Sad Facial Expressions Research Articles

Do Children with High Callous-Unemotional Traits Have Attentional Deficits to Emotional Stimuli? Evidence from a Multi-Method and Multi-Informant Study.

Callous-unemotional (CU) traits in children and adolescents are linked to severe and persistent antisocial behavior. Based on past empirical research, several theoretical models have suggested that CU traits may be partly explained by difficulties in correctly identifying others' emotional states as well as their reduced attention to others' eyes, which could be important for both causal theory and treatment. This study tested the relationships among CU traits, emotion recognition of facial expressions and visual behavior in a sample of 52 boys referred to a clinic for conduct problems (Mage = 10.29years; SD = 2.06). We conducted a multi-method and multi-informant assessment of CU traits through the Child Problematic Traits Inventory (CPTI), the Inventory of Callous-Unemotional (ICU), and the Clinical Assessment of Prosocial Emotions-Version 1.1 (CAPE). The primary goal of the study was to compare the utility of these methods for forming subgroups of youth that differ in their emotional processing abilities. An emotion recognition task assessed recognition accuracy (percentage of mistakes) and absolute dwell time on the eyes or mouth region for each emotion. Results from repeated measures ANOVAs revealed that low and high CU groups did not differ in emotion recognition accuracy, irrespective of the method of assessing CU traits. However, the high CU group showed reduced attention to the eyes of fearful and sad facial expressions (using the CPTI) or to all emotions (using the CAPE). The high CU group also showed a general increasein attention to the mouth area, but only when assessed by the CAPE. These findings provide evidence to support abnormalities in how those elevated on CU traits process emotional stimuli, especially when assessed by a clinical interview, which could guide appropriate assessment and more successful interventions for this group of youth.

Are older adults less generous? Age differences in emotion-related social decision making

In social interaction, age-related differences in emotional processing may lead to varied social decision making between young and older adults. However, previous studies of social decision making have paid less attention to the interactants' emotions, leaving age differences and underlying neural mechanisms unexplored. To address this gap, the present study combined functional and structural magnetic resonance imaging, employing a modified dictator game task with recipients displaying either neutral or sad facial expressions. Behavioral results indicated that although older adults' overall allocations did not differ significantly from those of young adults, older adults' allocations showing a decrease in emotion-related generosity compared to young adults. Using representational similarity analysis, we found that older adults showed reduced neural representations of recipients' emotions and gray matter volume in the right anterior cingulate gyrus (ACC), right insula, and left dorsomedial prefrontal cortex (DMPFC) compared to young adults. More importantly, mediation analyses indicated that age influenced allocations not only through serial mediation of neural representations of the right insula and left DMPFC, but also through serial mediation of the mean gray matter volume of the right ACC and left DMPFC. This study identifies the potential neural pathways through which age affects emotion-related social decision making, advancing our understanding of older adults' social interaction behavior that they may not be less generous unless confronted with individuals with specific emotions.

People Attribute a Range of Highly-Varied and Socially-Bound Meanings to Naturalistic Sad Facial Expressions

Depictions of sadness are commonplace, and here we aimed to discover and catalogue the complex and nuanced ways that people interpret sad facial expressions. We used a rigorous qualitative methodology to build a thematic framework from 3,243 open-ended responses from 41 people who participated in 2020 and described what they thought sad expressors in 80 images were thinking, feeling, and/or intending to do. Face images were sourced from a novel set of naturalistic expressions (ANU Real Facial Expression Database), as well as a traditional posed expression database (Radboud Faces Database). The resultant framework revealed clear themes around the expressors’ thoughts (e.g., acceptance, contemplation, disbelief), social needs (e.g., social support or withdrawal), social behaviours/intentions (e.g., mock or manipulate), and the precipitating events (e.g., social or romantic conflict). Expressions that were perceived as genuine were more frequently described as thinking deeply, reflecting, or feeling regretful, whereas those perceived as posed were more frequently described as exaggerated, overamplified, or dramatised. Overall, findings highlight that facial expressions — even with high levels of consensus about the emotion category they belong to — are interpreted in nuanced and complex ways that emphasise their role as other-oriented social tools, and convey semantically related emotion categories that share smooth gradients with one another. Our novel thematic framework also provides an important foundation for future work aimed at understanding variation in the social functions of sadness, including exploring potential differences in interpretations across cultural settings.

Impact of babyface schema on time perception: Insights from neutral and crying facial expressions.

Facial expressions in infants have been noted to create a spatial attention bias when compared with adult faces. Yet, there is limited understanding of how adults perceive the timingof infant facial expressions. To investigate this, we used both infant and adult facial expressions in a temporal bisection task. In Experiment 1, we compared duration judgments of neutral infant and adult faces. The results revealed that participants felt that neutral infant faces lasted for a shorter time than neutral adult faces, independent of participant sex. Experiment 2 employed sad (crying) facial expressions. Here, the female participants perceived that the infants' faces were displayed for a longer duration than the adults' faces, whereas this distinction was not evident among the male participants. These findings highlight the influence of the babyface schema on time perception, nuanced by emotional context and sex-based individual variances.

Optimal processing of surface facial EMG to identify emotional expressions: A data-driven approach

Surface facial electromyography (EMG) is commonly used to detect emotions from subtle facial expressions. Although there are established procedures for collecting EMG data and some aspects of their processing, there is little agreement among researchers about the optimal way to process the EMG signal, so that the study-unrelated variability (noise) is removed, and the emotion-related variability is best detected. The aim of the current paper was to establish an optimal processing pipeline for EMG data for identifying emotional expressions in facial muscles. We identified the most common processing steps from existing literature and created 72 processing pipelines that represented all the different processing choices. We applied these pipelines to a previously published dataset from a facial mimicry experiment, where 100 adult participants observed happy and sad facial expressions, whilst the activity of their facial muscles, zygomaticus major and corrugator supercilii, was recorded with EMG. We used a resampling approach and subsets of the original data to investigate the effect and robustness of different processing choices on the performance of a logistic regression model that predicted the mimicked emotion (happy/sad) from the EMG signal. In addition, we used a random forest model to identify the most important processing steps for the sensitivity of the logistic regression model. Three processing steps were found to be most impactful: baseline correction, standardisation within muscles, and standardisation within subjects. The chosen feature of interest and the signal averaging had little influence on the sensitivity to the effect. We recommend an optimal processing pipeline, share our code and data, and provide a step-by-step walkthrough for researchers.

Social impairment in survivors of pediatric brain tumors via reduced social attention and emotion-specific facial expression recognition.

Survivors of pediatric brain tumors (SPBT) experience significant social challenges, including fewer friends and greater isolation than peers. Difficulties in face processing and visual social attention have been implicated in these outcomes. This study evaluated facial expression recognition (FER), social attention, and their associations with social impairments in SPBT. SPBT (N=54; ages 7-16) at least 2years post treatment completed a measure of FER, while parents completed measures of social impairment. A subset (N=30) completed a social attention assessment that recorded eye gaze patterns while watching videos depicting pairs of children engaged in joint play. Social Prioritization scores were calculated, with higher scores indicating more face looking. Correlations and regression analyses evaluated associations between variables, while a path analysis modeling tool (PROCESS) evaluated the indirect effects of Social Prioritization on social impairments through emotion-specific FER. Poorer recognition of angry and sad facial expressions was significantly correlated with greater social impairment. Social Prioritization was positively correlated with angry FER but no other emotions. Social Prioritization had significant indirect effects on social impairments through angry FER. Findings suggest interventions aimed at improving recognition of specific emotions may mitigate social impairments in SPBT. Further, reduced social attention (i.e., diminished face looking) could be a factor in reduced face processing ability, which may result in social impairments. Longitudinal research is needed to elucidate temporal associations between social attention, face processing, and social impairments.

Behavioral and neuroanatomical correlates of facial emotion processing in post-stroke depression

BackgroundEmotion processing deficits are known to accompany depressive symptoms and are often seen in stroke patients. Little is known about the influence of post-stroke depressive (PSD) symptoms and specific brain lesions on altered emotion processing abilities and how these phenomena develop over time. This potential relationship may impact post-stroke rehabilitation of neurological and psychosocial function. To address this scientific gap, we investigated the relationship between PSD symptoms and emotion processing abilities in a longitudinal study design from the first days post-stroke into the early chronic phase. MethodsTwenty-six ischemic stroke patients performed an emotion processing task on videos with emotional faces ('happy,' 'sad,' 'anger,' 'fear,' and 'neutral') at different intensity levels (20%, 40%, 60%, 80%, 100%). Recognition accuracies and response times were measured, as well as scores of depressive symptoms (Montgomery-Åsberg Depression Rating Scale). Twenty-eight healthy participants matched in age and sex were included as a control group. Whole-brain support-vector regression lesion-symptom mapping (SVR-LSM) analyses were performed to investigate whether specific lesion locations were associated with the recognition accuracy of specific emotion categories. ResultsStroke patients performed worse in overall recognition accuracy compared to controls, specifically in the recognition of happy, sad, and fearful faces. Notably, more depressed stroke patients showed an increased processing towards specific negative emotions, as they responded significantly faster to angry faces and recognized sad faces of low intensities significantly more accurately. These effects obtained for the first days after stroke partly persisted to follow-up assessment several months later. SVR-LSM analyses revealed that inferior and middle frontal regions (IFG/MFG) and insula and putamen were associated with emotion-recognition deficits in stroke. Specifically, recognizing happy facial expressions was influenced by lesions affecting the anterior insula, putamen, IFG, MFG, orbitofrontal cortex, and rolandic operculum. Lesions in the posterior insula, rolandic operculum, and MFG were also related to reduced recognition accuracy of fearful facial expressions, whereas recognition deficits of sad faces were associated with frontal pole, IFG, and MFG damage. ConclusionPSD symptoms facilitate processing negative emotional stimuli, specifically angry and sad facial expressions. The recognition accuracy of different emotional categories was linked to brain lesions in emotion-related processing circuits, including insula, basal ganglia, IFG, and MFG. In summary, our study provides support for psychosocial and neural factors underlying emotional processing after stroke, contributing to the pathophysiology of PSD.

Crying victims deserve more? how victim image, facial expression, entitativity and victim story impact charity advertising persuasiveness

We propose that the choice between presenting a single victim or a group of victims in a charity ad should take into consideration the facial expression of the victim(s), entitativity, and the victim story, since these visual and verbal cues affect donors’ emotional responses and their perceived outcome efficacy, which have an impact on charitable giving behaviors. Four experiments are conducted. When a happy facial expression is presented, an ad showing a group of victims is found to be more persuasive than the same ad showing a single victim. When a sad facial expression is presented, an ad showing a single victim is more persuasive (vs. a group of victims). When presenting a group of happy-faced victims, we observe the advantageous effects of entitativity: high-entitativity (vs. low-entitativity) enhances people’s willingness to donate. However, no such differences between high- and low-entitativity are found when the ads present a group of sad-faced victims. When a victim story is included in the ad (i.e. a narrative ad), different versions of the ad are similarly persuasive regardless of victim image and facial expression. Non-profits and for-profit companies can maximize the success of their charitable campaigns by choosing the right victim image that suits their visual-verbal combination.

Activity increases in empathy-related brain regions when children contribute to peers’ sadness and happiness

Responding empathically when causing peers’ emotions is critical to children’s interpersonal functioning, yet there are surprising gaps in the literature. Previous research has focused on empathy when witnessing others’ emotions instead of causing others’ emotions, on negative emotions instead of positive emotions, and on behavioral correlates instead of neural correlates. In this study, children (N = 38; Mage = 9.28 years; 50% female) completed a functional magnetic resonance imaging block design task in which they played a rigged game where they won and lost coins for themselves or peers and viewed their peers’ happiness and sadness. We used a region of interest approach to test whether activity in brain regions associated with positive and negative empathy in adults showed significantly greater activity in each condition (i.e., when children won and lost tokens for themselves and peers) compared with a fixation baseline. We predicted that experiencing self-conscious emotions, such as pride and guilt, would heighten the experience of empathy. Activity in the amygdala, which is associated with visceral arousal, and in the anterior insula and dorsal anterior cingulate cortex, which are associated with integrated arousal, increased significantly when winning and losing for oneself and peers and observing their resulting happy and sad facial expressions. Activity did not differ when playing for oneself versus peers, indicating that self-conscious emotions do not heighten empathy and instead support similar neural processes underlying firsthand and secondhand (empathic) emotions. These findings support that empathy during middle childhood involves the same brain regions as empathy during adulthood and that children experience firsthand and secondhand positive and negative emotions in similar ways.

The Role of In-Group and Out-Group Facial Feedback in Implicit Rule Learning.

Implicit learning refers to the fact that people acquire new knowledge (structures or rules) without conscious awareness. Previous studies have shown that implicit learning is affected by feedback. However, few studies have investigated the role of social feedback in implicit learning concretely. Here, we conducted two experiments to explore how in-group and out-group facial feedback impact different difficulty levels of implicit rule learning. In Experiment 1, the Chinese participants in each group could only see one type of facial feedback, i.e., either in-group (East Asian) or out-group (Western) faces, and learned the implicit rule through happy and sad facial expressions. The only difference between Experiment 2 and Experiment 1 was that the participants saw both the in-group and out-group faces before group assignment to strengthen the contrast between the two group identities. The results showed that only in Experiment 2 but not Experiment 1 was there a significant interaction effect in the accuracy of tasks between the difficulty levels and groups. For the lowest difficulty level, the learning accuracy of the in-group facial feedback group was significantly higher than that of the out-group facial feedback group, whereas this did not happen at the two highest levels of difficulty. In conclusion, when the contrast of group identities was highlighted, out-group feedback reduced the accuracy of the least difficult task; on the contrary, there was no accuracy difference between out-group and in-group feedback conditions. These findings have extensively important implications for our understanding of implicit learning and improving teaching achievement in the context of educational internationalization.

Effects of two different social exclusion paradigms on ambiguous facial emotion recognition

ABSTRACT Social exclusion is an emotionally painful experience that leads to various alterations in socio-emotional processing. The perceptual and emotional consequences that may arise from experiencing social exclusion can vary depending on the paradigm used to manipulate it. Exclusion paradigms can vary in terms of the severity and duration of the leading exclusion experience, thereby classifying it as either a short-term or long-term experience. The present study aimed to study the impact of exclusion on socio-emotional processing using different paradigms that caused experiencing short-term and imagining long-term exclusion. Ambiguous facial emotions were used as socio-emotional cues. In study 1, the Ostracism Online paradigm was used to manipulate short-term exclusion. In study 2, a new sample of participants imagined long-term exclusion through the future life alone paradigm. Participants of both studies then completed a facial emotion recognition task consisting of morphed ambiguous facial emotions. By means of Point of Subjective Equivalence analyses, our results indicate that the experience of short-term exclusion hinders recognising happy facial expressions. In contrast, imagining long-term exclusion causes difficulties in recognising sad facial expressions. These findings extend the current literature, suggesting that not all social exclusion paradigms affect socio-emotional processing similarly.

Depression Detection System

The Depression Detection System is an innovative technology designed to assist in the early detection and monitoring of depression. This system utilizes advanced machine learning algorithms and data analysis techniques to analyze various indicators andpatterns associated with depression, such as speech, facial expressions, and behavior. By continuously monitoring these signals, the system can identify potential signs of depression and provide valuable insights to healthcare professionals for accuratediagnosis and timely intervention. Major depressive disorder (MDD) or depression is among the most prevalent psychiatric disorders, affecting more than 300 million people globally. Early detection is critical for rapid intervention, which can potentially reduce the escalation of the disorder. The system operates by collecting data from various sources, including audio recordings of conversations, video recordings of facial expressions, and user- generated content from social media platforms. Through natural language processing and computer vision techniques, it extracts relevant features and patterns that may indicate depressive symptoms, such as changes in speech patterns, facial expressions of sadness or despair, or negative sentiment expressed in written content. Once the data is analyzed, the system generates comprehensive reports and visualizations, highlighting potential depressive indicators and their severity levels. These reports can assist healthcare providers in making informed decisions regarding further assessment and treatment planning. Additionally, the system can track the progression of depression over time, enabling clinicians to monitor the effectiveness of interventions and adjust treatment strategies accordingly. The Depression Detection System aims to complement traditional diagnostic methods by providing an objective and continuous assessment of depressive symptoms. By leveraging cutting-edge technology, this system has the potential to improve early detection rates, enhance patient outcomes, and facilitate timely interventions in the field of mental health. However, it is important to note that the system should always be used as a supportive tool and not as a replacement for professional clinical judgment and human interaction.

Facial and Vocal Emotion Recognition in Adolescence: A Systematic Review

AbstractThe ability to recognize emotion is important to wellbeing and building relationships with others, making this skill important in adolescence. Research investigating adolescents’ ability to recognize facial and vocal emotion expressions has reported differing conclusions about the pattern of emotion recognition across this developmental period. This systematic review aimed to clarify the pattern of recognition for facial and vocal emotion expressions, and the relationship of performance to different task and emotion expression characteristics. A comprehensive and systematic search of the literature was conducted using six databases. To be eligible for inclusion, studies had to report data for adolescents between 11 and 18 years of age and measure accuracy of the recognition of emotion cues in either the face or voice. A total of 2333 studies were identified and 47 met inclusion criteria. The majority of studies focused on facial emotion recognition. Overall, early, mid-, and late-adolescents showed a similar pattern of recognition for both facial and vocal emotion expressions with the exception of Sad facial expressions. Sex of the participant also had minimal impact on the overall recognition of different emotions. However, analysis showed considerable variability according to task and emotion expression characteristics. Future research needs to increase focus on recognition of complex emotions, and low-intensity emotion expressions as well as the influence of the inclusion of Neutral as a response option.

The Predictive Role of the Posterior Cerebellum in the Processing of Dynamic Emotions.

Recent studies have bolstered the important role of the cerebellum in high-level socio-affective functions. In particular, neuroscientific evidence shows that the posterior cerebellum is involved in social cognition and emotion processing, presumably through its involvement in temporal processing and in predicting the outcomes of social sequences. We used cerebellar transcranial random noise stimulation (ctRNS) targeting the posterior cerebellum to affect the performance of 32 healthy participants during an emotion discrimination task, including both static and dynamic facial expressions (i.e., transitioning from a static neutral image to a happy/sad emotion). ctRNS, compared to the sham condition, significantly reduced the participants' accuracy to discriminate static sad facial expressions, but it increased participants' accuracy to discriminate dynamic sad facial expressions. No effects emerged with happy faces. These findings may suggest the existence of two different circuits in the posterior cerebellum for the processing of negative emotional stimuli: a first-time-independent mechanism which can be selectively disrupted by ctRNS, and a second time-dependent mechanism of predictive "sequence detection"which can be selectively enhanced by ctRNS. This latter mechanism might be included among the cerebellar operational models constantly engaged in the rapid adjustment of social predictions based on dynamic behavioral information inherent to others' actions. We speculate that it might be one of the basic principles underlying the understanding of other individuals' social and emotional behaviors during interactions.

Measurement of the N170 during facial neuromuscular electrical stimulation (fNMES)

BackgroundStudies on facial feedback effects typically employ props or posed facial expressions, which often lack temporal precision and muscle specificity. New methodFacial Neuromuscular Electrical Stimulation (fNMES) allows for a controlled influence of contractions of facial muscles, and may be used to advance our understanding of facial feedback effects, especially when combined with Electroencephalography (EEG). However, electrical stimulation introduces significant interference that can mask underlying brain dynamics. Whether established signal processing methods can allow for a reduction of said interference whilst retaining effects of interest, remains unexplored. ResultsWe addressed these questions focusing on the classic N170 visual evoked potential, a face-sensitive brain component: 20 participants viewed images of houses, and of sad, happy, and neutral faces. On half of the trials, fNMES was delivered to bilateral lower-face muscles during the presentation of visual stimuli. A larger N170 amplitude was found for faces relative to houses. Interestingly, this was the case both without and during fNMES, regardless of whether the fNMES artefact was removed or not. Moreover, sad facial expressions elicited a larger N170 amplitude relative to neutral facial expressions, both with and without fNMES. Comparison with existing methodsfNMES offers a more precise way of manipulating proprioceptive feedback from facial muscles, which affords greater diversity in experimental design for studies on facial feedback effects. ConclusionsWe show that the combining of fNMES and EEG can be achieved and may serve as a powerful means of exploring the impact of controlled proprioceptive inputs on various types of cognitive processing.

Investigating mechanism of the effect of emotional facial expressions on attentional processing by data clustering approach

To explore the mechanism of the effect of emotional facial expression on attentional process, time course and topographic map of Electroencephalographic activities affected by emotional stimuli were investigated. Emotional Stroop task was used to collect 64-channel event-related potentials (ERP) in nonclinical participants, and data clustering was applied to find significant effect of sad and happy facial expression on ERP. Several significant ERP clusters were found in the sad and happy conditions respectively. In the sad condition, the decreased N170 in the bilateral parietooccipital areas, the increased P3 in the right centroparietal region and the increased negative deflection between 600 and 650 ms in the prefrontal regions were observed, these alterations reflected inhibited perceptual processing of sad facial expression, and increased activations of the orienting network and the executive control network in attentional system, respectively. In the happy condition, increased negative slow wave was found in the left centroparietal region indicating strengthened awareness and readiness for successive trials. Importantly, nonpathological attentional bias to sad facial expression in nonclinical participants was associated with inhibited perceptual processing and increased activations of the orienting and executive control networks. It provides the basis for better understanding and application of attentional bias in psychiatric clinical utilization.

Attentional bias for sad facial expressions in adults with a history of peer victimization.

Previous research has indicated altered attentional processing in individuals with experiences of maltreatment or victimization in childhood and adolescence. The present study examined the impact of child and adolescent experiences of relational peer victimization on attentional processes in adulthood when confronted with emotional facial expressions. As part of an online study, a community sample of adults completed a facial dot-probe task. In the present task, pictures of facial expressions displaying four different emotions (anger, disgust, happiness, and sadness) were used. The results of the hierarchical regression analyses showed that retrospective reports of peer victimization made a significant contribution to the prediction of facilitated orienting processes for sad facial expressions. Experiences of emotional child maltreatment, on the other hand, made a significant contribution to the prediction of attentional biases for angry facial expressions. Our results emphasize the relevance of experiences of emotional and relational maltreatment in childhood and in adolescence for the processing of social stimuli in adulthood. The findings regarding emotional child maltreatment are more indicative of attentional biases in the context of threat detection, whereas the altered attentional processes in peer victimization are more indicative of mood-congruent biases. These altered processes may be active in social situations and may therefore influence future social situations, behavior, feelings, and thus mental health.

Correlations Between Psychological Status and Perception of Facial Expression.

Objective Facial affect recognition is associated with neuropsychological status and psychiatric diseases. We hypothesized that facial affect recognition is associated with psychological status and perception of other affects. Methods A total of 80 images depicting facial affect, including 20 Neutral, 20 Angry, 20 Fear, and 20 Sad, were screened for use in our research. A total of 100 healthy individuals were asked to rate these images using a 10-point Likert scale and complete psychological scales assessing the emotional statuses and cognitive functions. Results The participants’ emotional state of aggression, attention, and impulsivity may have been associated with their interpretation of the Angry facial expressions. The participants often rated the Angry facial expressions as Fear. The participants rated Fear images as Angry or Sad. In response to a Sad facial expression, the participants reported psychological statuses of attention and impulsivity which were associated with the facial expression rating. The participants rated the Sad expression as Angry or Fear. Conclusion The psychological statuses of the participants were significantly correlated with their interpretation of facial affects. In particular, a psychological state of attention was often correlated with incorrect affect ratings. Attention and impulsivity could affect the rating of the sad facial expressions.

Intranasal oxytocin alters attention to emotional facial expressions, particularly for males and those with depressive symptoms

Intranasal oxytocin (OT) can enhance emotion recognition, perhaps by promoting increased attention to social cues. Some studies indicate that individuals with difficulties processing social information, including those with psychopathology, show more pronounced effects in response to OT. As such, there is interest in the potential therapeutic use of OT in populations with deficits in social cognition. The present study examined the effects of intranasal OT on the processing of facial features and selective attention to emotional facial expressions, as well as whether individual differences in depressive symptom severity predict sensitivity to intranasal OT. In a double-blind placebo-controlled within-subject design, eye tracking was used to measure attention to facial features in an emotional expression appraisal task, and attention to emotional expressions in a free-viewing task with a quadrant of multiple faces. OT facilitated the processing of positive cues, enhancing the maintenance of attention to the mouth region of happy faces and to happy faces within a quadrant, with similar effect sizes, despite the latter effect not being statistically significant. Further, persons with depressive symptoms, and particularly males, were sensitive to OT’s effects. For males only, OT, relative to placebo, increased attentional focus to the mouth region of all faces. Individuals with depressive symptoms showed less attentional focus on angry (males only) and sad facial expressions, and more attention to happy faces (particularly for males). Results indicate increased sensitivity to OT in males and persons at risk for depression, with OT administration promoting a positive bias in selective attention to social stimuli.

An experimental medicine study of the effects of simvastatin on emotional processing, reward learning, verbal memory, and inflammation in healthy volunteers

RationaleClinical studies suggest that the highly lipophilic, anti-inflammatory molecule, simvastatin, might be an ideal candidate for drug repurposing in the treatment of depression. The neuropsychological effects of simvastatin are not known, but their ascertainment would have significant translational value about simvastatin’s influence on mood and cognition.ObjectivesWe aimed to investigate the effects of simvastatin on a battery of psychological tests and inflammatory markers in healthy volunteers.MethodsFifty-three healthy subjects were randomly assigned to 7 days of either simvastatin (N = 27) or sucrose-based placebo (N = 26) given in a double-blind fashion. Then, participants were administered questionnaires measuring subjective rates of mood and anxiety, and a battery of tasks assessing emotional processing, reward learning, and verbal memory. Blood samples for C-reactive protein were also collected.ResultsCompared to placebo, participants on simvastatin showed a higher number of positively valenced intrusions in the emotional recall task (F1,51 = 4.99, p = 0.03), but also an increase in anxiety scores (F1,51 = 5.37, p = 0.02). An exploratory analysis of the females’ subgroup (N = 27) showed lower number of misclassifications as sad facial expression in the simvastatin arm (F1,25 = 6.60, p = 0.02). No further statistically significant changes could be observed on any of the other outcomes measured.ConclusionsWe found limited evidence that 7-day simvastatin use in healthy volunteer induces a positive emotional bias while also being associated with an increase in anxiety, potentially reflecting the early effects of antidepressants in clinical practice. Such effect might be more evident in female subjects. Different drug dosages, treatment lengths, and sample selection need consideration in further experimental medicine and clinical studies.Trial registrationClinicaltrials.gov: NCT04652089.