Research Report: A Link between Sertraline Treatment and Susceptibility to (Mis)information.

Recent research revealed that several psycho-cognitive processes, such as insensitivity to positive and negative feedback, cognitive rigidity, pessimistic judgment bias, and anxiety, are involved in susceptibility to fake news. All of these processes have been previously associated with depressive disorder and are sensitive to serotoninergic manipulations. In the current study, a link between chronic treatment with the selective serotonin reuptake inhibitor (SSRI) sertraline and susceptibility to true and fake news was examined. Herein, a sample of 1162 participants was recruited via Prolific Academic for an online study. Half of the sample reported taking sertraline (Zoloft) for at least 8 weeks (sertraline group), and the other half confirmed not taking any psychiatric medication (control group). The sertraline group was further divided according to their daily dosage (50, 100, 150, and 200 mg/day). All participants completed a susceptibility to misinformation scale, wherein they were asked to determine the veracity of the presented true and fake news and their willingness to behaviorally engage with the news. The results were compared between those of the sertraline groups and the control group. The results showed that sertraline groups did not differ significantly in the assessment of the truthfulness of information or their ability to discern the truth. However, those taking sertraline appeared to have a significantly increased likelihood of behavioral engagement with the information, and this effect was observed for both true and fake news. The research presented here represents the initial endeavor to comprehend the neurochemical foundation of the susceptibility to misinformation. The association between sertraline treatment and increased behavioral engagement with information observed in this study can be explained in light of previous studies showing positive correlations between serotonin (5-HT) system activity and the inclination to engage in social behaviors. It can also be attributed to the anxiolytic effects of sertraline treatment, which mitigate the fear of social judgment. The heightened behavioral engagement with information in people taking sertraline may, as part of a general phenomenon, also shape their interactions with fake news. Future longitudinal studies should reveal the specificity and exact causality of these interactions.

Identification of genes regulated by trait sensitivity to negative feedback and prolonged alcohol consumption in rats.

BACKGROUND: The results of our previous studies demonstrated that low sensitivity to negative feedback (NF) is associated with increased vulnerability to the development of compulsive alcohol-seeking in rats. In the present study, we investigated the molecular underpinnings of this relationship. METHODS: Using TaqMan Gene Expression Array Cards, we analyzed the expression of the genes related to NF sensitivity and alcohol metabolism in three cortical regions (medial prefrontal cortex [mPFC], anterior cingulate cortex [ACC], orbitofrontal cortex [OFC]) and two subcortical regions (nucleus accumbens [Nacc], amygdala [Amy]). Gene expression differences were confirmed at the protein level with Western blot. RESULTS: Sensitivity to NF was characterized by differences in Gad2, Drd2, and Slc6a4 expression in the ACC, Maoa in the mPFC, and Gria1, Htr3a, and Maoa in the OFC. Chronic alcohol consumption was associated with differences in the expression of Comt and Maoa in the ACC, Comt, Adh1, and Htr2b in the mPFC, Adh1, and Slc6a4 in the Nacc, Gad2, and Htr1a in the OFC, and Drd2 in the Amy. Interactions between the sensitivity to NF and alcohol consumption were observed in the expression of Gabra1, Gabbr2, Grin2a, Grin2b, and Grm3 in the ACC, and Grin2a in the OFC. The observed differences were confirmed at the protein level for MAO-A in the mPFC, and ADH1 in the mPFC and Nacc. CONCLUSIONS: Our findings contribute to a better understanding of the molecular mechanisms underlying the relationship between trait sensitivity to NF and compulsive alcohol consumption.

Trait sensitivity to positive feedback is a predisposing factor for several aspects of compulsive alcohol drinking in male rats: behavioural, physiological, and molecular correlates.

INTRODUCTION: Alcohol use disorder (AUD) is one of the most common psychiatric disorders and a leading cause of mortality worldwide. While the pathophysiology underlying AUD is relatively well known, the cognitive mechanisms of an individual's susceptibility to the development of alcohol dependence remain poorly understood. In this study, we investigated the theoretical claim that sensitivity to positive feedback (PF), as a stable and enduring behavioural trait, can predict individual susceptibility to the acquisition and maintenance of alcohol-seeking behaviour in rats. METHODS: Trait sensitivity to PF was assessed using a series of probabilistic reversal learning tests. The escalation of alcohol intake in rats was achieved by applying a mix of intermittent free access and instrumental paradigms of alcohol drinking. The next steps included testing the influence of sensitivity to PF on the acquisition of compulsive alcohol-seeking behaviour in the seeking-taking punishment task, measuring motivation to seek alcohol, and comparing the speed of extinction and reinstatement of alcohol-seeking after a period of abstinence between rats expressing trait insensitivity and sensitivity to PF. Finally, trait differences in the level of stress hormones and in the expression of genes and proteins in several brain regions of interest were measured to identify potential physiological and neuromolecular mechanisms of the observed interactions. RESULTS: We showed that trait sensitivity to PF in rats determines the level of motivation to seek alcohol following the experience of its negative consequences. They also revealed significant differences between animals classified as insensitive and sensitive to PF in their propensity to reinstate alcohol-seeking behaviours after a period of forced abstinence. The abovementioned effects were accompanied by differences in blood levels of stress hormones and differences in the cortical and subcortical expression of genes and proteins related to dopaminergic, serotonergic, and GABAergic neurotransmission. CONCLUSION: Trait sensitivity to PF can determine the trajectory of alcohol addiction in rats. This effect is, at least partially, mediated via distributed physiological and molecular changes within cortical and subcortical regions of the brain.

The role of perceived minority-group status in the conspiracy beliefs of factual majority groups.

Research suggests that minority-group members sometimes are more susceptible to misinformation. Two complementary studies examined the influence of perceived minority status on susceptibility to misinformation and conspiracy beliefs. In study 1 (n = 2140), the perception of belonging to a minority group, rather than factually belonging to it, was most consistently related with an increased susceptibility to COVID-19 misinformation across national samples from the USA, the UK, Germany and Poland. Specifically, perceiving that one belongs to a gender minority group particularly predicted susceptibility to misinformation when participants factually did not belong to it. In pre-registered study 2 (n = 1823), an experiment aiming to manipulate the minority perceptions of men failed to influence conspiracy beliefs in the predicted direction. However, pre-registered correlational analyses showed that men who view themselves as a gender minority were more prone to gender conspiracy beliefs and exhibited a heightened conspiracy mentality. This effect was correlationally mediated by increased feelings of system identity threat, collective narcissism, group relative deprivation and actively open-minded thinking. Especially, the perception of being a minority in terms of power and influence (as compared to numerically) was linked to these outcomes. We discuss limitations and practical implications for countering misinformation.

Are we willing to share what we believe is true? Factors influencing susceptibility to fake news.

Background: The contemporary media landscape is saturated with the ubiquitous presence of misinformation. One can point to several factors that amplify the spread and dissemination of false information, such as blurring the line between expert and layman's opinions, economic incentives promoting the publication of sensational information, the zero cost of sharing false information, and many more. In this study, we investigate some of the mechanisms of fake news dissemination that have eluded scientific scrutiny: the evaluation of veracity and behavioral engagement with information in light of its factual truthfulness (either true or false), cognitive utility (either enforcing or questioning participants' beliefs), and presentation style (either sober or populistic). Results: Two main results emerge from our experiment. We find that the evaluation of veracity is mostly related to the objective truthfulness of a news item. However, the probability of engagement is more related to the congruence of the information with the participants' preconceived beliefs than to objective truthfulness or information presentation style. Conclusion: We conclude a common notion that the spread of fake news can be limited by fact-checking and educating people might not be entirely true, as people will share fake information as long as it reduces the entropy of their mental models of the world. We also find support for the Trojan Horse hypothesis of fake news dissemination.

Hallucinogenic activity, neurotransmitters release, anxiolytic and neurotoxic effects in Rat's brain following repeated administration of novel psychoactive compound 25B-NBOMe.

2-(4-Bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)etanoamine (25B-NBOMe) is a highly selective 5-HT2A receptor agonist, exhibiting a potent hallucinogenic activity. In the present study, we investigated the effect of a 7-day treatment with 25B-NBOMe in a dose of 0.3 mg/kg on the following: the neurotransmitter release in vivo using microdialysis in freely moving animals, hallucinogenic activity measured in the Wet Dog Shake (WDS) test, anxiety level as measured in the light/dark box (LDB) and locomotor activity in the open field (OF) test, DNA damage with the comet assay, and on a number of neuronal and glial cells with immunohistochemistry. Repeated administration of 25B-NBOMe decreased the response to a challenge dose (0.3 mg/kg) on DA, 5-HT and glutamatergic neurons in the rats' frontal cortex, striatum, and nucleus accumbens. The WDS response dropped drastically after the second day of treatment, suggesting a rapid development of tolerance. LDB and OF tests showed that the effect of 25B-NBOMe on anxiety depends on the treatment and environmental settings. Results obtained with the comet assay indicate a genotoxic properties in the frontal cortex and hippocampus. An increase in immunopositive glial but not neuronal cells was observed in the cortical regions but not in the hippocampus. In conclusion, our study showed that a chronic administration of 25B-NBOMe produces the development of tolerance observed in the neurotransmitters release and hallucinogenic activity. The oxidative damage of cortical and hippocampal DNA implies the generation of free radicals by the drug, resulting in genotoxicity but rather not in neurotoxic tissue damage. Behavioral tests show that 25B-NBOMe exerts anxiogenic effect after single and repeated treatment.

Importance of additional behavioral observation in psychopharmacology: a case study on agomelatine's effects on feedback sensitivity in probabilistic reversal learning in rats.

Since the second half of the twentieth century, many important discoveries in the field of behavioral psychopharmacology have been made using operant conditioning cages. These cages provide objective data collection and have revolutionized behavioral research. Unfortunately, in the rush towards automation, many mistakes may have been made that could have been avoided by observing experimental animals. The study described in this paper is an excellent example of how important additional behavioral observation can be for interpreting instrumental data. In this study, we evaluated the effects of single injections of 3 different doses of agomelatine (5, 10, and 40 mg/kg) on feedback sensitivity in rats. To this end, we tested 40 animals in the instrumental probabilistic reversal learning task in a Latin square design. The highest applied dose of agomelatine, prima facie, reduced the sensitivity of rats to negative feedback - an effect that can be considered antidepressant. However, additional behavioral observation dramatically changed the interpretation of the results and revealed that the perceived effect of agomelatine on sensitivity to negative feedback can actually be attributed to drug-induced drowsiness.

Trait sensitivity to negative feedback in rats is associated with increased expression of serotonin 5-HT2A receptors in the ventral hippocampus.

One of the most important yet still underappreciated mechanisms of depression is distorted cognition, with aberrant sensitivity to negative feedback being one of the best-described examples. As serotonin has been identified as an important modulator of sensitivity to feedback and because the hippocampus has been implicated in the mediation of learning from positive and negative outcomes, the present study aimed to identify differences in the expression of various genes encoding 5-HT receptors in this brain region between the rats displaying trait sensitivity and insensitivity to negative feedback. The results demonstrated that trait sensitivity to negative feedback is associated with increased mRNA expression of the 5-HT2A receptors in the rat ventral hippocampus (vHipp). Further analysis revealed that this increased expression might be modulated epigenetically by miRNAs with a high target score for the Htr2a gene (miR-16-5p and miR-15b-5p). Additionally, although not confirmed at the protein level, trait sensitivity to negative feedback was associated with decreased expression of mRNA encoding the 5-HT7 receptor in the dorsal hippocampus (dHipp). We observed no statistically significant intertrait differences in the expression of the Htr1a, Htr2c, and Htr7 genes in the vHipp and no statistically significant intertrait differences in the expression of the Htr1a, Htr2a, and Htr2c genes in the dHipp of the tested animals. These results suggest that resilience to depression manifested by reduced sensitivity to negative feedback may be mediated via these receptors.

Trait sensitivity to negative feedback determines the effects of chronic stress and chronic mirtazapine treatment on anxiety and stress-coping strategies in rats.

In this study, we examined whether trait sensitivity to negative feedback (NF) can interact with the effects of chronic stress and antidepressant treatment on anxiety and stress-induced coping strategies in rats. Results of the conducted experiments indicated that animals displaying trait insensitivity to NF were more prone to develop stress-induced anxiety than their NF-sensitive conspecifics. Moreover, an analysis of the behavioral patterns displayed by the NF-insensitive animals during the forced swim test (FST) revealed complementary (anxiety-driven) effects of trait sensitivity to NF on the strategy of coping with an acute, stressful situation. Finally, an analysis of the interactions between NF sensitivity and the effects of antidepressant drug - mirtazapine - revealed that in animals subjected to chronic stress, the effects of the drug on anxiety and coping strategies differ significantly between animals classified as NF insensitive and NF sensitive. The present results suggest that NF sensitivity screening could be potentially used to determine individual vulnerability to development of affective disorders and effectivity of their treatment.

Trait sensitivity to negative feedback determines the intensity of compulsive alcohol seeking and taking in male rats.

BACKGROUND: Alcohol use disorder is one of the most common psychiatric disorders, and it is a leading cause of mortality worldwide. It has been demonstrated previously that people with alcohol use disorder are less sensitive to the negative outcomes of their actions and less able to use negative feedback to guide and adjust their ongoing behaviour. However, far less is known about the aberrant processing of negative feedback before the onset of alcohol use disorder. In this study, we investigated the theoretical claim that sensitivity to negative feedback - as a stable and enduring behavioural trait - can predict vulnerability to the development of compulsive alcohol consumption in rats. METHODS: We trained and tested rats in a series of probabilistic reversal learning tests, and based on this "negative feedback sensitivity screening," we classified each rat as more or less sensitive to negative feedback. Then, in the intermittent-access 2-bottle choice paradigm, we measured alcohol consumption in the animals classified above. In the next step, using the instrumental second-order chained schedule of alcohol reinforcement task, we examined the influence of sensitivity to negative feedback on the development of compulsive alcohol seeking behaviour. Finally, we measured how trait sensitivity to negative feedback affected the extinction and reinstatement of alcohol seeking after a period of abstinence. RESULTS: Trait sensitivity to negative feedback predicted the vulnerability of rats to the development of compulsive alcohol seeking and consumption. We also found significant differences between the more sensitive and less sensitive groups in their propensity to extinguish alcohol seeking behaviours when the alcohol was no longer available. LIMITATIONS: The findings from our study did not answer the question of whether individual differences in sensitivity to negative feedback have a genetic basis or develop in response to postnatal experiences. CONCLUSION: The results of our study suggest that negative feedback sensitivity screening could be used to evaluate individual vulnerability to the development and maintenance of alcohol use disorder.

Cognitive Processes and Personality Traits Underlying Four Phenotypes of Susceptibility to (Mis)Information.

Misinformation on social media poses a serious threat to democracy, sociopolitical stability, and mental health. Thus, it is crucial to investigate the nature of cognitive mechanisms and personality traits that contribute to the assessment of news items' veracity, failures in the discernment of their truthfulness, and behavioral engagement with the news, especially if one wants to devise any intervention to stop the spread of misinformation in social media. The current research aimed to develop and test a 4-fold taxonomy classifying people into four distinct phenotypes of susceptibility to (mis)information. In doing so, it aimed to establish differences in cognitive and psychological profiles between these phenotypes. The investigated cognitive processes included sensitivity to feedback, belief updating, and cognitive judgment bias. Psychological traits of interest included the Big Five model, grandiose narcissism, anxiety, and dispositional optimism. The participants completed online surveys that consisted of a new scale designed to classify people into one of four phenotypes of susceptibility to (mis)information, advanced cognitive tests, and reliable psychological instruments. The four identified phenotypes, Doubters, Knowers, Duffers, and Consumers, showed that believing in misinformation does not imply denying the truth. In contrast, the numerically largest phenotypes encompassed individuals who were either susceptible (Consumers) or resistant (Doubters), in terms of veracity judgment and behavioral engagement, to any news, regardless of its truthfulness. Significantly less frequent were the phenotypes characterized by excellent and poor discernment of the news' truthfulness (the Knowers and the Duffers, respectively). The phenotypes significantly differed in sensitivity to positive and negative feedback, cognitive judgment bias, extraversion, conscientiousness, agreeableness, emotional stability, grandiose narcissism, anxiety, and dispositional optimism. The obtained results constitute a basis for a new and holistic approach in understanding susceptibility to (mis)information as a psycho-cognitive phenotype.

Psychological interventions countering misinformation in social media: A scoping review.

Introduction: The rise of social media users and the explosive growth in misinformation shared across social media platforms have become a serious threat to democratic discourse and public health. The mentioned implications have increased the demand for misinformation detection and intervention. To contribute to this challenge, we are presenting a systematic scoping review of psychological interventions countering misinformation in social media. The review was conducted to (i) identify and map evidence on psychological interventions countering misinformation, (ii) compare the viability of the interventions on social media, and (iii) provide guidelines for the development of effective interventions. Methods: A systematic search in three bibliographic databases (PubMed, Embase, and Scopus) and additional searches in Google Scholar and reference lists were conducted. Results: 3,561 records were identified, 75 of which met the eligibility criteria for the inclusion in the final review. The psychological interventions identified during the review can be classified into three categories distinguished by Kozyreva et al.: Boosting, Technocognition, and Nudging, and then into 15 types within these. Most of the studied interventions were not implemented and tested in a real social media environment but under strictly controlled settings or online crowdsourcing platforms. The presented feasibility assessment of implementation insights expressed qualitatively and with numerical scoring could guide the development of future interventions that can be successfully implemented on social media platforms. Discussion: The review provides the basis for further research on psychological interventions counteracting misinformation. Future research on interventions should aim to combine effective Technocognition and Nudging in the user experience of online services. Systematic review registration: [https://figshare.com/], identifier [https://doi.org/10.6084/m9.figshare.14649432.v2].

Reinforcement-based cognitive biases as vulnerability factors in alcohol addiction: From humans to animal models.

Alcohol use disorder (AUD) is one of the most common, but still poorly treated, psychiatric conditions. Developing new treatments requires a better understanding of the aetiology of symptoms and evaluation of novel therapeutic targets in preclinical studies. Recent developments in our understanding of the reinforcement-based cognitive biases (RBCBs) that contribute to the development of AUD and its treatment offer new opportunities for both clinical and preclinical research. In this review, we first briefly describe psychological and cognitive theories that involve various aspects of reinforcement sensitivity in the development, maintenance, and recurrence of alcohol addiction. Furthermore, in separate sections, we describe studies investigating RBCBs and their neural, neurochemical, and pharmacological correlates, and we discuss possible interactions between RBCBs and trajectories of AUD. Finally, we describe how recent translational studies using state-of-the-art animal models can facilitate our understanding of the role of reinforcement sensitivity and RBCBs in various aspects of AUD. LINKED ARTICLES: This article is part of a themed issue on New discoveries and perspectives in mental and pain disorders. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.17/issuetoc.

Neuromolecular Underpinnings of Negative Cognitive Bias in Depression.

This selective review aims to summarize the recent advances in understanding the neuromolecular underpinnings of biased cognition in depressive disorder. We begin by considering the cognitive correlates of depressed mood and the key brain systems implicated in its development. We then review the core findings across two domains of biased cognitive function in depression: pessimistic judgment bias and abnormal response to negative feedback. In considering their underlying substrates, we focus on the neurochemical mechanisms identified by genetic, molecular and pharmacological challenge studies. We conclude by discussing experimental approaches to the treatment of depression, which are derived largely from an improved understanding of its cognitive substrates.

Tolerance to neurochemical and behavioral effects of the hallucinogen 25I-NBOMe.

RATIONALE: 4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) is a potent serotonin 5-HT2A/2C receptor agonist with hallucinogenic activity. There is no data on the 25I-NBOMe effect on brain neurotransmission and animal performance after chronic administration. OBJECTIVES: We examined the effect of a 7-day treatment with 25I-NBOMe (0.3 mg/kg/day) on neurotransmitters' release and rats' behavior in comparison to acute dose. METHODS: Changes in dopamine (DA), serotonin (5-HT), acetylcholine (ACh), and glutamate release were studied using microdialysis in freely moving rats. The hallucinogenic activity was measured in the wet dog shake (WDS) test. The animal locomotion was examined in the open field (OF) test, short-term memory in the novel object recognition (NOR) test. The anxiogenic/anxiolytic properties of the drug were tested using the light/dark box (LDB) test. RESULTS: Repeated administration of 25I-NBOMe decreased the response to a challenge dose of DA, 5-HT, and glutamatergic neurons in the frontal cortex as well as weakened the hallucinogenic activity in comparison to acute dose. In contrast, striatal and accumbal DA and 5-HT release and accumbal but not striatal glutamate release in response to the challenge dose of 25I-NBOMe was increased in comparison to acute treatment. The ACh release was increased in all brain regions. Behavioral tests showed a motor activity reduction and memory deficiency in comparison to a single dose and induction of anxiety after the drug's chronic and acute administration. CONCLUSIONS: Our findings suggest that multiple injections of 25I-NBOMe induce tolerance to hallucinogenic activity and produce alterations in neurotransmission. 25I-NBOMe effect on short-term memory, locomotor function, and anxiety seems to be the result of complex interactions between neurotransmitter pathways.

Phenotypes of reinforcement sensitivity as predictors of the response to acute antidepressant treatment in rats.

One of the biggest threats to modern societies is the increasing prevalence of mood disorders. Cognitive deficits associated with depressive and bipolar disorders are a major driver of functional impairment and the ensuing disability of the suffering individuals. Growing evidence has indicated strong inter-individual differences in the vulnerability to development and effectivity of treatment of these psychiatric conditions, linking various levels of reinforcement sensitivity with specific mood conditions. In this study, we took a unique opportunity to investigate how trait sensitivity to reinforcement determines the reactivity of rats to acute antidepressant treatment. For this, using a preclinical version of the probabilistic reversal-learning (PRL) paradigm, we identified 4 phenotypes of sensitivity to negative and positive feedback in rats, which could represent various types of potential vulnerability to affective disorders. Subsequently, using the light/dark box (LDB) and progressive ratio schedule of reinforcement (PRSR) tests, we evaluated inter-phenotypic differences in the effects of acute treatment with 3 different antidepressant drugs (escitalopram, mirtazapine and clomipramine, each in 3 doses) on anxiety and appetitive motivation of experimental animals. We report statistically significant differences between the investigated phenotypes of reinforcement sensitivity in the effects of acute escitalopram treatment on anxiety in the LDB test. We also report phenotype-independent effects of mirtazapine on motivation and anxiety and a lack of effect of clomipramine. These results demonstrate for the first time that trait sensitivity to reinforcement could have important implications for the effectiveness of treatment in affective disorders.

Trait Sensitivity to Negative and Positive Feedback Does Not Interact With the Effects of Acute Antidepressant Treatment on Hedonic Status in Rats.

Aberrant cognition plays a pivotal role in the development and maintenance of depression. One of the most important cognitive distortions associated with depression is aberrant sensitivity to performance feedback. Under clinical conditions, this sensitivity can be measured using the probabilistic reversal learning (PRL) test, which has also been recently implemented in animal studies. Although the evidence for the coexistence of depression and altered feedback sensitivity is relatively coherent, it is unclear whether this sensitivity can influence the effectiveness of antidepressant treatment. In the present research, we investigated how trait sensitivity to negative and positive feedback interacts with the effects of acute antidepressant treatment on hedonic status in rats. We tested a cohort of rats with a series of 10 PRL tests, and based on this screening, we classified each animal as sensitive or insensitive to negative and positive feedback. Subsequently, in the Latin square design, we evaluated the effects of a single administration of two antidepressant drugs (each at three different doses: agomelatine: 5, 10, and 40 mg/kg; mirtazapine 0.5, 1, and 3 mg/kg) on the hedonic status of rats in the sucrose preference tests. There was no statistically significant interaction between trait sensitivity to feedback and the effects of acute antidepressant treatment on hedonic status in rats.