C-reactive protein: A differential biomarker for major depressive disorder and bipolar II disorder

Objectives We aimed to examine whether the C-reactive protein (CRP) level could be used to differentiate between major depressive disorder (MDD) and bipolar II disorder (BD II). Methods Ninety-six healthy controls, 88 BD II and 72 MDD drug-naïve patients in their major depressive episodes were enrolled. The fasting plasma level of high-sensitivity CRP was assessed at baseline and after treatment. Results The BD II patients presented significantly higher 17-item Hamilton Depression Rating Scale (HDRS) scores and CRP levels at baseline when adjustment for age, gender, and body mass index (P?< 0.001 and P?< 0.001, respectively). After treatment the CRP levels remained significantly different (P?< 0.001), although the HDRS score was not significantly different between the BD II and MDD patients. A receiver-operating characteristic analysis showed that a baseline CRP level of 621.6?ng/mL could discriminate between BD II and MDD, with an area under the curve of 0.816 and a sensitivity and specificity of 0.699 and 0.882, respectively. Furthermore, the baseline CRP level greater than 621.6?ng/ml had 28.2 higher odds of a diagnosis of BD II (P?< 0.001, 95% confidence interval: 10.96–72.35). Conclusions The level of CRP plays a role of biomarker to differentiate between MDD and BD II depression in both their depressed and euthymic state.     

Frequency and clinical correlates of bipolar features in acute coronary syndrome patients

BackgroundDepression and acute coronary syndrome (ACS) are both extremely prevalent diseases. Studies aimed at evaluating whether depression is an independent risk factor for cardiac events provided no definitive results. In most of these studies, depression has been broadly defined with no differentiation between unipolar (MDD) versus bipolar forms (BD). The aim of this study was to evaluate the frequency of DSM-IV BD (bipolar I and bipolar II subtypes, cyclothymia), as well as temperamental or isolated bipolar features in a sample of 171 patients hospitalized for ACS. We also explored whether these psychopathological conditions were associated with some clinical characteristics of ACS.MethodsPatients with ACS admitted to three neighboring Cardiac Intensive Care Units (CICUs) in a 12-month continuative period of time were eligible for inclusion if they met the criteria for either acute myocardial infarct with or without ST-segment elevation or unstable angina, verified by standard ACS criteria. All patients underwent standardized cardiological and psychopathological evaluations.ResultsOf the 171 ACS patients enrolled, 37 patients (21.7%) were found to have a DSM-IV mood disorder. Of these, 20 (11.7%) had bipolar type I or type II or cyclothymia, while 17 (10%) were the cases of MDD. Rapid mood switches ranged from 11% of ACS patients with no mood disorders, to 47% of those with MDD to 55% of those with BD. Linear regression analysis showed that a diagnosis of BD (p = .023), but not that of MDD (p = .721), was associated with a significant younger age at the index episode of ACS. A history of previous coronary events was more frequent in ACS patients with BD than in those with MDD.ConclusionsOur data indicate that bipolar features and diagnosis are frequent in ACS patients. Bipolar disorder has a negative impact on cardiac symptomatology. Further research in this area is warranted.     

Genetic variants for morningness in relation to habitual sleep-wake behavior and diurnal preference in a population-based sample of 17,243 adults

ObjectiveAssociations of eveningness with health hazards benefit from analyzing to what extent the polygenic score for morningness correlates with the assessments of the behavioral trait of morningness-eveningness and chronotype.MethodsWith a population-based sample of 17,243 Finnish adults, aged 25–74 years, this study examines the associations of four feasible assessment methods of chronotype, a) biological the genetic liability based on the polygenic score for morningness (PGS_morn), b) the widely-used single item for self-assessed morningness/eveningness (MEQ_i19) of the original Morningness-Eveningness Questionnaire (MEQ), c) the behavioral trait of morningness-eveningness as assessed with the score on the shortened version (sMEQ) of the original MEQ, and d) the phase of entrainment as assessed with the habitual midpoint of sleep based on the self-reported sleep-wake schedule during weekend (Sleep_mid-wknd) as well as the sleep debt corrected midpoint of sleep (Sleep_mid-corr).ResultsAll self-report measures correlated with each other, but very weakly with the PGS_morn, which explained 1–2% of the variation in diurnal preference or habitual sleep-wake schedule. The influence of age was greater on Sleep_mid-wknd and Sleep_mid-corr than on the sMEQ or MEQ_i19, indicating that the diurnal preference might be a more stable indicator for morningness-eveningness than the sleep-wake schedule. Analyses of the discrepancies between sMEQ and MEQ_i19 indicated that eveningness can be over-estimated when relying on only the single-item self-assessment.ConclusionsThe current polygenic score for morningness explains only a small proportion of the variation in diurnal preference or habitual sleep-wake schedule. The molecular genetic basis for morningness-eveningness needs further elucidation.     

Measurement and predictors of resilience among community-dwelling older women

BackgroundResilience, the ability to adapt positively to adversity, may be an important factor in successful aging. However, the assessment and correlates of resilience in elderly individuals have not received adequate attention.MethodA total of 1395 community-dwelling women over age 60 who were participants at the San Diego Clinical Center of the Women’s Health Initiative completed the Connor–Davidson Resilience Scale (CD-RISC), along with other scales pertinent to successful cognitive aging. Internal consistency and predictors of the CD-RISC were examined, as well as the consistency of its factor structure with published reports.ResultsThe mean age of the cohort was 73 (7.2) years and 14% were Hispanic, 76% were non-Hispanic white, and nearly all had completed a high school education (98%). The mean total score on the CD-RISC was 75.7 (sd = 13.0). This scale showed high internal consistency (Cronbach’s alpha = 0.92). Exploratory factor analysis yielded four factors (somewhat different from those previously reported among younger adults) that reflected items involving: (1) personal control and goal orientation, (2) adaptation and tolerance for negative affect, (3) leadership and trust in instincts, and (4) spiritual coping. The strongest predictors of CD-RISC scores in this study were higher emotional well-being, optimism, self-rated successful aging, social engagement, and fewer cognitive complaints.ConclusionsOur study suggests that the CD-RISC is an internally consistent scale for assessing resilience among older women, and that greater resilience as assessed by the CD-RISC related positively to key components of successful aging.     

The genetic association between personality and major depression or bipolar disorder. A polygenic score analysis using genome-wide association data

The relationship between major depressive disorder (MDD) and bipolar disorder (BD) remains controversial. Previous research has reported differences and similarities in risk factors for MDD and BD, such as predisposing personality traits. For example, high neuroticism is related to both disorders, whereas openness to experience is specific for BD. This study examined the genetic association between personality and MDD and BD by applying polygenic scores for neuroticism, extraversion, openness to experience, agreeableness and conscientiousness to both disorders. Polygenic scores reflect the weighted sum of multiple single-nucleotide polymorphism alleles associated with the trait for an individual and were based on a meta-analysis of genome-wide association studies for personality traits including 13 835 subjects. Polygenic scores were tested for MDD in the combined Genetic Association Information Network (GAIN-MDD) and MDD2000+ samples (N=8921) and for BD in the combined Systematic Treatment Enhancement Program for Bipolar Disorder and Wellcome Trust Case–Control Consortium samples (N=6329) using logistic regression analyses. At the phenotypic level, personality dimensions were associated with MDD and BD. Polygenic neuroticism scores were significantly positively associated with MDD, whereas polygenic extraversion scores were significantly positively associated with BD. The explained variance of MDD and BD, ∼0.1%, was highly comparable to the variance explained by the polygenic personality scores in the corresponding personality traits themselves (between 0.1 and 0.4%). This indicates that the proportions of variance explained in mood disorders are at the upper limit of what could have been expected. This study suggests shared genetic risk factors for neuroticism and MDD on the one hand and for extraversion and BD on the other.     

Increased Serum Immunoglobulin Responses to Gut Commensal Gram-Negative Bacteria in Unipolar Major Depression and Bipolar Disorder Type 1, Especially When Melancholia Is Present

Major depressive disorder (MDD) is accompanied by higher serum IgM/IgA responses to LPS of Gram-negative bacteria, suggesting increased bacterial translocation and gut dysbiosis while the latter may occur in bipolar disorder (BD). There are differences between MDD and BD type 1 (BP1) and 2 (BP2) in nitro-oxidative stress biomarkers associated with leaky gut. This study examines serum IgM/IgA responses directed to LPS of 6 Gram-negative bacteria as well as IgG responses to oxidized LDL (oxLDL) in 29 BP1, 37 BP2, 44 MDD, and 30 healthy individuals. Increased IgM/IgA responses to Pseudomonas aeruginosa significantly discriminated patients with affective disorders (MDD plus BD) from controls. BP1 patients showed higher IgM responses to Morganella morganii as compared with MDD and BP2 patients. Patients with melancholia showed higher IgA responses to Citrobacter koseri as compared to controls and non-melancholic depression. The total score on the Hamilton Depression Rating Scale was significantly associated with IgA responses to C. koseri. IgG to oxLDL was significantly associated with increased bacterial translocation. In conclusion, MDD, BP1, and BP2 are accompanied by an immune response due to the increased load of LPS while these aberrations in the gut-brain axis are most pronounced in BP1 and melancholia. Activated oxidative stress pathways and autoimmune responses to oxidative specific epitopes in mood disorders may be driven by a breakdown in gut paracellular, transcellular, and/or vascular pathways. If replicated, drugs that protect the integrity of the gut barrier may offer novel therapeutic opportunities for BP1 and MDD.

     

Self-reported inhibition predicts history of suicide attempts in bipolar disorder and major depression

BackgroundStudies have reliably identified an association between suicide attempts and executive functions such as decision making (DM) and inhibitory control (IC) in patients with mood disorders. As such, the present study aimed to investigate the association between inhibition, DM, impulsivity and the history of suicide attempts in individuals with bipolar (BD) or major depressive disorder (MDD), identifying which assessment instruments may be most strongly associated with suicide in clinical samples.MethodsThe sample included 80 control subjects and two groups of patients with BD and MDD, matched by age and education (26 with a history of suicide attempts [MD+], and 26 with no such history [MD−]). Participants completed behavioral and self-report measures of DM and IC, which were compared between groups using ANCOVA, followed by logistic regression for patients with mood disorders only, and the presence or absence of a history of suicide as the outcome.ResultsCognitive performance did not differ between groups. The MD+ group showed significantly higher motor and attentional impulsivity on the BIS-11 than the MD− and control groups. A regression analysis containing these scores showed that motor impulsivity was the only significant predictor of a history of suicide (OR = 1.14; 95%CI 1.00–1.30).ConclusionsSelf-reported motor impulsivity was a significant predictor of suicide. These findings underscore the importance of self-report measures in neuropsychological assessment, and their contributions to the management and prognosis of patients with mood disorders. Lastly, they point to the role of impulsivity as a target for interventions and public policy on suicide prevention.     

Impulsivity in children and adolescents with mood disorders and unaffected offspring of bipolar parents

Objective

Increased impulsivity seems to be present across all phases of bipolar disorder (BD). Impulsivity may therefore represent an endophenotype for BD, if it is also found among normal individuals at high genetic risk for mood disorders. In this study, we assessed impulsivity across four different groups of children and adolescents: patients with BD, major depressive disorder (MDD) patients, unaffected offspring of bipolar parents (UO), and healthy controls (HC).

Subjects and Methods

52 patients with BD, 31 with MDD, 20 UO, and 45 HC completed the Barratt Impulsiveness Scale (BIS-11), an instrument designed to measure trait impulsivity.

Results

UO displayed significantly higher total BIS-11 impulsivity scores than HC (p = 0.02) but lower scores than BD patients (F = 27.12, p < 0.01). Multiple comparison analysis revealed higher BIS-11 total scores among BD patients when compared to HC (p < 0.01) and UO (p < 0.01). MDD patients had higher BIS-11 scores when compared to HC (p < 0.01). Differences between MDD patients and UO, as well as between MDD and BD patients, were not statistically significant.

Conclusion

Our findings suggest that trait impulsivity is increased among children and adolescents with mood disorders, as well as in unaffected individuals at high genetic risk for BD.     

Influence of temperament and character on resilience

Objective

The purpose of this study was to examine the influence of temperament and character on resilience.

Methods

A total of 4355 participants completed two questionnaires: the Conner–Davison Resilience Scale (CD-RISC) and the Temperament and Character Inventory-Revised Short (TCI-RS). We used Pearson's correlations to evaluate the correlation between the dimensions of the TCI and the CD-RISC. To determine the most influential TCI dimension with respect to the CD-RISC, a backward multiple regression analysis was performed.

Results

The resilience of both men and women was positively correlated with persistence, self-directedness, and cooperativeness. Conversely, harm avoidance was negatively correlated with resilience. In addition, reward dependence in men and self-transcendence in women were positively correlated with resilience. In the multiple regression analysis, persistence, self-directedness, and harm avoidance significantly predicted resilience after adjusting for age and gender.

Conclusion

This results show that social support is affected by personality, which consists of both temperament and character. High persistence and self-directedness as well as low harm avoidance are found to contribute to a better stress response.     

Towards a blood-based diagnostic panel for bipolar disorder

BackgroundBipolar disorder (BD) is a costly, devastating and life shortening mental disorder that is often misdiagnosed, especially on initial presentation. Misdiagnosis frequently results in ineffective treatment. We investigated the utility of a biomarker panel as a diagnostic test for BD.Methods and findingsWe performed a meta-analysis of eight case-control studies to define a diagnostic biomarker panel for BD. After validating the panel on established BD patients, we applied it to undiagnosed BD patients. We analysed 249 BD, 122 pre-diagnostic BD, 75 pre-diagnostic schizophrenia and 90 first onset major depression disorder (MDD) patients and 371 controls. The biomarker panel was identified using ten-fold cross-validation with lasso regression applied to the 87 analytes available across the meta-analysis studies.We identified 20 protein analytes with excellent predictive performance [area under the curve (AUC) ⩾ 0.90]. Importantly, the panel had a good predictive performance (AUC 0.84) to differentiate 12 misdiagnosed BD patients from 90 first onset MDD patients, and a fair to good predictive performance (AUC 0.79) to differentiate between 110 pre-diagnostic BD patients and 184 controls. We also demonstrated the disease specificity of the panel.ConclusionsAn early and accurate diagnosis has the potential to delay or even prevent the onset of BD. This study demonstrates the potential utility of a biomarker panel as a diagnostic test for BD.     

Quantitative separation of the depressive phase of bipolar disorder and major depressive disorder using electrovestibulography

Abstract

Objectives: No electrophysiological, neuroimaging or genetic markers have been established that strongly relate to the diagnostic separation of bipolar disorder (BD) and major depressive disorder (MDD). This paper’s objective is to describe the potential of features, extracted from the recording of electrical activity from the outer ear canal, in a process called electrovestibulography (EVestG), for identifying depressed and partly remitted/remitted MDD and BD patients from each other.

Methods: From EVestG data four sensory vestibulo-acoustic features were extracted from both background (no movement) and using a single supine-vertical translation stimulus to distinguish 27 controls, 39 MDD and 43 BD patients.

Results: Using leave-one-out-cross-validation, unbiased parametric and non-parametric classification routines resulted in 78–83% (2–3 features), 80–81% (1–2 features) and 66–68% (3 features) accuracies for separation of MDD from BD, controls from depressed (BD & MDD) and the 3-way separation of BD from MDD from control groups, respectively. The main limitations of this study were the inability to fully disentangle the impact of prescribed medication from the responses and also the limited sample size.

Conclusions: EVestG features can reliably identify depressed and partly remitted/remitted MDD and BD patients from each other.     

Quality of life in major depressive disorder: the role of pain and pain catastrophizing cognition

ObjectivePain symptoms are frequent complaints in patients with major depressive disorder (MDD). Although it is known that pain intensity and pain-related cognition predict quality of life (QOL) in patients with chronic pain, limited studies have examined their roles in MDD. The study aimed to determine whether pain and pain catastrophizing were independent predictors of QOL in MDD after accounting for the impact of anxiety and depression.MethodsThis is a prospective, naturalistic follow-up study. Ninety-one Chinese patients were enrolled during an acute episode of MDD, 82 of them were reassessed 3 months later using the same assessment on pain, anxiety, depression, and QOL. Pain intensity was evaluated using a verbal rating scale and a visual analog scale. Quality of life was assessed using the 36-item Short Form Health Survey. Pain-related cognition was assessed at baseline with the Pain Catastrophizing Scale.ResultsThere was significant improvement in pain, anxiety, depression, and QOL from baseline to 3-month follow-up. Hierarchical regression analyses showed that pain intensity was significantly associated with QOL at baseline and 3 months. Pain complaint was more important than anxiety and depressive symptoms in predicting changes in both physical and psychosocial domains of QOL. After controlling for the severity of pain, anxiety, and depression, Pain Catastrophizing Scale score was independently associated with QOL in MDD.ConclusionThe study supports the specific role of pain and pain-related cognition in predicting QOL in depressed patients. Further studies targeting pain-related cognition for improving the outcome of MDD are necessary.     

Factorial structure and familial aggregation of the Hypomania Checklist-32 (HCL-32): Results of the NIMH Family Study of Affective Spectrum Disorders

BackgroundThere is substantial evidence that bipolar disorder (BD) manifests on a spectrum rather than as a categorical condition. Detection of people with subthreshold manifestations of BD is therefore important. The Hypomania Checklist-32 (HCL-32) was developed as a tool to identify such people.PurposeThe aims of this paper were to: (1) investigate the factor structure of HCL-32; (2) determine whether the HCL-32 can discriminate between mood disorder subtypes; and (3) assess the familial aggregation and cross-aggregation of hypomanic symptoms assessed on the HCL with BD.ProceduresNinety-six probands recruited from the community and 154 of their adult first-degree relatives completed the HCL-32. Diagnosis was based on semi-structured interviews and family history reports. Explanatory factor analysis and mixed effects linear regression models were used.FindingsA four-factor (“Activity/Increased energy,” “Distractibility/Irritability”, “Novelty seeking/Disinhibition, "Substance use") solution fit the HCL-32, explaining 11.1% of the total variance. The Distractibility/Irritability score was elevated among those with BP-I and BP-II, compared to those with depression and no mood disorders. Higher HCL-32 scores were associated with increased risk of BD-I (OR = 1.22, 95%CI 1.14–1.30). The “Distractibility/Irritability” score was transmitted within families (β = 0.15, p = 0.040). However, there was no familial cross-aggregation between mood disorders and the 4 HCL factors.ConclusionsOur findings suggest that the HCL-32 discriminates the mood disorder subtypes, is familial and may provide a dimensional index of propensity to BD. Future studies should explore the heritability of symptoms, rather than focusing on diagnoses.     

Emotional reactivity to daily life stress in psychosis and affective disorder: an experience sampling study

OBJECTIVE: To investigate the emotional reactivity to small disturbances in daily life in patients with non-affective psychosis (NAP), bipolar disorder (BD) and major depression [major depressive disorder (MDD)]. METHOD: Forty-two patients with NAP, 38 with BD, 46 with MDD, and 49 healthy controls were studied with the experience sampling method to assess (i) appraised subjective stress of small disturbances in daily life and (ii) emotional reactivity, reflected in changes in positive affect (PA) and negative affect (NA). RESULTS: Multilevel regression analyses showed an increase in NA in MDD, a decrease in PA in BD and both an increase in NA and a decrease in PA in NAP in association with the subjectively stressful situations, compared with the control subjects. CONCLUSION: Individuals with NAP, MDD and BD display differences in emotional stress reactivity. Type of mood disorder may exert a pathoplastic effect on emotional reactivity in individuals with MDD and BD. Individuals with NAP may be most vulnerable to the effects of daily life stress.     

Shared and Specific Patterns of Structural Brain Connectivity Across Affective and Psychotic Disorders

BackgroundAltered brain structural connectivity has been implicated in the pathophysiology of psychiatric disorders including schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). However, it is unknown which part of these connectivity abnormalities are disorder specific and which are shared across the spectrum of psychotic and affective disorders. We investigated common and distinct brain connectivity alterations in a large sample (N = 1743) of patients with SZ, BD, or MDD and healthy control (HC) subjects.MethodsThis study examined diffusion-weighted imaging-based structural connectome topology in 720 patients with MDD, 112 patients with BD, 69 patients with SZ, and 842 HC subjects (mean age of all subjects: 35.7 years). Graph theory–based network analysis was used to investigate connectome organization. Machine learning algorithms were trained to classify groups based on their structural connectivity matrices.ResultsGroups differed significantly in the network metrics global efficiency, clustering, present edges, and global connectivity strength with a converging pattern of alterations between diagnoses (e.g., efficiency: HC > MDD > BD > SZ, false discovery rate–corrected p = .028). Subnetwork analysis revealed a common core of edges that were affected across all 3 disorders, but also revealed differences between disorders. Machine learning algorithms could not discriminate between disorders but could discriminate each diagnosis from HC. Furthermore, dysconnectivity patterns were found most pronounced in patients with an early disease onset irrespective of diagnosis.ConclusionsWe found shared and specific signatures of structural white matter dysconnectivity in SZ, BD, and MDD, leading to commonly reduced network efficiency. These results showed a compromised brain communication across a spectrum of major psychiatric disorders.     

Higher serum VGF protein levels discriminate bipolar depression from major depressive disorder

Misdiagnosis between major depressive disorder (MDD) and bipolar depression (BD) is quite common. Our previous study found significantly lower serum VGF (non-acronymic) in MDD patients. However, it is unclear whether same changes occur in BD patients. Therefore, we aimed to investigate the relationship between serum VGF levels in BD and MDD patients. General information, scores of 17-item Hamilton Depression Rating Scale (HDRS), and fasting blood samples of all participants including 30 MDD patients, 20 BD patients, and 30 healthy controls (HC) were collected. Serum VGF levels were measured by Enzyme-linked immunosorbent assay kits. Pearson correlation analysis was used to analyze correlations between serum VGF levels and clinical information. Receiver operating characteristic (ROC) curve and likelihood ratios (LRs) were used to analyze the differential potential of serum VGF. Serum VGF levels were significantly lower in MDD patients but higher in BD patients compared with HC (both P_Tukey < 0.01). No correlation was found between serum VGF levels and any data of subjects. The optimal cutoff for serum VGF in discriminating BD patients from MDD patients was ≥1093.85 pg/ml (AUC = 0.990, sensitivity of 95%, specificity of 100% and accuracy of 95%). LRs further confirmed the differential efficiency of serum VGF in distinguishing BD and MDD patients with +LR of infinity and –LR of 0. The results suggest that serum VGF level changed significantly in MDD and BD patients and serum VGF may be an indicator for differentiating BD patients from MDD patients.     

Elevated triglyceride levels are associated with cognitive impairments among patients with major depressive disorder

BackgroundCognitive deficits have been identified as one of core clinical symptoms of major depressive disorder (MDD). Accumulating evidence indicated that triglycerides (TG) might be associated with MDD and cognitive decline.ObjectiveThis study examined whether patients with MDD had poorer cognitive functions than healthy controls, and further investigate whether TG levels were involved in MDD, and its cognitive impairments in a Han Chinese population.Method115 patients with MDD and 119 healthy controls were enrolled. Cognitive functions were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and serum TG levels were examined using enzymatic colorimetry.ResultsTG levels were higher in patients with MDD than healthy controls after controlling for the variables. Cognitive test scores were lower in patients with MDD than healthy controls except for visuospatial/constructional index after controlling for the variables. TG levels were negatively correlated with visuospatial/constructional score, delayed memory score and RBANS total score of MDD. Further multivariate regression analysis showed that TG levels were negatively associated with visuospatial/constructional score, attention score, delayed memory score and RBANS total score of MDD.ConclusionsOur findings supported that serum TG levels might be involved in MDD, and play an important role in cognitive impairments of MDD, especially in delayed memory. Moreover, patients with MDD experienced greater cognitive impairments than healthy controls except for visuospatial/constructional index.     

Stigma: a core factor on predicting functionality in bipolar disorder

ObjectiveExtant literature indicates that bipolar disorder (BD) is associated with significant poor psychosocial functioning. However, the relationship between functioning and demographic and clinical variables is unclear. The aim of this study is to investigate the predictors of functioning such as demographic and clinical variables, social support, self-perceived stigma, and insight in remitted patients with BD.MethodsEighty patients with a diagnosis of BD, complete remission according to the criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were included in the final assessment. Bipolar Disorder Functioning Questionnaire, Beck Depression Inventory, Young Mania Rating Scale, Internalized Stigma of Mental Illness Scale, Multidimensional Scale of Perceived Social Support, and Schedule for Assessing the Three Components of Insight were used. Student t test, Pearson correlation analyses, and linear regression analyses were used to assess the pathways effecting on functioning.ResultsThe 3 predictors of functioning were severity of depression, perceived social support, and internalized stigmatization. Severity of depression is considered the strongest predictor, whereas internalized stigmatization has a core role in predicting functioning. Clinical variables such as years of education and number of hospitalization probably have indirect effects on functioning.ConclusionInterventions that oppose stigmatization and consideration of mild depressive symptoms will positively affect functioning in remitted patients with BD.     

Understanding emotion and emotional scarring in recurrent depression

BackgroundA single-item assessment of sad mood after remission from MDD is predictive of relapse, yet the mechanisms that play a role in depressive relapse remain poorly understood.MethodsIn 283 patients, remitted from recurrent depression (DSM-IV-TR criteria; HAM-D₁₇ score ≤10), we examined emotional scarring, that is, whether the number of previous depressive episodes was associated with higher levels of sad mood as assessed with a 1-item Visual Analogue Mood Scale (VAMS). We then fitted a cross-sectional multivariate regression model to predict sad mood levels, including the Dysfunctional Attitude Scale Version-A, cognitive reactivity (Leiden Index of Depression Sensitivity), Ruminative Response Scale, and Everyday Problem Checklist.ResultsPatients with greater numbers of prior episodes experienced higher levels of sad mood after remission. In multivariate regression, intensity of daily stress and dysfunctional beliefs were associated with the VAMS (Adj. R² = .091) although not over and above depressive symptomatology (Adj. R² = .114). Cognitive reactivity was not associated with sadness.ConclusionsOur finding that patients with more previous MDEs reported higher levels of sad mood while remitted could be indicative of emotional scarring. Dysfunctional beliefs and intensity of daily stress were associated with sad mood but not over and above residual symptoms. Thus, illness related characteristics especially are associated with sad mood after remission. More negative affect after remission could result in lower stress tolerance or more stress intensity could result in negative affect. Future studies should examine premorbid sadness in a longitudinal cohort, and should study the exact pathway from stress, affect, and cognition to relapse.     

Case-control association study of 14 variants of CREB1, CREBBP and CREM on diagnosis and treatment outcome in major depressive disorder and bipolar disorder

Some evidence suggests an association between genetic variants within the cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), CREB binding protein (CREBBP) and cAMP response element-modulator (CREM) and several psychiatric disorders. The present study investigated whether some single nucleotide polymorphisms (SNPs) within these genes could be associated with major depressive disorder (MDD) and bipolar disorder (BD) and whether they could predict clinical outcomes in Korean in-patients treated with antidepressants and mood stabilizers, respectively. The sample comprised 145 patients with MDD, 132 patients with BD and 170 psychiatrically healthy controls. Participants were genotyped for 14 SNPs within CREB1, CREBBP and CREM. Baseline and final clinical measures, including the Montgomery-?sberg Depression Rating Scale and Young Mania Rating Scale for patients with MDD and BD, respectively, were recorded. All p-values were 2-tailed, and statistical significance was conservatively set at the 0.006 level in order to reduce the likelihood of false positive results. We failed to observe any association of the 14 SNPs genotypes or alleles with clinical improvement, response and remission rates as well as final outcomes in any of such disorders. Our findings suggest that the 14 SNP under investigation in our study do not influence diagnosis and treatment response in patients with MDD and BD. However, taking into account the several limitations of our study, further research is needed to draw more definitive conclusions.