The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=−0.14, % difference=−1.24). This effect was driven by patients with recurrent MDD (Cohen's d=−0.17, % difference=−1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=−0.20, % difference=−1.85) and a trend toward smaller amygdala (Cohen's d=−0.11, % difference=−1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

These data suggest that a possible mechanism of action of EN in inducing disease remission in CD is the capacity of modification of gut microflora. Possible explanations of such capacity are both low residue and prebiotic properties of the polymeric liquid formula.

Cow’s milk proteins cause allergic symptoms in 2% to 3% of all infants. In these individuals, the physiological mechanism of tolerance is broken with subsequent possible sensitization to antigens, which can lead eventually to allergic responses. The present review aims to provide an overview of different aspects of immune modulation by dietary intervention in cow’s milk allergy (CMA). It focuses on pathogenetic mechanisms of different CMA related disorders, e.g., gastroesophageal reflux and eosinophilic esophagitis, highlighting the role of dietary management on innate and adaptive immune systems. The traditional dietary management of CMA has greatly changed in the last years, moving from a passive approach, consisting of an elimination diet to relieve symptoms, to a “proactive” one, meaning the possibility to actively modulate the immune system. Thus, new insights into the role of hydrolysates and baked milk in immunomodulation are addressed here. Additionally, nutritional components, such as pre- and probiotics, may target the immune system via microbiota, offering a possible road map for new CMA prevention and treatment strategies.

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Word Count: 247 Full Text Word Count: 5192 Figures: 3 Tables: 1 Supplement: 1Abstract Alterations in regional subcortical brain volumes have been widely investigated as part of the efforts of an international consortium, ENIGMA, to determine reliable structural brain signatures for Major Depressive Disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work to precisely map localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus.Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with MDD had lower surface area in the subiculum of the hippocampus, the basolateral amygdala, and the nucleus accumbens shell. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum of the hippocampus and the basolateral amygdala. Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala.Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.

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doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.