Objective: Duration of untreated illness represents a potentially modifiable component of any diagnosis‐treatment pathway. In bipolar disorder (BD), this concept has rarely been systematically ...defined or not been applied to large clinically representative samples.
Method: In a well‐characterized sample of 501 patients with BD, we estimated the duration of untreated bipolar disorder (DUB: the interval between the first major mood episode and first treatment with a mood stabilizer). Associations between DUB and clinical onset and the temporal sequence of key clinical milestones were examined.
Results: The mean DUB was 9.6 years (SD 9.7; median 6). The median DUB for those with a hypomanic onset (14.5 years) exceeded that for depressive (13 years) and manic onset (8 years). Early onset BD cases have the longest DUB (P < 0.0001). An extended DUB was associated with more mood episodes (P < 0.0001), more suicidal behaviour (P = 0.0003) and a trend towards greater lifetime mood instability (e.g. rapid cycling, possible antidepressant‐induced mania).
Conclusion: Duration of untreated bipolar disorder (DUB) will only be significantly reduced by more aggressive case finding strategies. Reliable diagnosis (especially for BD‐II) and/or instigation of recommended treatments is currently delayed by insufficient awareness of the early, polymorphous presentations of BD, lack of systematic screening and/or failure to follow established guidelines.
Objective
Sleep dysregulation is highly prevalent in bipolar disorders (BDs), with previous actigraphic studies demonstrating sleep abnormalities during depressive, manic, and interepisode periods. ...We undertook a meta‐analysis of published actigraphy studies to identify whether any abnormalities in the reported sleep profiles of remitted BD cases differ from controls.
Method
A systematic review identified independent studies that were eligible for inclusion in a random effects meta‐analysis. Effect sizes for actigraphy parameters were expressed as standardized mean differences (SMD) with 95% confidence intervals (95% CI).
Results
Nine of 248 identified studies met eligibility criteria. Compared with controls (N = 210), remitted BD cases (N = 202) showed significant differences in SMD for sleep latency (0.51 0.28–0.73), sleep duration (0.57 0.30–0.84), wake after sleep onset (WASO) (0.28 0.06–0.50) and sleep efficiency (−0.38 −0.70–0.07). Moderate heterogeneity was identified for sleep duration (I2 = 44%) and sleep efficiency (I2 = 44%). Post hoc meta‐regression analyses demonstrated that larger SMD for sleep duration were identified for studies with a greater age difference between BD cases and controls (β = 0.22; P = 0.03) and non‐significantly lower levels of residual depressive symptoms in BD cases (β = −0.13; P = 0.07).
Conclusion
This meta‐analysis of sleep in remitted bipolar disorder highlights disturbances in several sleep parameters. Future actigraphy studies should pay attention to age matching and levels of residual depressive symptoms.
This paper initiates a study of upper and lower generalized Drazin invertible linear relations classes. We first aim to give a characterization of these classes via a generalized Kato decomposition. ...Then, we establish some characterizations of these classes in terms of an associated projection. Some issues of the local spectral theory of linear relations in Banach spaces are also thought of. Finally, we apply these results to deduce a new characterization of these classes by means of the analytic residuum concept.
Objective
Obsessive–compulsive disorder (OCD) is a chronic, prevalent, and highly impairing psychiatric illness. Although the pathophysiology of OCD remains unknown, pathways involved in oxidative ...and nitrosative stress (O&NS) have been implicated. The present study aims to systematically review the literature for quantitative evidence that patients with OCD have altered measures of blood O&NS markers.
Methods
Independent random‐effects meta‐analyses using standardized mean differences were conducted to assess each marker separately. Additionally, data from multiple markers were pooled together in a meta‐analysis for measures of oxidant activity and another for measures of antioxidant activity.
Results
Thirteen studies met inclusion criteria, involving 433 OCD patients and 459 controls. Eleven blood O&NS markers were eligible for independent quantitative analyses. We found that, in OCD patients, the oxidant markers 8‐hydroxydeoxyguanosine and malondialdehyde, and the antioxidants glutathione peroxidase and superoxide dismutase, were significantly increased while total antioxidant status, vitamin C, and vitamin E were significantly decreased, when comparing with controls. Regarding pooled meta‐analyses, we found a statistically significant increase in oxidant markers, but non‐significant results regarding antioxidant markers.
Conclusions
Our meta‐analysis suggests that OCD patients have a systemic oxidative imbalance that is not adequately buffered by the antioxidant system. Additional studies are needed in order to support this association.
Many studies have shown associations between a history of childhood trauma and more severe or complex clinical features of bipolar disorders (BD), including suicide attempts and earlier illness ...onset. However, the psychopathological mechanisms underlying these associations are still unknown. Here, we investigated whether affective lability mediates the relationship between childhood trauma and the severe clinical features of BD.
A total of 342 participants with BD were recruited from France and Norway. Diagnosis and clinical characteristics were assessed using the Diagnostic Interview for Genetic Studies (DIGS) or the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). Affective lability was measured using the short form of the Affective Lability Scale (ALS-SF). A history of childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Mediation analyses were performed using the SPSS process macro.
Using the mediation model and covariation for the lifetime number of major mood episodes, affective lability was found to statistically mediate the relationship between childhood trauma experiences and several clinical variables, including suicide attempts, mixed episodes and anxiety disorders. No significant mediation effects were found for rapid cycling or age at onset.
Our data suggest that affective lability may represent a psychological dimension that mediates the association between childhood traumatic experiences and the risk of a more severe or complex clinical expression of BD.
Objectives
Reliable predictors of response to lithium are still lacking in bipolar disorders (BDs). However, childhood trauma has been hypothesized to be associated with poor response to lithium.
...Methods
We included 148 patients with BD, euthymic when retrospectively and clinically assessed for response to lithium and childhood trauma using reliable scales.
Results
According to the ‘Alda scale’, the sample consisted in 20.3% of excellent responders, 49.3% of partial responders and 30.4% of non‐responders to lithium. A higher level of physical abuse significantly correlated with a lower level of response to lithium (P = 0.009). As compared to patients not exposed to any abuse, patients with at least two trauma abuses (emotional, physical or sexual) were more at risk of belonging to the non‐responders group (OR = 4.91 95% CI (1.01–27.02)). Among investigated clinical variables, lifetime presence of mixed episodes and alcohol misuse were associated with non‐response to lithium. Multivariate analyses demonstrated that physical abuse and mixed episodes were independently associated with poor response to lithium (P = 0.005 and P = 0.013 respectively).
Conclusions
Childhood physical abuse might be involved in a poor future response to lithium prophylaxis, this effect being independent of the association between clinical expression of BD and poor response to lithium.
This study aims at testing for paths from childhood abuse to clinical indicators of complexity in bipolar disorder (BD), through dimensions of affective dysregulation, impulsivity and hostility.
485 ...euthymic patients with BD from the FACE-BD cohort were included from 2009 to 2014. We collect clinical indicators of complexity/severity: age and polarity at onset, suicide attempt, rapid cycling and substance misuse. Patients completed questionnaires to assess childhood emotional, sexual and physical abuses, affective lability, affect intensity, impulsivity, motor and attitudinal hostility.
The path-analysis demonstrated significant associations between emotional abuse and all the affective/impulsive dimensions (p < 0.001). Sexual abuse was moderately associated with emotion-related dimensions but not with impulsivity nor motor hostility. In turn, affect intensity and attitudinal hostility were associated with high risk for lifetime presence of suicide attempts (p < 0.001), whereas impulsivity was associated with a higher risk of lifetime presence of substance misuse (p < 0.001). No major additional paths were identified when including Emotional and Physical Neglect in the model.
This study provides refinement of the links between early adversity, dimensions of psychopathology and the complexity/severity of BD. Mainly, dimensions of affective dysregulation, impulsivity/hostility partially mediate the links between childhood emotional to suicide attempts and substance misuse in BD.
•We modelled the links between childhood trauma and outcomes in bipolar disorders.•The path-analysis integrated psychological dimensions as mediators.•Emotional abuse increased the levels of affective instability and impulsivity.•Affective instability partially mediated the association between trauma and suicidal behaviours.•Impulsivity/hostility partially mediated the association between trauma and substance misuse.
We aimed to study the relationship between tobacco smoking and attenuated psychosis measures taking into account several aspects of tobacco consumption that to date have not been explored and that ...could help understand this association, such as age of onset, the influence of former consumption and the duration of abstinence.
We investigated, in a sample of 580 students, the relationship between schizotypy (using the schizotypal personality questionnaire-brief in a Likert format) and smoking status, nicotine dependence (measured with the Fagerström test for nicotine dependence), age of onset of smoking and in former smokers, duration of smoking abstinence.
35.2% of the students were current smokers and 13.4% were former smokers. We found that current but not former smokers had higher scores of schizotypy (total, positive and disorganized) than non-smokers. We found no association between schizotypy scores and nicotine dependence or earlier age of onset of smoking. The duration of smoking abstinence, in former smokers, was inversely correlated to the score of positive and total schizotypy.
Our results suggest that tobacco has a reversible effect on schizotypy, but more studies with a different design (controlled, longitudinal) and a more thorough exploration of potential confounders (e.g. cannabis) are needed before a firm conclusion can be reached.
Abstract Study objectives Obesity and excess bodyweight are highly prevalent in individuals with bipolar disorders (BD) and are associated with adverse consequences. Multiple factors may explain ...increased bodyweight in BD including side effects of psychotropic medications, and reduced physical activity. Research in the general population demonstrates that sleep disturbances may also contribute to metabolic burden. We present a cross-sectional study of the associations between body mass index (BMI) and sleep parameters in patients with BD as compared with healthy controls (HC). Methods Twenty-six French outpatients with remitted BD and 29 HC with a similar BMI completed a 21-day study of sleep parameters using objective (actigraphy) and subjective (PSQI: Pittsburgh Sleep Quality Index) assessments. Results In BD cases, but not in HC, higher BMI was significantly correlated with lower sleep efficiency ( P = 0.009) and with several other sleep parameters: shorter total sleep time ( P = 0.01), longer sleep onset latency ( P = 0.05), higher fragmentation index ( P = 0.008), higher inter-day variability ( P = 0.05) and higher PSQI total score ( P = 0.004). Conclusions The findings suggest a link between a high BMI and several sleep disturbances in BD, including lower sleep efficiency. Physiological mechanisms in BD cases may include an exaggeration of phenomena observed in non-clinical populations. However, larger scale studies are required to clarify the links between metabolic and sleep-wake cycle disturbances in BD.
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