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SignificanceAlcohol-dependent subjects frequently develop emotional symptoms that contribute to the persistence of alcohol drinking. These subjects are also characterized by gastrointestinal disturbances. In this study, we showed that alcohol-dependent subjects with altered intestinal permeability had also altered gut-microbiota composition and activity and remained with high scores of depression, anxiety, and alcohol craving after a short-term detoxification program. These results are consistent with the existence of a gut–brain axis in alcohol dependence, in which the gut microbiota could alter the gut-barrier function and influence behavior in alcohol dependence. Therefore, this study opens a previously unidentified field of research for the treatment and the management of alcohol dependence, targeting the gut microbiota. Alcohol dependence has traditionally been considered a brain disorder. Alteration in the composition of the gut microbiota has recently been shown to be present in psychiatric disorders, which suggests the possibility of gut-to-brain interactions in the development of alcohol dependence. The aim of the present study was to explore whether changes in gut permeability are linked to gut-microbiota composition and activity in alcohol-dependent subjects. We also investigated whether gut dysfunction is associated with the psychological symptoms of alcohol dependence. Finally, we tested the reversibility of the biological and behavioral parameters after a short-term detoxification program. We found that some, but not all, alcohol-dependent subjects developed gut leakiness, which was associated with higher scores of depression, anxiety, and alcohol craving after 3 wk of abstinence, which may be important psychological factors of relapse. Moreover, subjects with increased gut permeability also had altered composition and activity of the gut microbiota. These results suggest the existence of a gut–brain axis in alcohol dependence, which implicates the gut microbiota as an actor in the gut barrier and in behavioral disorders. Thus, the gut microbiota seems to be a previously unidentified target in the management of alcohol dependence.

The gut-brain communication is mostly driven by the immune, metabolic and neural pathways which remained poorly explored in patients with alcohol use disorder (AUD). The metabolites arising from the tryptophan-kynurenine pathway have gained considerable attention since they are at the interface between intestinal bacteria, host immune response and brain functions. This study described the circulating levels of kynurenine metabolites in AUD patients, at the onset (T1) and end (T2) of a 3-week detoxification program, and tested correlations between those metabolites and inflammatory markers, the gut microbiota and the psychological symptoms. Increased concentration of the neurotoxic metabolite quinolinic acid (QUIN) and decreased levels of the neuroprotector metabolite kynurenic acid (KYNA) which both modulate glutamatergic neurotransmission were observed in AUD patients, particularly at T2. The inflammatory marker hsCRP was associated with several metabolic ratios of the kynurenine pathway. Tryptophan, KYNA and QUIN were correlated with depression, alcohol craving and reaction time, respectively. Analysis of gut microbiota revealed that bacteria known as short-chain fatty acid producers, as well as bacterial metabolites including butyrate and medium-chain fatty acids were associated with some metabolites of the tryptophan-kynurenine pathway. Targeting the glutamatergic neurotransmission through the modulation of the kynurenine pathway, by manipulating the gut microbiota, might represent an interesting alternative for modulating alcohol-related behavior.

Probiotics have been used to treat a variety of diseases for decades; however, what is the rationale for their application? Such a treatment was first proposed in the early nineteenth century based on observations of decreased bifidobacterial populations in children suffering from diarrhea, suggesting that oral intake of bifidobacteria could replete this subpopulation of the microbiota and improve health. Since then, studies have shown modifications in the gut or skin microbiota in the course of a variety of diseases and suggested positive effects of certain probiotics. Most studies failed to report any impact on the microbiota. The impact of probiotics as well as of bacteria colonizing food does not reside in their ability to graft in the microbiota but rather in sharing genes and metabolites, supporting challenged microbiota, and directly influencing epithelial and immune cells. Such observations argue that probiotics could be associated with conventional drugs for insulin resistance, infectious diseases, inflammatory diseases, and psychiatric disorders and could also interfere with drug metabolism. Nevertheless, in the context of a plethora of probiotic strains and associations produced in conditions that do not allow direct comparisons, it remains difficult to know whether a patient would benefit from taking a particular probiotic. In other words, although several mechanisms are observed when studying a single probiotic strain, not all individual strains are expected to share the same effects. To clarify the role of probiotics in the clinic, we explored the relation between probiotics and the gut and skin microbiota.

Background Anxiety and depression are psychopathological states frequently co‐occurring with severe alcohol use disorder (SAUD). These symptoms generally disappear with abstinence but may persist in some patients, increasing the relapse risk. Methods The cerebral cortex thickness of 94 male patients with SAUD was correlated with symptoms of depression and anxiety, both measured at the end (2–3 weeks) of the detoxification treatment. Cortical measures were obtained using surface‐based morphometry implemented with Freesurfer. Results Depressive symptoms were associated with reduced cortical thickness in the superior temporal gyrus of the right hemisphere. Anxiety level was correlated with lower cortical thickness in the rostral middle frontal region, inferior temporal region, and supramarginal, postcentral, superior temporal, and transverse temporal regions of the left hemisphere, as well as with a large cluster in the middle temporal region of the right hemisphere. Conclusions At the end of the detoxification stage, the intensity of depressive and anxiety symptoms is inversely associated with the cortical thickness of regions involved in emotions‐related processes, and the persistence of the symptoms could be explained by these brain deficits. At the end of the detoxification stage in men with severe alcohol use disorders, the intensity of depressive and anxiety symptoms is inversely associated with the cortical thickness of regions involved in emotions‐related processes, and the persistence of the symptoms despite of alcohol cessation could be explained by these brain deficits.

Background: Antipsychotic polypharmacy (APP) prescribing and clozapine underuse are considered inappropriate prescribing in schizophrenia. Psychiatric hospitalisations may be suitable occasions to re-evaluate patient pharmacotherapy and to switch to monotherapy. Objectives: To explore the evolution of APP and other psychotropic prescribing patterns during psychiatric hospitalisations, to detect characteristics associated with APP on admission and at discharge, and to examine clozapine prescribing patterns. Design: We performed a retrospective observational study based on electronic health records. Methods: Data on adult inpatients diagnosed with schizophrenia spectrum disorders were collected retrospectively from 6 Belgian hospitals in 2020-2021. Results: Of the 516 patients included, APP prescribing increased significantly from 47.9% on hospital admission to 59.1% at discharge. On admission and at discharge, APP was associated with prior clozapine use (ORadmission = 2.53, CI = 1.1–5.84, ORdischarge = 11.01, CI = 4.45–27.28), treatment with a first-generation antipsychotic (ORadmission = 26.79, CI = 13.08–54.86, ORdischarge = 25.2, CI = 12.2–52.04), increased antipsychotic exposure (ORadmission = 8.93, CI = 5.13–15.56, ORdischarge = 19.89, CI = 10–39.54), and a greater number of hypno-sedatives (ORadmission = 1.88, CI = 1.23–2.88, ORdischarge = 4.18, CI = 2.53–6.91). APP was negatively associated with involuntary admission (ORadmission = 0.31, CI = 0.14–0.7, ORdischarge = 0.3, CI = 0.13–0.68). When using an alternative definition of monotherapy (i.e. including patients with an add-on low-dose antipsychotic for sleep disorders), alcohol use disorder (ORadmission = 0.26, CI = 0.13–0.54) and higher age (ORdischarge = 0.53, CI = 0.29–0.95) were negatively associated with APP, and living in a residential facility (ORdischarge = 2.39 CI = 1.21–4.71) and a higher daily dosage of benzodiazepines during the stay (ORdischarge = 1.32 CI = 1.03–1.69) increased the odds of being discharged on APP. On admission, 9.3% of patients were being treated with clozapine. Although 28.1% of patients were eligible for clozapine treatment, only 11% of patients were discharged with a clozapine prescription. For 7 of the 10 patients with a new clozapine prescription, it was directly prescribed in combination with another antipsychotic, without a prior trial of clozapine monotherapy. Conclusion: Suboptimal prescriptions of antipsychotics in patients with schizophrenia persist after psychiatric hospitalisations and are associated with identifiable characteristics.

•Neural source of motor preparatory suppression remains largely unknown.•Extent of preparatory suppression was related to structural brain measures.•Thinner medial prefrontal cortex was related to weaker preparatory suppression.•Motor excitability appears as a valuable read-out of upstream cognitive processes. Inhibitory control underlies the ability to inhibit inappropriate responses and involves processes that suppress motor excitability. Such motor modulatory effect has been largely described during action preparation but very little is known about the neural circuit responsible for its implementation. Here, we addressed this point by studying the degree to which the extent of preparatory suppression relates to brain morphometry. We investigated this relationship in patients suffering from severe alcohol use disorder (AUD) because this population displays an inconsistent level of preparatory suppression and major structural brain damage, making it a suitable sample to measure such link. To do so, 45 detoxified patients underwent a structural magnetic resonance imaging (MRI) and performed a transcranial magnetic stimulation (TMS) experiment, in which the degree of preparatory suppression was quantified. Besides, behavioral inhibition and trait impulsivity were evaluated in all participants. Overall, whole-brain analyses revealed that a weaker preparatory suppression was associated with a decrease in cortical thickness of a medial prefrontal cluster, encompassing parts of the anterior cingulate cortex and superior-frontal gyrus. In addition, a negative association was observed between the thickness of the supplementary area (SMA)/pre-SMA and behavioral inhibition abilities. Finally, we did not find any significant correlation between preparatory suppression, behavioral inhibition and trait impulsivity, indicating that they represent different facets of inhibitory control. Altogether, the current study provides important insight on the neural regions underlying preparatory suppression and allows highlighting that the excitability of the motor system represents a valuable read-out of upstream cognitive processes.

The aim of the study was to assess drug adherence, as well as association of psychological factors with both drug adherence and severity of hypertension in two subtypes of patients with apparently treatment‐resistant hypertension (ATRH): younger patients with uncomplicated hypertension (YURHTN) versus patients ≥60‐year‐old and/or with a history of cardio‐ or cerebrovascular complication (OCRHTN). Drug adherence was assessed in urine by targeted Liquid Chromatography‐Mass Spectrometry. The severity of hypertension was assessed by 24‐h ambulatory blood pressure adjusted for the number of antihypertensive drugs and for drug adherence. Psychological profile was assessed using five validated questionnaires. The proportion of totally non‐adherent patients was three times higher (24.1 vs. 7.1%, P = 0.026) in the YURHTN (n = 54) than in OCRHTN subgroup (n = 43). Independent predictors of drug adherence in YURHTN were ability to use adaptive strategies, male sex and family history of hypertension, accounting for 39% of variability in drug adherence. In the same subgroup, independent predictors of severity of hypertension were somatization and lower recourse to planification, accounting for 40% of variability in the severity of hypertension. In contrast, in the OCRHTN subgroup, independent predictors of drug adherence and severity of hypertension were limited to the number of yearly admissions to the emergency room and the total number of prescribed drugs. In conclusion, poor drug adherence and altered psychological profiles appear to play a major role in younger patients with ATRH devoid of cardiovascular complication. This subgroup should be prioritized for chemical detection of drug adherence and psychological evaluation.

Metadehumanization, the perception of being treated as less than a human by others, is a pervasive phenomenon in intergroup relations. It is dissociated from stigmatization or stereotypes, and it has been recently identified as a critical process in severe alcohol use disorders (SAUD). Metadehumanization is associated with a wide array of negative consequences for the victim, including negative emotions, aversive self-awareness, cognitive deconstruction, and psychosomatic strains, which are related to anxiety and depression. This study aims to investigate if metadehumanization occurring among patients with SAUD is associated with clinical factors involved in the maintence of the disease, mely symptoms of depression or anxiety and drinking refusal self-efficacy. A cross-sectiol study was conducted among 120 patients with SAUD. Self-reported questionires measured metadehumanization, self-dehumanization (i.e., the feeling of being less than a human), anxiety, depression, drinking refusal self-efficacy, and demographics. Metadehumanization was significantly associated with self-dehumanization, anxiety, depression, and drinking refusal self-efficacy. Additiolly, path alyses showed that self-dehumanization mediated the links between metadehumanization and clinical variables. These results indicate that metadehumanization and self-dehumanization could be essential factors to consider during SAUD treatment, as they are associated with increased psychiatric symptoms and reduced drinking refusal self-efficacy.

In this longitudinal study, 37 patients with severe alcohol use disorder (SAUD) were tested at the beginning (T1) and end (T2) of supervised detoxification to explore the evolution of and relationship between systemic inflammation, volumetric changes for brain grey matter (GM) and choroid plexus (ChP), and clinical symptoms. At T1, patients exhibited high levels of anxiety, depression, and craving, and had elevated plasmatic pro-inflammatory cytokines, indicating low-grade systemic inflammation. Monocyte chemoattractant protein-1 (CCL2) (MCP-1) levels correlated positively with ChP volume and severity of withdrawal symptoms, while macrophage inflammatory protein-1 beta (CCL4) (MIP-1β) also correlated with ChP volume, together suggesting an acute immune response at T1, and underscoring the ChP as a potential neuroimmune biomarker to be further evaluated in future studies. During three weeks’ abstinence, Interleukin-8 (IL-8), MIP-1β, and MCP-1 levels decreased, although MIP-1β did not return to control levels, and tumor necrosis factor-alpha (TNF-α) showed no significant reduction. Volumetric MRI analyses suggested two concurrent trajectories during detoxification. First, an overall “recovery-driven” pattern of rapidly increasing GM volume in widespread forebrain regions with parallel declines in ventricle size and craving. Second, GM in limbic cortical areas, temporal and inferior frontal cortex showed no significant volumetric gain. However, these regional volumes correlated significantly with declining MCP-1, indicative of a “deflation”, potentially related to declining microglial activation. These findings highlight the role of inflammatory processes in shaping early neuroplastic changes during detoxification and point to a central role of MCP-1 in inflammation-driven morphometric changes.