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Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear.
Methods:
Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response.
Results:
Compared to participants with WBC counts of 4.5–10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses.
Conclusions:
An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.
To characterize the multiple dimensions and benefits of the Mediterranean diet as a sustainable diet, in order to revitalize this intangible food heritage at the country level; and to develop a multidimensional framework – the Med Diet 4.0 – in which four sustainability benefits of the Mediterranean diet are presented in parallel: major health and nutrition benefits, low environmental impacts and richness in biodiversity, high sociocultural food values, and positive local economic returns.
Design
A narrative review was applied at the country level to highlight the multiple sustainable benefits of the Mediterranean diet into a single multidimensional framework: the Med Diet 4.0.
Setting/subjects
We included studies published in English in peer-reviewed journals that contained data on the characterization of sustainable diets and of the Mediterranean diet. The methodological framework approach was finalized through a series of meetings, workshops and conferences where the framework was presented, discussed and ultimately refined.
Results
The Med Diet 4.0 provides a conceptual multidimensional framework to characterize the Mediterranean diet as a sustainable diet model, by applying principles of sustainability to the Mediterranean diet.
Conclusions
By providing a broader understanding of the many sustainable benefits of the Mediterranean diet, the Med Diet 4.0 can contribute to the revitalization of the Mediterranean diet by improving its current perception not only as a healthy diet but also a sustainable lifestyle model, with country-specific and culturally appropriate variations. It also takes into account the identity and diversity of food cultures and systems, expressed within the notion of the Mediterranean diet, across the Mediterranean region and in other parts of the world. Further multidisciplinary studies are needed for the assessment of the sustainability of the Mediterranean diet to include these new dimensions.
Lack of coordination between screening studies for common mental disorders in primary care and community epidemiological samples impedes progress in clinical epidemiology. Short screening scales based on the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI), the diagnostic interview used in community epidemiological surveys throughout the world, were developed to address this problem.
Method
Expert reviews and cognitive interviews generated CIDI screening scale (CIDI-SC) item pools for 30-day DSM-IV-TR major depressive episode (MDE), generalized anxiety disorder (GAD), panic disorder (PD) and bipolar disorder (BPD). These items were administered to 3058 unselected patients in 29 US primary care offices. Blinded SCID clinical reinterviews were administered to 206 of these patients, oversampling screened positives.
Results
Stepwise regression selected optimal screening items to predict clinical diagnoses. Excellent concordance [area under the receiver operating characteristic curve (AUC)] was found between continuous CIDI-SC and DSM-IV/SCID diagnoses of 30-day MDE (0.93), GAD (0.88), PD (0.90) and BPD (0.97), with only 9–38 questions needed to administer all scales. CIDI-SC versus SCID prevalence differences are insignificant at the optimal CIDI-SC diagnostic thresholds (χ21 = 0.0–2.9, p = 0.09–0.94). Individual-level diagnostic concordance at these thresholds is substantial (AUC 0.81–0.86, sensitivity 68.0–80.2%, specificity 90.1–98.8%). Likelihood ratio positive (LR+) exceeds 10 and LR− is 0.1 or less at informative thresholds for all diagnoses.
Conclusions
CIDI-SC operating characteristics are equivalent (MDE, GAD) or superior (PD, BPD) to those of the best alternative screening scales. CIDI-SC results can be compared directly to general population CIDI survey results or used to target and streamline second-stage CIDIs.
Previous studies have reported prefrontal cortex (PFC) pathophysiology in bipolar disorder.
Method
We examined the hemodynamics of the PFC during resting and cognitive tasks in 29 patients with bipolar disorder and 27 healthy controls, matched for age, verbal abilities and education. The cognitive test battery consisted of letter and category fluency (LF and CF), Sets A and B of the Raven's Colored Progressive Matrices (RCPM-A and RCPM-B) and the letter cancellation test (LCT). The tissue oxygenation index (TOI), the ratio of oxygenated hemoglobin (HbO2) concentration to total hemoglobin concentration, was measured in the bilateral PFC by spatially resolved near-infrared spectroscopy. Changes in HbO2 concentration were also measured.
Results
The bipolar group showed slight but significant impairment in performance for the non-verbal tasks (RCPM-A, RCPM-B and LCT), with no significant between-group differences for the two verbal tasks (LF and CF). A group×task×hemisphere analysis of variance (ANOVA) on the TOI revealed an abnormal pattern of prefrontal oxygenation across different types of cognitive processing in the bipolar group. Post hoc analyses following a group×task×hemisphere ANOVA on HbO2 concentration revealed that the bipolar group showed a greater increase in HbO2 concentration in the LCT and in RCPM-B, relative to controls.
Conclusions
Both indices of cortical activation (TOI and HbO2 concentration) indicated a discrepancy in the PFC function between verbal versus non-verbal processing, indicating task-specific abnormalities in the hemodynamic control of the PFC in bipolar disorder.
Few controlled studies have examined the use of atypical antipsychotic drugs for prevention of relapse in patients with bipolar I disorder.
Aims
To evaluate whether olanzapine plus either lithium or valproate reduces the rate of relapse, compared with lithium or valproate alone.
Method
Patients achieving syndromic remission after 6 weeks'treatment with olanzapine plus either lithium (0.6–1.2 mmol/l) or valproate (50–125 μg/ml) received lithium or valproate plus either olanzapine 5–20 mg/day (combination therapy) or placebo (monotherapy), and were followed in a double-masked trial for 18 months.
Results
The treatment difference in time to relapse into either mania or depression was not significant for syndromic relapse (median time to relapse: combination therapy 94 days, monotherapy40.5 days; P=0.742), but was significant for symptomatic relapse (combination therapy 163 days, monotherapy42 days; P=0.023).
Conclusions
Patients taking olanzapine added to lithium or valproate experienced sustained symptomatic remission, but not syndromic remission, for longer than those receiving lithium or valproate monotherapy.
During the development of a new treatment for bipolar disorder, maintenance studies are used to evaluate the ability of the putative mood stabiliser to prevent relapse and recurrence of further episodes. Comparisons with the early bipolar disorder maintenance studies indicate that the methodologies of recent trials have evolved substantially.
Aims
To review the methods used in the first- and second-generation maintenance studies, highlighting the differences of the various designs.
Method
Literature review.
Results
Methods that have evolved the most include patient enrolment, randomisation schemes and the use of outcome measures and statistical analyses. In addition, regulatory and commercial issues have also influenced study design.
Conclusion
There is little consensus on the methodology of bipolar disorder maintenance studies. As the integration of newer therapies into routine clinical practice is dependent on the evidence from controlled studies, it is essential that future maintenance trials in bipolar disorder achieve adequate methodological rigour without sacrificing overall feasibility.
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