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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.

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).

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BackgroundChildren who are exposed to natural disasters are at greater risk of developing mental and behavior problems. Prior studies have suggested that positive parenting practices could prevent child mental and behavior problems among those who were exposed to natural disasters. Parent–child interaction increases oxytocin level in parents and infants; however, studies assessing the change in oxytocin level after positive parent-child interaction and its effect on child behavior problems among preadolescents who were exposed to natural disasters are lacking. This study investigated whether playful interaction stimulated oxytocin levels in 34 mother–child dyads who experienced the 2011 Great East Japan Earthquake in Kesennuma City in Miyagi Prefecture, Japan, and the effect of the maternal oxytocin changes on child behavior problems.MethodsParticipants were recruited in 2012 after the Great East Japan Earthquake. Annual surveys were conducted from 2012 to 2017. Salivary oxytocin level was assessed before and after the playful interaction in 2015. Behavior problems were evaluated by caregivers, using the Child Behavior Checklist (CBCL) in 2017. Fixed effect regression analyses were conducted to determine the effect of playful mother–child interaction on oxytocin level by comparing the change in the 10 min after the interaction with the change in the 10 min before the interaction. We also examined the effect of maternal oxytocin changes before and after the playful interaction on the onset of child behavior problems in 2017.ResultsA significant increase in maternal oxytocin level was detected following playful interaction, especially among mothers of first-born boys (2.63 pg/mg protein. 95% CI: 0.45, 4.81). Maternal psychological distress and trauma were also negatively associated with an increase of oxytocin levels. The increase in maternal oxytocin level was significantly associated with lower externalizing problem score of children 2 years later.ConclusionOur results might suggest a rational for potential preventive intervention for child behavior problems through playful mother–child interaction after natural disasters.

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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.

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Abstract Domestication is of unquestionable importance to the technological revolution that has given rise to modern human societies. In this study, we analyzed the DNA and protein sequences of six genes of the oxytocin and arginine vasopressin systems (OXT-OXTR; AVP-AVPR1a, AVPR1b and AVPR2) in 40 placental mammals. These systems play an important role in the control of physiology and behavior. According to our analyses, neutrality does not explain the pattern of molecular evolution found in some of these genes. We observed specific sites under positive selection in AVPR1b (ω = 1.429, p = 0.001) and AVPR2 (ω= 1.49, p = 0.001), suggesting that they could be involved in behavior and physiological changes, including those related to the domestication process. Furthermore, AVPR1a, which plays a role in social behavior, is under relaxed selective constraint in domesticated species. These results provide new insights into the nature of the domestication process and its impact on the OXT-AVP system.