Postpartum depression: we know the risks, can it be prevented?

In the past 20 years, there has been increasing recognition that for some women, pregnancy may be burdened with mood problems, in particular depression, that may impact both mother and child. With identification of risk factors for postpartum depression and a growing knowledge about a biologic vulnerability for mood change following delivery, research has accumulated on attempts to prevent postpartum depression using various psychosocial, psychopharmacologic, and hormonal strategies. The majority of psychosocial and hormonal strategies have shown little effect on postpartum depression. Notwithstanding, results from preliminary trials of interpersonal therapy, cognitive-behavioural therapy, and antidepressants indicate that these strategies may be of benefit. Information on prevention of postpartum depression using dietary supplements is sparse and the available evidence is inconclusive. Although a few studies show promising results, more rigorous trials are required. The abounding negative evidence in the literature indicates that postpartum depression cannot be easily prevented, yet.     

Studying new antidepressants: if there were a light at the end of the tunnel, could we see it?

This commentary began with the proposition that the SSRIs have become the standard of comparison for new antidepressants. It is also suggested that the conventional wisdom that all antidepressants are equally effective is no longer true. Rather, it is asserted that the same factors that have compromised the sensitivity of RCTs to detect drug-placebo differences similarly have impaired discriminations between effective and even more effective antidepressants. In order to have the power to make such a distinction, an RCT may need to enroll 300 or more patients per cell. Few studies thus have adequate statistical power. Alternatively, conclusions can be drawn from quantitative methods that combine data from groups of smaller studies. The relative merits and limitations of 2 strategies used to examine the results of comparative studies, meta-analysis and pooled analysis, were discussed. The former method is preferred when there are a large number of relevant RCTs; however, failure to include unpublished data from all relevant studies may inflate results. The latter method, unless biased by selective inclusion of studies or marked heterogeneity of results, is preferred when there are only a handful of comparable studies. Although the task of selecting among a number of good choices remains more clinical art than science, quantitative methods are now available to help determine if there are clinically meaningful differences in antidepressant efficacy. The conventional RCT provides a low power telescope for visualizing differences between effective medications. If there were a light at the end of the tunnel, it would be difficult to see it. Until methods that can improve the ability to discriminate between an active antidepressant and a placebo are identified and implemented, the ability to see modest differences necessitates the use of statistical methods such as meta-analysis and pooled analysis of original data.     

Flow diverter stents in the treatment of intracranial aneurysms: Where are we?

Flow diverter stents are devices designed to treat complex aneurysms. According to preliminary series published in the literature, treatment of aneurysms with flow diverters is highly efficacious with acceptable morbidity and mortality. Delayed aneurysm ruptures have been reported but mechanisms are actually not completely elucidated. In-stent thrombosis or stenosis was also observed. Indications of flow diverters are complex aneurysms (fusiform, large and giant, wide neck, small aneurysms untreatable by conventional coiling) as well as recurrences. Several randomized studies and registries are actually in progress and will contribute to a more precise knowledge of the place of the flow diverters in the treatment of intracranial aneurysms.     

What do we know about the mechanism of action of the placebo?

The placebo is a substance or a procedure capable to induce a subjective or objective healing effect, but which efficacy or mechanism of action could not be demonstrated by the conventional scientific procedures. The main objective of this review is to synthesize the theories about the way the placebo acts. Conditioning, expectancy and desire theories, as well as the possible symbolic level in which placebo acts are reviewed. Some recent investigations showed that nerobiological responses elicited by placebo administration mimic those induced by it corresponding active drug. Finally, following evidences from development research, we suggest, that early expierences provide individuals with a "correction program of physiological functions" which could be eventually activated by contextual clues, as placebo.     

Racial/ethnic disparities in the treatment of epilepsy: what do we know? What do we need to know?

We examine current understanding of the minority disadvantage in the clinical management of epilepsy. We performed an online literature search using several keywords (race, ethnicity, epilepsy, treatment, and quality of life) and identified additional literature through cross-referencing/manual search. The search produced 58 items published between 1977 and 2005. Of 49 original research studies, 38 were quantitative, 7 were qualitative, and 4 used mixed methods. Three or more articles were published in Epilepsia, Epilepsy &Behavior, Epilepsy Research, Neurology, and Seizure. Research concerning racial/ethnic differences in epilepsy treatment is scarce and limited by methodology, but suggests underutilization of state-of-the-art therapies by minorities. Racial/ethnic minorities also appear to have limited knowledge about epilepsy and its treatment, experience barriers to care, lack social support, and seek alternative therapies for epilepsy. We propose a framework to identify the array of disparities, points of intervention, and interventions.     

Impact of the lunar cycle on the incidence of intracranial aneurysm rupture: Myth or reality?

OBJECTIVE: To analyze the impact of the lunar cycle and season on the incidence of aneurysmal subarachnoid hemorrhage (SAH). PATIENTS AND METHODS: The medical records of 111 patients who were admitted over a 5-year period to our department because of aneurysmal SAH were retrospectively reviewed. The date of aneurysm rupture was matched with the corresponding season and moon phase. RESULTS: An incidence peak for aneurysm rupture (28 patients) was seen during the phase of new moon, which was statistically significant (p < 0.001). In contrast, no seasonal variation in the incidence of SAH was observed. CONCLUSION: The lunar cycle seems to affect the incidence of intracranial aneurysm rupture, with the new moon being associated with an increased risk of aneurysmal SAH.     

Do we know enough about the immune pathogenesis of acute coronary syndromes to improve clinical practice?

Morbidities related to atherosclerosis, such as acute coronary syndromes (ACS) including unstable angina and myocardial infarction, remain leading causes of mortality. Unstable plaques are inflamed and infiltrated with macrophages and T lymphocytes. Activated dendritic cells interact with T cells, yielding predominantly Th1 responses involving interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α), while the role of interleukin 17 (IL-17) is questionable. The expansion of CD28nullCD4 or CD8 T cells as well as pattern recognition receptors activation (especially Toll-like receptors; TLR2 and TLR4) is characteristic for unstable plaque. Inflammation modifies platelet and fibrin clot characteristics, which are critical for ACS. Understanding of the inflammatory mechanisms of atherothrombosis, bridging inflammation, oxidative stress and immune regulation, will allow for the detection of subjects at risk, through the use of novel biomarkers and imaging techniques including intravascular ultrasound, molecular targeting, magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). Moreover, understanding the specific inflammatory pathways of plaque rupture and atherothrombosis may allow for immunomodulation of ACS. Statins and anti-platelet drugs are anti-inflammatory, but importance of immune events in ACS warrants the introduction of novel, specific treatments directed either on cytokines, TLRs or inflammasomes. While the prime time for the introduction of immunologically inspired diagnostic tests and treatments for atherosclerosis have not come yet, we are closer than ever before to finally being able to benefit from this vast body of experimental and clinical evidence. This paper provides a comprehensive review of the role of the immune system and inflammation in ACS.     

Repeating patterns of sleep restriction and recovery: Do we get used to it?

Despite its prevalence in modern society, little is known about the long-term impact of restricting sleep during the week and ‘catching up’ on weekends. This common sleep pattern was experimentally modeled with three weeks of 5 nights of sleep restricted to 4 h followed by two nights of 8-h recovery sleep. In an intra-individual design, 14 healthy adults completed both the sleep restriction and an 8-h control condition, and the subjective impact and the effects on physiological markers of stress (cortisol, the inflammatory marker IL-6, glucocorticoid receptor sensitivity) were assessed. Sleep restriction was not perceived to be subjectively stressful and some degree of resilience or resistance to the effects of sleep restriction was observed in subjective domains. In contrast, physiological stress response systems remain activated with repeated exposures to sleep restriction and limited recovery opportunity. Morning IL-6 expression in monocytes was significantly increased during week 2 and 3 of sleep restriction, and remained increased after recovery sleep in week 2 (p < 0.05) and week 3 (p < 0.09). Serum cortisol showed a significantly dysregulated 24 h-rhythm during weeks 1, 2, and 3 of sleep restriction, with elevated morning cortisol, and decreased cortisol in the second half of the night. Glucocorticoid sensitivity of monocytes was increased, rather than decreased, during the sleep restriction and sleep recovery portion of each week. These results suggest a disrupted interplay between the hypothalamic-pituitary-adrenal and inflammatory systems in the context of repeated exposure to sleep restriction and recovery. The observed dissociation between subjective and physiological responses may help explain why many individuals continue with the behavior pattern of restricting and recovering sleep over long time periods, despite a cumulative deleterious physiological effect.     

What do we know about the long-term consequences of stress on ageing and the progression of age-related neurodegenerative disorders?

The aim of this paper is to review evidences that stressful events throughout life can have a long-term impact on ageing and the progression of Alzheimer's disease. As early as the prenatal or neonatal period, stress can alter the rate of cognitive decline and neurodegenerative changes in the brain in a stressor-dependent manner, with prenatal restraint and maternal separation usually causing damage to the brain, whereas neonatal handling was found protective. The occurrence of negative outcomes of early stress can, however, be reversed by subsequent events known to be beneficial to the ageing process. After the early developmental period, it is currently unknown how stress will impact on the ageing process, due to a lack of studies. On the other hand, there is evidence of a lack of plasticity of the brain monoaminergic systems in response to stress with age, and of age-dependent changes in the immediate impact of stress, which is greater in subjects vulnerable to age-related cognitive decline. In addition, vulnerability to stress enhances the risk of developing Alzheimer's disease in humans and chronic substantial stress in animal models of the disease accelerates both the onset and progression of pathological markers in the brain. In an attempt to integrate these findings, a hypothesis is presented here whereby stress, in susceptible individuals, would precipitate age-related cognitive decline and hippocampal integrity during normal and pathological ageing, but will only affect the progression of pathological markers of Alzheimer's disease in the presence of other risk factors to this neuropathological disorder.