Potential gene-editing treatment for anxiety and alcohol use disorder in adult rats who were exposed to binge drinking in their adolescence

Targeted epigenomic editing ameliorates adult anxiety and excessive drinking after adolescent alcohol exposure. John Peyton Bohnsack, Huaibo Zhang, Gabriela M. Wandling, Donghong He, Evan J. Kyzar, Amy W. Lasek and Subhash C. Pandey. Science Advances, May 4 2022. DOI: 10.1126/sciadv.abn2748

Abstract: Adolescent binge drinking is a major risk factor for psychiatric disorders later in life including alcohol use disorder. Adolescent alcohol exposure induces epigenetic reprogramming at the enhancer region of the activity-regulated cytoskeleton-associated protein (Arc) immediate-early gene, known as synaptic activity response element (SARE), and decreases Arc expression in the amygdala of both rodents and humans. The causal role of amygdalar epigenomic regulation at Arc SARE in adult anxiety and drinking after adolescent alcohol exposure is unknown. Here, we show that dCas9-P300 increases histone acetylation at the Arc SARE and normalizes deficits in Arc expression, leading to attenuation of adult anxiety and excessive alcohol drinking in a rat model of adolescent alcohol exposure. Conversely, dCas9-KRAB increases repressive histone methylation at the Arc SARE, decreases Arc expression, and produces anxiety and alcohol drinking in control rats. These results demonstrate that epigenomic editing in the amygdala can ameliorate adult psychopathology after adolescent alcohol exposure.

Popular version: A study by researchers from the University of Illinois Chicago has found a potential gene-editing treatment for anxiety and alcohol use disorder in adults who were exposed to binge drinking in their adolescence. Binge drinking in adolescence alters brain chemistry in the enhancer region of the Arc gene and reduces Arc expression in the amygdala for both rodents and humans. This contributes to a predisposition to alcohol use disorder in adulthood. Rats that had been exposed to alcohol during adolescence showed fewer indicators of anxiety and lower alcohol consumption when Arc gene expression was increased using CRISPR technology. Normal rats showed more indicators of anxiety and increased their alcohol consumption when Arc gene expression was decreased.

DISCUSSION

Our results indicate that targeted epigenomic editing at the Arc SARE can bidirectionally modulate behavioral changes caused by adolescent alcohol exposure (Fig. 5). Furthermore, we demonstrate that these changes are largely due to an epigenetic circuit involving transcription of eRNAs from the Arc SARE, which causes epigenetic remodeling at the Arc promoter by looping of the chromatin to allow localized release of NELF. In addition, our results indicate that activating the Arc SARE site through histone acetylation using dCas9-P300 facilitates Arc eRNA transcription and long-range promoter-enhancer interactions and modulates transcription factor binding, which is consistent with other findings (25, 39, 40). Conversely, dCas9-KRAB–mediated epigenetic suppression at Arc SARE decreases eRNA transcription and increases NELF binding at the promoter without changing enhancer and promoter interactions and promotes anxiety and excessive drinking (Fig. 5). This contrasts with other studies in which KRAB is involved in heterochromatin spreading and transcriptional repression via alternative mechanisms (41). Here, we demonstrate that dCas9-KRAB increases repressive H3K27me3, which has previously been shown to be involved in repressing eRNA transcription (35). We observed no change in H3K9me3 occupancy at the Arc SARE site after dCas9-KRAB manipulations. Other studies have shown that targeting dCas9-KRAB to specific genomic loci increases H3K9me3, but these changes have been shown to be transitory and not sufficient for transcriptional repression (38, 42). While it is likely that increased H3K27me3 at the Arc SARE contributes to repressed Arc eRNA and mRNA expression and subsequent behavioral correlates, the current study did not investigate other repressive mechanisms induced by dCas9-KRAB.

Fig. 5. Model showing that adolescent alcohol exposure produces epigenetic reprogramming in the CeA as well as anxiety and excessive alcohol intake in adulthood.

dCas9-P300 infusion in the CeA was able to increase H3K27ac at Arc SARE, increase Arc eRNA and mRNA expression, and ameliorate anxiety and excessive alcohol intake induced by AIE exposure in adulthood. On the other hand, dCas9-KRAB increased repressive epigenetic marks, H3K27me3 at Arc SARE, leading to decreased Arc eRNA and mRNA expression and development of anxiety and alcohol drinking behaviors in control adult rats. These data causally link epigenetic modifications at an enhancer region of synaptic gene Arc to adult AUD and anxiety after adolescent alcohol exposure.

OPEN IN VIEWER

Preclinical and clinical data clearly suggest that adolescent alcohol consumption can increase the susceptibility of an individual to anxiety and AUD (4–7, 9, 10). Several studies in the field have shown that various biological mechanisms, including epigenetic changes, may be involved in the persistence of the effects of adolescent alcohol exposure into adulthood (9, 10, 43). It has been shown that epigenetic drugs such as histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors can attenuate adolescent alcohol exposure–induced anxiety-like and alcohol drinking behaviors in adult rats (28, 44). Similar to what was found in the current study using dCas9-P300, treatment with either a systemic HDAC inhibitor or DNMT inhibitor did not result in anxiolysis or reduce alcohol intake in AIS adult rats (28, 44). Here, there was a trend toward an increase in Arc expression and histone acetylation after dCas9-P300 treatment, but this was not statistically significant. Conversely, acute ethanol challenge in AIS adult rats increased Arc expression and produced anxiolysis that was associated with increased KDM6B/CBP, decreased H3K27me3, and increased H3K27ac occupancy at the Arc SARE site in the amygdala. These epigenetic modifications were associated with a significant increase in Arc expression in the amygdala of AIS rats (11). We therefore suggest that the dCas9-P300 manipulation did not reach the set point or biological threshold of Arc expression to induce anxiolysis, and this may be a possible explanation for the lack of observed effects of dCas9-P300 on anxiety and alcohol intake in AIS control rats.

The Arc gene is one of the most interactive genes in the altered synaptic gene network in the adult amygdala after adolescent alcohol exposure in rats (11). Arc interacts with a brain-derived neurotrophic factor (BDNF), and both are down-regulated via epigenetic mechanisms in the amygdala of rodents and humans in adulthood after adolescent alcohol consumption (11, 12, 30). Arc protein expression is lower in the CeA of alcohol-preferring rats as compared with alcohol nonpreferring rats, and this is most likely the result of increased HDAC2-mediated deficits in histone acetylation of Arc gene. Inhibition of HDAC2 expression in the CeA of preferring rats attenuated anxiety-like behaviors and excessive drinking and increased histone acetylation and Arc protein expression in the CeA (45). Furthermore, HDAC and DNMT inhibitors are also effective in preventing excessive drinking and alcohol self-administration in other animal models of AUD (46–48). These studies suggest that Arc expression is regulated via histone acetylation mechanisms and that pharmacological epigenetic agents are effective in attenuating anxiety and alcohol intake in several models of AUD. However, these studies do not establish the specific epigenetically regulated genomic regions implicated in these effects. Here, we used epigenomic editing (25–27) to modulate histone acetylation/methylation levels at a specific genomic locus regulating anxiety and excessive drinking.

AIE is associated with diminished synaptic events that are characterized by decreased mRNA and protein levels of Arc and decreased dendritic spines and synapses in the CeA in adulthood (11, 28). Our previous studies showed that up-regulation of EZH2 and down-regulation of KDM6B and CBP after AIE initiate repression of the Arc gene through increases in H3K27me3 and decreases in H3K27ac occupancy at the Arc SARE, providing an endogenous mechanism for epigenetic reprogramming in the amygdala of rodents (11) and AUD subjects with early age of onset (12). All these studies are correlative in nature, and we now causally demonstrate in detail how epigenetic activation and repression at the Arc SARE site can drive adult excessive drinking and anxiety induced by adolescent alcohol exposure. Our results further indicate that epigenetic editing using dCas9-P300 at the Arc SARE is sufficient for enhancer-mediated activation of Arc expression and can drive increased H3K27ac at the promoter site, most likely via chromatin looping (34, 39). There are few caveats to the present study. One caveat is that it was only performed in male animals, and since sex-specific effects of ethanol have been shown in the literature (49), a future study in female animals needs to be conducted. Another caveat is that we chose to mechanistically interrogate only the CeA, whereas previous studies have shown similar changes in Arc expression in the medial nucleus of amygdala (MeA) after AIE in adulthood (28). While the results of current study imply that epigenomic editing of Arc SARE in the CeA is sufficient to modulate anxiety-like and alcohol drinking behaviors, we cannot rule out the involvement of other brain regions that are implicated in these behaviors and addiction (2, 50).

Previous reports have indicated that the use of dCas9-induced epigenetic modulation at promoter regions can modulate behavior (51–53) as well as CRISPR-mediated chromosomal looping (54). Here, we demonstrate that this technology can also be used to investigate the role of noncoding RNAs, such as eRNAs, in regulating the interplay between three-dimensional chromatin structure, genetic regulatory elements, transcription factor binding, and RNA to influence adult anxiety and drinking after adolescent alcohol exposure. The current study focused on reversing epigenetic and behavioral changes in adulthood that were induced by adolescent alcohol exposure. However, we have previously observed that histone acetylation and behavioral changes also occur immediately after the AIE paradigm in adolescence and persist into adulthood (28). While the current study only focused on the long-term changes that persist until adulthood to better model what is seen in humans (4–7), the findings support the idea that activating the Arc SARE with dCas9-P300 could be applied as an intervention in adolescence. Our previous study showed that KDM6B siRNA infusion into the CeA of control adult rats produced anxiety-like behaviors, decreases in KDM6B, and increases in H3K27me3 occupancy at the Arc SARE site and suppressed Arc eRNA and mRNA expression in the amygdala (11). In addition, inhibition of Arc eRNA (−) levels in the CeA increased NELF binding, decreased Arc expression, and provoked anxiety-like behaviors in control adult rats (11). Here, we demonstrate that dCas9-KRAB infusion into CeA produces an increase in repressive H3K27me3 at the Arc SARE, decreases eRNA levels, increases NELF binding at the promoter, down-regulates Arc expression, and increases anxiety-like behavior and alcohol intake in control adult rats. Together, this suggests that epigenetic regulation at the Arc SARE site in the CeA is involved in modulating anxiety and alcohol intake. Thus, both developmental alcohol exposure–induced suppression of Arc expression and direct suppression of Arc expression in adulthood in the CeA appear to be crucial in anxiety and AUD.

Our findings regarding epigenomic editing allow for the analysis of gene- and amygdala nuclei–specific epigenetic changes that occur after adolescent alcohol exposure and persist until adulthood, driving complex behavior. The Cas9 system is easier to use and more modular than previous iterations [e.g., transcription activator–like effector nucleases (TALENs)] designed to alter precise epigenetic marks (55). In addition, the use of dCas9 to modulate gene expression, in lieu of a Cas9 enzyme with active endonuclease activity, could confer additional therapeutic and research benefit. Considerable effort has gone into reducing “off-target” double-stranded breaks that result in genome instability (56). The use of the dCas9 system avoids many of these off-target effects since DNA is not cut and not subject to error-prone nonhomologous end joining or spontaneous recombination events. The use of a dCas9 system is especially useful in the context of epigenetic regulation, and it has broad applications in the interrogation of long-lasting epigenetic changes that drive AUD and anxiety after adolescent alcohol exposure and the identification of tractable targets for the treatment of AUD and comorbid anxiety.

Although men who expressed a desire to have children were generally considered more desirable than those who did not, if a man did not want children, he could still be considered desirable if his previous partner spoke highly of him

Call Me Daddy: How Long-term Desirability Is Influenced by Intention for Fatherhood. Ryan C. Anderson & Michele K. Surbey. Evolutionary Psychological Science, May 16 2022. https://link.springer.com/article/10.1007/s40806-022-00324-1

Abstract: One of the most important decisions an individual can make involves investing in a mating relationship. For women, the process of mate selection can be time-intensive and fraught with costs and dangers. However, these risks can be minimised by attending to relevant social information and modelling the mate choices of others. The propensity of imitating another’s mate choices is referred to as mate copying. Most research has focused on this behaviour in non-humans, but evidence of its existence in humans is emerging. The current study sought to determine conditions that modify a man’s desirability. The present study examined 267 women’s evaluations of men depicted in silhouetted images who varied in terms of their intentions for fatherhood and relationship history. Results showed that a man’s desirability as a long term mate was enhanced if he wished to become a father, and/or if he had a previous relationship experience, indicating he had been formerly chosen or preferred. These findings add to the existing body of knowledge on mate copying and attention to social information by demonstrating how women incorporate social learning and innate evolutionary predispositions to facilitate decision-making and behaviour relating to mate selection.

Discussion

Employing silhouetted representations of men, women participating in the current study gave mate-relevant evaluations of target men in varying relationship experience conditions and who either did or did not intend to be fathers. The hypothesis that men with intentions of fatherhood (would like to be a father one day) would be considered by women to be more romantically desirable than men indicating the opposite (does not have children at the moment and does not wish to have any) was supported. By demonstrating that men without relationship experience were evaluated as less desirable than men with relationship experience, the results supported the idea that women copy the mate preferences of other women under certain conditions. Positive mate-relevant information provided by a former partner positively contributed to a man’s romantic desirability and fatherly intention (‘his most recent ex-partner speaks highly of him as a romantic partner’) was found to be highly desirable to women. An interaction between the variables of fatherly intention and relationship experience suggested that having a positive former partner seemed to compensate for a man’s expressed lack of intention to become a father. Although men who expressed a desire to have children were generally considered more desirable than those who did not, if a man did not want children, he could still be considered desirable if his previous partner spoke highly of him.

Mate Copying

A propensity to mate copy was demonstrated in the current study by virtue of the fact that the participants rated currently single men who had formerly been in romantic relationships as being more desirable as a long-term partner than men who had not been in a romantic relationship. These results are consistent with previous research indicating that men are more ‘desirable’ (variously operationalised) if they have previously been chosen as a partner, than if they have not. Whereas many studies within the mate copying literature have employed various dependent measures as proxies of a man’s mate value and yielded inconsistent results (see Anderson & Surbey, 2020 for a discussion), the current study used an explicitly stated measure of long-term desirability. While actual mate copying was not measured in this study, a propensity to copy the preferences of other women was indicated by women finding men with former partners to be more desirable than men without former partners. Such a propensity would presumably motivate or underlie actual instances of mate copying.

Departing from other methodological procedures employing photographs or morphed photographs of real men (Chu, 2012; Eva & Wood, 2006; Little et al., 2008, 2011; Vakirtzis & Roberts, 2010; Waynforth, 2007; Yorzinski & Platt, 2010), the current study used small generic silhouettes of men in an attempt to decrease the perceived importance of visual information and thereby increase the relative importance of the text manipulations. Some of the target men were explicitly described as currently single, but having been in either one or no former relationships in the last 4 years. This procedure is similar to that employed by Anderson and Surbey (2014), who also used silhouette representations and found formerly partnered men to be more desirable than those without former partners.

Consistent with previous research (Scammell & Anderson, 2020), positive mate-relevant evaluations offered by former partners positively contributed to a man’s desirability. The positive opinion of a previous partner enhanced a target man’s perceived desirability as a long-term partner above that of other men (formerly partnered or not). In other words, a positive evaluation from a former partner enhances the mate copying effect. The fact that having a former partner speak positively of him increases a man’s desirability as a long-term partner is consistent with the idea that the perceived value of something can be meaningfully enhanced by a positive endorsement (Erdogan, 1999), especially when it is coming from an authoritative or reputable source (in this case a former partner). An unexpected interaction suggested that a positive assessment by a former partner may compensate for an undesirable anti-fatherhood intention (‘does not wish to have children’), but this possibility requires further exploration and consideration of alternative interpretations.

For example, while it may be reasonable to expect that being ‘endorsed’ by an authority source (former partner) would theoretically make someone seem more appealing (desirable), the enhancement in appeal they receive may be counteracted by female intrasexual aggression. It may be that a former partner who speaks highly of a man is doing so because she is not entirely detached from him. The intrasexual competition that she poses to prospective female suitors may be enough to deter them from pursuing a relationship with the man, or at least make them suspicious of how close the two remain. If their relationship is unresolved, there is a chance that he will go back to her. This may be problematic if he has followed through with his intention to have children with his newest partner but subsequently abandons her and the child to reunite with his former partner.

The availability and accessibility of potential mates have been shown to affect intrasexual competition and aggression among a number of non-human taxa (see Rosvall, 2011). It was found that heterosexual undergraduate students were both more jealous and willing to aggress when they were led to believe that potential mates were scarce (inaccessible) than if they thought potential mates were abundant (Arnocky et al., 2014). In the current study participant ‘aggression’ toward an anonymous former partner of a target man (potential mate) manifested as disinterest toward dating him. Such an explanation may also be consistent with a cognitive dissonance appraisal (Festinger, 1962), whereby a difficult-to-obtain article is disfavoured (‘I did not want it anyway’).

The present results suggest that having intentions for fatherhood increases one’s desirability as a long-term partner and are generally consistent with the findings of a review examining gender differences in mate preferences (Feingold, 1992). Predictions were derived from Trivers’ (1972) parental investment model, which suggests that women (as the sex with higher obligate investment in offspring) more than men seek mates who possess non-physical characteristics that maximise the survival and reproductive prospects of their offspring. A recurrent finding in the literature is that men indicating fatherly intention or competence, or the ability to provision offspring with resources, are considered desirable as romantic partners. The general idea is that men with a favourable attitude toward children will be more likely to contribute to their well-being by providing them with survival-promoting resources.

The current results suggest that having a former partner speak highly of a man makes him somewhat more desirable as a long-term partner and that men expressing a willingness to have children are considered far more desirable than men not wanting children. Curiously, these two characteristics in concert were considered undesirable. Men with positive former partners were more desirable as a long-term partner if they did not want children than if they did. It may be that men with too many positive characteristics (has a positive ex, wants children) seem unrealistic and are thus evaluated poorly. It has been shown that claims or offers seeming ‘too good to be true’ can elicit suspicion and lead to rejection (Steinel et al., 2014). This seemingly paradoxical finding is inconsistent with other findings reported here and awaits further enquiry.

Mate Poaching

Mate poaching was defined as the difference in desirability between men with a current partner and those without one currently, but with a former partner. Based on previous inconsistencies in the literature (Eva & Wood, 2006; Uller & Johansson, 2003), it was unclear whether the current study would detect mate poaching. However, the results suggested that men currently in a relationship were considered more desirable as long-term partners than single men, regardless of whether their most recent romantic partner gave positive mate-relevant information about them. While these results are consistent with the phenomenon of mate copying, we maintain that the processes of mate copying and mate poaching are systematically different. While mate poaching typically involves the additional elements of pursuing or stealing someone already in a relationship, these elements are not pre-requisites of mate copying (Anderson & Surbey, 2020). While indicating that an attached other is desirable as a long-term partner may be morally problematic and may possibly invoke some degree of cognitive dissonance (I want it, but I cannot have it), it is different to indicating that someone is willing to couple with a currently attached man, or otherwise steal him from his current partner. The latter carries with it an implicit suggestion that a person is willing to violate an unwritten social law—namely, that individuals in relationships are (generally) not open to pursuit by individuals outside of the relationship.

Methodological Considerations

The sample in the current study largely comprised university students and was therefore non-random. Presumably, many individuals attend university because they wish to enhance their qualifications and further their career (Battle & Wigfield, 2003). Although there is evidence suggesting that career-oriented individuals (especially younger ones) are less concerned with parenthood (Bass, 2014) and may therefore value parental intentions less in a partner, the employment of a non-random university sample did not appear to significantly impair finding the predicted effects.

There is evidence that mate copying is more common among younger and less experienced women than among their older counterparts (Anderson & Surbey, 2014; Bowers et al., 2011; Waynforth, 2007). Although the sample age range (18–40) was ideal for studying mate selection in general (for example, post-reproductive women may employ entirely different mate selection criteria), the mean age of the present sample was low (21.73 years) and the distribution had a strong skew. Instead of being problematic, however, employing this sample may have enhanced the ability to detect mate copying as well as the strength of its effect.

Finally, it is worth considering that previous research has suggested that physically strong men are more attractive. Muscularity can be an indicator of genetic quality and a capacity to protect offspring (Sell et al., 2017). Therefore, limited visibility of target men, presented in cropped close-up photographs, may make it difficult for women to visually assess a potential mate’s body—their strength, leanness and height (Lu & Chang, 2012; Sell et al., 2017). It is certainly possible that stimuli presented in the current study influenced perceptions of paternal ability. Future studies may wish to consider presenting ‘more comprehensive’ stimuli in an effort to account for this variable.

Political incompatibility between romantic partners gnaws away at relationship satisfaction

Love and Politics: The Influence of Politically (Dis)Similar Romantic Relationships on Political Participation and Relationship Satisfaction. Cynthia Peacock, Joshua R Pederson. Human Communication Research, hqac011, May 10 2022. https://doi.org/10.1093/hcr/hqac011

Abstract: People are more likely to seek out romantic partners who are politically similar to themselves. Nonetheless, romantic partners who disagree politically do exist. This study examines the influence of political (dis)similarity in romantic relationships on both political participation and relationship satisfaction. We found that (1) people in politically similar romantic relationships are more satisfied in their relationships and more politically participative than those who are in dissimilar relationships, (2) discussion expressiveness mediates the relationships between political similarity and satisfaction, (3) discussion frequency and expressiveness mediate the relationship between political similarity and participation, and (4) whereas political conflict intensity mediates the relationship between political similarity and satisfaction, it does not affect participation. Findings indicate that the quality of discussion and conflict, not merely their occurrence, help explain the political and relational results of political (dis)similarity within romantic relationships.

A person with anterograde amnesia (complete loss of the ability to memorize new information after 20-30 min of the event), is highly functional by using the smartphone as a cognitive prosthesis, checking his phone more than 100 times per day

Annese, Jacopo, Ruth Klaming, Lori Hasse-Alasandro, and Justin S. Feinstein. 2022. “Severe Anterograde Amnesia in the Era of Smartphone Technology.” PsyArXiv. May 15. doi:10.31234/osf.io/wu9f2

Abstract: A.V. is a young Herpes simplex Encephalitis (HSE) survivor with extensive bilateral damage to the medial temporal lobe (MTL) and one of the most severe forms of anterograde amnesia on record. In spite of the demonstrable deficit, A.V. regained a much higher degree of functioning and autonomy than previously-documented amnesic patients with major bilateral MTL damage. The distinguishing feature of A.V.’s adaptation and his advantage as a millennial, is that he is able to offload onto his smartphone those cognitive tasks that were previously supported by the MTL, as evidenced by our analysis of app usage.

The topography of A.V.’s brain injury combined with purity of the ensuing amnesia represent unique neuropsychological conditions that can advance the scientific study of human memory systems. A.V.’s relative success in coping with profound amnesia further offers unique insight into the potential of smartphone technology to become integrated with neural mnemonic functions, a phenomenon that has broad implications at the societal level and for public health, specifically in the management of memory disorders like Alzheimer’s disease.

Pornography consumption is relatively frequent in all age groups, not only the overstudied 18-30 age range; the most popular topic is two people having ordinary sex

Pornography Consumption in People of Different Age Groups: an Analysis Based on Gender, Contents, and Consequences. Rafael Ballester-Arnal, Marta García-Barba, Jesús Castro-Calvo, Cristina Giménez-García & Maria Dolores Gil-Llario. Sexuality Research and Social Policy, May 14 2022. https://link.springer.com/article/10.1007/s13178-022-00720-z

Abstract

Introduction: Pornography consumption has increased exponentially in recent decades. Most studies conducted so far are focused on adult samples (typically, between 18 and 30 years old), limiting the generalizability of their results. This study aims to create a taxonomy that groups various pornographic contents and thus explore different aspects of its use (e.g., preference for different pornographic content, excessive and problematic use) in people at different life stages.

Methods: Between 2016 and 2019, 8,040 individuals (71.3% men) between 12 and 85 years old (M = 33.25, SD = 14.31) completed a battery that explores pathological and non-pathological pornography use. Participants were distributed into five age groups (< 18 years old, between 18–25, 26–40, 41–60, and > 60) to perform the different analyses (ANOVA and chi-square tests for the differences between the groups, EFA for the analyses of categories of pornographic content, and hierarchical linear regressions to identify the factors related to problematic use).

Results: Pornography use was highly prevalent (> 85%) in all age groups. Using a data-driven approach, we found that the pornographic content explored in this research can be classified within four categories. Using this taxonomy, we found differences according to the age for most of the pornographic content explored (e.g., sexual intercourse with opposite-sex partners [71.6–84.5% in males and 70.2–89.5% in females]). Finally, we found that age conditions the way in which preference for different pornographic content increases the risk of excessive and problematic use.

Conclusions: Pornography consumption is frequent in different age groups, although it varies depending on age and content. In addition, some particular pornographic contents were identified that increase the risk of developing an addiction in different developmental stages.

Policy Implications: This study provides a preliminary foundation for identifying the unique characteristics of pornography use in different age groups as well as content related to increased problematic use.

Discussion

In this study, we aimed to (1) generate a data-driven taxonomy of pornographic contents, (2) analyze and compare the use of different pornographic materials in different age groups, and (3) explore whether the use of different pornographic content predicted an increased risk of cybersex addiction. In this sense, we found four categories of pornography to classify the wide variety of normophilic (i.e., vaginal, anal, oral, and group sex) and paraphilic or non-mainstream contents (i.e., sadomasochism, fetish, bondage and dominance, violent coercive, and bizarre/extreme) (Hald, 2006; Hald & Štulhofer, 2016; Štulhofer et al., 2010). As for the preference for different pornographic contents in different age groups, contents depicting sexual intercourse were the most consumed in practically all age groups, with hardly any variation according to age and gender. Other content that may be classified as unusual or uncommon such as sexual relations with more than two people or sexual activity involving domination and submission are also relatively frequent in men and women, although they decrease in the more extreme age ranges (children and adolescents and elderly). Finally, this study provides a nuanced description of which particular pornographic contents increase the risk of cybersex addiction in different developmental stages.

As one of our main objectives, in this study, we have created a taxonomy of pornographic content that comprises four categories: soft pornography, sexual intercourse, unusual sexual interests, and chronophilias. This classification resonates with other more theoretical proposals that have not been empirically proven, such as that proposed by Leonhardt et al. (2019) with their categories sexually suggestive, sexually explicit, and paraphilic, according to the degree of sexual explicitness and the kind of sexual content. Except for the small nuance of the chronophilias where according to our results seem to have some distinction of what could be considered "paraphilic" or "unusual sexual interest", although both categories have a high correlation with each other. On the contrary, our taxonomy differs from that proposed by Hald and Štulhofer (2016). With a methodology similar to that employed in this study, they suggested a classification into three categories, focusing on gender, sexual orientation, or non-mainstream pornographic contents. These differences may be due to the number of participants (being much larger in our study) and, above all, to the age range of the respondents. In our study, we cover much broader age ranges that help us to take into account the differences in the consumption of pornography that can occur at different stages of life (Ballester-Arnal et al., 2021; Ševčíková et al., 2020), offering us a taxonomy of pornographic content with greater validity and internal consistency.

Analyzing the consumption of pornography following this categorization, we observe that, in general, there are hardly any variations in the pornographic content searched based on age, and, following the same line as the most recent research, we show a slight decrease in the consumption of pornography in older adults compared to younger people (Price et al., 2016). The most frequent pornography preferences in both genders in the different age groups explored is classified as normophilic (i.e., sexual intercourse with opposite or same sex partners). These data would not support the hypothesis that some authors hold about the increase in recent decades in exposure to paraphilic pornography, mainly among men, especially that containing sexual violence or child pornography (Davis et al., 2018; Romito & Beltramini, 2015). This hypothesis is given by the apparent increase in aggressive content in pornographic videos, especially the more subtle violence (Bridges et al., 2010; Carrotte et al., 2020) and how viewing of this pornographic material can favor the acquisition of these sexual scripts in offline sexual behaviors (Bridges et al., 2016; Wright, 2011). However, as studies like those of Baer et al. (2015) or Shor and Seida (2019) show, despite the increase in paraphilic content available online, this type of online sexual content is the least consumed by users, as well as the worst valued. Except for the use of online pornography with adolescents’ sexual content, whose frequency is logically higher among the group of children and adolescents who would seek sexual practices with their peers, so it could not be considered a paraphilic practice. Our results reflect lower percentages of paraphilic pornography interests than other studies, which may be due to methodological differences, including the characteristics of the participants (clinical vs non-clinical sample, cultural differences, etc.) or the limited list of pornographic content provided (Hald & Štulhofer, 2016; Neutze et al., 2011; Sun et al., 2015).

Lastly, we explore the relationship between different pornographic content and cybersex addiction. Our results show that only a few types of pornography have been linked to cybersex addiction. Specifically, viewing some pornography content classified as unusual (pornography involving domination or submission or sexual intercourse with more than two people) or paraphilic (chronophilias) is related to cybersex addiction measured by the ISST. Some studies suggest that persistent pornography users may exhibit habituation to normophilic content, which translates into an increase in the use of unusual and extreme pornographic material (Foubert, 2016; Hilton & Clark, 2011; Tripodi et al., 2015). This habituation may be due to the development of tolerance, one of the characteristic symptoms of addictions which, in the particular case of cybersex addiction, may be reflected in a need to seek more exciting and extreme content (i.e., paraphilic) to achieve previous sexual satisfaction (Lewczuk et al., 2021). This phenomenon may explain why the consumption of this particular pornographic content may be related to the development of cybersex addiction. However, as some authors suggest, this relationship may occur in the opposite direction: a previous interest in paraphilic sexual content (in the most severe cases, the presence of a previous paraphilic disorder) may increase the use of the Internet for sexual purposes (Griffiths, 2012; Ross et al., 2012). It would therefore be necessary to further investigate the relationship between these two variables to determine how they are interrelated.

In our study, we also found that the use of non-paraphilic pornographic contents (sexual intercourse with same-sex partners or nude people showing their genitals) increased the risk of developing cybersex addiction, although not in all age groups. This may be due to factors such as anonymity and accessibility, cybersex factors related to its addictive potential (Cooper et al., 1999; Griffiths, 2012). These characteristics of cybersex allow people to experiment with sexuality over the Internet by facilitating access to sexual content that cannot be accessed offline. For example, in sexual relations with same-sex partner –punished in many contexts– or fulfilling certain sexual fantasies that are not easily accessible offline may increase the consumption in people (Castro-Calvo et al., 2018; Giménez-García et al., 2021; Green et al., 2012; Ross et al., 2012). This would explain why factors such as belonging to a sexual minority or sexual dissatisfaction, regardless of having paraphilic sexual attractions or not, have been linked to the problematic cybersex use (Daspe et al., 2018; Studer et al., 2019). Another factor that has been related to a predisposition to problematic cybersex use is gender, specifically being a man (Ballester-Arnal et al., 2021; Weinstein et al., 2015; Wéry & Billieux, 2016). Our results also show this relationship in all age groups; however, in general, the different pornography content does not affect cybersex addiction in a different way. These data show the need to take into account the type of pornography content consumed online when evaluating addiction to pornography and/or cybersex, regardless of age and gender.

This study is not without its limitations. On the one hand, we find limitations related to the sample, including a smaller sample size in some groups (children, adolescents, and the elderly) and the type of sampling (convenience sampling). Furthermore, as it is a cross-sectional study, we do not take into account the effect of the birth cohort which, as other studies such as Price et al. (2016) or Wright (2013) show, could further enrich the study and provide data on both effects (age and year of birth) on pornography consumption. Another limitation of our study is related to the percentage of women in the sample: the proportion of women in the sample notably decreased with age (in particular, in older age ranges), meaning that women in these age ranges are underrepresented in our research. This underrepresentation of women in older age ranges may be explained by the traditional values and social norms related to the expression of sexuality in women: compared to men, women have been more often judged when expressing their sexual experiences and interests (Lai & Hynie, 2011; Zaikman & Marks, 2017). These negative experiences may explain their lower rates of participation in a study focused on sexual behavior and also explain why younger girls (less exposed to traditional sexual scripts) are more likely to participate and report their sexual experiences. Other sociodemographic variables—such as sexual orientation or cultural differences—have also been related to the use of the Internet for sexual purposes (Bőthe et al., 2020b; Green et al., 2012; Velezmoro et al., 2012) but are not analyzed in this research. Therefore, future studies analyzing the effect that these variables have on the use of pornography in different life stages warrant further research.

Another important limitation of this study is the evaluation of cybersex addiction. Due to the multiple manifestations it represents (including the problematic consumption of pornography) (Varfi et al., 2019), the discrepancies in its definition and diagnostic criteria (Wéry & Billieux, 2017) and the limited number of validated questionnaires, especially in Spanish; in this study we decided to use a more general measure of cybersex addiction to assess the excessive and problematic use of pornography. Our taxonomy of pornography was based on only 10 types of content, not including others such as MILF or hentai that can also be prevalent in society (Ogas & Gaddam, 2011; PornHub, 2019), which is another limitation. In future studies, it would be interesting to include a greater number of types of pornography, as well as to explore the frequency of use of each type to know if the negative consequences are associated with a single or prolonged viewing (Kingston et al., 2008; Lewczuk et al, 2021), or the level of arousal, being also an important aspect in the development of addiction (Laier et al., 2013). Despite the limitations described above, we consider that our work provides relevant information on some issues very little studied so far, such as pornographic preferences in men and women in different age groups or how it affects the viewing of specific sexual pornographic content in cybersex addiction, among others.