Depression occurs in people of all ages across all world regions; it is the second leading cause of disability and its global burden increased by 37.5% between 1990 and 2010. Autonomic changes are often found in altered mood states and appear to be a central biological substrate linking depression to a number of physical dysfunctions. Alterations of autonomic nervous system functioning that promotes vagal withdrawal are reflected in reductions of heart rate variability (HRV) indexes. Reduced HRV characterizes emotional dysregulation, decreased psychological flexibility and defective social engagement, which in turn are linked to prefrontal cortex hypoactivity. Altogether, these pieces of evidence support the idea that HRV might represent a useful endophenotype for psychological/physical comorbidities, and its routine application should be advised to assess the efficacy of prevention/intervention therapies in a number of psychosomatic and psychiatric dysfunctions. Further research, also making use of appropriate animal models, could provide a significant support to this point of view and possibly help to identify appropriate antidepressant therapies that do not interefere with physical health.
Psychological resilience can be defined as individual's ability to withstand and adapt to adverse and traumatic events. Resilience is traditionally assessed by subjective reports, a method that is susceptible to self-report bias. An ideal solution to this challenge is the introduction of standardised and validated physiological and/or biological predictors of resilience. We provide a summary of the major concepts in the field of resilience followed by a detailed critical review of the literature around physiological, neurochemical and immune markers of resilience. We conclude that in future experimental protocols, biological markers of resilience should be assesses both during baseline and during laboratory stressors. In the former case the most promising candidates are represented by heart rate variability and by in vitro immune cells assay; in the latter case-by startle responses (especially their habituation) during stress challenge and by cardiovascular recovery after stress, and by cortisol, DHEA and cytokine responses. Importantly, they should be used in combination to enhance predictive power.
Gamma aminobutyric acid (GABA) is the principal inhibitory neurotransmitter playing a key role in anxiety and depression disorders in mammals. Recent studies revealed that members of the gut microbiota are able to produce GABA modulating the gut-brain axis response. Among members of the human gut microbiota, bifidobacteria are well known to establish many metabolic and physiologic interactions with the host. In this study, we performed genome analyses of more than 1,000 bifidobacterial strains publicly available revealing that Bifidobacterium adolescentis taxon might represent a model GABA producer in human gastrointestinal tract. Moreover, the in silico screening of human/animal metagenomic datasets showed an intriguing association/correlation between B. adolescentis load and mental disorders such as depression and anxiety. Interestingly, in vitro screening of 82 B. adolescentis strains allowed identifying two high GABA producers, i.e. B. adolescentis PRL2019 and B. adolescentis HD17T2H, which were employed in an in vivo trial in rats. Feeding Groningen rats with a supplementation of B. adolescentis strains, confirmed the ability of these microorganisms to stimulate the in vivo production of GABA highlighting their potential implication in gut-brain axis interactions. Gamma-Aminobutyric acid (GABA) is a non-protein amino acid that is widely distributed in plants, animals and microorganisms 1,2. GABA is synthetized by a pyridocal-5′-phosphate (PLP)-dependent glutamate decarboxylase (GAD) enzyme by irreversible α-decarboxylation of l-glutamate and consummation of one cytoplasmic proton 1,2. GABA has several well-known physiological and psychological functions. Different studies highlighted that it is predominantly present in the brain where it acts as a major inhibitory neurotransmitter in the mammalian central nervous system (CNS) 1,2. Specifically, dysfunctions in GABA metabolism are involved in anxiety and depression 3-5. Furthermore, it is involved in the regulation of blood pressure and heart rate and plays a role in the perception of pain and anxiety 5,6. Other potential health benefits of GABA are control of growth hormone secretion, protection against glycerol-induced acute renal failure in rats and anti-proliferative activity 7. Recently, the term "psychobiotic" has been introduced to designate live bacterial strains, including lactobacilli and bifidobacteria, which are able to influence the CNS function 8. There are several compounds produced by these bacteria, such as proteins, peptides and components of cell wall that are potential mediators between bacteria and their hosts. Neurotransmitters, such as GABA, represent an example of neuroactive molecules
In humans, there are large individual differences in the levels of vagal modulation of resting heart rate (HR). High levels are a recognized index of cardiac health, whereas low levels are considered an important risk factor for cardiovascular morbidity and mortality. Several factors are thought to contribute significantly to this inter-individual variability. While regular physical exercise seems to induce an increase in resting vagal tone, chronic life stress, and psychosocial factors such as negative moods and personality traits appear associated with vagal withdrawal. Preclinical research has been attempting to clarify such relationships and to provide insights into the neurobiological mechanisms underlying vagal tone impairment/enhancement. This paper focuses on rat studies that have explored the effects of stress, psychosocial factors and physical exercise on vagal modulation of resting HR. Results are discussed with regard to: (i) individual differences in resting vagal tone, cardiac stress reactivity and arrhythmia vulnerability; (ii) elucidation of the neurobiological determinants of resting vagal tone.
The composition of the gut microbiota of mammals is greatly influenced by diet. Therefore, evaluation of different food ingredients that may promote changes in the gut microbiota composition is an attractive approach to treat microbiota disturbances. In this study, three dietary fibers, such as inulin (I, 10%), resistant starch (RS, 10%), and citrus pectin (3%), were employed as supplements to normal chow diet of adult male rats for 2 weeks. Fecal microbiota composition and corresponding metabolite profiles were assessed before and after prebiotics supplementation. A general increase in the Bacteroidetes phylum was detected with a concurrent reduction in Firmicutes, in particular for I and RS experiments, while additional changes in the microbiota composition were evident at lower taxonomic levels for all the three substrates. Such modifications in the microbiota composition were correlated with changes in metabolic profiles of animals, in particular changes in acetate and succinate levels. This study represents a first attempt to modulate selectively the abundance and/or metabolic activity of various members of the gut microbiota by means of dietary fiber.
Stressful life events are an important cause of psychopathology. Humans exposed to aversive or stressful experiences show considerable inter-individual heterogeneity in their responses. However, the majority does not develop stress-related psychiatric disorders. The dynamic processes encompassing positive and functional adaptation in the face of significant adversity have been broadly defined as resilience. Traditionally, the assessment of resilience has been confined to self-report measures, both within the general community and putative high-risk populations. Although this approach has value, it is highly susceptible to subjective bias and may not capture the dynamic nature of resilience, as underlying construct. Recognizing the obvious benefits of more objective measures of resilience, research in the field has just started investigating the predictive value of several potential biological markers. This review provides an overview of theoretical views and empirical evidence suggesting that individual differences in heart rate variability (HRV), a surrogate index of resting cardiac vagal outflow, may underlie different levels of resilience toward the development of stress-related psychiatric disorders. Following this line of thought, recent studies describing associations between regional brain morphometric characteristics and resting state vagally-mediated HRV are summarized. Existing studies suggest that the structural morphology of the anterior cingulated cortex (ACC), particularly its cortical thickness, is implicated in the expression of individual differences in HRV. These findings are discussed in light of emerging structural neuroimaging research, linking morphological characteristics of the ACC to psychological traits ascribed to a high-resilient profile and abnormal structural integrity of the ACC to the psychophysiological expression of stress-related mental health consequences. We conclude that a multidisciplinary approach integrating brain structural imaging with HRV monitoring could offer novel perspectives about brain-body pathways in resilience and adaptation to psychological stress.
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