BACKGROUND AND AIMS Stress may be an important factor in exacerbating inflammatory bowel disease but the underlying mechanism is unclear. Defective epithelial barrier function may allow uptake of ...luminal antigens that stimulate an immune/inflammatory response. Here, we examined the effect of chronic stress on colonic permeability and the participation of mast cells in this response. METHODS Mast cell deficient Ws/Ws rats and +/+ littermate controls were submitted to water avoidance stress or sham stress (one hour/day) for five days. Colonic epithelial permeability to a model macromolecular antigen, horseradish peroxidase, was measured in Ussing chambers. Epithelial and mast cell morphology was studied by light and electron microscopy. RESULTS Chronic stress significantly increased macromolecular flux and caused epithelial mitochondrial swelling in +/+ rats, but not in Ws/Ws rats, compared with non-stressed controls. Stress increased the number of mucosal mast cells and the proportion of cells showing signs of activation in +/+ rats. No mast cells or ultrastructural abnormalities of the epithelium were present in Ws/Ws rats. Increased permeability in +/+ rats persisted for 72 hours after stress cessation. CONCLUSIONS Chronic stress causes an epithelial barrier defect and epithelial mitochondrial damage, in parallel with mucosal mast cell hyperplasia and activation. The study provides further support for an important role for mast cells in stress induced colonic mucosal pathophysiology.
Introduction
Major depressive episodes (MDE) occur in major depressive (MDD) and bipolar disorders (BD), and are frequently complicated by borderline personality disorder (BPD). Mixed affective ...symptomatology is a hallmark of BD, and affective lability of BPD; both may markedly influence illness course. However, direct comparisons of outcome of depression in MDD, BD and BPD are scarce.
Objectives
To investigate course of illness and outcome of depression in MDD, bipolar and borderline patients.
Methods
In this six-month, prospective cohort study of secondary-level psychiatric MDE patients (n = 95), after initial assessment, the patients (N = 95) completed biweekly online assessments of mood symptoms. We divided the follow up period into qualitatively different mood state periods based on multiple prospective information sources. We examined mixed affective symptoms and borderline symptom severity dimensionally. Outcomes assessed included clinical course, time to first full symptomatic remission, and factors predicting these.
Results
Remission rates according to DSM-5 were similar in MDD, MDE/BD and MDE/BPD patients. Bipolar patients experienced more shorter qualitatively distinct mood state periods during follow-up than the others. Bipolar disorder was associated with shorter (HR = 2.44, 95% CI = 1.27–4.67, see fig. 1) and dimensionally assessed BPD severity with longer time to first remission (HR = 0.95 per point., CI = 0.91–1.00).
Conclusions
Course of illness differs between the three depressive groups in the medium term. Bipolar depressive patients have the most alternating course and the shortest time to first remission. Dimensionally assessed severity of BPD may be prognostic of longer depressive remission latency.
Disclosure
I am employed by a psychiatric treatment provider, treating e.g. patients suffering from depression, bipolar disorder and borderline personality disorder.
Major depressive episodes (MDEs) of major depressive (MDD) or bipolar disorders (BD) are frequently complicated by features of borderline personality disorder (BPD). Mixed features are a hallmark of ...BD and affective lability of BPD, and both may markedly influence illness course. However, direct comparisons of outcome of depression in MDD, BD, and BPD are scarce.
In a cohort study based on stratified sampling, we diagnosed psychiatric MDE patients with SCID-I/P and SCID-II interviews and examined mixed symptoms using the Mix-MDE scale and borderline symptoms using the Borderline Personality Disorder Severity Index. During a six-month prospective follow-up, the MDE patients with MDD (n = 39), BD (n = 33), or BPD (n = 23) completed biweekly online assessments. Using life chart methodology, we divided the follow-up period into qualitatively different mood state periods. We investigated durations of mood episodes, times to first full symptomatic remission, and their predictors.
Remission rates were similar in MDD, MDE/BD, and MDE/BPD patients. MDE/BD patients experienced more numerous and shorter distinct mood state periods during follow-up than the others. MDE/BD was associated with shorter (HR = 2.44, 95 % CI = 1.27–4.67) and dimensionally assessed BPD severity with longer time to first remission (HR = 0.95, 95 % CI = 0.91–1.00).
Moderate sample size and follow-up duration.
Course of illness over six months differs between the three depressive groups. Bipolar depressive patients have the most alternating course and the shortest time to first period of remission. Dimensionally assessed severity of BPD may predict longer time to remission from depression.
•Prospective outcome study of depression in unipolar, bipolar and borderline patients•Time to remission shortest among bipolar and longest among borderline patients•Bipolar patients had the most variable illness course, but hypomanic switch was rare.•Severity of borderline features was related to longer time to remission.•Assessment of borderline features among depressive patients may be clinically useful.
•Differentiating bipolar symptoms and borderline features may often be difficult.•Unspecific symptoms of irritability and distractibility blur differential diagnosis.•Presence of hypomania may ...aggravate perceived borderline personality features.•MIX-MDE is a novel tool for quantifying (hypo)manic features during depression.
Bipolar symptoms and borderline personality features occur in both unipolar and bipolar major depressive episodes (MDEs). We investigated their prevalence, severity, co-occurrence and overlap.
We interviewed 124 psychiatric outpatients with MDE using the Structured Clinical Interview for DSM-IV-TR Axis I and II Disorders, the Borderline Personality Disorder Severity Index (BPDSI-IV), and about past (hypo)manic episodes, and stratified them according to the principal diagnosis into subcohorts of major depressive disorder (MDD, n = 50), bipolar disorder (BD, n = 43), and borderline personality disorder (BPD, n = 31). We quantified (hypo)manic symptoms using a novel semi-structured interview (MIXed symptoms during MDE, MIX-MDE) with good psychometric qualities.
The subcohorts did not differ in MDE severity. They differed significantly in some (hypo)manic symptoms being present on most days in 24% of MDD, 30% of BD, and 42% of BPD subcohort, but only 5% of the BD subcohort fulfilled the DSM-5 mixed features. The mean MIX-MDE scores were 5.7 (SD 4.0), 12.0 (8.2) and 10.5 (7.5), and BPDSI-IV scores 15.6 (7.0), 17.2 (6.2) and 26.9 (8.7), respectively (both p < 0.001). (Hypo)manic days and unspecific symptoms of distractibility and irritability inflated the correlation of observed (hypo)manic symptoms and borderline features.
Moderate sample size, limited age variation (18-50 years); no previous validation of MIX-MDE.
Presence of some mixed and borderline features is common in MDEs, with overlap and diagnosis-specific differences. Unspecific symptoms of irritability and distractibility and the aggravating impact of hypomania on perceived BPD features blur the differential diagnosis.
Background
Suicide risk is high in patients with major depressive disorder (MDD), bipolar disorder (BD) and borderline personality disorder (BPD). Whether risk levels of and risk factors for suicidal ...ideation (SI) and suicide attempts (SA) are similar or different in these disorders remains unclear, as few directly comparative studies exist. The relationship of short‐term changes in depression severity and SI is underinvestigated, and might differ across groups, for example, between BPD and non‐BPD patients.
Methods
We followed, for 6 months, a cohort of treatment‐seeking, major depressive episode (MDE) patients in psychiatric care (original n = 124), stratified into MDE/MDD, MDE/BD and MDE/BPD subcohorts. We examined risks of suicide‐related outcomes and their risk factors prospectively. We examined the covariation of SI and depression over time with biweekly online modified Patient Health Questionnaire 9 surveys and analysed this relationship through multi‐level modelling.
Results
Risk of SA in BPD (22.2%) was higher than non‐BPD (4.23%) patients. In regression models, BPD severity was correlated with risk of SA and clinically significant SI. During follow‐up, mean depression severity and changes in depression symptoms were associated with SI risk regardless of diagnosis.
Conclusions
Concurrent BPD in depression seems predictive for high risk of SA. Severity of BPD features is relevant for assessing risk of SA and SI in MDE. Changes in depressive symptoms indicate concurrent changes in risk of SI. BPD status at intake can index risk for future SA, whereas depressive symptoms appear a useful continuously monitored risk index.
We investigated risk factors for suicidal ideation and behavior among currently depressed patients with major depressive disorder (MDD), major depressive episode (MDE) in bipolar disorder (BD), or ...MDE with comorbid borderline personality disorder (MDE/BPD). We compared current and lifetime prevalence of suicidal ideation and behavior, and investigated dimensional measures of BPD or mixed affective features of the MDE as indicators of risk.
Based on screening of 1,655 referrals, we recruited 124 psychiatric secondary care outpatients with MDE and stratified them into three subcohorts (MDD, BD, and MDE/BPD) using the Structured Clinical Interview for DSM-IV I and II. We examined suicidal ideation and behavior with the Columbia Suicide Severity Rating Scale (CSSRS). In addition, we quantified the severity of BPD symptoms and BD mixed features both categorically/diagnostically and dimensionally (using instruments such as the Borderline Personality Disorder Severity Index) in two time frames.
There were highly significant differences between the lifetime prevalences of suicide attempts between the subcohorts, with attempts reported by 16% of the MDD, 30% of the BD, and 60% of the BPD subcohort. Remarkably, the lifetime prevalence of suicide attempts in patients with comorbid BD and BPD exceeded 90%. The severity of BPD features was independently associated with risk of suicide attempts both lifetime and during the current MDE. It also associated in a dose-dependent manner with recent severity of ideation in both BPD and non-BPD patients. In multinominal logistic regression models, hopelessness was the most consistent independent risk factor for severe suicidal ideation in both time frames, whereas younger age and more severe BPD features were most consistently associated with suicide attempts.
Among patients with major depressive episodes, diagnosis of bipolar disorder, or presence of comorbid borderline personality features both imply remarkably high risk of suicide attempts. Risk factors for suicidal ideation and suicidal acts overlap, but may not be identical. The estimated severity of borderline personality features seems to associate with history of suicidal behavior and current severity of suicidal ideation in dose-dependent fashion among all mood disorder patients. Therefore, reliable assessment of borderline features may advance the evaluation of suicide risk.
Differentiating major depressive episodes (MDEs) of major depressive disorder (MDD), bipolar disorder (MDE/BD) and the MDEs comorbid with borderline personality disorder (MDE/BPD) is crucial for ...appropriate treatment, and knowledge of phenomenological differences may aid this. However, studies comparing affect experiences of these three patient groups and healthy subjects are scarce. In our study, participants (N = 114), including patients with MDD (n = 34), MDE/BD (n = 27), and MDE/BPD (n = 24), and healthy controls (HC, n = 29) responded to ecological momentary assessment (EMA) with ten circumplex model affect items ten times daily for seven days (7709 recordings). Explorative factor analysis resulted in two affect dimensions. The positive dimension included active, excited, cheerful (high arousal), and content (low arousal) affects, and the negative dimension irritated, angry, and nervous (high arousal) affects. Relative to HC, patients reported 3.5-fold negative affects (mean MDD 1.36 (SD 0.92), MDE/BD 1.43 (0.76), MDE/BPD 1.81 (0.95) vs. HC 0.44 (0.49) (p < 0.01)) but 0.5-fold positive affects (2.01 (0.90), 1.95 (0.89), 2.24 (1.03), vs. 3.2 (0.95), respectively (p < 0.01)). We used multilevel modelling. Negative-affect within-individual stability was lowest in MDE/BPD and highest in MDD. Negative affect predicted concurrent positive affect more in MDE/BPD than in MDD. Moderate size of subcohorts and no inpatients were limitations. Despite apparently similar MDEs, affective experiences may differ between BPD, BD, and MDD patients. Clinical subgroups of patients with depression may vary in affective instability and concurrent presence of negative and positive affects during depression.
Background: Crohn's disease is associated with deranged intestinal permeability in vivo, suggesting dysfunction of tight junctions. The luminal contents are important for development of ...neoinflammation following resection. Regulation of tight junctions by luminal factors has not previously been studied in Crohn's disease. Aims: The aim of the study was to investigate the effects of a luminal stimulus, known to affect tight junctions, on the distal ileum in patients with Crohn's disease. Patients: Surgical specimens from the distal ileum of patients with Crohn's disease (n=12) were studied, and ileal specimens from colon cancer patients (n=13) served as controls. Methods: Mucosal permeability to 51Cr-EDTA and electrical resistance were studied in Ussing chambers during luminal exposure to sodium caprate (a constituent of milk fat, affecting tight junctions) or to buffer only. The mechanisms involved were studied by mucosal ATP levels, and by electron and confocal microscopy. Results: Baseline permeability was the same in non-inflamed ileum of Crohn's disease and controls. Sodium caprate induced a rapid increase in paracellular permeability—that is, increased permeation of 51Cr-EDTA and decreased electrical resistance—which was more pronounced in non-inflamed ileum of Crohn's disease, and electron microscopy showed dilatations within the tight junctions. Moreover, sodium caprate induced disassembly of perijunctional filamentous actin was more pronounced in Crohn's disease mucosa. Mucosal permeability changes were accompanied by mitochondrial swelling and a fall in epithelial ATP content, suggesting uncoupling of oxidative phosphorylation. Conclusions: The tight junctions in the non-inflamed distal ileum of Crohn's disease were more reactive to luminal stimuli, possibly mediated via disturbed cytoskeletal contractility. This could contribute to the development of mucosal neoinflammation in Crohn's disease.
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