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Targeted protein degradation is a new therapeutic modality based on drugs that destabilize proteins by inducing their proximity to E3 ubiquitin ligases. Of particular interest are molecular glues that can degrade otherwise unligandable proteins by orchestrating direct interactions between target and ligase. However, their discovery has so far been serendipitous, thus hampering broad translational efforts. Here, we describe a scalable strategy toward glue degrader discovery that is based on chemical screening in hyponeddylated cells coupled to a multi-omics target deconvolution campaign. This approach led us to identify compounds that induce ubiquitination and degradation of cyclin K by prompting an interaction of CDK12–cyclin K with a CRL4B ligase complex. Notably, this interaction is independent of a dedicated substrate receptor, thus functionally segregating this mechanism from all described degraders. Collectively, our data outline a versatile and broadly applicable strategy to identify degraders with nonobvious mechanisms and thus empower future drug discovery efforts. Chemical profiling in hyponeddylated cells coupled with multi-omics target deconvolution led to the identification of molecular glue degraders of cyclin K that function by inducing proximity between the CRL adaptor DDB1 and a CDK12–cyclin K complex.

The use of online-communication applications including messengers (e.g. WhatsApp) or social networking services (e.g. Facebook) on the smartphone has turned into daily practice for billions of people, for example during waiting times. An increasing number of individuals show diminished control over their usage of these applications despite negative consequences in everyday life. This can be referred to as Internet-communication disorder (ICD). The current study investigated the effect of boredom proneness on symptoms of an ICD. It further examined the mediating role of cognitive and affective mechanisms, namely expectancies to avoid negative feelings online and cue-induced craving. The results of a structural equation model (N = 148) illustrate that boredom proneness is a risk factor for the development and maintenance of an ICD as it had a significant direct effect on ICD symptoms. Furthermore, boredom proneness predicted avoidance expectancies as well as cue-induced craving. Both in turn enhanced the risk of developing ICD tendencies. Moreover, both variables mediated the effect of boredom proneness on ICD and interacted among each other. In summary, the results demonstrate that people who have a higher susceptibility to experience boredom show higher expectancies to avoid negative emotions online, which promotes higher craving reactions when being confronted with specific cues (e.g. an incoming message), and could result in ICD tendencies.

Most people use the Internet as a functional tool to perform their personal goals in everyday-life such as making airline or hotel reservations. However, some individuals suffer from a loss of control over their Internet use resulting in personal distress, symptoms of psychological dependence, and diverse negative consequences. This phenomenon is often referred to as Internet addiction. Only Internet Gaming Disorder has been included in the appendix of the DSM-5, but it has already been argued that Internet addiction could also comprise problematic use of other applications with cybersex, online relations, shopping, and information search being Internet facets at risk for developing an addictive behavior. Neuropsychological investigations have pointed out that certain prefrontal functions in particular executive control functions are related to symptoms of Internet addiction, which is in line with recent theoretical models on the development and maintenance of the addictive use of the Internet. Control processes are particularly reduced when individuals with Internet addiction are confronted with Internet-related cues representing their first choice use. For example, processing Internet-related cues interferes with working memory performance and decision making. Consistent with this, results from functional neuroimaging and other neuropsychological studies demonstrate that cue-reactivity, craving, and decision making are important concepts for understanding Internet addiction. The findings on reductions in executive control are consistent with other behavioral addictions, such as pathological gambling. They also emphasize the classification of the phenomenon as an addiction, because there are also several similarities with findings in substance dependency. The neuropsychological and neuroimaging results have important clinical impact, as one therapy goal should enhance control over the Internet use by modifying specific cognitions and Internet use expectancies.

Beyond gaming disorder and gambling disorder, pornography-use disorder, buying-shopping disorder, and social-networksuse disorders are discussed as further disorders due to addictive behaviors. For addictive behaviors, it is assumed that the experience of gratification and the experience of compensation due to the specific behavior represent reinforcing processes involved in the development and maintenance of the problematic behaviors. We aimed to develop two questionnaires that capture the experienced gratification and experienced compensation while using online activities. We additionally assume significant relationships with further addiction-related constructs such as symptom severity, use expectancies, and craving experiences. We conducted three studies for the development of the “Experience of Gratification Scale” (EGS) and the “Experience of Compensation Scale” (ECS). In each study, participants answered the questionnaires modified for their preferred online activity (gaming, gambling, buying-shopping, social-networks use, pornography use). Additional questionnaires were used, assessing further addiction-related constructs. The results of the gradual approach by using exploratory and confirmatory factor analyses indicated for both scales a two-factor solution resulting in “gratification of needs” and “experience of pleasure” for the EGS, and “compensation of needs” and “experience of relief from negative feelings” for the ECS. The factors were significantly correlated with each other as well as with craving experiences, use expectancies, and symptom severity. Moreover, we found significant differences in the experienced gratification and experienced compensation for specific online behaviors. The theoretically plausible specific factors for experienced gratification and experienced compensation could be identified and were related to constructs considered important in addictive online behaviors. Further studies should investigate the relevance of these constructs for different types of addictive behaviors, but also within the addiction process addressing specific needs and motives as well as further positive and negative reinforcement mechanisms. •Experienced gratification is related to addictive behaviors.•Experienced compensation is associated with addictive behaviors.•Both constructs are concisely located in addiction research and theory.

The study aimed to investigate different factors of vulnerability for pathological buying in the online context and to determine whether online pathological buying has parallels to a specific Internet addiction. According to a model of specific Internet addiction by Brand and colleagues, potential vulnerability factors may consist of a predisposing excitability from shopping and as mediating variable, specific Internet use expectancies. Additionally, in line with models on addiction behavior, cue-induced craving should also constitute an important factor for online pathological buying. The theoretical model was tested in this study by investigating 240 female participants with a cue-reactivity paradigm, which was composed of online shopping pictures, to assess excitability from shopping. Craving (before and after the cue-reactivity paradigm) and online shopping expectancies were measured. The tendency for pathological buying and online pathological buying were screened with the Compulsive Buying Scale (CBS) and the Short Internet Addiction Test modified for shopping (s-IATshopping). The results demonstrated that the relationship between individual's excitability from shopping and online pathological buying tendency was partially mediated by specific Internet use expectancies for online shopping (model's R² = .742, p < .001). Furthermore, craving and online pathological buying tendencies were correlated (r = .556, p < .001), and an increase in craving after the cue presentation was observed solely in individuals scoring high for online pathological buying (t(28) = 2.98, p < .01, d = 0.44). Both screening instruments were correlated (r = .517, p < .001), and diagnostic concordances as well as divergences were indicated by applying the proposed cut-off criteria. In line with the model for specific Internet addiction, the study identified potential vulnerability factors for online pathological buying and suggests potential parallels. The presence of craving in individuals with a propensity for online pathological buying emphasizes that this behavior merits potential consideration within the non-substance/behavioral addictions.

Social networks are frequently used to distract, procrastinate, or cope with stress. We aimed to investigate how (problematic) social-networks use affect stress perception in interaction with different stress recovery conditions. A total of 104 participants were randomly assigned to one of four groups. Three groups underwent a stress induction with subsequent stress recovery via (1) using Facebook, (2) reading magazines, or (3) waiting. Another group (4) waited without stress induction. Stress perception was repeatedly assessed with the State-Trait-Anxiety-Inventory. Facebook use and reading magazines decreased acute stress indicating adaptive coping strategies. Stress-recovery conditions and symptom severity showed significant interactions. Facebook use was not effective for individuals with high symptom severity in contrast to non-digital strategies or for individuals with low symptom severity. The usage of social networks may be an adaptive strategy for coping with stress for some people, it is maladaptive for individuals having a problematic usage.

As a response to the COVID-19 pandemic, many governments have introduced steps such as spatial distancing and “staying at home” to curb its spread and impact. The fear resulting from the disease, the ‘lockdown’ situation, high levels of uncertainty regarding the future, and financial insecurity raise the level of stress, anxiety, and depression experienced by people all around the world. Psychoactive substances and other reinforcing behaviors (e.g., gambling, video gaming, watching pornography) are often used to reduce stress and anxiety and/or to alleviate depressed mood. The tendency to use such substances and engage in such behaviors in an excessive manner as putative coping strategies in crises like the COVID-19 pandemic is considerable. Moreover, the importance of information and communications technology (ICT) is even higher in the present crisis than usual. ICT has been crucial in keeping parts of the economy going, allowing large groups of people to work and study from home, enhancing social connectedness, providing greatly needed entertainment, etc. Although for the vast majority ICT use is adaptive and should not be pathologized, a subgroup of vulnerable individuals are at risk of developing problematic usage patterns. The present consensus guidance discusses these risks and makes some practical recommendations that may help diminish them. •The COVID-19 pandemic is impacting on individuals' mental health.•Technology is being used to help alleviate stress and anxiety caused by the pandemic.•The risk of problematic internet use (PIU) is increased during the pandemic.•Guidance is needed related to decreasing the risk of PIU.•Practical recommendations to diminish the risk of PIU are presented.

Purpose of Review There are ongoing debates about specific features of compulsive sexual behavior disorder (CSBD) relating to classification and diagnoses. We aim to address current discussions relating to potential subtypes of CSBD, the aspect of compulsivity in CSBD, and the aspect of moral incongruence and CSBD. Recent Findings CSBD includes multiple specific sexual behaviors that might be related to specific psychological processes. Problematic pornography use may be considered a subtype of CSBD, which may have multiple parallels with addictive behaviors. The feature of compulsivity in CSBD may be different from compulsivity in other disorders and may be differently involved in early versus later stages of CSBD. Moral incongruence is important to consider in the context of CSBD, although moral disapproval is not a general exclusion criterion for diagnosing CSBD. Summary Considering the current debates of specific features of CSBD, future research and clinical practice may benefit from a trans-diagnostic approach to contribute to a more fine-grained understanding of the multiple facets of CSBD.

The activation of permissive beliefs is a cognitive mechanism through which individuals permit themselves to engage in pleasurable, yet potentially unregulated activities. Existing measures are heterogenous, focusing either on specific behaviors or on particular licensing mechanisms. The new Permissive Beliefs Questionnaire (PBQ) seeks to integrate self-licensing mechanisms from various research domains and to be applicable to different behaviors. Study 1 aimed at exploring the factor structure and reduce the number of items. In study 2, we used confirmatory factor analysis and tested convergent and discriminant validity in three subsamples of individuals playing videogames (n = 489), shopping online (n = 506), and drinking alcohol (n = 511). We tested the hypothesis whether individuals who experience a self-regulatory conflict show a greater expression of permissive beliefs. The final version of the PBQ consists of 12 items which represent two factors: Deserving Reward and Defensive Optimism. The PBQ exhibited robust model fit indices and internal consistencies in the three samples. Permissive beliefs were heightened among individuals intending to downregulate their gaming, shopping, or drinking behaviors as compared to individuals without this intention. The PBQ is a valid measure of permissive beliefs for gaming, online shopping, and drinking alcohol. It serves an ecologic and psychometrically valid tool to address empirical research questions regarding the functioning of permissive beliefs. Additionally, it may be used in clinical settings to measure and raise an understanding for permissive beliefs in clients. •The PBQ measures permissive beliefs across various behaviors.•The PBQ factors are deserving reward and defensive optimism.•Individuals with self-regulatory intentions exhibit higher permissive beliefs.•The PBQ may be suitable for researching self-regulation dynamics.

With the inclusion of gaming disorder in the ICD-11, diagnostic criteria were introduced for this relatively new disorder. These criteria may be applied to other potential specific Internet-use disorders. The 11-item Assessment of Criteria for Specific Internet-use Disorders (ACSID-11) was developed for consistent screening of gaming disorder, online buying-shopping disorder, online pornography-use disorder, social networks-use disorder, and online gambling disorder. This study tested the construct validity of the ACSID-11, including convergent and divergent measures. The ACSID-11 measures five behavioral addictions with the same set of items by following the principles of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). The ACSID-11 was administered to a convenience sample of active Internet users (N = 1597) together with validated and established measures of each specific Internet-use disorder along with screeners for mental health. Included are the Ten-Item Internet Gaming Disorder Test (IGDT-10), the Bergen Shopping Addiction Scale (BSAS), the Problematic Pornography Consumption Scale (PPCS), the Bergen Social Media Addiction Scale (BSMAS) and the Berlin Inventory of Gambling behavior – Screening (BIG-S). The ACSID-11 was compared convergently and divergently through a multitrait-multimethod approach along with contingency tables with the other Internet-use disorder screeners. The multitrait-multimethod results shows that each behavior assessed with the ACSID-11 has moderate to strong correlations (r's from 0.462 to 0.609) with the scores of the corresponding established measures and, furthermore, positive correlations (r's from 0.122 to 0.434) with measures of psychological distress and further shows that the ACSID-11 can be used for a comprehensive assessment of different behaviors. The contingency tables reveal large divergences between the ACSID-11 and other screening instruments concerning the classification of problematic specific Internet use based on the given cut-off values. The current work provides additional validation for the ACSID-11. Accordingly, this tool can be considered as reliable and valid for the simultaneous assessment of different Internet-use disorders: gaming disorder, online buying-shopping disorder, online pornography use disorder, social networks use disorder, and online gambling disorder. With a subsequent clinical validation of the scale and the proposed cut-off score, the ACSID-11 will be a thoroughly validated useful screening tool for clinical practice. •The ACSID-11 measures 5 specific Internet-use disorders with the same set of items.•The current work provides additional validation for ACSID-11.•A cut-off score for the ACSID-11 is proposed.•The ACSID-11 provides a consistent screening for specific Internet-use disorders.•The ACSID-11 shows large divergencies to non-ICD-11-based screening instruments.