Search

Objective: Contemporary research suggests reduced telomere length in schizophrenia spectrum disorders (SZ) compared to age-adjusted non-affected individuals. However, the role of telomere maintenance and telomere repair in SZ is poorly understood as well as the involvement of telomere biology in cognitive abnormalities in SZ., Methods: The study consisted of 758 participants (SZ [n = 357] and healthy controls, HC [n = 401]) collected as part of the Norwegian TOP study. Participants were assessed with standardized neuropsychological tests measuring five cognitive domains. Leucocyte telomere length (TL) was measured via blood and determined by quantitative real-time Polymerase Chain Reaction (qPCR) providing a telomere to single copy ratio (T/S ratio), used to estimate the mean telomere length. Telomerase activity was assessed by the expression levels of the Telomerase Reverse Transcriptase (TERT) and Telomerase RNA Component (TERC) genes. To assess telomere maintenance and telomere repair we calculated the telomerase expression to TL ratio (TERT/TL and TERC/TL respectively)., Results: Patients had reduced TERT (F = 5.03, p = 0.03), but not TERC expression (F = 1.04, p = 0.31), and higher TERT/TL (F = 6.68, p = 0.01) and TERC/TL (F = 6.71, p = 0.01), adjusted for age, sex, and ethnicity. No statistically significant association was observed between any of the telomere biology markers and the cognitive domains (p > 0.05)., Conclusion: Our study shows changes in TERT expression and telomere maintenance and telomere repair in SZ compared HC. However, the role of telomere biology in the mechanism underlying cognitive impairment in psychosis seems limited., Competing Interests: Declaration of competing interest Authors declare no conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Oxytocin administration has demonstrated considerable promise for providing individualized support for autistic people. However, studies evaluating the effects of oxytocin administration on autistic characteristics have yielded inconsistent results. This systematic review and meta-analysis investigates the effect of oxytocin administration on social and routinized behaviors in autism using recently developed methods to accurately assess the potential impact of effect size dependency and publication bias. Our frequentist meta-analysis yielded a significant summary effect size estimate for the impact of oxytocin administration on social outcomes in autism (d = 0.22, p < 0.001). The summary effect size estimate for routinized behavior outcomes was not statistically significant (d = 0.14, p = 0.22), with a follow up test indicating that the effect size estimate was not either statistically equivalent (Z = -1.06, p = 0.2), assuming a smallest effect size of interest of 0.25. Frequentist and Bayesian assessments for publication bias, as well as results from Robust Bayesian meta-analysis of oxytocin effects on social outcomes in autism, indicated that summary effect sizes might be inflated due to publication bias. Future studies should aim to reduce bias by preregistering analysis plans and to increase precision with larger sample sizes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The neuropeptide oxytocin has historically been associated with reproduction and maternal behavior. However, more recent research has uncovered that oxytocin has a much wider range of roles in physiology and behavior. Despite the excitement surrounding potential therapeutical applications of intranasally administered oxytocin, the results of these intervention studies have been inconsistent. Various reasons for these mixed results have been proposed, which tend to focus on methodological issues, such as study design. While methodological issues are certainly important, emerging evidence suggests that the interaction between oxytocin and sex hormones may also account for these varied findings. To better understand the purpose and function of the interaction of oxytocin with sex hormones, with a focus on estrogens, progesterone, and testosterone, we conducted a comprehensive thematic review via four perspectives: evolutionary, developmental, mechanistic, and survival. Altogether, this synergistic approach highlights the critical function of sex hormone activity for accomplishing the diverse roles of oxytocin via the modulation of oxytocin release and oxytocin receptor activity, which is also likely to contribute to the heterogeneity of outcomes after oxytocin administration., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Oxytocin is a neuropeptide associated with both psychological and somatic processes like parturition and social bonding. Although oxytocin homologs have been identified in many species, the evolutionary timeline of the entire oxytocin signaling gene pathway has yet to be described. Using protein sequence similarity searches, microsynteny, and phylostratigraphy, we assigned the genes supporting the oxytocin pathway to different phylostrata based on when we found they likely arose in evolution. We show that the majority (64%) of genes in the pathway are 'modern'. Most of the modern genes evolved around the emergence of vertebrates or jawed vertebrates (540 - 530 million years ago, 'mya'), including OXTR, OXT and CD38. Of those, 45% were under positive selection at some point during vertebrate evolution. We also found that 18% of the genes in the oxytocin pathway are 'ancient', meaning their emergence dates back to cellular organisms and opisthokonta (3500-1100 mya). The remaining genes (18%) that evolved after ancient and before modern genes were classified as 'medium-aged'. Functional analyses revealed that, in humans, medium-aged oxytocin pathway genes are highly expressed in contractile organs, while modern genes in the oxytocin pathway are primarily expressed in the brain and muscle tissue., (© 2024. The Author(s).)

Introduction: Effect sizes are often used to interpret the magnitude of a result and in power calculations when planning research studies. However, as effect size interpretations are context-dependent, Jacob Cohen's suggested guidelines for what represents a small, medium, and large effect are unlikely to be suitable for a diverse range of research populations and interventions. Our objective here is to determine empirically-derived effect size thresholds associated with psychotherapy randomized controlled trials (RCTs) in depression by calculating the effect size distribution., Methods: We extracted effect sizes from 366 RCTs provided by the systematic review of Cuijpers and colleagues (2020) on psychotherapy for depressive disorders across all age groups. The 50th percentile effect size, as this represents a medium effect size, and the 25th (small) and 75th (large) percentile effect sizes were calculated to determine empirically-derived effect size thresholds., Results: After adjusting for publication bias, 0.27, 0.53, and 0.86 represent small, medium, and large effect sizes, respectively, for psychotherapy treatment for depressive disorders., Discussion: The effect size distribution for psychotherapy treatment of depression indicates that observed effect size thresholds are larger than Cohen's suggested effect size thresholds (0.2, 0.5, and 0.8). These results have implications for the interpretation of study effects and the planning of future studies via power analyses, which often use effect size thresholds., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Recent studies indicate accelerated ageing processes, shorter telomere length and poorer cognitive functioning in patients with bipolar disorder. The neurobiology underlying cognitive function in bipolar disorder is yet to be established. We anticipated that accelerated ageing as indicated by shortened telomere length, would be associated with reduced cognitive performance in bipolar disorder, particularly for ageing sensitive functions such as memory and learning., Methods: The study consisted of 647 participants (bipolar disorder [n = 246] and healthy controls [n = 401]). All participants underwent a standardized neuropsychological test battery, including working memory, executive functioning, processing speed, verbal learning, and verbal memory. Leucocyte telomere length was measured via blood and determined by quantitative real-time Polymerase Chain Reaction (qPCR) providing a telomere to single copy ratio (T/S ratio). The T/S ratio was used as an estimate of the mean telomere length of each participant. All analyses were adjusted for medication, Daily Defined Dose (DDD), chronological age, sex, and ethnicity., Results: Patients had shorter telomere lengths than healthy controls (Cohen's d = 0.11, p = 0.01). Within patients', a positive association was observed for verbal learning and telomere length (β = 0.14, p = 0.025), along with a trend for verbal memory and telomere length (β = 0.11, p = 0.07). No other associations were observed for telomere length and cognitive functioning in the patient or the control group (p > 0.1)., Conclusion: Our study may suggest poorer brain health in bipolar disorder as indexed by shorter telomere length and reduced learning correlates. However, the role of telomere length on cognitive functioning in bipolar disorder seems limited., Competing Interests: Declaration of competing interest No conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Girls and boys might differ in autistic symptoms and associated cognitive difficulties such as executive function (EF). We investigated sex differences in the relationship between parent rated EF and autistic symptoms in 116 children and adolescents (25 girls) aged 5-19 years with an intelligence quotient above 70 and an autism spectrum disorder (ASD) diagnosis. They were rated with the behavior rating inventory of executive function (BRIEF) and the autism diagnostic interview revised (ADI-R). We found a positive association between EF and the ADI-R domains of reciprocal social interaction (p < 0.001) and communication (p = 0.001) in girls, while these relationships were small and non-significant in boys. Our results provide a greater understanding of the sex-specific characteristics of children and adolescents with ASD., (© 2022. The Author(s).)

Human neuroscience has always been pushing the boundary of what is measurable. During the last decade, concerns about statistical power and replicability - in science in general, but also specifically in human neuroscience - have fueled an extensive debate. One important insight from this discourse is the need for larger samples, which naturally increases statistical power. An alternative is to increase the precision of measurements, which is the focus of this review. This option is often overlooked, even though statistical power benefits from increasing precision as much as from increasing sample size. Nonetheless, precision has always been at the heart of good scientific practice in human neuroscience, with researchers relying on lab traditions or rules of thumb to ensure sufficient precision for their studies. In this review, we encourage a more systematic approach to precision. We start by introducing measurement precision and its importance for well-powered studies in human neuroscience. Then, determinants for precision in a range of neuroscientific methods (MRI, M/EEG, EDA, Eye-Tracking, and Endocrinology) are elaborated. We end by discussing how a more systematic evaluation of precision and the application of respective insights can lead to an increase in reproducibility in human neuroscience., Competing Interests: SN, MR, DB, JB, GD, MG, AG, CG, CG, KH, PJ, LK, AL, SM, MM, CM, TP, LP, DQ, TS, AS, MS, AV, TL, GF No competing interests declared, (© 2023, Nebe, Reutter et al.)

The patient-physician relationship is a critical determinant of patient health outcomes. Verbal and non-verbal communication, such as eye gaze, are vital aspects of this bond. Neurobiological studies indicate that oxytocin may serve as a link between increased eye gaze and social bonding. Therefore, oxytocin signaling could serve as a key factor influencing eye gaze as well as the patient-physician relationship. We aimed to test the effects of oxytocin on gaze to the eyes of the physician and the patient-physician relationship by conducting a randomized placebo-controlled crossover trial in healthy volunteers with intranasally administered oxytocin (with a previously effective single dose of 24 IU, EudraCT number 2018-004081-34). The eye gaze of 68 male volunteers was studied using eye tracking during a simulated video call consultation with a physician, who provided information about vaccination against the human papillomavirus. Relationship outcomes, including trust, satisfaction, and perceived physician communication style, were measured using questionnaires and corrected for possible confounds (social anxiety and attachment orientation). Additional secondary outcome measures for the effect of oxytocin were recall of information and pupil diameter and exploratory outcomes included mood and anxiety measures. Oxytocin did not affect the eye-tracking parameters of volunteers' gaze toward the eyes of the physician. Moreover, oxytocin did not affect the parameters of bonding between volunteers and the physician nor other secondary and exploratory outcomes in this setting. Bayesian hypothesis testing provided evidence for the absence of effects. These results contradict the notion that oxytocin affects eye gaze patterns or bonding.

The etiology of anorexia nervosa (AN) remains elusive. Recent genome-wide association studies identified the first genes liked to AN which reached genome-wide significance, although our understanding of how these genes confer risk remains preliminary. Here, we leverage the Allen Human Brain Atlas to characterize the spatially distributed gene expression patterns of genes linked to AN in the non-disordered human brain, developing whole-brain maps of AN gene expression. We found that genes associated with AN are most expressed in the brain, relative to all other body tissue types, and demonstrate gene-specific expression patterns which extend to cerebellar, temporal and basal ganglia structures in particular. fMRI meta-analyses reveal that AN gene expression maps correspond with functional brain activity involved in processing and anticipating appetitive and aversive cues. Findings offer novel insights around putative mechanisms through which genes associated with AN may confer risk., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Autism entails reduced communicative abilities. Approximately 30% of individuals with autism have intellectual disability (ID). Some people with autism and ID are virtually non-communicative and unable to notify their caregivers when they are in pain. In a pilot study, we showed that heart rate (HR) monitoring may identify painful situations in this patient group, as HR increases in acutely painful situations., Objectives: This study aims to generate knowledge to reduce the number of painful episodes in non-communicative patients' everyday lives. We will 1) assess the effectiveness of HR as a tool for identifying potentially painful care procedures, 2) test the effect of HR-informed changes in potentially painful care procedures on biomarkers of pain, and 3) assess how six weeks of communication through HR affects the quality of communication between patient and caregiver., Methods: We will recruit 38 non-communicative patients with autism and ID residing in care homes., Assessments: HR is measured continuously to identify acutely painful situations. HR variability and pain-related cytokines (MCP-1, IL-1RA, IL-8, TGFβ1, and IL-17) are collected as measures of long-term pain. Caregivers will be asked to what degree they observe pain in their patients and how well they believe they understand their patient's expressions of emotion and pain. Pre-intervention: HR is measured 8 h/day over 2 weeks to identify potentially painful situations across four settings: physiotherapy, cast use, lifting, and personal hygiene., Intervention: Changes in procedures for identified painful situations are in the form of changes in 1) physiotherapy techniques, 2) preparations for putting on casts, 3) lifting techniques or 4) personal hygiene procedures., Design: Nineteen patients will start intervention in week 3 while 19 patients will continue data collection for another 2 weeks before procedure changes are introduced. This is done to distinguish between specific effects of changes in procedures and non-specific effects, such as caregivers increased attention., Discussion: This study will advance the field of wearable physiological sensor use in patient care., Trial Registration: Registered prospectively at ClinicalTrials.gov (NCT05738278)., (© 2023. The Author(s).)

Objectives: Systematic reviews and meta-analyses are proliferating as they are an important building block to inform evidence-based guidelines and decision-making. Enforcement of best practice in clinical trials is firmly on the research agenda of good clinical practice, but there is less clarity as to how evidence syntheses that combine these studies can be influenced by bad practice. Our aim was to conduct a living systematic review of articles that highlight flaws in published systematic reviews to formally document and understand these problems., Study Design and Setting: We conducted a comprehensive assessment of all literature examining problems, which relate to published systematic reviews., Results: The first iteration of our living systematic review (https://systematicreviewlution.com/) has found 485 articles documenting 67 discrete problems relating to the conduct and reporting of systematic reviews which can potentially jeopardize their reliability or validity., Conclusion: Many hundreds of articles highlight that there are many flaws in the conduct, methods, and reporting of published systematic reviews, despite the existence and frequent application of guidelines. Considering the pivotal role that systematic reviews have in medical decision-making due to having apparently transparent, objective, and replicable processes, a failure to appreciate and regulate problems with these highly cited research designs is a threat to credible science., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The relationship between wellbeing and personality has been studied extensively, but few studies have examined these in the period of adolescence and emerging adulthood. Moreover, the influence of contextual factors such as engagement in leisure activities are rarely considered., Methods: The present study employs a combination of frequentist and Bayesian analyses to evaluate the concurrent impact of personality traits and leisure activities on five conceptions of wellbeing (life satisfaction; positive affect; negative affect; mental health; flourishing) in three cohorts of young people (aged 14-15; 16-17; 18-20 years)., Results: Personality traits were the only significant predictors of life satisfaction and negative affect, but leisure activities in the form of socialising or physical activity, in addition to personality traits, predicted positive affect, mental health and flourishing. Neuroticism was the largest predictor of wellbeing overall, whereas conscientiousness was the most consistent. Lower levels of wellbeing were also associated with higher levels of creative potential., Conclusions: The study not only confirms the importance of personality traits as predictors of wellbeing in adolescents and young adults, but also indicates the necessity to consider the impact of leisure activities in different conceptions of wellbeing. The negative relationship between creative potential and wellbeing is in line with the literature which shows a link between mental illness, particularly at subclinical levels, and creativity., (© 2022. The Author(s).)

Alcohol dependence is associated with difficulties in processing emotional stimuli, which can lead to interpersonal problems. The neuropeptide oxytocin has been shown to modulate the processing of emotional stimuli, however, oxytocin treatment has not yet been examined in patients with withdrawal symptoms during alcohol detoxification. The aim of the present study was to investigate the effect of oxytocin on the reading the mind in the eyes test (RMET), which indexes theory of mind ability, during a three-day period of alcohol detoxification at an addiction treatment centre in Norway. We performed a randomized, double-blind, placebo-controlled trial in 39 patients fulfilling criteria for ICD-10 diagnosis of alcohol dependence admitted for alcohol detoxification and withdrawal treatment. Participants were randomized to receive either intranasal oxytocin (24 IU) or placebo, twice daily for three days. We evaluated RMET performance on day 2 and day 3 of detoxification and differences in RMET scores between day 2 and day 3 of detoxification. Frequentist and Bayesian statistical inference suggested that oxytocin administration during alcohol withdrawal in alcohol-dependent patients did not improve RMET performance. However, exploratory analyses provided preliminary evidence that oxytocin might improve performance on the RMET negative emotion subscale (uncorrected p value = 0.038), and that oxytocin treatment might show the most promise for those with high levels of alcohol consumption (i.e., ≥20 alcohol units per day; uncorrected p value = 0.023). Moreover, alcohol consumption levels significantly predicted RMET performance on day 2, but not on day 3, of withdrawal., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Increasing evidence has shown adverse effects of loneliness on cardiometabolic health. The neuromodulator and hormone oxytocin has traditionally been linked with social cognition and behaviour. However, recent implications of the oxytocin system in energy metabolism and the overrepresentation of metabolic issues in psychiatric illness suggests that oxytocin may represent a mechanism bridging mental and somatic traits. To clarify the role of the oxytocin signalling system in the link between cardiometabolic risk factors and loneliness, we calculated the contribution of single nucleotide polymorphisms (SNPs) in the oxytocin signalling pathway gene-set (154 genes) to the polygenic architecture of loneliness and body mass index (BMI). We investigated the associations of these oxytocin signalling pathway polygenic scores with body composition measured using body magnetic resonance imaging (MRI), bone mineral density (BMD), haematological markers, and blood pressure in a sample of just under half a million adults from the UK Biobank (BMD subsample n = 274,457; body MRI subsample n = 9796). Our analysis revealed significant associations of the oxytocin signalling pathway polygenic score for BMI with abdominal subcutaneous fat tissue, HDL cholesterol, lipoprotein(a), triglycerides, and BMD. We also found an association between the oxytocin signalling pathway polygenic score for loneliness and apolipoprotein A1, the major protein component of HDL. Altogether, these results provide additional evidence for the oxytocin signalling pathway's role in energy metabolism, lipid homoeostasis, and bone density, and support oxytocin's complex pleiotropic effects., Competing Interests: Conflicts of Interest OAA has received speaker's honorarium from Lundbeck and is a consultant to HealthLytix. The remaining authors have no conflicts of interest to disclose., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

There are emerging concerns that loot boxes-digital video game items that can be purchased for a chance at randomized rewards-are associated with problematic gambling behaviours and, in turn, are potentially harmful. Current research suggests consistent correlations between loot box spending (LS) and problematic gambling symptomology; however, little research has looked at relationships with mental wellbeing. Here, we used a Bayesian hypothesis testing framework to assess the relative strength of evidence for relationships between LS, excessive gaming, problem gambling, mental wellbeing and psychological distress. Two thousand seven hundred twenty-eight participants who reported playing games containing loot box mechanics in the past month answered a survey assessing the above measures, as well as other forms of digital spending. The results showed extremely strong evidence for a positive correlation between LS and problem gambling; however, there was no evidence to suggest relationships between such spending and mental wellbeing or psychological distress. Exploratory results suggested that individuals who spend money on loot boxes also spend more across a range of digital purchases generally. The findings highlight an urgent need to understand what constitutes harm when considering LS effects and provide further context for discussions regarding how best to regulate such mechanisms., (© 2022 The Authors.)

Background: The development of COVID-19 vaccines has been crucial in fighting the pandemic. However, misinformation about the COVID-19 pandemic and vaccines is spread on social media platforms at a rate that has made the World Health Organization coin the phrase infodemic. False claims about adverse vaccine side effects, such as vaccines being the cause of autism, were already considered a threat to global health before the outbreak of COVID-19., Objective: We aimed to synthesize the existing research on misinformation about COVID-19 vaccines spread on social media platforms and its effects. The secondary aim was to gain insight and gather knowledge about whether misinformation about autism and COVID-19 vaccines is being spread on social media platforms., Methods: We performed a literature search on September 9, 2021, and searched PubMed, PsycINFO, ERIC, EMBASE, Cochrane Library, and the Cochrane COVID-19 Study Register. We included publications in peer-reviewed journals that fulfilled the following criteria: original empirical studies, studies that assessed social media and misinformation, and studies about COVID-19 vaccines. Thematic analysis was used to identify the patterns (themes) of misinformation. Narrative qualitative synthesis was undertaken with the guidance of the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 Statement and the Synthesis Without Meta-analysis reporting guideline. The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal tool. Ratings of the certainty of evidence were based on recommendations from the Grading of Recommendations Assessment, Development and Evaluation Working Group., Results: The search yielded 757 records, with 45 articles selected for this review. We identified 3 main themes of misinformation: medical misinformation, vaccine development, and conspiracies. Twitter was the most studied social media platform, followed by Facebook, YouTube, and Instagram. A vast majority of studies were from industrialized Western countries. We identified 19 studies in which the effect of social media misinformation on vaccine hesitancy was measured or discussed. These studies implied that the misinformation spread on social media had a negative effect on vaccine hesitancy and uptake. Only 1 study contained misinformation about autism as a side effect of COVID-19 vaccines., Conclusions: To prevent these misconceptions from taking hold, health authorities should openly address and discuss these false claims with both cultural and religious awareness in mind. Our review showed that there is a need to examine the effect of social media misinformation on vaccine hesitancy with a more robust experimental design. Furthermore, this review also demonstrated that more studies are needed from the Global South and on social media platforms other than the major platforms such as Twitter and Facebook., Trial Registration: PROSPERO International Prospective Register of Systematic Reviews CRD42021277524; https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42021277524., International Registered Report Identifier (irrid): RR2-10.31219/osf.io/tyevj., (©Ingjerd Skafle, Anders Nordahl-Hansen, Daniel S Quintana, Rolf Wynn, Elia Gabarron. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 04.08.2022.)

Oxytocin plays a vital role in social behavior and homeostatic processes, with animal models indicating that oxytocin receptor (OXTR) expression patterns in the brain influence behavior and physiology. However, the developmental trajectory of OXTR gene expression is unclear. By analyzing gene expression data in human post-mortem brain samples, from the prenatal period to late adulthood, we demonstrate distinct patterns of OXTR gene expression in the developing brain, with increasing OXTR expression along the course of the prenatal period culminating in a peak during early childhood. This early life OXTR expression peak pattern appears slightly earlier in a comparative macaque sample, which is consistent with the relative immaturity of the human brain during early life compared to macaques. We also show that a network of genes with strong spatiotemporal couplings with OXTR is enriched in several psychiatric illness and body composition phenotypes. Taken together, these results demonstrate that oxytocin signaling plays an important role in a diverse set of psychological and somatic processes across the lifespan., (© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

The error-related negativity (ERN) and the error positivity (Pe) are electrophysiological components associated with error processing that are thought to exhibit distinctive developmental trajectories from childhood to adulthood. To investigate the age and age moderation effects on the ERN and the Pe strength during development, we conducted a preregistered three-level meta-analysis synthesizing 120 and 41 effect sizes across 18 group comparison studies and 19 correlational studies, respectively. The meta-analysis included studies with mean age between 3.6 and 28.7 (min-max age range: 3.5 and 49.8) years for age-group comparisons and 6.1 to 18.7 (min-max age range: 4.0-35.7) years for age correlations. Results showed that age was associated with a more negative ERN (SMD = -.433, r = -.230). No statistically significant association between age and the Pe was found (SMD = .059, r = -.091), except for in a group comparison between younger and older adolescents. The age effects were not significantly moderated by whether a Flanker or a Go/No-Go task was used, whereas a probabilistic learning task moderated the age effect on the Pe. Moreover, the Fz and Cz electrode sites yielded stronger negative associations between age and the ERN and the Pe, respectively. The results confirm that the ERN and the Pe show differential development courses and suggest that sample and methodological characteristics influence the age effects, and lay the foundation for investigations of developmental patterns of the ERN and the Pe in relation to psychopathology and early genetic and environmental risk factors., (© 2022 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Various factors have been attributed to the inconsistent reproducibility of human oxytocin research in the cognitive and behavioral sciences. These factors include small sample sizes, a lack of pre-registered studies, and the absence of overarching theoretical frameworks that can account for oxytocin's effects over a broad range of contexts. While there have been efforts to remedy these issues, there has been very little systematic scrutiny of the role of auxiliary assumptions, which are claims that are not central for testing a hypothesis but nonetheless critical for testing theories. For instance, the hypothesis that oxytocin increases the salience of social cues is predicated on the assumption that intranasally administered oxytocin increases oxytocin levels in the brain. Without robust auxiliary assumptions, it is unclear whether a hypothesis testing failure is due to an incorrect hypothesis or poorly supported auxiliary assumptions. Consequently, poorly supported auxiliary assumptions can be blamed for hypothesis failure, thereby safeguarding theories from falsification. In this article, I will evaluate the body of evidence for key auxiliary assumptions in human behavioral oxytocin research in terms of theory, experimental design, and statistical inference, and highlight assumptions that require stronger evidence. Strong auxiliary assumptions will leave hypotheses vulnerable for falsification, which will improve hypothesis testing and consequently advance our understanding of oxytocin's role in cognition and behavior., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Older adults have been neglected in biobehavioral oxytocin research. Emerging research indicates that oxytocin signaling activity fluctuates over the lifespan, which suggests that results from studies investigating youth and young adults cannot be easily generalized to older adults. The recruitment of a wider age range of research participants using a variety of research tools is required to uncover the role of the oxytocin signaling system over the lifespan and may reveal novel treatment target candidates in older adults, beyond social cognition and behavior., (© 2022 The Authors.)

The measurement of gene expression levels in the human brain can help accelerate our understanding of complex mental states and psychiatric illnesses. Mental states are typically associated with whole-brain networks; however, gene expression levels from postmortem brain samples have traditionally been measured in a limited number of brain regions due to resource limitations. The recent availability of whole-brain gene expression data from the Allen Human Brain Atlas (AHBA) provides the opportunity to generate gene expression patterns for over 20,000 genes. By linking these expression patterns with brain activity patterns that are associated with specific mental states, researchers can better understand which genes may support given mental states, via forward inference. Conversely, reverse inference can also be used to determine which mental state activation patterns are most strongly associated with a given gene expression map. This chapter provides a step-by-step guide on how to use the AHBA in conjunction with the NeuroSynth fMRI meta-analysis tool to identify the mental state correlates of specific gene expression patterns, using genes from oxytocin signaling pathway as an example. We also demonstrate how to perform an out-of-sample validation and assess the specificity of results for genes of interest., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

While a growing literature links cardiac autonomic dysregulation to a variety of psychiatric disorders, the relationship between cardiac autonomic functioning and specific symptoms in schizophrenia (SZ) and bipolar disorder (BD) remains elusive. Thus, we investigated heart rate variability (HRV), a proxy for vagal activity, as a biological marker for symptom severity in patients with SZ and BD. HRV was calculated in 35 patients with SZ and 52 patients with BD, as well as in 149 healthy controls. In the patient groups, symptom severity and function were measured by the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) scale. Results showed that HRV was significantly lower in both clinical groups compared to the healthy controls, with no significant HRV differences between patient groups. PANSS general psychopathology scores, GAF symptom scores, and GAF function scores showed statistically significant associations with HRV across groups. These results suggest that disease severity is associated with autonomic dysfunction and that HRV may provide a potential biomarker of disease severity in SZ and BD., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Shorter telomere length is a putative biomarker of accelerated aging and has been associated with affective disorders and mortality. Psychological factors and behaviors associated with telomere shortening are yet to be clarified. Here, we investigate the association between history of suicide attempts and telomere length in patients with affective disorders., Methods: Leucocyte telomere length was determined by quantitative real-time Polymerase Chain Reaction (qPCR) in patients with affective disorders (n = 248) including bipolar disorders type I (n = 159), type II (n = 67), major depressive disorder (n = 22), and healthy controls (n = 401). Diagnosis, duration of illness, and age at onset were assessed using the Structural Clinical Interview for DSM-IV (SCID-I). Number of lifetime suicide attempts were based on self-reports. Effect size was calculated using Cohen's d., Results: Telomere length was reduced in patients with affective disorders relative to healthy controls (d = 0.18, F = 5.26, p = 0.02). Among patients, a higher number of suicide attempts was associated with shorter telomere length (β = -0.24, t = -3.83, CI = -0.44 to -0.14, p < 0.001), also when controlling for duration of illness and age at onset (β = -.23, CI = -.42 to -.12, p = 0.001). Multiple suicide attempts were associated with telomere length reduction comparable to eight years lifespan, adjusted for demographic and clinical characteristics., Conclusions: While longitudinal data are needed to clarify the temporal course, previous suicide attempts and related distress may accelerate telomere shortening and aging in patients with affective disorders., (Copyright © 2021. Published by Elsevier B.V.)

Oxytocin is a neuromodulator and hormone that is typically associated with social cognition and behavior. In light of its purported effects on social cognition and behavior, research has investigated its potential as a treatment for psychiatric illnesses characterized by social dysfunction, such as schizophrenia and bipolar disorder. While the results of these trials have been mixed, more recent evidence suggests that the oxytocin system is also linked with cardiometabolic conditions for which individuals with severe mental disorders are at a higher risk for developing. To investigate whether the oxytocin system has a pleiotropic effect on the etiology of severe mental illness and cardiometabolic conditions, we explored oxytocin's role in the shared genetic liability of schizophrenia, bipolar disorder, type-2 diabetes, and several phenotypes linked with cardiovascular disease and type 2 diabetes risk using a polygenic pathway-specific approach. Analysis of a large sample with about 480,000 individuals (UK Biobank) revealed statistically significant associations across the range of phenotypes analyzed. By comparing these effects to those of polygenic scores calculated from 100 random gene sets, we also demonstrated the specificity of many of these significant results. Altogether, our results suggest that the shared effect of oxytocin-system dysfunction could help partially explain the co-occurrence of social and cardiometabolic dysfunction in severe mental illnesses., (© 2021. The Author(s).)

There is widespread public and academic interest in understanding the uses and effects of digital media. Scholars primarily use self-report measures of the quantity or duration of media use as proxies for more objective measures, but the validity of these self-reports remains unclear. Advancements in data collection techniques have produced a collection of studies indexing both self-reported and log-based measures. To assess the alignment between these measures, we conducted a pre-registered meta-analysis of this research. Based on 106 effect sizes, we found that self-reported media use correlates only moderately with logged measurements, that self-reports were rarely an accurate reflection of logged media use and that measures of problematic media use show an even weaker association with usage logs. These findings raise concerns about the validity of findings relying solely on self-reported measures of media use., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Loneliness is linked to increased risk for Alzheimer's disease, but little is known about factors potentially contributing to adverse brain health in lonely individuals. In this study, we used data from 24,867 UK Biobank participants to investigate risk factors related to loneliness and estimated brain age based on neuroimaging data. The results showed that on average, individuals who self-reported loneliness on a single yes/no item scored higher on neuroticism, depression, social isolation, and socioeconomic deprivation, performed less physical activity, and had higher BMI compared to individuals who did not report loneliness. In line with studies pointing to a genetic overlap of loneliness with neuroticism and depression, permutation feature importance ranked these factors as the most important for classifying lonely vs. not lonely individuals (ROC AUC = 0.83). While strongly linked to loneliness, neuroticism and depression were not associated with brain age estimates. Conversely, objective social isolation showed a main effect on brain age, and individuals reporting both loneliness and social isolation showed higher brain age relative to controls - as part of a prominent risk profile with elevated scores on socioeconomic deprivation and unhealthy lifestyle behaviours, in addition to neuroticism and depression. While longitudinal studies are required to determine causality, this finding may indicate that the combination of social isolation and a genetic predisposition for loneliness involves a risk for adverse brain health. Importantly, the results underline the complexity in associations between loneliness and adverse health outcomes, where observed risks likely depend on a combination of interlinked variables including genetic as well as social, behavioural, physical, and socioeconomic factors., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research., (© 2020 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

The deviation between chronological age and age predicted using brain MRI is a putative marker of overall brain health. Age prediction based on structural MRI data shows high accuracy in common brain disorders. However, brain aging is complex and heterogenous, both in terms of individual differences and the underlying biological processes. Here, we implemented a multimodal model to estimate brain age using different combinations of cortical area, thickness and sub-cortical volumes, cortical and subcortical T1/T2-weighted ratios, and cerebral blood flow (CBF) based on arterial spin labeling. For each of the 11 models we assessed the age prediction accuracy in healthy controls (HC, n = 750) and compared the obtained brain age gaps (BAGs) between age-matched subsets of HC and patients with Alzheimer's disease (AD, n = 54), mild (MCI, n = 90) and subjective (SCI, n = 56) cognitive impairment, schizophrenia spectrum (SZ, n = 159) and bipolar disorder (BD, n = 135). We found highest age prediction accuracy in HC when integrating all modalities. Furthermore, two-group case-control classifications revealed highest accuracy for AD using global T1-weighted BAG, while MCI, SCI, BD and SZ showed strongest effects in CBF-based BAGs. Combining multiple MRI modalities improves brain age prediction and reveals distinct deviations in patients with psychiatric and neurological disorders. The multimodal BAG was most accurate in predicting age in HC, while group differences between patients and HC were often larger for BAGs based on single modalities. These findings indicate that multidimensional neuroimaging of patients may provide a brain-based mapping of overlapping and distinct pathophysiology in common disorders., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice., Competing Interests: EK and SK are employed by company SzeleSTIM GmbH. JS received honoraria from SzeleSTIM GmbH and owns patents in the field of the auricular vagus nerve stimulation. EK, SK, and JS are shareholders of SzeleSTIM GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer TS declared a shared affiliation, with no collaboration, with one of the authors HJ, to the handling editor at the time of review., (Copyright © 2021 Farmer, Strzelczyk, Finisguerra, Gourine, Gharabaghi, Hasan, Burger, Jaramillo, Mertens, Majid, Verkuil, Badran, Ventura-Bort, Gaul, Beste, Warren, Quintana, Hämmerer, Freri, Frangos, Tobaldini, Kaniusas, Rosenow, Capone, Panetsos, Ackland, Kaithwas, O'Leary, Genheimer, Jacobs, Van Diest, Schoenen, Redgrave, Fang, Deuchars, Széles, Thayer, More, Vonck, Steenbergen, Vianna, McTeague, Ludwig, Veldhuizen, De Couck, Casazza, Keute, Bikson, Andreatta, D'Agostini, Weymar, Betts, Prigge, Kaess, Roden, Thai, Schuster, Montano, Hansen, Kroemer, Rong, Fischer, Howland, Sclocco, Sellaro, Garcia, Bauer, Gancheva, Stavrakis, Kampusch, Deuchars, Wehner, Laborde, Usichenko, Polak, Zaehle, Borges, Teckentrup, Jandackova, Napadow and Koenig.)

Clinical and epidemiological evidence suggest that loneliness is associated with severe mental disorders (SMDs) and increases the risk of cardiovascular disease (CVD). However, the mechanisms underlying the relationship between loneliness, SMDs, and CVD risk factors remain unknown. Here we explored overlapping genetic architecture and genetic loci shared between SMDs, loneliness, and CVD risk factors. We analyzed large independent genome-wide association study data on schizophrenia (SCZ), bipolar disorder (BD), major depression (MD), loneliness and CVD risk factors using bivariate causal mixture mode (MiXeR), which estimates the total amount of shared variants, and conditional false discovery rate to evaluate overlap in specific loci. We observed substantial genetic overlap between SMDs, loneliness and CVD risk factors, beyond genetic correlation. We identified 149 loci jointly associated with loneliness and SMDs (MD n = 67, SCZ n = 54, and BD n = 28), and 55 distinct loci jointly associated with loneliness and CVD risk factors. A total of 153 novel loneliness loci were found. Most of the shared loci possessed concordant effect directions, suggesting that genetic risk for loneliness may increase the risk of both SMDs and CVD. Functional analyses of the shared loci implicated biological processes related to the brain, metabolic processes, chromatin and immune system. Altogether, the study revealed polygenic overlap between loneliness, SMDs and CVD risk factors, providing new insights into their shared genetic architecture and common genetic mechanisms.

Podcasts are emerging as popular fora for discussing science. Here, we describe how podcasts can benefit scientific communities by disseminating career-specific information that is often unwritten and hidden to those outside academic social knowledge networks. We also provide practical advice on how scientists can launch their own podcasts., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Reports on the modulatory role of the neuropeptide oxytocin on social cognition and behavior have steadily increased over the last two decades, stimulating considerable interest in its psychiatric application. Basic and clinical research in humans primarily employs intranasal application protocols. This approach assumes that intranasal administration increases oxytocin levels in the central nervous system via a direct nose-to-brain route, which in turn acts upon centrally-located oxytocin receptors to exert its behavioral effects. However, debates have emerged on whether intranasally administered oxytocin enters the brain via the nose-to-brain route and whether this route leads to functionally relevant increases in central oxytocin levels. In this review we outline recent advances from human and animal research that provide converging evidence for functionally relevant effects of the intranasal oxytocin administration route, suggesting that direct nose-to-brain delivery underlies the behavioral effects of oxytocin on social cognition and behavior. Moreover, advances in previously debated methodological issues, such as pre-registration, reproducibility, statistical power, interpretation of non-significant results, dosage, and sex differences are discussed and integrated with suggestions for the next steps in translating intranasal oxytocin into psychiatric applications.

The neuropeptide oxytocin has been popularized for its role in social behaviour and nominated as a candidate treatment for several psychiatric illnesses due to promising preclinical results. However, these results so far have failed to reliably translate from animal models to human research. In response, there have been justified calls to improve intranasal oxytocin delivery methodology in terms of verifying that intranasal administration increases central levels of oxytocin. Nonetheless, improved methodology needs to be coupled with a robust theory of the role of oxytocin in behaviour and physiology to ask meaningful research questions. Moreover, stringent methodology based on robust theory may yield interesting results, but such findings will have limited utility if they are not reproducible. We outline how the precision of intranasal oxytocin research can be improved by the complementary consideration of methodology, theory and reproducibility.

The neuropeptide oxytocin has attracted substantial research interest for its role in behaviour and cognition; however, the evidence for its effects have been mixed. Meta-analysis is viewed as the gold-standard for synthesizing evidence, but the evidential value of a meta-analysis is dependent on the evidential value of the studies it synthesizes, and the analytical approaches used to derive conclusions. To assess the evidential value of oxytocin administration meta-analyses, this study calculated the statistical power of 107 studies from 35 meta-analyses and assessed the statistical equivalence of reported results. The mean statistical power across all studies was 12.2% and there has been no noticeable improvement in power over an eight-year period. None of the 26 non-significant meta-analyses were statistically equivalent, assuming a smallest effect size of interest of 0.1. Altogether, most oxytocin treatment study designs are statistically underpowered to either detect or reject a wide range of worthwhile effect sizes., Competing Interests: The author declares that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

Oxytocin has garnered considerable interest for its role in social behavior, as well as for the potential of intranasal administration to treat social difficulties. However, current theoretical models for the role of oxytocin in social behavior pay little consideration to its evolutionary and developmental history. This article aims to broaden our understanding of the role of oxytocin in social behavior by adopting an ethological approach through the lens of Nikolaas Tinbergen's 'four questions' - how does oxytocin work; how does the role of oxytocin change during development; how does oxytocin enhance survival; and how did the oxytocin system evolve? We argue that oxytocin is most accurately described as an allostatic hormone that modulates both social and non-social behavior by maintaining stability through changing environments., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: A growing number of studies suggest that social isolation and loneliness are associated with premature mortality and are more prevalent among people with mental illness than in the general population, outlining many potential paths to disease still to be elucidated. The purpose of this meta-analysis is to examine the relationship between loneliness, social isolation, and established cardiovascular/metabolic risk factors and disorders, especially in severe mental illness, and to account for potential heterogeneity in the literature., Methods/design: Studies that report measures of loneliness and/or social isolation along with cardiovascular/metabolic risk factors will be identified. PubMed, EMBASE (through Ovid SP), Scopus, and PsycINFO (through Ovid SP) will be searched, along with citation lists of retrieved articles and the Cochrane Database of Systematic Reviews. Grey literature will be searched using Google Scholar. Data will be extracted from eligible studies for a random effects meta-analysis. For each study, a summary effect size, heterogeneity, risk of bias, publication bias, and the effect of categorical and continuous moderator variables will be determined., Discussion: This proposed systematic review and meta-analysis will identify and synthesise evidence to determine if there is an association between loneliness, social isolation, and cardiovascular/metabolic risk factors, with a special focus on severe mental illnesses. The results will help determine links and promising avenues of further research., Systematic Review Registration: PROSPERO CRD42018111911.

Open research data provide considerable scientific, societal, and economic benefits. However, disclosure risks can sometimes limit the sharing of open data, especially in datasets that include sensitive details or information from individuals with rare disorders. This article introduces the concept of synthetic datasets, which is an emerging method originally developed to permit the sharing of confidential census data. Synthetic datasets mimic real datasets by preserving their statistical properties and the relationships between variables. Importantly, this method also reduces disclosure risk to essentially nil as no record in the synthetic dataset represents a real individual. This practical guide with accompanying R script enables biobehavioural researchers to create synthetic datasets and assess their utility via the synthpop R package. By sharing synthetic datasets that mimic original datasets that could not otherwise be made open, researchers can ensure the reproducibility of their results and facilitate data exploration while maintaining participant privacy., Competing Interests: DQ No competing interests declared, (© 2020, Quintana.)