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Introduction

This note describes the data sets used for all analyses contained in the manuscript 'Oxytocin - a social peptide?’[1] that is currently under review.

Data Collection

The data sets described here were originally retrieved from Web of Science (WoS) Core Collection via the University of Edinburgh’s library subscription [2]. The aim of the original study for which these data were gathered was to survey peer-reviewed primary studies on oxytocin and social behaviour. To capture relevant papers, we used the following query:

TI = (“oxytocin” OR “pitocin” OR “syntocinon”) AND TS = (“social*” OR “pro$social” OR “anti$social”)

The final search was performed on the 13 September 2021. This returned a total of 2,747 records, of which 2,049 were classified by WoS as ‘articles’. Given our interest in primary studies only – articles reporting original data – we excluded all other document types. We further excluded all articles sub-classified as ‘book chapters’ or as ‘proceeding papers’ in order to limit our analysis to primary studies published in peer-reviewed academic journals. This reduced the set to 1,977 articles. All of these were published in the English language, and no further language refinements were unnecessary.

All available metadata on these 1,977 articles was exported as plain text ‘flat’ format files in four batches, which we later merged together via Notepad++. Upon manually examination, we discovered examples of papers classified as ‘articles’ by WoS that were, in fact, reviews. To further filter our results, we searched all available PMIDs in PubMed (1,903 had associated PMIDs - ~96% of set). We then filtered results to identify all records classified as ‘review’, ‘systematic review’, or ‘meta-analysis’, identifying 75 records 3. After examining a sample and agreeing with the PubMed classification, these were removed these from our dataset - leaving a total of 1,902 articles.

From these data, we constructed two datasets via parsing out relevant reference data via the Sci2 Tool [4]. First, we constructed a ‘node-attribute-list’ by first linking unique reference strings (‘Cite Me As’ column in WoS data files) to unique identifiers, we then parsed into this dataset information on the identify of a paper, including the title of the article, all authors, journal publication, year of publication, total citations as recorded from WoS, and WoS accession number. Second, we constructed an ‘edge-list’ that records the citations from a citing paper in the ‘Source’ column and identifies the cited paper in the ‘Target’ column, using the unique identifies as described previously to link these data to the node-attribute-list.

We then constructed a network in which papers are nodes, and citation links between nodes are directed edges between nodes. We used Gephi Version 0.9.2 [5] to manually clean these data by merging duplicate references that are caused by different reference formats or by referencing errors. To do this, we needed to retain both all retrieved records (1,902) as well as including all of their references to papers whether these were included in our original search or not. In total, this produced a network of 46,633 nodes (unique reference strings) and 112,520 edges (citation links). Thus, the average reference list size of these articles is ~59 references. The mean indegree (within network citations) is 2.4 (median is 1) for the entire network reflecting a great diversity in referencing choices among our 1,902 articles.

After merging duplicates, we then restricted the network to include only articles fully retrieved (1,902), and retrained only those that were connected together by citations links in a large interconnected network (i.e. the largest component). In total, 1,892 (99.5%) of our initial set were connected together via citation links, meaning a total of ten papers were removed from the following analysis – and these were neither connected to the largest component, nor did they form connections with one another (i.e. these were ‘isolates’).

This left us with a network of 1,892 nodes connected together by 26,019 edges. It is this network that is described by the ‘node-attribute-list’ and ‘edge-list’ provided here. This network has a mean in-degree of 13.76 (median in-degree of 4). By restricting our analysis in this way, we lose 44,741 unique references (96%) and 86,501 citations (77%) from the full network, but retain a set of articles tightly knitted together, all of which have been fully retrieved due to possessing certain terms related to oxytocin AND social behaviour in their title, abstract, or associated keywords.

Before moving on, we calculated indegree for all nodes in this network – this counts the number of citations to a given paper from other papers within this network – and have included this in the node-attribute-list. We further clustered this network via modularity maximisation via the Leiden algorithm [6]. We set the algorithm to resolution 1, and allowed the algorithm to run over 100 iterations and 100 restarts. This gave Q=0.43 and identified seven clusters, which we describe in detail within the body of the paper. We have included cluster membership as an attribute in the node-attribute-list.

Data description

We include here two datasets: (i) ‘OTSOC-node-attribute-list.csv’ consists of the attributes of 1,892 primary articles retrieved from WoS that include terms indicating a focus on oxytocin and social behaviour; (ii) ‘OTSOC-edge-list.csv’ records the citations between these papers. Together, these can be imported into a range of different software for network analysis; however, we have formatted these for ease of upload into Gephi 0.9.2. Below, we detail their contents:

1. ‘OTSOC-node-attribute-list.csv’ is a comma-separate values file that contains all node attributes for the citation network (n=1,892) analysed in the paper. The columns refer to:

Id, the unique identifier

Label, the reference string of the paper to which the attributes in this row correspond. This is taken from the ‘Cite Me As’ column from the original WoS download. The reference string is in the following format: last name of first author, publication year, journal, volume, start page, and DOI (if available).

Wos_id, unique Web of Science (WoS) accession number. These can be used to query WoS to find further data on all papers via the ‘UT= ’ field tag.

Title, paper title.

Authors, all named authors.

Journal, journal of publication.

Pub_year, year of publication.

Wos_citations, total number of citations recorded by WoS Core Collection to a given paper as of 13 September 2021

Indegree, the number of within network citations to a given paper, calculated for the network shown in Figure 1 of the manuscript.

Cluster, provides the cluster membership number as discussed within the manuscript (Figure 1). This was established via modularity maximisation via the Leiden algorithm (Res 1; Q=0.43|7 clusters)

1. ‘OTSOC-edge -list.csv’ is a comma-separate values file that contains all citation links between the 1,892 articles (n=26,019). The columns refer to:

Source, the unique identifier of the citing paper.

Target, the unique identifier of the cited paper.

Type, edges are ‘Directed’, and this column tells Gephi to regard all edges as such.

Syr_date, this contains the date of publication of the citing paper.

Tyr_date, this contains the date of publication of the cited paper.

Software recommended for analysis

Gephi version 0.9.2 was used for the visualisations within the manuscript, and both files can be read and into Gephi without modification.

Notes

[1] Leng, G., Leng, R. I., Ludwig, M. (Submitted). Oxytocin – a social peptide? Deconstructing the evidence.

[2] Edinburgh University’s subscription to Web of Science covers the following databases: (i) Science Citation Index Expanded, 1900-present; (ii) Social Sciences Citation Index, 1900-present; (iii) Arts & Humanities Citation Index, 1975-present; (iv) Conference Proceedings Citation Index- Science, 1990-present; (v) Conference Proceedings Citation Index- Social Science & Humanities, 1990-present; (vi) Book Citation Index– Science, 2005-present; (vii) Book Citation Index– Social Sciences & Humanities, 2005-present; (viii) Emerging Sources Citation Index, 2015-present.

[3] For those interested, the following PMIDs were identified as ‘articles’ by WoS, but as ‘reviews’ by PubMed: ‘34502097’ ‘33400920’ ‘32060678’ ‘31925983’ ‘31734142’ ‘30496762’ ‘30253045’ ‘29660735’ ‘29518698’ ‘29065361’ ‘29048602’ ‘28867943’ ‘28586471’ ‘28301323’ ‘27974283’ ‘27626613’ ‘27603523’ ‘27603327’ ‘27513442’ ‘27273834’ ‘27071789’ ‘26940141’ ‘26932552’ ‘26895254’ ‘26869847’ ‘26788924’ ‘26581735’ ‘26548910’ ‘26317636’ ‘26121678’ ‘26094200’ ‘25997760’ ‘25631363’ ‘25526824’ ‘25446893’ ‘25153535’ ‘25092245’ ‘25086828’ ‘24946432’ ‘24637261’ ‘24588761’ ‘24508579’ ‘24486356’ ‘24462936’ ‘24239932’ ‘24239931’ ‘24231551’ ‘24216134’ ‘23955310’ ‘23856187’ ‘23686025’ ‘23589638’ ‘23575742’ ‘23469841’ ‘23055480’ ‘22981649’ ‘22406388’ ‘22373652’ ‘22141469’ ‘21960250’ ‘21881219’ ‘21802859’ ‘21714746’ ‘21618004’ ‘21150165’ ‘20435805’ ‘20173685’ ‘19840865’ ‘19546570’ ‘19309413’ ‘15288368’ ‘12359512’ ‘9401603’ ‘9213136’ ‘7630585’

[4] Sci2 Team. (2009). Science of Science (Sci2) Tool. Indiana University and SciTech Strategies. Stable URL: https://sci2.cns.iu.edu

[5] Bastian, M., Heymann, S., & Jacomy, M. (2009).

Experimental studies exploring the effects of intranasal oxytocin are typically underpowered due to small samples. Open access to experimental data and procedures and the use of previously employed measures is critical to building more robust and replicable findings, especially in less studied areas of oxytocin research. In this paper, data is provided from a double-blind placebo-controlled crossover study exploring the effects of intranasal oxytocin (IN-OT: 24 IU) on social preference to romantic partners, parents, peers, and strangers. Young adults (N=44; 91% female) in committed dating relationships completed three phases of data collection including a screening survey followed by two laboratory visits. In addition to romantic partner-, and stranger attraction ratings, the data is the first to provide comparisons between attachment and social preference ratings to parents, close friends, and romantic partners under placebo and IN-OT conditions. The data also include differences by situational and life history factors known to moderate oxytocin effects. The detailed protocol, and dataflow can be accessed to verify the analysis and findings or to conduct a replication study. The standardized experimental design and common IN-OT protocol add to the capacity for a meta-analysis exploring oxytocin effects on partner preference, and may also be directly ported to existing or future studies with related questions to increase sample size and power.

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This database contains data collected from a double-blind randomized controlled trial that assessed the impact of route of oxytocin administration on postpartum blood loss and rates of postpartum hemorrhage (PPH) when administered during the third stage of labor following vaginal delivery. Participants who gave birth at a hospital in Argentina were assigned to receive 10 IU oxytocin via intravenous (IV) infusion or intramuscular injection (IM) injection and a matching saline ampoule for the other route . Blood loss was measured using a calibrated receptacle for a 1-hour minimum.

Oxytocin (OXT) (OT) - BioCentury Target Profiles for the biopharma industry

Anonymized, aggregated first-party data among about 683 ProtocolPlus users tracking PT-141 (bremelanotide) or oxytocin for sexual desire and intimacy. Adoption split: PT-141 62% (421 users), oxytocin 38% (262 users). About 19% (130 users) co-track both. Switching leans toward PT-141: roughly 27% of oxytocin users (71) later moved to or added PT-141, versus about 9% of PT-141 users (38) the other way (net about 33 toward PT-141). No structured side-effect comparison or per-use cost data is available for this pair. This is a usage and switching signal reflecting what the community DOES for desire; it is NOT a statement that either compound is effective, safe, or recommended. PT-141 (Vyleesi) is FDA-approved only for acquired, generalized HSDD in premenopausal women; intranasal/sublingual oxytocin for libido is off-label.

The neurohormone oxytocin regulates many aspects of physiology primarily by binding to its receptor, the oxytocin receptor. The oxytocin receptor gene (Oxtr) has been shown to have alternative transcripts in the mouse brain which may each have different biological functions or be used in specific contexts. A popular animal model for studying oxytocin-dependent social behaviors is the prairie vole, a biparental and monogamous rodent. Alternative transcriptional capacity of Oxtr in prairie voles is unknown. We used 5′ rapid amplification of cDNA ends to identify alternative Oxtr transcription start sites in prairie vole brain tissue and uterine tissue. We then validated expression of specific transcripts in fetal brains and assessed the impact of exogenous oxytocin administration in utero on offspring brain development. We identified seven distinct Oxtr transcripts, all of which are present in both brain and uterine tissue. We then demonstrated that maternal oxytocin administration alters expression of a specific subset of Oxtr transcripts and that these different transcripts are under unique epigenetic regulation, such that in the perinatal period only one of the alternative transcripts is associated with DNA methylation in the Oxtr promoter. These data establish the existence of multiple Oxtr transcripts in prairie vole brain and uterine tissue and implicate oxytocin in the regulation of alternative transcript expression. These data have significant implications for our understanding of null mutant models in both mice and voles and translation in human birth and behavior.

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Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by impaired skills in social interaction and communication in addition to restricted and repetitive behaviors. Many different factors may contribute to ASD development; in particular, oxytocin receptor (OXTR) deficiency has been reported to be associated with ASD, although the detailed mechanism has remained largely unknown. Epidemiological study has shown that maternal diabetes is associated with ASD development. In this study, we aim to investigate the potential role of OXTR on maternal diabetes-mediated social deficits in offspring. Our in vitro study of human neuron progenitor cells showed that hyperglycemia induces OXTR suppression and that this suppression remains during subsequent normoglycemia. Further investigation showed that OXTR suppression is due to hyperglycemia-induced persistent oxidative stress and epigenetic methylation in addition to the subsequent dissociation of estrogen receptor β (ERβ) from the OXTR promoter. Furthermore, our in vivo mouse study showed that maternal diabetes induces OXTR suppression; prenatal OXTR deficiency mimics and potentiates maternal diabetes-mediated anxiety-like behaviors, while there is less of an effect on autism-like behaviors. Additionally, postnatal infusion of OXTR partly, while infusion of ERβ completely, reverses maternal diabetes-induced social deficits. We conclude that OXTR may be an important factor for ASD development and that maternal diabetes-induced suppression of oxytocin receptor contributes to social deficits in offspring.

IntroductionRole-play, a key creative process in theatre, is used in therapeutic interventions to improve social skills, emotion regulation, and memory. Although role-play is widely used as a psychotherapeutic technique, its mechanisms of action are not fully understood.MethodsOur study introduces a standardized controlled procedure for promoting role-play in the laboratory based on the portrayal of a fictional persona and examines its effects on anxiety, affect, prosocial attitudes, and salivary oxytocin dynamics in 38 participants.ResultsIn our experiment, role-play significantly increased positive affect and prosocial attitudes and decreased anxiety compared to a control condition. Basal salivary oxytocin levels predicted higher gains in positive affect following role-play, suggesting a specific moderating effect of oxytocin. The fictional persona used in the procedure was rated as very happy by subjects, creating a positive social context for the role-play social interaction.DiscussionsWe propose that the observed moderation effect of oxytocin in our study is specific to the role-play condition due to the capacity of role-play to generate an affective regulatory context based on congruency toward the emotional state of the fictional persona. Our findings indicate that basal oxytocin levels could predict specific outcomes of role-play in therapeutical setting. We discuss several psychological and biological mechanisms that could account for the observed effects of role-play and how oxytocin could act as a substrate for them.

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