Adolescence is a critical time of social learning in which both the quantity and quality of social interactions shape adult behavior and social function. During adolescence, social instability such as disrupting or limiting social interactions can lead to negative life-long effects on mental health and well-being in humans. Animal models on social instability are critically important in understanding those underlying neurobiological mechanisms. However, studies in rats using these models have produced partly inconsistent results and can be difficult to generalize. Here we assessed in a sex and age consistent manner the long-term behavioural consequences of social instability stress (SIS - 1-hr daily isolation and change in cage mate between postnatal day (PD30–45)) in Wistar rats. Female and male rats underwent a battery of tests for anxiety-like, exploratory, and social behaviour over five days beginning either in adolescence (PD46) or in adulthood (PD70). Social instability led to reduced anxiety-like behaviour in the elevated plus maze in both sexes in adolescence and in adulthood. Social interactions were also reduced in rats that underwent SIS – an effect that was independent of sex and age when tested. SIS improved social recognition memory in both sexes whereas a sex-dependent effect was seen in the social novelty preference test where male rats that underwent SIS spent more time in social approach toward a novel peer than toward their cage mate. In comparison, control male and female groups did not differ in this test, in time spent with novel versus the cage mate. Thus, overall, social instability stress in Wistar rats altered the behavioural repertoire, with enduring alterations in social behaviour, enhanced exploratory behaviour, and reduced anxiety-like behaviour. In conclusion, the social instability stress paradigm may better be interpreted as a form of enrichment in Wistar rats than as a stressor.
Gender is one of the well-recognized risk factors for idiopathic nightmares, but rarely connected to posttraumatic nightmare characteristics. Thus, this study aims to test gender differences in (posttraumatic) nightmare characteristics after controlling for trauma-related psychopathology in a large sample of people who experienced trauma. Research participants were 707 soldiers (mean age 31.3 years, 19.5% women) admitted to a hospital-based treatment program for veterans who completed extensive assessments consisting of clinical interviews and self-rating measures with respect to socio-demographic characteristics and psychopathology, as well as dream-related variables. Results indicate no gender differences with respect to nightmare frequency, psychophysical and emotional involvement, reorientation, and dream recall after awakening. Differences between men and women in the amount of replicative content are fully, and in case of nightmare related impairment, explained mainly by the presence of PTSD diagnosis, nightmare frequency, and age. This study questions the significance of gender as a risk factor or predictor of specific (posttraumatic) nightmare characteristics in traumatized and military samples. Further research needs to test if our findings are restricted to military contexts or can be generalized to civilian samples.
A previous highly controlled pilot study revealed that body mass index (BMI) predicts outcome of in‐patients with alcohol use disorder (AUD) in a sex‐specific manner. We here provide translational evidence from a daily clinical routine setting and investigated whether BMI and sex interact to predict 24‐month readmission risk in four naturalistic cohorts of a specialized addiction clinic (i.e., all patients admitted to the clinic from 2016 to 2020): (i) in‐patients (443 males and 197 females) and (ii) day clinic patients (241 males and 103 females) with a primary diagnosis of AUD; (iii) in‐patients (175 males and 98 females) and (iv) day clinic patients (174 males and 64 females) with a primary substance use disorder (SUD) other than alcohol. In the in‐patients with AUD, BMI interacted with sex to predict the 24‐month readmission risks (p = 0.008; after adjustment for age and liver enzyme activities: p = 0.012); with higher BMI, the risk increases significantly in males, whereas for females, the risk tends to decrease. In the group of overweight in‐patients, we found higher readmission rates in males relative to females with an odds ratio of 1.8 (p = 0.038). No such significant effects were found in the other cohorts. This study's findings support previous results, suggesting that the easily accessible BMI may serve as a predictive and sex‐sensitive biomarker for outcome in in‐patients with AUD. Future studies are necessary to elucidate the underlying aetiopathological mechanisms. Better outcome predictors are needed to improve treatments of patients with alcohol use disorder. Here, we confirmed in a clinical care setting an interaction of body mass index and sex to predict hospital readmissions; that is, higher body mass index related to higher risk in males and tended to associate with lower risk in females. The body mass index is a promising and easily accessible biomarker that might become relevant for the goals of precision medicine.
Aberrant limbic circuit reactivity to negative stimuli might be related to alterations in emotion processing and regulation in alcohol use disorder (AUD). The current study tested for the first time in AUD the hypothesis of aberrant amygdala habituation to repeated aversive stimuli—a robust and reliable neuroimaging marker for emotion processing. We explored the link between deficits in habituation to adverse childhood experience (ACE), a common risk factor for impaired emotion regulation and AUD. AUD individuals (N = 36) and healthy controls (HC; N = 26) participated in an observational case–control functional magnetic resonance imaging (fMRI) study. An established habituation index was used to investigate processing of aversive emotional faces of the amygdala. AUD individuals showed an overall deficit in amygdala habituation (right: t = 4.26, pFWE = 0.004; left: t = 4.79, pFWE ≤ 0.001). Amygdala habituation was significantly related to increased exposure to ACE in HC (t = 3.88, pFWE = 0.012), whereas this association was not observed in AUD individuals (T = 1.80, pFWE = 0.662). Further, a significant association between higher alcohol consumption and reduced amygdala habituation (right: R2 = −0.356, F = 8.736, p = 0.004; left: R2 = −0.309, F = 6.332, p = 0.015) was observed. We found novel evidence for neural alterations in emotion processing in AUD individuals, indexed by deficient amygdala habituation to negative emotional content. We replicated a prior report on a link between ACE and amygdala habituation, a well‐established environmental risk factor for mental disorders and emotion dysregulation, in our control sample. Additionally, deficient amygdala habituation related to the amount of alcohol consumption in the overall sample might indicate a short‐term substance effect. Aberrant limbic circuit reactivity to negative stimuli relates to alterations in emotion processing and regulation in alcohol use disorder (AUD). We observed deficient amygdala habituation to negative emotional content in AUD individuals. This further related to the amount of alcohol consumption in the overall sample, possibly indicating a short‐term substance effect. We replicated a prior report on a link between ACE and amygdala habituation, a well‐established environmental risk factor for mental disorders and emotion dysregulation, in our control sample.
Background: Difficulties in emotion regulation are a core symptom of borderline personality disorder (BPD) and often interfere with cognitive functions, such as working memory (WM). Traumatic childhood experiences, including severe maltreatment, can contribute to emotion dysregulation, possibly mediated by changes in high-frequency heart rate variability (HF-HRV). However, it is not yet entirely understood if HF-HRV alterations underlie impaired WM during emotional distraction in BPD and if this is related to traumatic childhood experiences and to comorbid post-traumatic stress disorder (PTSD). Objective: Our aim was to investigate performance (reaction times, RTs) and HF-HRV during an emotional working memory task (EWMT) in relation to childhood maltreatment severity and comorbid PTSD in BPD. Method: Eighty-one women (n = 28 healthy controls (HC) and n = 53 BPD patients of which n = 18 had comorbid PTSD) performed an adapted Sternberg item recognition WM task with neutral and negative social cues (interpersonal scenes from the International Affective Picture System (IAPS), and neutral, fearful, and angry faces) as distractors. Dependent variables were RTs of correct trials and HF-HRV. Childhood maltreatment was assessed with the Childhood Trauma Questionnaire. Results: Compared to healthy participants, patients with BPD showed prolonged RTs across all distractor conditions with social cues, regardless of their emotional valence. Patients with BPD, especially those with PTSD, demonstrated reduced HF-HRV both at rest and during EWMT. Severity of childhood maltreatment predicted longer RTs and lower HF-HRV during the EWMT. Conclusions: Findings suggest that adverse childhood experiences accelerate difficulties in shifting attention away from social information and that these are more pronounced in individuals with BPD. Reduced HF-HRV (low parasympathetic-tonus) may be an important psychophysiological mechanism underlying impaired WM in the presence of distracting social cues in patients with BPD, especially in those with comorbid PTSD. Highlights: This study provides evidence that childhood maltreatment experiences are associated with hypersensitivity to social information and reduced high-frequency heart rate variability during a working memory task in borderline personality disorder.
Negative symptoms and cognitive deficits are common in individuals with schizophrenia, greatly affect their outcome, and have been associated with alterations in cerebral gray and white matter volume (GMV, WMV). In the last decade, aerobic endurance training has emerged as a promising intervention to alleviate these symptoms and improved aerobic fitness has been suggested as a key moderator variable. In the present study, we investigated, whether aerobic fitness is associated with fewer cognitive deficits and negative symptoms and with GMVs and WMVs in individuals with schizophrenia in a cross-sectional design. In the largest study to date on the implications of fitness in individuals with schizophrenia, 111 participants at two centers underwent assessments of negative symptoms, cognitive functioning, and aerobic fitness and 69 underwent additional structural magnetic resonance imaging. Multilevel Bayesian partial correlations were computed to quantify relationships between the variables of interest. The main finding was a positive association of aerobic fitness with right hippocampal GMV and WMVs in parahippocampal and several cerebellar regions. We found limited evidence for an association of aerobic fitness with cognitive functioning and negative symptoms. In summary, our results strengthen the notion that aerobic fitness and hippocampal plasticity are interrelated which holds implications for the design of exercise interventions in individuals with schizophrenia.
Purpose : To raise attention to the quality of published validation protocols while comparing (in)consistencies and providing an overview on wearables, and whether they show promise or not. Methods : Searches from five electronic databases were included concerning the following eligibility criteria: (a) laboratory conditions with humans (<18 years), (b) device outcome must belong to one dimension of the 24-hr physical behavior construct (i.e., intensity, posture/activity type outcomes, biological state), (c) must include a criterion measure, and (d) published in a peer-reviewed English language journal between 1980 and 2021. Results : Out of 13,285 unique search results, 123 articles were included. In 86 studies, children <13 years were recruited, whereas in 26 studies adolescents (13–18 years) were recruited. Most studies (73.2%) validated an intensity outcome such as energy expenditure; only 20.3% and 13.8% of studies validated biological state or posture/activity type outcomes, respectively. We identified 14 wearables that had been used to validate outcomes from two or three different dimensions. Most ( n = 72) of the identified 88 wearables were only validated once. Risk of bias assessment resulted in 7.3% of studies being classified as “low risk,” 28.5% as “some concerns,” and 71.5% as “high risk.” Conclusion : Overall, laboratory validation studies of wearables are characterized by low methodological quality, large variability in design, and a focus on intensity. No identified wearable provides valid results across all three dimensions of the 24-hr physical behavior construct. Future research should more strongly aim at biological state and posture/activity type outcomes, and strive for standardized protocols embedded in a validation framework.
Exposure to Stressful Life Events (SLEs) has been linked to psychosis. However, the combined effect of SLEs and familial risk on subclinical psychotic symptoms over time remains unknown. The objective of the present study was to investigate the effect of SLEs on the level of subclinical psychotic symptoms in individuals with and without familial vulnerability for psychosis. Data were collected from siblings of individuals diagnosed with psychotic disorder and healthy controls at baseline (N = 293) and three years later at follow-up (N = 928). We assessed self-reported and observer-rated subclinical positive, negative, and depressive psychotic symptoms. Participants reported the number of SLEs in the preceding 6 months. A multilevel multivariate regression analysis revealed a positive association between the retrospectively assessed number of SLEs and symptom levels, regardless of vulnerability status (p < .001 for all outcomes). The prospective analysis demonstrated that exposure to SLEs at baseline predicted higher levels of subclinical psychotic symptoms at follow-up. However, after controlling for the level of symptoms at baseline, these associations were no longer significant. Again, the vulnerability status did not modify these results. Nevertheless, siblings in our sample were approximating the end of the critical period for the development of psychotic disorder (mean age at baseline M = 29 and follow-up M = 34). The findings partly support the vulnerability-stress model of psychosis, yet do not confirm the role of familial risk in this association. SLEs may represent a risk factor for psychosis at a population level, thus supporting the continuity of the psychosis spectrum in terms of associated risk factors.
MicroRNAs (miRNAs) may contribute to the development of depression and its treatment. Here, we used the hypothesis-neutral approach of next-generation sequencing (NGS) to gain comprehensive understanding of the effects of a course of electroconvulsive stimulation (ECS), the animal model equivalent of electroconvulsive therapy (ECT), on rat hippocampal miRNAs. Significant differential expression (p < 0.001) of six hippocampal miRNAs was noted following NGS, after correcting for multiple comparisons. Three of these miRNAs were upregulated (miR-132, miR-212, miR-331) and three downregulated (miR-204, miR-483, miR-301a). qRT-PCR confirmed significant changes in four of the six miRNAs (miR-132, miR-212, miR-204, miR-483). miR-483 was also significantly reduced in frontal cortex, though no other significant alterations were noted in frontal cortex, cerebellum, or whole blood. Assessing the translatability of the results, miR-132 and miR-483 were significantly reduced in whole blood samples from medicated patients with depression (n = 50) compared to healthy controls (n = 45), though ECT had no impact on miRNA levels. Notably, pre-ECT miR-204 levels moderately positively correlated with depression severity at baseline and moderately negatively correlated with mood score reduction post-ECT. miRNAs were also examined in cerebrospinal fluid and serum from a separate cohort of patients (n = 8) treated with ECT; no significant changes were noted post-treatment. However, there was a large positive correlation between changes in miR-212 and mood score post-ECT in serum. Though replication studies using larger sample sizes are required, alterations in miRNA expression may be informative about the mechanism of action of ECS/ECT and in turn might give insight into the neurobiology of depression.
Continuous real‐time functional magnetic resonance imaging (fMRI) neurofeedback is gaining increasing scientific attention in clinical neuroscience and may benefit from the short repetition times of modern multiband echoplanar imaging sequences. However, minimizing feedback delay can result in technical challenges. Here, we report a technical problem we experienced during continuous fMRI neurofeedback with multiband echoplanar imaging and short repetition times. We identify the possible origins of this problem, describe our current interim solution and provide openly available workflows and code to other researchers in case they wish to use a similar approach. Continuous functional magnetic resonance imaging (fMRI) neurofeedback may benefit from the short repetition times of modern multiband echoplanar imaging sequences to minimize feedback delay. Here, we report a technical problem we experienced during continuous fMRI neurofeedback with multiband echoplanar imaging and short repetition times. We share our thoughts on the possible origins of this problem, describe our current interim solution and provide openly available workflows and code to other researchers wishing to use a similar approach.
Background Novel approaches in mobile mental health (mHealth) apps that make use of Artificial Intelligence (AI), Ecological Momentary Assessments, and Ecological Momentary Interventions have the potential to support young people in the achievement of mental health and wellbeing goals. However, little is known on the perspectives of young people and mental health experts on this rapidly advancing technology. This study aims to investigate the subjective needs, attitudes, and preferences of key stakeholders towards an AI–informed mHealth app, including young people and experts on mHealth promotion and prevention in youth. Methods We used a convergent parallel mixed–method study design. Two semi–structured online focus groups (n = 8) and expert interviews (n = 5) to explore users and stakeholders perspectives were conducted. Furthermore a representative online survey was completed by young people (n = 666) to investigate attitudes, current use and preferences towards apps for mental health promotion and prevention. Results Survey results show that more than two-thirds of young people have experience with mHealth apps, and 60% make regular use of 1–2 apps. A minority (17%) reported to feel negative about the application of AI in general, and 19% were negative about the embedding of AI in mHealth apps. This is in line with qualitative findings, where young people displayed rather positive attitudes towards AI and its integration into mHealth apps. Participants reported pragmatic attitudes towards data sharing and safety practices, implying openness to share data if it adds value for users and if the data request is not too intimate, however demanded transparency of data usage and control over personalization. Experts perceived AI-informed mHealth apps as a complementary solution to on–site delivered interventions in future health promotion among young people. Experts emphasized opportunities in regard with low-threshold access through the use of smartphones, and the chance to reach young people in risk situations. Conclusions The findings of this exploratory study highlight the importance of further participatory development of training components prior to implementation of a digital mHealth training in routine practice of mental health promotion and prevention. Our results may help to guide developments based on stakeholders’ first recommendations for an AI-informed mHealth app.
Analyzing COVID-19-related stress in children with affective dysregulation (AD) seems especially interesting, as these children typically show heightened reactivity to potential stressors and an increased use of maladaptive emotion regulation strategies. Children in out-of-home care often show similar characteristics to those with AD. Since COVID-19 has led to interruptions in psychotherapy for children with mental health problems and to potentially reduced resources to implement treatment strategies in daily life in families or in out-of-home care, these children might show a particularly strong increase in stress levels. In this study, 512 families of children without AD and 269 families of children with AD reported on COVID-19-related stress. The sample comprised screened community, clinical, and out-of-home care samples. Sociodemographic factors, characteristics of child and caregiver before the pandemic, and perceived change in external conditions due to the pandemic were examined as potential risk or protective factors. Interestingly, only small differences emerged between families of children with and without AD or between subsamples: families of children with AD and families in out-of-home care were affected slightly more, but in few domains. Improvements and deteriorations in treatment-related effects balanced each other out. Overall, the most stable and strongest risk factor for COVID-19-related stress was perceived negative change in external conditions—particularly family conditions and leisure options. Additionally, caregiver characteristics emerged as risk factors across most models. Actions to support families during the pandemic should, therefore, facilitate external conditions and focus on caregiver characteristic to reduce familial COVID-19-related stress. Trial registration: German Clinical Trials Register (DRKS), ADOPT Online: DRKS00014963 registered 27 June 2018, ADOPT Treatment: DRKS00013317 registered 27 September 2018, ADOPT Institution: DRKS00014581 registered 04 July 2018.
Recent technological advances enable the collection of intensive longitudinal data. This scoping review aimed to provide an overview of methods for collecting intensive time series data in mental health research as well as basic principles, current applications, target constructs, and statistical methods for this type of data. In January 2021, the database MEDLINE was searched. Original articles were identified that (1) used active or passive data collection methods to gather intensive longitudinal data in daily life, (2) had a minimum sample size of N ⩾ 100 participants, and (3) included individuals with subclinical or clinical mental health problems. In total, 3799 original articles were identified, of which 174 met inclusion criteria. The most widely used methods were diary techniques (e.g. Experience Sampling Methodology), various types of sensors (e.g. accelerometer), and app usage data. Target constructs included affect, various symptom domains, cognitive processes, sleep, dysfunctional behaviour, physical activity, and social media use. There was strong evidence on feasibility of, and high compliance with, active and passive data collection methods in diverse clinical settings and groups. Study designs, sampling schedules, and measures varied considerably across studies, limiting the generalisability of findings. Gathering intensive longitudinal data has significant potential to advance mental health research. However, more methodological research is required to establish and meet critical quality standards in this rapidly evolving field. Advanced approaches such as digital phenotyping, ecological momentary interventions, and machine-learning methods will be required to efficiently use intensive longitudinal data and deliver personalised digital interventions and services for improving public mental health.
The neurobiological bases of the association between development and psychopathology remain poorly understood. Here, we identify a shared spatial pattern of cortical thickness (CT) in normative development and several psychiatric and neurological disorders. Principal component analysis (PCA) was applied to CT of 68 regions in the Desikan-Killiany atlas derived from three large-scale datasets comprising a total of 41,075 neurotypical participants. PCA produced a spatially broad first principal component (PC1) that was reproducible across datasets. Then PC1 derived from healthy adult participants was compared to the pattern of CT differences associated with psychiatric and neurological disorders comprising a total of 14,886 cases and 20,962 controls from seven ENIGMA disease-related working groups, normative maturation and aging comprising a total of 17,697 scans from the ABCD Study® and the IMAGEN developmental study, and 17,075 participants from the ENIGMA Lifespan working group, as well as gene expression maps from the Allen Human Brain Atlas. Results revealed substantial spatial correspondences between PC1 and widespread lower CT observed in numerous psychiatric disorders. Moreover, the PC1 pattern was also correlated with the spatial pattern of normative maturation and aging. The transcriptional analysis identified a set of genes including KCNA2, KCNS1 and KCNS2 with expression patterns closely related to the spatial pattern of PC1. The gene category enrichment analysis indicated that the transcriptional correlations of PC1 were enriched to multiple gene ontology categories and were specifically over-represented starting at late childhood, coinciding with the onset of significant cortical maturation and emergence of psychopathology during the prepubertal-to-pubertal transition. Collectively, the present study reports a reproducible latent pattern of CT that captures interregional profiles of cortical changes in both normative brain maturation and a spectrum of psychiatric disorders. The pubertal timing of the expression of PC1-related genes implicates disrupted neurodevelopment in the pathogenesis of the spectrum of psychiatric diseases emerging during adolescence.
Background Psilocybin is a serotonin type 2A (5-HT 2A ) receptor agonist and naturally occurring psychedelic. 5-HT 2A receptor density is known to be associated with body mass index (BMI), however, the impact of this on psilocybin therapy has not been explored. While body weight-adjusted dosing is widely used, this imposes a practical and financial strain on the scalability of psychedelic therapy. This gap between evidence and practice is caused by the absence of studies clarifying the relationship between BMI, the acute psychedelic experience and long-term psychological outcomes. Method Data were pooled across three studies using a fixed 25 mg dose of psilocybin delivered in a therapeutic context to assess whether BMI predicts characteristics of the acute experience and changes in well-being 2 weeks later. Supplementing frequentist analysis with Bayes Factors has enabled for conclusions to be drawn regarding the null hypothesis. Results Results support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes or emotional breakthroughs during the acute experience. There was weak evidence for greater ‘dread of ego dissolution’ in participants with lower BMI, however, further analysis suggested BMI did not meaningfully add to the combination of the other covariates (age, sex and study). While mystical-type experiences and emotional breakthroughs were strong predictors of improvements in well-being, BMI was not. Conclusions These findings have important implications for our understanding of pharmacological and extra-pharmacological contributors to psychedelic-assisted therapy and for the standardization of a fixed therapeutic dose in psychedelic-assisted therapy.
Introduction: Recently, several mindfulness-based programs showed promising clinical effects in the treatment of psychiatric disorders including substance use disorders. However, very little is known about the effects of mindfulness-based interventions (MBIs) on brain structure in such patients. Methods: This study aimed to detect changes in gray matter volume (GMV) in opioid-dependent patients receiving MBI during their first month of treatment. Thirty patients were assigned to either 3 weeks of MBI (n = 16) or treatment as usual (TAU, n = 14) and were investigated using structural magnetic resonance imaging before and after treatment. Longitudinal pipeline of the Computational Anatomy Toolbox for SPM (CAT12) was used to detect significant treatment-related changes over time. The identified GMV changes following treatment were related to clinically relevant measures such as impulsivity, distress tolerance, and mindfulness. Results: After treatment, increased mindfulness scores were found in individuals receiving MBI compared to TAU. In the MBI group, there were also significant differences with respect to distress tolerance and impulsivity. Effects on mindfulness, distress tolerance, and impulsivity were also found in the TAU group. Longitudinal within-group analysis revealed increased left anterior insula GMV in individuals receiving MBI. Anterior insula volume increase was associated with decreased impulsivity levels. In the TAU group, significant GMV changes were found in the right lingual gyrus and right entorhinal cortex. Discussion/conclusion: MBI can yield significant clinical effects during early abstinence from opioid dependence. MBI is particularly associated with increased insula GMV, supporting an important role of this region in the context of MBI-induced neural changes.
Background Dimensional models of personality disorders postulate interpersonal dysfunction as the core feature of personality pathology, and describe maladaptive personality traits that characterize the specific pattern of dysfunction that is experienced. Herein, we examined whether maladaptive traits predict prosocial and trusting behavior, both of which are highly relevant behaviors for interpersonal functioning. Specifically, we examined antagonism as a predictor of prosocial behavior in a dictator game, and suspiciousness as a predictor of trust in the faith game. Materials and methods The study was preregistered and conducted online. The preregistration protocol is available at https://osf.io/er43j. Data and code are available at https://osf.io/2rvbg/. Participants (N = 445) completed the German version of the Personality Inventory for DSM-5 to measure antagonism and suspiciousness. Additionally, they played the dictator game (more money taken away from another person indicates less prosocial behavior) and the faith game (choosing the sure choice instead of the faith choice indicates less trust). We conducted a linear regression model to test whether antagonism is associated with prosocial behavior in the dictator game and a logistic regression model to test whether suspiciousness predicts selection of the sure choice in the faith game. Results As hypothesized, higher levels of antagonism were associated with less prosocial behavior in the dictator game. The remaining hypotheses were not supported, as suspiciousness was not significantly associated with the likelihood of choosing the sure choice in the faith game. Exploratory analyses on participants’ estimates of the sure choice amount suggest successful experimental manipulation in the faith game. Conclusions The results on antagonism and prosocial behavior are consistent with those of previous studies that used categorial classification systems of personality disorders or examined non-pathological personality traits. Potential explanations for the non-significant effects of suspiciousness are discussed, including the small size and range of the sure choice payoff and that the anonymity of the game may have precluded suspicious traits from expressing. Future research with higher stakes and known interaction partners is needed to further probe the effects of suspiciousness.
Alcohol use disorder (AUD) is a chronic and fatal disease. The main impediment of the AUD therapy is a high probability of relapse to alcohol abuse even after prolonged abstinence. The molecular mechanisms of cue-induced relapse are not well established, despite the fact that they may offer new targets for the treatment of AUD. Using a comprehensive animal model of AUD, virally-mediated and amygdala-targeted genetic manipulations by CRISPR/Cas9 technology and ex vivo electrophysiology, we identify a mechanism that selectively controls cue-induced alcohol relapse and AUD symptom severity. This mechanism is based on activity-regulated cytoskeleton-associated protein (Arc)/ARG3.1-dependent plasticity of the amygdala synapses. In humans, we identified single nucleotide polymorphisms in the ARC gene and their methylation predicting not only amygdala size, but also frequency of alcohol use, even at the onset of regular consumption. Targeting Arc during alcohol cue exposure may thus be a selective new mechanism for relapse prevention.
Background Difficulties in social communication are a defining clinical feature of autism. However, the underlying neurobiological heterogeneity has impeded targeted therapies and requires new approaches to identifying clinically relevant bio-behavioural subgroups. In the largest autism cohort to date, we comprehensively examined difficulties in facial expression recognition, a key process in social communication, as a bio-behavioural stratification biomarker, and validated them against clinical features and neurofunctional responses. Methods Between 255 and 488 participants aged 6–30 years with autism, typical development and/or mild intellectual disability completed the Karolinska Directed Emotional Faces task, the Reading the Mind in the Eyes Task and/or the Films Expression Task. We first examined mean-group differences on each test. Then, we used a novel intersection approach that compares two centroid and connectivity-based clustering methods to derive subgroups based on the combined performance across the three tasks. Measures and subgroups were then related to clinical features and neurofunctional differences measured using fMRI during a fearful face-matching task. Results We found significant mean-group differences on each expression recognition test. However, cluster analyses showed that these were driven by a low-performing autistic subgroup (~ 30% of autistic individuals who performed below 2SDs of the neurotypical mean on at least one test), while a larger subgroup (~ 70%) performed within 1SD on at least 2 tests. The low-performing subgroup also had on average significantly more social communication difficulties and lower activation in the amygdala and fusiform gyrus than the high-performing subgroup. Limitations Findings of autism expression recognition subgroups and their characteristics require independent replication. This is currently not possible, as there is no other existing dataset that includes all relevant measures. However, we demonstrated high internal robustness (91.6%) of findings between two clustering methods with fundamentally different assumptions, which is a critical pre-condition for independent replication. Conclusions We identified a subgroup of autistic individuals with expression recognition difficulties and showed that this related to clinical and neurobiological characteristics. If replicated, expression recognition may serve as bio-behavioural stratification biomarker and aid in the development of targeted interventions for a subgroup of autistic individuals.
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