Microbial transmission in the social microbiome and host health and disease.

Although social interactions are known to drive pathogen transmission, the contributions of socially transmissible host-associated mutualists and commensals to host health and disease remain poorly explored. We use the concept of the social microbiome-the microbial metacommunity of a social network of hosts-to analyze the implications of social microbial transmission for host health and disease. We investigate the contributions of socially transmissible microbes to both eco-evolutionary microbiome community processes (colonization resistance, the evolution of virulence, and reactions to ecological disturbance) and microbial transmission-based processes (transmission of microbes with metabolic and immune effects, inter-specific transmission, transmission of antibiotic-resistant microbes, and transmission of viruses). We consider the implications of social microbial transmission for communicable and non-communicable diseases and evaluate the importance of a socially transmissible component underlying canonically non-communicable diseases. The social transmission of mutualists and commensals may play a significant, under-appreciated role in the social determinants of health and may act as a hidden force in social evolution.

Implementing digital mental health interventions at scale: one-year evaluation of a national digital CBT service in Ireland.

BACKGROUND: In recent years, exponential growth in digital innovations and internet access has provided opportunities to deliver health services at a much greater scale than previously possible. Evidence-based technology-enabled interventions can provide cost-effective, accessible, and resource-efficient solutions for addressing mental health issues. This study evaluated the first year of a supported digital cognitive behavioral therapy (CBT) service provided by the national health service in Ireland, which has been accessible to individuals who receive a referral from one of five referring groups: General Practitioners, Primary Care Psychology, Counselling Primary Care, Community Mental Health, and Jigsaw (a nationwide youth mental health service). METHODS: A retrospective, observational study examining data from the service between April 2021 to April 2022 was conducted. Descriptive statistics on referrals, account activations, user demographics, program usage, and user satisfaction were extracted, and pre-to-post clinical outcomes for depression measured by the Patient Health Questionnaire-9 and for anxiety measured by the Generalised Anxiety Disorder-7 were analysed using linear mixed effect models. RESULTS: There were 5,298 referrals and 3,236 (61%) account activations within the year. Most users were female (72.9%) and aged between 18 and 44 years (75.4%). The CBT programs were associated with significant reductions in both depression (ß = 3.34, 95% CI [3.03, 3.65], p < 0.001) and anxiety (ß = 3.64, 95% CI [3.36, 3.93], p < 0.001), with large effect sizes (Cohen's d > 0.8). Time spent using the programs was also found to be a predictor of the variability in these clinical outcomes (p < 0.001), and accounting for this resulted in significantly better model fits (p < 0.001). User satisfaction ratings were also very high, exceeding 94%. CONCLUSIONS: Efforts to improve the representation of male and older adult users are warranted. However, overall, the results demonstrate how digital CBT can be provided at scale and lead to symptom reductions with large effect sizes for patients seeking help for depression and anxiety. The findings substantiate the continued use and expansion of this service in Ireland and the more widespread implementation of similar services in other international public healthcare settings.

An observational treatment study of metacognition in anxious-depression.

Prior studies have found metacognitive biases are linked to a transdiagnostic dimension of anxious-depression, manifesting as reduced confidence in performance. However, previous work has been cross-sectional and so it is unclear if under-confidence is a trait-like marker of anxious-depression vulnerability, or if it resolves when anxious-depression improves. Data were collected as part of a large-scale transdiagnostic, four-week observational study of individuals initiating internet-based cognitive behavioural therapy (iCBT) or antidepressant medication. Self-reported clinical questionnaires and perceptual task performance were gathered to assess anxious-depression and metacognitive bias at baseline and 4-week follow-up. Primary analyses were conducted for individuals who received iCBT (n=649), with comparisons between smaller samples that received antidepressant medication (n=82) and a control group receiving no intervention (n=88). Prior to receiving treatment, anxious-depression severity was associated with under-confidence in performance in the iCBT arm, replicating previous work. From baseline to follow-up, levels of anxious-depression were significantly reduced, and this was accompanied by a significant increase in metacognitive confidence in the iCBT arm (ß=0.17, SE=0.02, p<0.001). These changes were correlated (r(647)=-0.12, p=0.002); those with the greatest reductions in anxious-depression levels had the largest increase in confidence. While the three-way interaction effect of group and time on confidence was not significant (F(2, 1632)=0.60, p=0.550), confidence increased in the antidepressant group (ß=0.31, SE = 0.08, p<0.001), but not among controls (ß=0.11, SE = 0.07, p=0.103). Metacognitive biases in anxious-depression are state-dependent; when symptoms improve with treatment, so does confidence in performance. Our results suggest this is not specific to the type of intervention.

The Effectiveness of Low-Intensity Psychological Interventions for Comorbid Depression and Anxiety in Patients with Long-Term Conditions: A Real-World Naturalistic Observational Study in IAPT Integrated Care.

BACKGROUND: Low-intensity psychological interventions may be a cost-effective, accessible solution for treating depression and anxiety in patients with long-term conditions, but evidence from real-world service settings is lacking. This study examined the effectiveness of low-intensity psychological interventions provided in the Improving Access to Psychological Therapies programme in England for patients with and without long-term conditions. METHODS: A retrospective analysis was conducted on patients (total N = 21,051, long-term conditions n = 4024) enrolled in three low-intensity psychological interventions, i.e. Internet-delivered cognitive behavioural therapy (iCBT), guided self-help (GSH), and psychoeducational group therapy (PGT) within a Talking Therapies service from 2016 to 2020. Primary outcomes included pre-post-treatment changes in depression (Patient Health Questionnaire-9) and anxiety (Generalised Anxiety Disorder-7). RESULTS: Overall, both cohorts significantly improved on all outcomes post-treatment, with large effect sizes. Patients with long-term conditions experienced a greater reduction in depression while those without experienced a greater reduction in anxiety, but these differences were marginal (< 1 score difference on both measures). No difference between the cohorts was shown when comparing the differential effectiveness across interventions, but those engaging in iCBT showed greater reduction in depression and anxiety than those in GSH and PGT, while those in GSH improved more than PGT. CONCLUSIONS: Low-intensity psychological interventions, particularly iCBT, were effective in treating depression and anxiety in patients with long-term conditions in a real-world service setting. Our large-scale study supports the continued and increased implementation of low-intensity psychological interventions for this subpopulation via integrated care.

The Precision in Psychiatry (PIP) study: Testing an internet-based methodology for accelerating research in treatment prediction and personalisation.

BACKGROUND: Evidence-based treatments for depression exist but not all patients benefit from them. Efforts to develop predictive models that can assist clinicians in allocating treatments are ongoing, but there are major issues with acquiring the volume and breadth of data needed to train these models. We examined the feasibility, tolerability, patient characteristics, and data quality of a novel protocol for internet-based treatment research in psychiatry that may help advance this field. METHODS: A fully internet-based protocol was used to gather repeated observational data from patient cohorts receiving internet-based cognitive behavioural therapy (iCBT) (N = 600) or antidepressant medication treatment (N = 110). At baseline, participants provided > 600 data points of self-report data, spanning socio-demographics, lifestyle, physical health, clinical and other psychological variables and completed 4 cognitive tests. They were followed weekly and completed another detailed clinical and cognitive assessment at week 4. In this paper, we describe our study design, the demographic and clinical characteristics of participants, their treatment adherence, study retention and compliance, the quality of the data gathered, and qualitative feedback from patients on study design and implementation. RESULTS: Participant retention was 92% at week 3 and 84% for the final assessment. The relatively short study duration of 4 weeks was sufficient to reveal early treatment effects; there were significant reductions in 11 transdiagnostic psychiatric symptoms assessed, with the largest improvement seen for depression. Most participants (66%) reported being distracted at some point during the study, 11% failed 1 or more attention checks and 3% consumed an intoxicating substance. Data quality was nonetheless high, with near perfect 4-week test retest reliability for self-reported height (ICC = 0.97). CONCLUSIONS: An internet-based methodology can be used efficiently to gather large amounts of detailed patient data during iCBT and antidepressant treatment. Recruitment was rapid, retention was relatively high and data quality was good. This paper provides a template methodology for future internet-based treatment studies, showing that such an approach facilitates data collection at a scale required for machine learning and other data-intensive methods that hope to deliver algorithmic tools that can aid clinical decision-making in psychiatry.

Effectiveness of the internet-based Unified Protocol transdiagnostic intervention for the treatment of depression, anxiety and related disorders in a primary care setting: a randomized controlled trial.

BACKGROUND: Research has shown that internet-based cognitive behavioural therapy (iCBT) can be a very promising solution to increase access to and the dissemination of evidence-based treatments to all of the population in need. However, iCBT is still underutilized in clinical contexts, such as primary care. In order to achieve the effective implementation of these protocols, more studies in ecological settings are needed. The Unified Protocol (UP) is a transdiagnostic CBT protocol for the treatment of emotional disorders, which includes depression, anxiety and related disorders, that has shown its efficacy across different contexts and populations. An internet-based UP (iUP) programme has recently been developed as an emerging internet-based treatment for emotional disorders. However, the internet-delivered version of the UP (iUP) has not yet been examined empirically. The current project seeks to analyse the effectiveness of the iUP as a treatment for depression, anxiety and related emotional disorders in a primary care public health setting. METHODS: The current study will employ a parallel-group, randomized controlled trial design. Participants will be randomly assigned to (a) the internet-based Unified Protocol (iUP), or (b) enhanced waiting list control (eWLC). Randomization will follow a 2:1 allocation ratio, with sample size calculations suggesting a required sample of 120 (iUP=80; eWLC=40). The Mini-International Neuropsychiatric Interview (M.I.N.I.) will be used for assessing potential participants. The Overall Anxiety Severity and Impairment Scale (OASIS) and the Overall Depression Severity and Impairment Scale (ODSIS) as well as other standardized questionnaires will be used for assessments at baseline, 4 weeks, 8 weeks and 12 weeks from baseline and for the iUP condition during the follow-up. DISCUSSION: Combining the advantages of a transdiagnostic treatment with an online delivery format may have the potential to significantly lower the burden of emotional disorders in public health primary care setting. Anxiety and depression, often comorbid, are the most prevalent psychological disorders in primary care. Because the iUP allows for the treatment of different disorders and comorbidity, this treatment could represent an adequate choice for patients that demand mental health care in a primary care setting. TRIAL REGISTRATION: ISRCTN18056450 https://doi.org/10.1186/ISRCTN18056450 .

Durability of treatment effects following internet-delivered cognitive behavioural therapy for depression and anxiety delivered within a routine care setting.

OBJECTIVE: To investigate post-treatment relapse and remission rates 3, 6 and 9 months after completion of an acute phase of a clinician-supported internet-delivered cognitive-behavioural therapy (iCBT) for anxiety and depressive symptoms, within a routine care setting. METHOD: Secondary analysis from a 12-month pragmatic randomized-controlled trial delivered within the Improving Access to Psychological Therapies (IAPT) programme in England. Participants in the intervention arm were included if they met criteria for reliable recovery from depression (PHQ-9) and anxiety (GAD-7) at post-treatment assessment. Survival analysis was used to assess durability of treatment effects and determine predictors to relapse at 3-, 6- and 9-month follow-up. Hazard ratios predicting time-to-relapse were estimated with semi-parametric Cox proportional hazards model. RESULTS: Of the 241 participants in the intervention arm, 89 participants met the criteria for reliable recovery from depression and anxiety at the post-treatment assessment. Of these 89 eligible cases, 29.2% relapsed within the 9-month period, with 70.8% remaining in remission at 9 months post-treatment. Of those who relapsed, 53.8% experienced a relapse of depression and anxiety; 7.7% experienced a relapse of depression only; and 38.4% experienced a relapse of anxiety only. Younger age, having a long-term condition, and residual symptoms of anxiety at end-of-treatment were all significant predictors of relapse. CONCLUSIONS: This study is the first to explore the remission and relapse rates after an acute phase of iCBT treatment, within a routine, stepped-care setting. The results add to the scarce literature on the durability of the effects of iCBT treatment in routine care settings, where patients are not typically followed up after receiving a completed course of treatment.

The gut microbiome as a biomarker of differential susceptibility to SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) continues to exact a devastating global toll. Ascertaining the factors underlying differential susceptibility and prognosis following viral exposure is critical to improving public health responses. We propose that gut microbes may contribute to variation in COVID-19 outcomes. We synthesise evidence for gut microbial contributions to immunity and inflammation, and associations with demographic factors affecting disease severity. We suggest mechanisms potentially underlying microbially mediated differential susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These include gut microbiome-mediated priming of host inflammatory responses and regulation of endocrine signalling, with consequences for the cellular features exploited by SARS-CoV-2 virions. We argue that considering gut microbiome-mediated mechanisms may offer a lens for appreciating differential susceptibility to SARS-CoV-2, potentially contributing to clinical and epidemiological approaches to understanding and managing COVID-19.

Microbial transmission in animal social networks and the social microbiome.

Host-associated microbiomes play an increasingly appreciated role in animal metabolism, immunity and health. The microbes in turn depend on their host for resources and can be transmitted across the host's social network. In this Perspective, we describe how animal social interactions and networks may provide channels for microbial transmission. We propose the 'social microbiome' as the microbial metacommunity of an animal social group. We then consider the various social and environmental forces that are likely to influence the social microbiome at multiple scales, including at the individual level, within social groups, between groups, within populations and species, and finally between species. Through our comprehensive discussion of the ways in which sociobiological and ecological factors may affect microbial transmission, we outline new research directions for the field.

The role of the microbiome in the neurobiology of social behaviour.

Microbes colonise all multicellular life, and the gut microbiome has been shown to influence a range of host physiological and behavioural phenotypes. One of the most intriguing and least understood of these influences lies in the domain of the microbiome's interactions with host social behaviour, with new evidence revealing that the gut microbiome makes important contributions to animal sociality. However, little is known about the biological processes through which the microbiome might influence host social behaviour. Here, we synthesise evidence of the gut microbiome's interactions with various aspects of host sociality, including sociability, social cognition, social stress, and autism. We discuss evidence of microbial associations with the most likely physiological mediators of animal social interaction. These include the structure and function of regions of the 'social' brain (the amygdala, the prefrontal cortex, and the hippocampus) and the regulation of 'social' signalling molecules (glucocorticoids including corticosterone and cortisol, sex hormones including testosterone, oestrogens, and progestogens, neuropeptide hormones such as oxytocin and arginine vasopressin, and monoamine neurotransmitters such as serotonin and dopamine). We also discuss microbiome-associated host genetic and epigenetic processes relevant to social behaviour. We then review research on microbial interactions with olfaction in insects and mammals, which contribute to social signalling and communication. Following these discussions, we examine evidence of microbial associations with emotion and social behaviour in humans, focussing on psychobiotic studies, microbe-depression correlations, early human development, autism, and issues of statistical power, replication, and causality. We analyse how the putative physiological mediators of the microbiome-sociality connection may be investigated, and discuss issues relating to the interpretation of results. We also suggest that other candidate molecules should be studied, insofar as they exert effects on social behaviour and are known to interact with the microbiome. Finally, we consider different models of the sequence of microbial effects on host physiological development, and how these may contribute to host social behaviour.

Suboptimal Engagement of High-Level Cortical Regions Predicts Random-Noise-Related Gains in Sustained Attention.

Interindividual variability in outcomes across individuals poses great challenges for the application of noninvasive brain stimulation in psychological research. Here, we examined how the effects of high-frequency transcranial random-noise stimulation (tRNS) on sustained attention varied as a function of a well-studied electrocortical marker: spontaneous theta:beta ratio. Seventy-two participants received sham, 1-mA, and 2-mA tRNS in a double-blind, crossover manner while they performed a sustained-attention task. Receiving 1-mA tRNS was associated with improved sustained attention, whereas the effect of 2-mA tRNS was similar to the effect of sham tRNS. Furthermore, individuals' baseline theta:beta ratio moderated the effects of 1-mA tRNS and provided explanatory power beyond baseline behavioral performance. The tRNS-related effects on sustained attention were also accompanied by reductions in theta:beta ratio. These findings impart novel insights into mechanisms underlying tRNS effects and emphasize how designing studies that link variability in cognitive outcomes to variability in neurophysiology can improve inferential power in neurocognitive research.

Prefrontal Modulation of Visual Processing and Sustained Attention in Aging, a tDCS-EEG Coregistration Approach.

The ability to sustain attention is integral to healthy cognition in aging. The right PFC (rPFC) is critical for maintaining high levels of attentional focus. Whether plasticity of this region can be harnessed to support sustained attention in older adults is unknown. We used transcranial direct current stimulation to increase cortical excitability of the rPFC, while monitoring behavioral and electrophysiological markers of sustained attention in older adults with suboptimal sustained attention capacity. During rPFC transcranial direct current stimulation, fewer lapses of attention occurred and electroencephalography signals of frontal engagement and early visual attention were enhanced. To further verify these results, we repeated the experiment in an independent cohort of cognitively typical older adults using a different sustained attention paradigm. Again, prefrontal stimulation was associated with fewer attentional lapses. These experiments suggest the rPFC can be manipulated in later years to increase top-down modulation over early sensory processing and improve sustained attention performance. This holds valuable information for the development of neurorehabilitation protocols to ameliorate age-related deficits in this capacity.

The Microbiome in Psychology and Cognitive Neuroscience.

Psychology and microbiology make unlikely friends, but the past decade has witnessed striking bidirectional associations between intrinsic gut microbes and the brain, relationships with largely untested psychological implications. Although microbe-brain relationships are receiving a great deal of attention in biomedicine and neuroscience, psychologists have yet to join this journey. Here, we illustrate microbial associations with emotion, cognition, and social behavior. However, despite considerable enthusiasm and potential, technical and conceptual limitations including low statistical power and lack of mechanistic descriptions prevent a nuanced understanding of microbiome-brain-behavior relationships. Our goal is to describe microbial effects in domains of cognitive significance and the associated challenges to stimulate interdisciplinary research on the contribution of this hidden kingdom to psychological processes.

Modulating hemispheric lateralization by brain stimulation yields gain in mental and physical activity.

Imagery plays an important role in our life. Motor imagery is the mental simulation of a motor act without overt motor output. Previous studies have documented the effect of motor imagery practice. However, its translational potential for patients as well as for athletes, musicians and other groups, depends largely on the transfer from mental practice to overt physical performance. We used bilateral transcranial direct current stimulation (tDCS) over sensorimotor areas to modulate neural lateralization patterns induced by unilateral mental motor imagery and the performance of a physical motor task. Twenty-six healthy older adults participated (mean age = 67.1 years) in a double-blind cross-over sham-controlled study. We found stimulation-related changes at the neural and behavioural level, which were polarity-dependent. Specifically, for the hand contralateral to the anode, electroencephalographic activity induced by motor imagery was more lateralized and motor performance improved. In contrast, for the hand contralateral to the cathode, hemispheric lateralization was reduced. The stimulation-related increase and decrease in neural lateralization were negatively related. Further, the degree of stimulation-related change in neural lateralization correlated with the stimulation-related change on behavioural level. These convergent neurophysiological and behavioural effects underline the potential of tDCS to improve mental and physical motor performance.

Parsing the neural signatures of reduced error detection in older age.

Recent work has demonstrated that explicit error detection relies on a neural evidence accumulation process that can be traced in the human electroencephalogram (EEG). Here, we sought to establish the impact of natural aging on this process by recording EEG from young (18-35 years) and older adults (65-88 years) during the performance of a Go/No-Go paradigm in which participants were required to overtly signal their errors. Despite performing the task with equivalent accuracy, older adults reported substantially fewer errors, and the timing of their reports were both slower and more variable. These behavioral differences were linked to three key neurophysiological changes reflecting distinct parameters of the error detection decision process: a reduction in medial frontal delta/theta (2-7 Hz) activity, indicating diminished top-down input to the decision process; a slower rate of evidence accumulation as indexed by the rate of rise of a centro-parietal signal, known as the error positivity; and a higher motor execution threshold as indexed by lateralized beta-band (16-30 Hz) activity. Our data provide novel insight into how the natural aging process affects the neural underpinnings of error detection.

Mind the Brain: The Mediating and Moderating Role of Neurophysiology.

Most studies involving experimental manipulations or interventions tailored to modulate behavior do not account for variability in the critical antecedent of behavior, the brain. Here, we describe elegant approaches to model the role that neurophysiology can play in mediating or moderating relationships in this context. We highlight the capacity for these approaches to improve the inferential power of research, bridge the gap between neural and behavioral levels of analysis, and bolster the prospects for reproducibility.

Psychobiotics and the Manipulation of Bacteria-Gut-Brain Signals.

Psychobiotics were previously defined as live bacteria (probiotics) which, when ingested, confer mental health benefits through interactions with commensal gut bacteria. We expand this definition to encompass prebiotics, which enhance the growth of beneficial gut bacteria. We review probiotic and prebiotic effects on emotional, cognitive, systemic, and neural variables relevant to health and disease. We discuss gut-brain signalling mechanisms enabling psychobiotic effects, such as metabolite production. Overall, knowledge of how the microbiome responds to exogenous influence remains limited. We tabulate several important research questions and issues, exploration of which will generate both mechanistic insights and facilitate future psychobiotic development. We suggest the definition of psychobiotics be expanded beyond probiotics and prebiotics to include other means of influencing the microbiome.

Neural evidence accumulation persists after choice to inform metacognitive judgments.

The ability to revise one's certainty or confidence in a preceding choice is a critical feature of adaptive decision-making but the neural mechanisms underpinning this metacognitive process have yet to be characterized. In the present study, we demonstrate that the same build-to-threshold decision variable signal that triggers an initial choice continues to evolve after commitment, and determines the timing and accuracy of self-initiated error detection reports by selectively representing accumulated evidence that the preceding choice was incorrect. We also show that a peri-choice signal generated in medial frontal cortex provides a source of input to this post-decision accumulation process, indicating that metacognitive judgments are not solely based on the accumulation of feedforward sensory evidence. These findings impart novel insights into the generative mechanisms of metacognition.