Adolescent major depressive disorder (MDD) is associated with disrupted processing of emotional stimuli and difficulties in cognitive reappraisal. Little is known however about how current pharmacotherapies act to modulate the neural mechanisms underlying these key processes. The current study therefore investigated the neural effects of fluoxetine on emotional reactivity and cognitive reappraisal in adolescent depression.

Thirty-one adolescents with MDD were randomised to acute fluoxetine (10 mg) or placebo. Seventeen healthy adolescents were also recruited but did not receive any treatment for ethical reasons. During functional magnetic resonance imaging (fMRI), participants viewed aversive images and were asked to either experience naturally the emotional state elicited (‘Maintain’) or to reinterpret the content of the pictures to reduce negative affect (‘Reappraise’). Significant activations were identified using whole-brain analysis.

No significant group differences were seen when comparing Reappraise and Maintain conditions. However, when compared to healthy controls, depressed adolescents on placebo showed reduced visual activation to aversive pictures irrespective of the condition. The depressed adolescent group on fluoxetine showed the opposite pattern, i.e. increased visuo-cerebellar activity in response to aversive pictures, when compared to depressed adolescents on placebo.

These data suggest that depression in adolescence may be associated with reduced visual processing of aversive imagery and that fluoxetine may act to reduce avoidance of such cues. This could reflect a key mechanism whereby depressed adolescents engage with negative cues previously avoided. Future research combining fMRI with eye-tracking is nonetheless needed to further clarify these effects.

Observational studies provide evidence for an association between potassium intake and BP levels. However, uncertainties still exist about the size and the shape of this relation. Conversely, experimental studies have not been used to estimate dose-response curves, since standard methods can only be applied in trials including at least three exposure groups.

We carried out a systematic review of the evidence concerning the effect of potassium supplementation on blood pressure in epidemiologic experimental studies. Following a PubMed search up to June 20, 2019, we included randomized controlled trials (RCTs) encompassing potassium supplementation as the only intervention for at least four weeks. We used a restricted cubic spline model and the ‘one-stage’ approach to perform a dose-response meta-analysis, a newly-developed statistical procedure which allows inclusion of studies with as few as two categories of exposure (Stat Methods Med Res. 2019;28:1579–1596). Finally, we repeated the analyses stratifying for hypertensive status and use of anti-hypertensive medication.

Overall, we included 33 studies carried out in adult population, with potassium supplementation ranging from 30 to 140 mmol/day. RCTs’ duration ranged from 4 up to 26 weeks. Most of the studies have a cross-over design (N = 24), include hypertensive individuals (N = 27) and subjects not under anti-hypertensive medication (N = 27). Overall, an increase of 40, 80 and 120 mmol/day of potassium resulted in reductions of SBP by -5.64 (95% CI - 8.78, -2.50), -4.62 (-6.41, -2.84) and -2.54 mmHg (95% CI -5.14, + 0.06), respectively. Higher potassium intakes also resulted in reduced DBP levels by -3.57 (95% CI -5.55, -1.59), -3.07 (95% CI -5.07, -1.08), and -1.92 mmHg (95% CI -5.65, 1.81). The effect of increasing potassium intake on BP was larger among hypertensives than normotensives, and among pharmacologically untreated hypertensives compared to their treated counterparts. Subgroup analyses according to study design (parallel vs. crossover) yielded similar results.

With the application of advanced dose-response modeling on RCT results, we found a U-shaped relation between potassium intake and blood pressure. A low to moderate increase in potassium intake resulted in a progressive reduction in blood pressure, which was reversed at higher levels of potassium supplementation. The effect was stronger among untreated hypertensives.

Supported by grant GP-EFSA-AFSCO-2017-01 GA09 of the European Food Safety Authority - EFSA. The text reflects only the authors' view; and EFSA is not responsible for any use that may be made of the information it contains.

The contribution of education and intelligence to resilience against age-related cognitive decline is not clear, particularly in the presence of ‘normal for age’ minor brain abnormalities.

Participants (n = 208, mean age 69.2 years, s.d. = 5.4) in the Whitehall II imaging substudy attended for neuropsychological testing and multisequence 3T brain magnetic resonance imaging. Images were independently rated by three trained clinicians for global and hippocampal atrophy, periventricular and deep white matter changes.

Although none of the participants qualified for a clinical diagnosis of dementia, a screen for cognitive impairment (Montreal Cognitive Assessment (MoCA) <26) was abnormal in 22%. Hippocampal atrophy, in contrast to other brain measures, was associated with a reduced MoCA score even after controlling for age, gender, socioeconomic status, years of education and premorbid IQ. Premorbid IQ and socioeconomic status were associated with resilience in the presence of hippocampal atrophy.

Independent contributions from a priori risk (age, hippocampal atrophy) and resilience (premorbid function, socioeconomic status) combine to predict measured cognitive impairment.

Hypertension is associated with an increased risk of dementia and depression with uncertain longitudinal associations with brain structure.

To examine lifetime blood pressure as a predictor of brain structure in old age.

A total of 190 participants (mean age 69.3 years) from the Whitehall II study were screened for hypertension six times (1985–2013). In 2012–2013, participants had a 3T-magnetic resonance imaging (MRI) brain scan. Data from the MRI were analysed using automated and visual measures of global atrophy, hippocampal atrophy and white matter hyperintensities.

Longitudinally, higher mean arterial pressure predicted increased automated white matter hyperintensities (P<0.002). Cross-sectionally, hypertensive participants had increased automated white matter hyperintensities and visually rated deep white matter hyperintensities. There was no significant association with global or hippocampal atrophy.

Long-term exposure to high blood pressure predicts hyperintensities, particularly in deep white matter. The greatest changes are seen in those with severe forms of hypertension, suggesting a dose–response pattern.