classes of tracts are implicated. ES-SDM meta-analysis of VBA studies revealed three significant clusters of decreased FA in bipolar disorder (a right posterior temporoparietal cluster and two left cingulate clusters). Findings limited to the Bipolar Type I papers were more robust.

Limitations

Voxel-based studies do not accurately identify tracts, and our ES-SDM analysis used only published peak voxels rather than raw DTI data.

Conclusions

There is consistent data indicating widespread white matter involvement with decreased white matter FA demonstrated in three disparate areas in bipolar disorder. White matter alterations are not limited to anterior fronto-limbic pathways in bipolar disorder.     

High TNF-alpha and IL-8 levels predict low blood dendritic cell counts in primary cytomegalovirus infection

BackgroundIn vitro studies suggest that human cytomegalovirus (CMV) modulates the functions of dendritic cells (DCs). However, there are limited data on DC homeostasis in CMV-infected patients.ObjectivesThe aim of this study was to characterize circulating DCs and plasma cytokine levels in immunocompetent patients with primary, symptomatic CMV infections.Study designThe study population consisted of 14 patients suffering of CMV mononucleosis and 14 healthy volunteers (11 CMV-seropositive and 3 CMV-seronegative subjects) included as controls. Peripheral blood mononuclear cells were isolated and used to characterize DCs and to quantify CMV in the blood. Plasma levels of pro-inflammatory and anti-inflammatory cytokines were also measured.ResultsWe observed that patients who were developing CMV mononucleosis presented lower myeloid and plasmacytoid DC counts in peripheral blood compared with healthy controls. We also noted elevated levels of inflammatory mediators, of which tumor necrosis factor-α (TNF-α)—which activates DCs and endothelial cells—was the highest. Notably, the decrease in blood DCs correlated with high TNF-α and IL-8 levels by a hyperbolic function.ConclusionsOur results suggest that increased levels of inflammatory factors facilitate alterations in DC homeostasis during primary CMV infection, which may contribute to viral-induced modulation of host immunity.     

Cytokine profiles in bipolar affective disorder: focus on acutely ill patients

BACKGROUND: The role of the immune system in mood disorders is predominately supported by studies in unipolar major depression. However activation of the immune system has also been demonstrated in bipolar mania. Our study examines pro-inflammatory and anti-inflammatory cytokines in both phases of bipolar affective disorder (BPAD). METHODS: Plasma concentrations of IL-6, IL-8, IL-10, TNF-alpha and sIL-6R were measured with enzyme linked immunosorbent assays (ELISA) in patients with BPAD who were depressed, or manic and in healthy controls. RESULTS: Bipolar depression had significantly higher production of the pro-inflammatory cytokines, IL-8 (p < 0.001) and TNF-alpha (p < 0.05) compared to healthy subjects. The manic group also had increased production of IL-8 (p < 0.05) and TNF-alpha (p < 0.001) as compared to healthy subjects. Anti-inflammatory cytokine levels did not differ across the 3 groups. LIMITATIONS: A small sample size was studied. All patients remained on medication for this study. CONCLUSIONS: BPAD is associated with increased production of pro-inflammatory cytokines both in the manic and in the depressed phase as compared to healthy subjects. This is the first study, which examined both mania and bipolar depression.     

首发双相情感障碍躁狂发作患者垂体泌乳素和甲状腺轴的相关性研究

目的:寻找首发双相情感障碍躁狂发作患者的垂体前叶促甲状腺激素和泌乳素分泌水平的关系。方法:横断面研究65例首发符合ICD-10诊断标准的双相情感障碍躁狂发作病例组及年龄、性别匹配的62例对照组的垂体泌乳素、促甲状腺激素、游离三碘甲状腺原氨酸、游离甲状腺素、三碘甲状腺原氨酸、甲状腺素水平,探寻疾病临床特征和上述神经内分泌改变的相关性。结果:病例组与对照组比较,促甲状腺激素差异无统计学意义。按性别分组后,女性病例组与女性对照组比较,促甲状腺激素[1.94(1.23,2.89)mIU/L与1.49(1.07,2.04)mIU/L,Z=1.98]、垂体泌乳素[672.5(333.0,1 058.0)mIU/L与320.0(263.5,432.5)mIU/L,Z=3.50]升高,差异有统计学意义(P均0.05)。相关分析发现,女性BD患者垂体泌乳素与促甲状腺激素之间存在逆函数关系(r~2=0.25,F=9.53,P0.01),方程式y=b_0+b_1/x(b_0=291.50,b_1=793.92)。结论:TSH在性别间存在的差异提示性别可能影响垂体前叶激素分泌的代偿功能。女性患者垂体泌乳素、促甲状腺激素分泌增加可能与双相情感障碍躁狂期发病有关,但二者分泌可能存在倒数关系,男性患者未发现上述现象。     

Iowa gambling task performance in euthymic bipolar I disorder: A meta-analysis and empirical study

Background

The Iowa Gambling Task (IGT) has been recommended as an index of reward sensitivity, which is elevated in bipolar disorder. We conducted a meta-analysis of IGT performance in euthymic bipolar I disorder compared with control participants. Findings indicated that people with bipolar disorder make more risky choices than control participants, though the effect is small (g=0.35). It is not clear which of the many processes involved in IGT performance are involved in producing the observed group difference.

Methods

Fifty-five euthymic people with bipolar disorder and 39 control participants completed the IGT. The Expectancy Valence Model was used to examine differences in IGT. We also examined whether variation in IGT performance within the bipolar group was related to current mood, illness course, impulsivity, or demographics.

Results

Bipolar and control groups did not differ on the total number of risky choices, rate of learning, or any of the parameters of the Expectancy Valence Model. IGT performance in bipolar disorder was not related to any of the examined individual differences.

Limitations

It is possible that there are group differences that are too small to detect at our sample size or that are not amenable to study via the Expectancy Valence Model.

Conclusions

We were unable to identify group differences on the IGT or correlates of IGT performance within bipolar disorder. Though the IGT may serve as a useful model for decision-making, its structure may make it unsuitable for behavioral assessment of reward sensitivity independent of punishment sensitivity.     

Anxiety,stress and perfectionism in bipolar disorder

Background

Previous reports have highlighted perfectionism and related cognitive styles as a psychological risk factor for stress and anxiety symptoms as well as for the development of bipolar disorder symptoms. The anxiety disorders are highly comorbid with bipolar disorder but the mechanisms that underpin this comorbidity are yet to be determined.

Method

Measures of depressive, (hypo)manic, anxiety and stress symptoms and perfectionistic cognitive style were completed by a sample of 142 patients with bipolar disorder. Mediation models were used to explore the hypotheses that anxiety and stress symptoms would mediate relationships between perfectionistic cognitive styles, and bipolar disorder symptoms.

Results

Stress and anxiety both significantly mediated the relationship between both self-critical perfectionism and goal attainment values and bipolar depressive symptoms. Goal attainment values were not significantly related to hypomanic symptoms. Stress and anxiety symptoms did not significantly mediate the relationship between self-critical perfectionism and (hypo)manic symptoms.

Limitations

1.

These data are cross-sectional; hence the causality implied in the mediation models can only be inferred.

2.

The clinic patients were less likely to present with (hypo)manic symptoms and therefore the reduced variability in the data may have contributed to the null findings for the mediation models with (hypo)manic symptoms.

3.

Those patients who were experiencing current (hypo)manic symptoms may have answered the cognitive styles questionnaires differently than when euthymic.

Conclusion

These findings highlight a plausible mechanism to understand the relationship between bipolar disorder and the anxiety disorders. Targeting self-critical perfectionism in the psychological treatment of bipolar disorder when there is anxiety comorbidity may result in more parsimonious treatments.     

Cognitive functions and cognitive styles in young euthymic patients with bipolar I disorder

Background

Recent evidences suggest that bipolar disorder patients do not return to premorbid functioning levels during the inter-episode periods. Cognitive deficits may impair patients working and functioning status and may also have negative impact on other aspects of thinking.

Objectives

To assess the prevalence of cognitive dysfunction in patients with bipolar disorder in euthymic state and to explore any evident cognitive style problems.

Method

Case-control naturalistic study 60 patients with bipolar I disorder in euthymic state according to DSM-IV were recruited and subdivided into two groups each contains of 30 patients; (Group BPM) euthymic patients with recent manic episode, and Group BPD euthymic patients with recent depressive episode. Both groups were further compared with control group (Group C) consisted of 30 frequency matched healthy volunteers. Groups were subjected to the following: 1-clinical psychiatric examination, 2-Hamilton Depression Scale (HAMD-17) and Bech–Rafaelsen Melancholia Scale (MES) for patients’ group (BPD), 3-Young Mania Rating Scale (YMRS) and Bech–Rafaelsen Mania Scale (MAS) for patients’ group (BPM), 4-assessment of euthymic state of mood included both MAS and MES, 5-MMSE, MTS and CDT were performed to assess cognitive functions, 6-cognitive styles evaluation included Fear of Failure, Hopelessness Scale, (the Social Dysfunction and Aggression Scale SDAS-9 and Arabic Anger Scale.

Results

Definite cognitive function impairment and different patterns of cognitive style were detected in case groups. MMSE, MTS and CDT scores were statistically significant. Fear of Failure Scale Scores were higher in BPM; 16 (53.33%) reported severe intensity compared to 16 (53.33%) of BPD Group reporting moderate intensity and 30 (100%) of the control group reporting only mild intensity of fear of failure with statistically significant differences. Although patients were in euthymic state; Hopelessness Scale discriminated between those with affective disorders and controls and other scores for hostility SADS-9 and Arabic Anger Scale. Moreover, measures of cognitive styles showed differences among patients of the case groups who joined psychotherapy program in their management (28) compared to those who did not (32).

Limitation

Cognitive impact of psychotropic drugs could not be eliminated since the current study is naturalistic study.

Conclusions

Those with BAD in euthymic state suffer from cognitive dysfunction and some aspects of cognitive styles that may negatively interfere with their performance. Psychotherapeutic programs should consider these findings in their approaches for better impact on patients’ quality of life and overall treatment outcome.     

Imbalance between pro-inflammatory and anti-inflammatory cytokines in bipolar disorder

BACKGROUND: The role of cytokines in bipolar disorder is still controversial. Although a few studies have found alterations of cytokines in bipolar disorder, their findings were inconsistent. The aim of this study was to determine whether the cytokines are involved in the pathophysiology of bipolar disorder. METHODS: A total of 37 manic patients with bipolar disorder and 74 control subjects were recruited. The mitogen-induced production of tumor necrosis factor (TNF)-alpha, interleukin-6 (IL-6), IL-4, interferon (IFN)-gamma, and IL-2 was measured using quantitative sandwich ELISA at the time of admission and 6 weeks after mood stabilizer treatment. RESULTS: IL-6 and TNF-alpha production of bipolar manic patients was significantly higher than those of normal controls, while IL-4 values of the patients were significantly lower than normal controls. IL-6/IL-4, TNF-alpha/IL-4, IL-2/IL-4, and IFN-gamma/IL-4 ratios were significantly higher in bipolar manic patients than in normal controls. After 6 weeks of treatment, the levels of IL-6 significantly decreased compared with baseline. LIMITATIONS: The effect of various types of mood stabilizers on cytokine production should be considered. CONCLUSIONS: These findings suggest that the increased activity of pro-inflammatory cytokines and an imbalance between pro-inflammatory and anti-inflammatory cytokines may play a role in the pathophysiology of bipolar disorder.     

Genetic examination of the Mood Disorder Questionnaire and its relationship with bipolar disorder

The Mood Disorder Questionnaire (MDQ) is a common screening tool for bipolar disorder that assesses manic symptoms. Its utility for genetic studies of mania or bipolar traits has not been fully examined. We psychometrically compared the MDQ to self-reported bipolar disorder in participants from the United Kingdom National Institute of Health and Care Research Mental Health BioResource. We conducted genome-wide association studies of manic symptom quantitative traits and symptom subgroups, derived from the MDQ items (N = 11,568–19,859). We calculated genetic correlations with bipolar disorder and other psychiatric and behavioral traits. The MDQ screener showed low positive predictive value (0.29) for self-reported bipolar disorder. Neither concurrent nor lifetime manic symptoms were genetically correlated with bipolar disorder. Lifetime manic symptoms had a highest genetic correlation (r_g = 1.0) with posttraumatic stress disorder although this was not confirmed by within-cohort phenotypic correlations (r_p = 0.41). Other significant genetic correlations included attention deficit hyperactivity disorder (r_g = 0.69), insomnia (r_g = 0.55), and major depressive disorder (r_g = 0.42). Our study adds to existing literature questioning the MDQ's validity and suggests it may capture symptoms of general distress or psychopathology, rather than hypomania/mania specifically, in at-risk populations.