Psychiatry - Journal Articles
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Item A biological framework for emotional dysregulation in alcohol misuse: from gut to brain(Springer Nature Ltd., 2020-12-07) Carbia, Carina; Lannoy, Séverine; Maurage, Pierre; López-Caneda, Eduardo; O'Riordan, Kenneth J.; Dinan, Timothy G.; Cryan, John F.; Horizon 2020; Belgian American Educational Foundation; Fonds De La Recherche Scientifique - FNRS; Fundação para a Ciência e a TecnologiaAlcohol use disorder (AUD) has been associated with impairments in social and emotional cognition that play a crucial role in the development and maintenance of addiction. Repeated alcohol intoxications trigger inflammatory processes and sensitise the immune system. In addition, emerging data point to perturbations in the gut microbiome as a key regulator of the inflammatory cascade in AUD. Inflammation and social cognition are potent modulators of one another. At the same time, accumulating evidence implicates the gut microbiome in shaping emotional and social cognition, suggesting the possibility of a common underlying loop of crucial importance for addiction. Here we propose an integrative microbiome neuro-immuno-affective framework of how emotional dysregulation and alcohol-related microbiome dysbiosis could accelerate the cycle of addiction. We outline the overlapping effects of chronic alcohol use, inflammation and microbiome alterations on the fronto-limbic circuitry as a convergence hub for emotional dysregulation. We discuss the interdependent relationship of social cognition, immunity and the microbiome in relation to alcohol misuse- from binge drinking to addiction. In addition, we emphasise adolescence as a sensitive period for the confluence of alcohol harmful effects and emotional dysregulation in the developing gut-brain axis.Item Stress during puberty exerts sex-specific effects on depressive-like behavior and monoamine neurotransmitters in adolescence and adulthood(Elsevier Inc., 2022-10-07) Harris, Erin P.; Villalobos-Manriquez, Francisca; Melo, Thieza G.; Clarke, Gerard; O'Leary, Olivia F.; Health Research Board; Science Foundation IrelandPsychiatric disorders including major depression are twice as prevalent in women compared to men. This sex difference in prevalence only emerges after the onset of puberty, suggesting that puberty may be a sensitive period during which sex-associated vulnerability to stress-related depression might become established. Thus, this study investigated whether stress occurring specifically during the pubertal window of adolescence may be responsible for this sex difference in depression vulnerability. Male and female rats were exposed to a three-day stress protocol during puberty (postnatal days 35–37 in females, 45–47 in males) and underwent behavioral tests in adolescence or adulthood measuring anhedonia, anxiety-like behavior, locomotor activity and antidepressant-like behavior. Brainstem and striatum tissue were collected from a separate cohort of behavioral test-naïve rats in adolescence or adulthood to quantify the effect of pubertal stress on monoamine neurotransmitters. Pubertal stress increased immobility behavior in the forced swim test in both sexes in adolescence and adulthood. In adolescence, pubertal stress altered escape-oriented behaviors in a sex-specific manner: decreasing climbing in males but not females and decreasing swimming in females but not males. Pubertal stress decreased adolescent brainstem noradrenaline specifically in females and had opposing effects in adolescent males and females on brainstem serotonin turnover. Pubertal stress induced anhedonia in the saccharin preference test in adult males but not females, an effect paralleled by a male-specific decrease in striatal dopamine turnover. Pubertal stress did not significantly impact anxiety-like behavior or locomotor activity in any sex at either age. Taken together, these data suggest that although pubertal stress did not preferentially increase female vulnerability to depressive-like behaviors compared to males, stress during puberty exerts sex-specific effects on depressive-like behavior and anhedonia, possibly through discrete neurotransmitter systems.Item Enduring neurobehavioral effects induced by microbiota depletion during the adolescent period(Springer, 2020-11) Lach, Gilliard; Fulling, Christine; Bastiaanssen, Thomaz F. S.; Fouhy, Fiona; O'Donovan, Aoife; Ventura-Silva, Ana Paula; Stanton, Catherine; Dinan, Timothy G.; Cryan, John F.; Science Foundation IrelandThe gut microbiota is an essential regulator of many aspects of host physiology. Disruption of gut microbial communities affects gut-brain communication which ultimately can manifest as changes in brain function and behaviour. Transient changes in gut microbial composition can be induced by various intrinsic and extrinsic factors, however, it is possible that enduring shifts in the microbiota composition can be achieved by perturbation at a timepoint when the gut microbiota has not fully matured or is generally unstable, such as during early life or ageing. In this study, we investigated the effects of 3-week microbiota depletion with antibiotic treatment during the adolescent period and in adulthood. Following a washout period to restore the gut microbiota, behavioural and molecular hallmarks of gut-brain communication were investigated. Our data revealed that transient microbiota depletion had long-lasting effects on microbiota composition and increased anxiety-like behaviour in mice exposed to antibiotic treatment during adolescence but not in adulthood. Similarly, gene expression in the amygdala was more severely affected in mice treated during adolescence. Taken together these data highlight the vulnerability of the gut microbiota during the critical adolescent period and the long-lasting impact manipulations of the microbiota can have on gene expression and behaviour in adulthood.Item High and Mighty? Cannabinoids and the microbiome in pain(Elsevier B. V., 2021-01) Rea, Kieran; O'Mahony, Siobhain M.; Cryan, John F.Within the human gut, we each harbour a unique ecosystem represented by trillions of microbes that contribute to our health and wellbeing. These gut microbiota form part of a complex network termed the microbiota-gut-brain axis along with the enteric nervous system, sympathetic and parasympathetic divisions of the autonomic nervous system, and neuroendocrine and neuroimmune components of the central nervous system. Through endocrine, immune and neuropeptide/neurotransmitter systems, the microbiota can relay information about health status of the gut. This in turn can profoundly impact neuronal signalling not only in the periphery, but also in the brain itself and thus impact on emotional systems and behavioural responses. This may be true for pain, as the top-down facilitation or inhibition of pain processing occurs at a central level, while ascending afferent nociceptive information from the viscera and systemic areas travel through the periphery and spinal cord to the brain. The endogenous cannabinoid receptors are ubiquitously expressed throughout the gut, periphery and in brain regions associated with pain responding, and represent targets for endogenous and exogenous manipulation. In this review, we will focus on the potential role of the endogenous cannabinoids in modulating microbiota-driven changes in peripheral and central pain processing. We also focus on the overlap in mechanisms whereby commensal gut microbiota and endocannabinoid ligands can regulate inflammation and further aim to exploit our understanding of their role in microbiota-gut-brain axis communication in pain processing.Item Acute stress increases monocyte levels and modulates receptor expression in healthy females(Elsevier, 2021-05) van de Wouw, Marcel; Sichetti, Marzia; Long-Smith, Caitriona M.; Ritz, Nathaniel L.; Moloney, Gerard M.; Cusack, Anne-Marie; Berding, Kirsten; Dinan, Timothy G.; Cryan, John F.; Seventh Framework Programme; Science Foundation IrelandThere has been a growing recognition of the involvement of the immune system in stress-related disorders. Acute stress leads to the activation of neuroendocrine systems, which in turn orchestrate a large-scale redistribution of innate immune cells, such as monocytes. Even though acute stress/monocyte interactions have been wellcharacterized in mice, this is not the case for humans. As such, this study aimed to investigate whether acute stress modulates blood monocyte levels in a subtype-dependent manner and whether the receptor expression of stress-related receptors is affected in humans. Blood was collected from healthy female volunteers at baseline and 1 h after the socially evaluated cold pressor test, after which blood monocyte levels and receptor expression were assessed by flow cytometry. Our results reveal a stress-induced increase in blood monocyte levels, which was independent of monocyte subtypes. Furthermore, colony stimulating factor 1 receptor (CSF-1R) and CD29 receptor expression was increased, while CD62L showed a trend towards increased expression. These results provide novel insights into how acute stress affects the innate immune system.