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Microbiota might be considered as a pool for environmental epigenetic factors. Evidence is accumulating that environmental exposures – including microbes, diet, drugs – play a role in the pathogenesis of many neuropsychiatric disorders. Underlying mechanisms are complex, involving the sensitive interplay of genetics with epigenetics, neuroinflammation and the innate immune system. Modifications of microbiota affect neurogenesis and the maturation of microglia, influencing social behavior, stress-related responses and fear learning mechanisms. The excitatory neurons in the medial prefrontal cortex appear to play a key role. The mechanisms through which antibiotics administration may modulate microbiota and, therefore, behavior and neuropsychiatric disorders, may be influenced by several variables such as pre-existing gastrointestinal inflammation, the baseline microbiota composition, diet and stress perception. Probiotics, individualized diet, antibiotics and fecal transplantation could positively modulate the effects of epigenetic factors on neuropsychiatric disorders.

Background the possible relationship between dietary habits and the incidence of late-onset depression (LOD), defined as first depression onset at later age, is unclear. Objective to investigate the relationship between consumption of different food groups and incident LOD. Design longitudinal population-based study with a 12-year follow-up. Setting Castellana Grotte, Bari, Italy. Subjects five hundred and forty-six older subjects from the Salus in Apulia Study. Methods baseline data were recorded in 2003–06, and diagnostic data were recorded in 2013–18 at follow-up. Dietary intake was assessed with a food frequency questionnaire. Depressive disorders were assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders. Subjects who already suffered from depression or other psychiatric disorders at baseline were excluded from the analysis. The association between LOD and single dietary determinants was examined by Cox regression analysis and then applying the hazard ratio (HR). Results subjects with incident LOD (n = 34) had lower global cognition and total cholesterol levels and a higher body mass index (BMI) at baseline. Only processed meat significantly increased the risk of incident LOD of about 10% by 5 g/day intake (HR adjusted for age, sex, education, multimorbidity and BMI: 1.13, 95% confidence intervals: 1.04–1.22). A similar relationship was found for single foods in the processed meat food group such as sausages, salami and mortadella and baked ham, but not for raw ham. Conclusions in midlife, a higher intake of processed meat was not only associated with an increased risk of cardiovascular- and metabolic-related chronic diseases in older age but also with an increased risk of developing LOD.

The association between late-life depression (LLD) and age-related hearing loss (ARHL) was suggested by preliminary studies, but reliance on LLD subtypes may introduce significant bias. We examined the association between ARHL and LLD according to the age of onset (early-onset depression (EOD) and late-onset depression (LOD)). We investigated the association between ARHL and LLD diagnosed according to the Semi-structured Clinical Diagnostic Interview for DSM-IV-TR in 1749 Italian community-dwelling older subjects from the population-based GreatAGE Study, Southern Italy. Peripheral ARHL was assessed as a pure tone average (PTA) threshold > 40 dB hearing level in the better ear- and age-related CAPD as a score of

The amyloid hypothesis of Alzheimer's disease (AD) affirms that brain accumulation of amyloid-β (Aβ) oligomers and soluble aggregates represent the major pathological event of the disease. Several anti-Aβ small organic molecules, monoclonal antibodies and antigens were developed to interfere with Aβ production and clearance, including β-site amyloid precursor protein cleaving enzyme (BACE) inhibitors, blocking the first enzymatic step of Aβ formation. All these approaches, including BACE inhibitors, have failed in large randomized clinical trials (RCTs) in mild-to-moderate AD, but further studies are now being carried out in patients at early AD stages and in asymptomatic subjects at risk of developing AD. Areas covered: The paper provides a comprehensive review of BACE inhibitors for AD treatment, focusing on the most advanced compounds in Phase III RCTs. Expert commentary: BACE inhibitors inhibited robustly, and dose-dependently, Aβ formation in cerebrospinal fluid of AD patients, but without cognitive, clinical, or functional benefit in large RCTs. BACE inhibition may be not sufficient to decrease brain Aβ plaques and aggregates. Indeed, several BACE inhibitors were found to be poorly tolerated and some of them failed also in patients with prodromal AD. This may indicate that blocking the formation of nascent Aβ is not useful in AD.

OBJECTIVE: Previous studies have suggested that genetic factors, personality traits and coping strategies might play both independent and interacting roles when influencing stress-related anxiety symptoms. The aim of this study was to examine whether Neuroticism and maladaptive coping strategies mediate the association between the serotonin transporter gene-linked polymorphic region (5HTT-LPR) and symptoms of anxiety and depression in elite athletes who experience high levels of competitive stress. METHOD: One hundred and thirty-three participants were genotyped for the 5-HTTLPR polymorphism and then asked to complete the Cope Orientation to Problems Experienced Inventory and the NEO Five-Factor Inventory. A path analysis was used to test this hypothesis. RESULTS: The 5HTT-LPR was significantly associated with Neuroticism, the coping strategy of Focus on and Venting of Emotions’ (FVE) and symptoms of anxiety. FVE and Neuroticism mediated the association between the 5HTT-LPR and symptoms of anxiety (i.e., Cognitive Anxiety and Emotional Arousal Control). Also, Neuroticism was a mediator of the association between the 5HTT-LPR and FVE. Finally, FVE also mediated effects on the relationship between Neuroticism and symptoms of anxiety. CONCLUSIONS: The 5HTT-LPR may affect the susceptibility to develop symptoms of anxiety in elite athletes indirectly through mediation by maladaptive coping strategies and Neuroticism.