Eating disorders are evolutionarily novel conditions that lead to some of the highest mortality rates of all psychiatric disorders. Several evolutionary hypotheses have been proposed for eating disorders, but only the intrasexual competition hypothesis is extensively supported by evidence. We present the mismatch hypothesis as a necessary extension to the current theoretical framework of eating disorders. This hypothesis explains the evolutionarily novel adaptive metaproblem that has arisen when mating motives and readily available food rewards conflict with one another. This situation (...) is exacerbated in contemporary environments characterized by sedentary lifestyles, caloric surplus and the ubiquity of social comparisons that take place via social media. Our psychoneuroimmunological model connects ultimate-level causation with proximate mechanisms by showing how the adaptive metaproblem between mating motives and food rewards leads to chronic stress and, further, to disordered eating. Chronic stress causes neuroinflammation, which increases susceptibility to OCD-like behaviors that typically co-occur with eating disorders. Chronic stress upregulates the serotonergic system and causes dysphoric mood in patients with restricting-type anorexia nervosa. Dieting, however, reduces serotonin levels and dysphoric mood, leading to a vicious serotonergic-homeostatic stress/starvation cycle whereby cortisol and neuroinflammation increase through stringent dieting. Between-individual and within-individual variation in eating disorders partially arises from (co)variation in gut microbiota and stress responsivity, which influence neuroinflammation and the serotonergic system. In binge-related eating disorders, even a short period of fasting drops serotonin levels, a state alleviated by binge eating. Eating disorder treatments should aim to reduce the chronic stress, neuroinflammation, stress responsivity and gut dysbiosis that fuel the disorders. We review the advances that have been made in recent years in understanding how to best treat eating disorders, outlining directions for future clinical research. Connecting ultimate causes with proximate mechanisms and treating biopsychosocial causes rather than manifest symptoms will enable more effective and sophisticated long-term interventions for the millions of people who suffer from eating disorders. (shrink)

The World Health Organisation recently listed air pollution as the most significant threat to human health. Air pollution comprises particulate matter (PM), metals, black carbon and gases such as ozone (O3), nitrogen dioxide (NO2) and carbon monoxide (CO). In addition to respiratory and cardiovascular disease, PM exposure is linked with increased risk of neurodegeneration as well as neurodevelopmental impairments. Critically, studies suggest that PM crosses the placenta, making direct in utero exposure a reality. Rodent models reveal that neuroinflammation, neurotransmitter (...) imbalance and oxidative stress are triggered following gestational/early life exposure to PM, and may be exacerbated by concomitant mitochondrial dysfunction. Gestational PM exposure (potentiated by mitochondrial impairment in the metabolically active neonatal brain) not only impacts neurodevelopment but may sensitise the brain to subsequent cognitive impairment. Having reviewed this field, we conclude that strategies are urgently required to reduce exposure to PM during this sensitive developmental period. (shrink)

Major depressive disorder (MDD) is a severe mental illness that affects 5 to 20% of the general population. Current antidepressant drugs exerts only a partial clinical efficacy because approximately 30% of depressed patients failed to respond to these drugs and antidepressants produce remission only in 30% of patients. This can be explained by the fact that the complex pathophysiology of depression has not been completely elucidated, and treatments have been mainly developed following the “monoaminergic hypothesis” of depression without considering the (...) key role of other factors involved in the pathogenesis of MDD, such as the role of chronic stress and neuroinflammation. Chronic stress acts as a risk factor for the development of MDD through the impairment of neurotrophins signaling such as brain-derived neurotrophic factor (BDNF) and transforming-growth-factor-β1 (TGF-β1). Stress-induced depressive pathology contributes to altered BDNF level and function in MDD patients and, thereby, an impairment of neuroplasticity at the regional and circuit level. Recent studies demonstrate that aerobic exercise strongly increases BDNF production and it may contribute as a non-pharmacological strategy to improve the treatment of cognitive and affective symptoms in MDD. Here we will provide a general overview on the possible synergism between physical activity and antidepressants in MDD. Physical activity can synergize with antidepressant treatment by rescuing neurotrophin signaling in MDD patients, promoting neuronal health and recovery of function in MDD-related circuits, finally enhancing pharmacotherapeutic response. This synergism might be particularly relevant in elderly patients with late-life depression, a clinical subgroup with an increased risk to develop dementia. (shrink)

The Western diet pattern characterized by high daily intake of saturated fats and refined carbohydrates often leads to obesity and overweight, and it has been linked to cognitive impairment and emotional disorders in both animal models and humans. This dietary pattern alters the composition of gut microbiota, influencing brain function by different mechanisms involving the gut–brain axis. In addition, long-term exposure to highly palatable foods typical of WD could induce addictive-like eating behaviors and hypothalamic-pituitary-adrenal axis dysregulation associated with chronic stress, (...) anxiety, and depression. In turn, chronic stress modulates eating behavior, and it could have detrimental effects on different brain regions such as the hippocampus, hypothalamus, amygdala, and several cortical regions. Moreover, obesity and overweight induce neuroinflammation, causing neuronal dysfunction. In this review, we summarize the current scientific evidence about the mechanisms and factors relating WD consumption with altered brain function and behavior. Possible therapeutic interventions and limitations are also discussed, aiming to tackle and prevent this current pandemic. (shrink)

Cognitive dysfunction in Alzheimer’s disease is caused by disturbances in neuronal circuits of the brain underpinned by synapse loss, neuronal dysfunction and neuronal death. Amyloid beta and tau protein cause these pathological changes and enhance neuroinflammation, which in turn modifies disease progression and severity. Vagal nerve stimulation, via activation of the locus coeruleus, results in the release of catecholamines in the hippocampus and neocortex, which can enhance synaptic plasticity and reduce inflammatory signalling. Vagal nerve stimulation has shown promise to (...) enhance cognitive ability in animal models. Research in rodents has shown that VNS can have positive effects on basal synaptic function and synaptic plasticity, tune inflammatory signalling, and limit the accumulation of amyloid plaques. Research in humans with invasive and non-invasive VNS devices has shown promise for the modulation of cognition. However, the direct stimulation of the vagus nerve afforded with the invasive procedure carries surgical risks. In contrast, non-invasive VNS has the potential to be a broadly available therapy to manage cognitive symptoms in early AD, however, the magnitude and specificity of its effects remains to be elucidated, and the non-inferiority of the effects of non-invasive VNS as compared with invasive VNS still needs to be established. Ongoing clinical trials with healthy individuals and patients with early AD will provide valuable information to clarify the potential benefits of non-invasive VNS in cognition and AD. Whether invasive or non-invasive VNS can produce a significant improvement on memory function and whether its effects can modify the progression of AD will require further investigation. (shrink)