A problematic study of oxytocin receptor gene methylation, childhood abuse, and psychiatric symptoms

This 2016 Georgia human study found:

“A role for OXTR [oxytocin receptor gene] in understanding the influence of early environments on adult psychiatric symptoms.

Data on 18 OXTR CpG sites, 44 single nucleotide polymorphisms, childhood abuse, and adult depression and anxiety symptoms were assessed in 393 African American adults. The Childhood Trauma Questionnaire (CTQ), a retrospective self-report inventory, was used to assess physical, sexual, and emotional abuse during childhood.

While OXTR CpG methylation did not serve as a mediator to psychiatric symptoms, we did find that it served as a moderator for abuse and psychiatric symptoms.”

From the Limitations section:

  1. “Additional insight will likely be gained by including a more detailed assessment of abuse timing and type on the development of biological changes and adverse outcomes.
  2. The degree to which methylation remains fixed following sensitive developmental time periods, or continues to change in response to the environment, is still a topic of debate and is not fully known.
  3. Comparability between previous findings and our study is limited given different areas covered.
  4. Our study was limited to utilizing peripheral tissue [blood]. OXTR methylation should ideally be assessed in the tissues that are known to express OXTR and directly involved in psychiatric symptoms. The degree to which methylation of peripheral tissues can be used to study methylation changes in response to the environment or in association with behavioral outcomes is currently a topic of debate.
  5. Our study did not evaluate gene expression and thus cannot explore the role of study CpG sites on regulation and expression.”

Addressing the study’s limitations:

  1. Early-life epigenetic regulation of the oxytocin receptor gene demonstrated – with no hint of abuse – how sensitive an infant’s experience-dependent oxytocin receptor gene DNA methylation was to maternal care. Treating prenatal stress-related disorders with an oxytocin receptor agonist provided evidence for prenatal oxytocin receptor gene epigenetic changes.
  2. No human’s answers to the CTQ, Adverse Childhood Experiences, or other questionnaires will ever be accurate self-reports of their prenatal, infancy, and early childhood experiences. These early development periods were likely when the majority of the subjects’ oxytocin receptor gene DNA methylation took place. The CTQ self-reports were evidence of experiences at later times and places, distinct from earlier experience-dependent epigenetic changes.
  3. As one example, the 2009 Genomic and epigenetic evidence for oxytocin receptor deficiency in autism was cited in the Introduction section and again in the Limitations section item 4. Since that study was sufficiently relevant to be used as a reference twice, why didn’t the researchers provide at least a partial comparability map between its findings and the current study?
  4. Early-life epigenetic regulation of the oxytocin receptor gene provided evidence for an answer to the question of whether or not an individual’s blood could be used to make inferences about their brain oxytocin receptor gene DNA methylation. The evidence said: NO, it couldn’t.
  5. It’s assumed that oxytocin receptor gene DNA methylation directly impacted gene expression such that increased levels of methylation were associated with decreased gene transcription. The study assumed but didn’t provide evidence that higher levels of methylation indicated decreased ability to use available oxytocin due to decreased receptor expression. The study had no control group.

To summarize the study’s limitations:

  1. The study zeroed in on childhood abuse, and disregarded evidence for more relevant factors determining an individual’s experience-dependent oxytocin receptor gene DNA methylation. That smelled like an agenda.
  2. The study used CTQ answers as determinants, although what happened during the subjects’ earliest life was likely when the majority of epigenetic changes to the oxytocin receptor gene took place. If links existed between the subjects’ early-life DNA methylation and later-life conditions, they weren’t evidenced by CTQ answers about later-life that couldn’t self-report relevant early-life experiences that may have caused DNA methylation.
  3. There was no attempt to make findings comparable with cited studies. That practice and the lack of a control group reminded me of Problematic research with telomere length.
  4. The researchers tortured numbers until they confessed “that CpG methylation may interact with abuse to predict psychiatric symptoms” although the study provided no direct evidence that each subject’s blood oxytocin gene receptor DNA methylation interacted as such. Did the “may interact” phrase make the unevidenced inferences more plausible, or permit contrary evidence to be disregarded?
  5. See Testing the null hypothesis of oxytocin’s effects in humans for examples of what happens when researchers compound assumptions and unevidenced inferences.

The study’s institution, Emory University, and one of the study’s authors also conducted Conclusions without evidence regarding emotional memories. That 2015 study similarly disregarded relevant evidence from other research, and made statements that weren’t supported by that study’s evidence.

The current study used “a topic of debate” and other disclaimers to provide cover for unconvincing methods and analyses in pursuit of..what? What overriding goals were achieved? Who did the study really help?

http://onlinelibrary.wiley.com/enhanced/doi/10.1111/cdev.12493/ “Oxytocin Receptor Genetic and Epigenetic Variations: Association With Child Abuse and Adult Psychiatric Symptoms”


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