In this Papers Podcast, Dr. Stefanos Mastrotheodoros and Dr. Marco Boks discuss their co-authored JCPP paper ‘Negative parenting, epigenetic age, and psychological problems: prospective associations from adolescence to young adulthood’ (https://doi.org/10.1111/jcpp.13821).
There is an overview of the paper, methodology, key findings, and implications for practice.
Discussion points include:
- Definition of the term ‘epigenetic age’ and what is known about its association with stress.
- Insight into ‘softer negative parenting indicators’ in the context of the study.
- Should ‘epigenetic clocks’ be used as a diagnostic or assessment tool in mental health services?
- The implications of the findings for child and adolescent mental health professionals.
- The scientific importance of the paper as having being pre-registered.
In this series, we speak to authors of papers published in one of ACAMH’s three journals. These are The Journal of Child Psychology and Psychiatry (JCPP); The Child and Adolescent Mental Health (CAMH) journal; and JCPP Advances.
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Dr. Stefanos Mastrotheodoros is a postdoctoral researcher at the Department of Youth and Family, at Utrecht University, the Netherlands, and an Assistant Professor of Developmental Psychology at the University of Crete. His main research interests include changes in parent-adolescent relationships, adolescent development, and longitudinal modelling. He is also interested in investigating how changes in DNA methylation might play a role in adolescent psychosocial development.
Dr. Marco Boks is a psychiatrist and researcher at the University Medical Centre where he leads the stress and trauma program. One of the key questions of his research is what the biological mechanisms are that underlie the increased risk to many psychiatric and somatic disorders in individuals that suffered traumatic life events. One way to investigate this is to measure changes in the working of DNA. These epigenetic changes can be monitored using epigenetic clocks that report of several aging mechanism.
[00:00:07.520] Jo Carlowe: Hello, welcome to the Papers Podcast series for the Association for Child and Adolescent Mental Health, or ACAMH for short. I’m Jo Carlowe, a Freelance Journalist with a specialism in psychology. In this series, we speak to authors of papers published in one of ACAMH’s three journals. These are the Journal of Child Psychology and Psychiatry, commonly known as JCPP, the Child and Adolescent Mental Health, known as CAMH, and JCPP Advances.
Today, I’m interviewing Dr. Stefanos Mastrotheodoros, Postdoctoral Researcher at the Faculty of Social and Behavioural Sciences, Utrecht University, in the Netherlands, and Dr. Marco Boks, Associate Professor in the Department of Psychiatry, at the University Medical Centre, Utrecht. Both are co-authors of the paper, “Negative Parenting, Epigenetic Age, and Psychological Problems: Prospective Associations from Adolescence to Young Adulthood,” recently published in the JCPP. This paper will be the focus of today’s podcast.
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Stefanos and Marco, welcome, thank you for joining me. Can you each start with an introduction about who you are and what you do?
[00:01:24.500] Dr. Stefanos Mastrotheodoros: Thank you for having us. My name is Stefanos Mastrotheodoros. I am working as a Postdoctoral Researcher at Utrecht University, in the Netherlands, and I recently also started as an Assistant Professor of Developmental Psychology at the University of Crete, in Greece. In my PhD, I studied the development of parent-adolescent relationships during adolescence, and the family dynamics during adolescence, the changes that happen therein. And in my postdoc, I started investigating potential epigenetic indices and genetic effects that play a role in the development of parent-adolescent relationships.
[00:01:57.380] Jo Carlowe: Thank you, and Marco?
[00:01:59.100] Dr. Marco Boks: My name is Marco Boks. I’m a Psychiatrist in the University Medical Centre in Utrecht, and my research is focused around the question, how it is possible that early life experiences have such a long, enduring effect on both somatic as well as psychological health. And one way to study this is to investigate how the stress system is differently programmed in response to environmental stressors, and this sort of physical adaptation, even to the level of the DNA, works through increasing this risk. And whether these changes, in particular the epigenetic changes, may be actionable with respect to improve mental health treatments.
[00:02:43.590] Jo Carlowe: Thank you very much. We’re going to look at your paper today, but before we go into the detail, I want to look at the term “epigenetic age,” which is a central component of your research. For the lay listener, can you explain what is meant by “epigenetic age” and what is known about its association with stress?
[00:03:01.540] Dr. Marco Boks: Epigenetic age is primarily a research tool, at least to date, and it’s a way of investigating the relationship between normal age, the chronological age, and our biological age. We know that there are environmental stresses that accelerate aging, and make some people die earlier as a result of that. And one of these environmental stressors is childhood trauma, early life events, negative parenting, and the epigenetic clocks are using the results of DNA methylation data, in which we investigate the activity and the programming of genes, in order to estimate underlying aging processes.
[00:03:48.680] Jo Carlowe: That’s really clear, thank you. Let’s turn to the paper itself, so this is, “Negative Parenting, Epigenetic Age, and Psychological Problems: Prospective Associations from Adolescence to Young Adulthood,” published in the JCPP. Can you set the scene for us? What did you look at, and why?
[00:04:05.600] Dr. Stefanos Mastrotheodoros: There have been some studies showing effects of negative experiences and stressful experiences on epigenetic age. We know, regarding parenting and parental behaviour, we have seen – there have been studies showing that neglect and abuse or really harsh environmental effects do affect epigenetic age, so typically showing a larger epigenetic age under those circumstances. But we know much less about softer, let’s say, or more everyday aspects of negative parent-adolescent relationships, and how they potentially affect epigenetic age.
And it’s important to study that further, because those kind of behaviours are much broader in the population, so it happens to many more people, many more youth, and parents, of course, compared to abuse and neglect. So, this is one part of this study and we wanted to extend past papers, past studies, using a softer definition of “negative parenting.”
And then another important aspect is that we wanted to check changes in epigenetic age, longitudinally. So, we wanted to follow the same participants for more than one timepoints, and see whether there are actually observable changes in epigenetic age, following negative parental behaviours, and/or psychological symptoms.
[00:05:26.960] Jo Carlowe: You mentioned that the study focuses on everyday negative parenting, so softer negative parenting, indicators, rather than, say, obvious neglect or abuse. Can you elaborate on what you mean by these softer negative parenting indicators? What do they look like?
[00:05:46.300] Dr. Stefanos Mastrotheodoros: So, we conceptualised negative parenting in this study as compromising of parent-adolescent conflict intensity, so how bad parents or adolescents feel when they have a fight, so this is what we call conflict intensity, which is different from conflict frequency. So, that’s one aspect that we used in the study. The other aspect being psychological control, which is often conceptualised as the parent trying to control the adolescent in what they feel, what they think, and what they might want, it’s the opposite of autonomy.
And the third aspect that we used to conceptualise negative parenting in this study is parental expressed emotion, which is something that had to do with how often parents criticise adolescents and how often they express negative emotion towards the adolescents, and try to control them. So, those are aspects that are not necessarily clinically diagnosed or something like that, and they are aspects that might happen to every family, of course. So, in that sense, it’s a softer definition of negative parenting, because it might happen to anyone, right?
So, we wanted to see whether this – and when this is repeatedly experienced throughout adolescence, so, from age 13 to age 18, whether this has an effect. So, we also wanted to test the repetitiveness of those, kind of, behaviours, and whether the repetitiveness actually does have an effect.
[00:07:18.390] Jo Carlowe: Can you give us a brief overview of the methodology used for this study?
[00:07:23.250] Dr. Stefanos Mastrotheodoros: The most important aspect of this study is that we used a longitudinal design, and by longitudinal, it means that we used – we followed the same families, the same participants, across time. So, we gave surveys, questionnaires, to adolescents, and once a year from ages 13 to 18, and then again when they were age 25, so after seven years. So, this is the core aspect of the design.
We did that because we wanted to exactly capture, as I said, the repetitiveness of the experiences, be it negative parenting, so, conflicts, expressed emotion, or psychological control, or the other variables that we used in the study, internalising symptoms, so symptoms of anxiety and depression during adolescence, self-concept clarity, whether they had a clear concept of who they are, adolescents, and what they want to do, and then externalising problems, which is an indication of having problems with a question, for example. So, we used repetitive assessments in order to get this, kind of, repetitiveness of those events, and to get more robust predictions, in a sense. And we also used repetitive assessments of epigenetic age. Marco?
[00:08:37.269] Dr. Marco Boks: I just want to highlight that that’s actually a important aspect of the study, as it gives the opportunity to understand better, in a sequential way, what happens. So, is the age acceleration, does that precede mental health problems? Or is it a consequence of the mental health problems? Do they go along? Is epigenetic age accelerated in relationship to the mental health problems, and then even stays accelerated after mental health problems may have disappeared? And the RADAR cohort, which this study was conducted in, has this wonderful longitudinal setup that allows us to interrogate these kind of questions.
[00:09:22.190] Dr. Stefanos Mastrotheodoros: May I add something regarding the design?
[00:09:24.470] Jo Carlowe: Yeah, please do.
[00:09:25.470] Dr. Stefanos Mastrotheodoros: We used indeed data from the RADAR study, which is – which stands for Research on Adolescent Development And Relationships study, based in Utrecht, it’s done by Utrecht University in the Netherlands, and it follows the same participants from age 13, and now they are age 30. And it currently actually undergoes generation three of RADAR, because we also included parents of adolescents in the first wave, adolescents themselves, of course, and now adolescents have become parents themselves. So, we follow how they parent, how they behave towards their children. So, this is actually an ongoing longitudinal study that now is a three-generation study, and it’s still going on, thankfully.
[00:10:08.230] Jo Carlowe: So, let’s turn to the findings. What key findings from the study would you like to highlight?
[00:10:13.519] Dr. Stefanos Mastrotheodoros: I think one important finding is that we didn’t find an effect of negative parenting on epigenetic age, or change in epigenetic age. So, we didn’t find that having conflict or having higher psychological control or higher criticism in the family, but, that, of course, is in a community, so in a normal everyday le – we would say range, this doesn’t have any detectible effect on epigenetic age, or change thereof.
But we did find that change of epigenetic age did predict positively externalising symptoms at age 25, which means, actually, that those adolescents who actually showed a quicker increase in their epigenetic age, in their biological age, those adolescents later on showed an increase in their externalising symptoms. So, they showed a higher, let’s say, aggression, or problems with their behaviour.
We also found an effect of negative parenting during adolescence, so from 13 to 18, on externalising symptoms at age 25. So, we found that those adolescents who experienced higher negative parenting, so more challenging parent-adolescent relationships, they also experienced an increase in externalising symptoms seven or eight years later, even though negative parenting was not found to affect epigenetic age, it still had a longitudinal effect on child mental health.
[00:11:42.649] Jo Carlowe: Marco, is there anything you want to add on the findings?
[00:11:45.190] Dr. Marco Boks: I was particularly enthusiastic about the longitudinal relationship between accelerated epigenetic aging and the later onset of the externalising symptoms. And this is not a finding that stands on its own, it’s been found in other cohorts, for instance, in the Generation R study. And it, sort of, highlights the – I mean, sort of, fits the hypothesis that something is going on even before the onset of symptoms. And I think that, sort of, suits the practice; you can see children that are somehow in a very tough position, but they don’t exert any, sort of, symptoms yet. However, after a certain time, then the problem is starting to manifest.
And this accelerated epigenetic age, sort of, suggests that there are already underlying aging processes that are accelerated, sort of, that precede the onset of full-blown symptoms. We found that very intriguing, because it tells us something how the body, even to the level of the DNA, might indeed be involved in the responses to the environmental situation, and, sort of, precedes the onset of symptoms.
[00:12:56.790] Jo Carlowe: As you’ve described, your study showed that epigenetic age is a significant predictor of young adult problems, are you proposing that epigenetic clocks should be used as a diagnostic or assessment tool in mental health services? And if so, can you elaborate on this idea?
[00:13:15.770] Dr. Marco Boks: I mean, clearly, that’s highly desirable, and it’s the topic of a tremendous amount of research, finding the early predictors and, if possible, biological predictors of later on mental health problems. From the data that we’ve seen, it’s clear it will not function in that way. It, sort of, does inform us of some underlying bodily processes, and it hints to these processes, but, as a predictor, it really falls short. And, in fact, that’s the fate of a lot of biomarker studies, where they find all sort of indices that are correlated or vaguely predicting, but the early symptoms of the patients themselves, and what parents and children tell us, are in practice still much better prediction than any sort of biological measure.
[00:14:06.540] Jo Carlowe: So, what are the implications then, of your findings, overall, for CAMH professionals?
[00:14:13.790] Dr. Marco Boks: Well, if anything, I think that it is good to be aware that these processes are already ongoing, even before the onset of the mental health problems. And, personally, it encouraged me to look further to, let’s say, more bodily symptoms, that may be telling tales for mental health problems later on.
[00:14:40.050] Dr. Stefanos Mastrotheodoros: It’s important for mental health professionals that do have to consider the long arm, if I may say, of negative parenting, during adolescence, for later externalising problems during young adulthood. Even though negative parenting was not as extreme as abuse or neglect in the study, it still was found to actually have an effect eight or seven years later in how aggressive or how problematic youth behave. So, I think this is also something to take into account.
[00:15:12.360] Jo Carlowe: Is there anything else in the paper that you would like to highlight?
[00:15:16.250] Dr. Stefanos Mastrotheodoros: This paper was also pre-registered, so basically it means that we were not just looking at the pattern of findings and making a story out of it, but we actually pre-register. So we made a clear distinction in our hypothesis what we would expect based on the past studies, and based on the theory, and we followed a clear, predetermined path in how we would analyse our data. And this has important scientific implications, in the sense that the distinction between what we expect to find, or what we might find, but we don’t know whether it would be there, it’s made clear in this paper. So, this is one of the pillars and one of the core aspects of open science, which is an ongoing scientific debate, or a scientific move, and we applied practices of open science in this paper.
[00:16:13.810] Jo Carlowe: Marco, is there anything you want to add?
[00:16:15.730] Dr. Marco Boks: Particularly thanks the participants of the RADAR cohort, and all the Researchers from the study, and mention particularly Susan Branje, who’s been absolutely instrumental for setting up and maintaining this cohort, and we’re really grateful that we were able to use that data.
[00:16:34.319] Jo Carlowe: Are you planning any follow-up research, or is there anything else in the pipeline, for either of you, that you would like to share with us?
[00:16:41.199] Dr. Stefanos Mastrotheodoros: We are planning to follow-up this study with extending, let’s say, the epigenetic markers that we are examining. And we are currently at the design stage of another study that looks on the links, the potential links, between, again, parent-adolescent relationships and parental behaviours, but, also, are taking into account peer victimisation, so negative and stress-related experiences in the peer, in the friend sphere, let’s say, of adolescents, and whether they are linked with changes or with epigenetic indices of inflammation. So, whether there are mechanisms playing in the inflammation of the body basically. So, this is the study that we are setting up now, but we are still in the early stages of it.
[00:17:29.610] Jo Carlowe: Marco, anything, in addition, in terms of what’s in the pipeline for you?
[00:17:33.780] Dr. Marco Boks: Let’s say, just reiterating that environmental circumstances of young adults are tremendously important than to a high extent determining their mental health development. And I think we are in a era where, fortunately, this is becoming more and more apparent, and the attention towards environment, in terms of early life experiences, but also to more subtle measures like negative parenting, the awareness is increasing. And I think if – that’s well worth considering for all mental health professionals. And I think, as a field, it is very helpful that we are starting to acknowledge that more and more, and it may actually have important implications in the way we are assessing and treating young children.
[00:18:30.669] Jo Carlowe: And finally, what are your take home messages for our listeners?
[00:18:35.490] Dr. Stefanos Mastrotheodoros: I think it’s really an important field of study to examine further, whether epigenetic changes happen in association with the environmental influences of young adolescents, of young adults, and young people in general. So, I think this is really the take home message, that it is something to examine further, and it also makes sense to follow it, again, repeatedly and longitudinally.
[00:18:59.470] Jo Carlowe: Thank you both so much. For more details on Dr. Stefanos Mastrotheodoros and Dr Marco Boks, please visit the ACAMH website, www.acamh.org, and Twitter @acamh. ACAMH is spelt A-C-A-M-H, and don’t forget to follow us on your preferred streaming platform, let us know if you enjoy the podcast, with a rating or review, and do share with friends and colleagues.