Associated Brain Alterations and Future Suicide Ideation in Female Adolescents and Young Adults with Mood Disorders

In this Papers Podcast, Lejla Colic and Dr. Hilary Blumberg discuss their co-authored JCPP Advances paper ‘Brain grey and white matter structural associations with future suicidal ideation and behaviors in adolescent and young adult females with mood disorders’ (https://doi.org/10.1002/jcv2.12118).

There is an overview of the paper, methodology, key findings, and implications for practice.

Discussion points include;

• The age range included in the study.
• The significance of females with future suicide ideation and behaviours having shown decreases in cortical thickness, as well as some other differences in brain regions observing emotional and behavioural regulation.
• The importance of cortical thickness.
• The origins of these neurobiological differences – are they genetic, environmental, developmental, or some combination of all of these?
• The reason for focusing on young adult and adolescent females, and how these findings are relevant to males.
• How this research can be translated into practice to better identify and support adolescents at risk of suicidal ideation and behaviours.

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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Lejla is a junior group leader at the Jena University Clinic since April 2021. Her main research interest are stress response dynamics in youth and adulthood, effects of childhood adversity on the variability of the response dynamics measured with neuroimaging techniques and how the latter contribute to the onset and course of mood disorders. She is moreover studying association between childhood adversity and emergence of suicidal thoughts and behaviors with multimodal neuroimaging.

Dr. Hilary Patricia Blumberg is the John and Hope Furth Professor of Psychiatric Neuroscience, Professor of Psychiatry, Radiology and Biomedical Imaging and in the Child Center, and Director of the Mood Disorders Research Program, at the Yale School of Medicine. Dr. Blumberg’s research is devoted to understanding the brain circuitry differences that underlie mood disorders across the lifespan, with a focus on bipolar disorder and on suicide prevention. She directs the Mood Disorders Research Program at Yale that brings together a multi-disciplinary group of scientists to study the genetic, developmental and environmental factors that cause mood disorders to develop new methods for early detection, more effective interventions, and prevention of the disorders and their associated high risk for suicide. This research includes the use of new state-of-the-art brain scanning methods. She is a fellow of the American Psychiatric Association and of the American College of Neuropsychopharmacology and a member of the Society of Biological Psychiatry. (Bio from Yale School of Medicine)

Transcript

[00:00:01.360] 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 Lejla Colic of the Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany, and Professor Hilary Blumberg of the Department of Psychiatry at Yale School of Medicine in Connecticut. Both are authors on the paper, “Brain Grey and White Matter Structural Associations with Future Suicidal Ideation and Behaviours in Adolescent and Young Adult Females with Mood Disorders,” recently published in JCPP Advances. This will be the focus of today’s podcast.

If you’re a fan of our Papers Podcast series, please subscribe on your preferred streaming platform, let us know how we did, with a rating or review, and do share with friends and colleagues.

Lejla and Hilary, welcome, thanks for joining me. Can you each start with a brief introduction about who you are and what you do?

[00:01:25.320] Lejla Colic: So, my name is Lejla Colic, your pronunciation was perfect, thank you so much. I’m a Junior Group Leader in the Department of Psychiatry and Psychotherapy in University Hospital Jena and I focus on investigating childhood adversity in adulthood and in adolescence and their clinical and brain correlates, specifically focusing on suicidal thoughts and behaviours.

[00:01:47.220] Jo Carlowe: And Hilary?

[00:01:48.840] Dr. Hilary Blumberg: And I’m Hilary Blumberg. I’m a Psychiatrist and I’ve been on Yale’s faculty for about 25 years where I direct the Mood Disorder Research Program and when Dr Colic was at Yale, I was fortunate to work with her. So I’m very happy to be here today with her.

[00:02:05.570] Jo Carlowe: Great, thank you very much. So, let’s turn to your paper, this is “Brain Grey and White Matter Structural Associations with Future Suicidal Ideation and Behaviours in Adolescent and Young Adult Females with Mood Disorders,” which was recently published in JCPP Advances. Can you set the scene for us, what did you look at and why?

[00:02:25.970] Dr. Hilary Blumberg: Death by suicide is the second leading cause of death for adolescents and young adults worldwide. And these ages are also the times when suicide ideation behaviours often emerge and adolescents and young adults that are also very dynamic times for brain development. Frontal brain area’s implicated in suicide thoughts and behaviours and the white matter tracts that connect them are maturing, complex behaviours that are subserved by these brain areas, such as emotion regulation and decision-making are also important in suicidal ideation and behaviour are also maturing. So study of adolescents and young adults is important to identify the brain differences underlying the development of suicide risk, better understand the causes and to generate and improve methods for early detection and prevention of suicide.

And we were fortunate to receive funding from the MQ Foundation in the UK to bring together the work of Researchers across international sites in what we call the HOPES, or Help Overcome and Prevent the Emergence of Suicide Research Consortium, that made the work in this paper possible. And especially important aspects of the study were the age group, as most prior studies had been of adults, and also, most prior studies have looked at the brain in persons who had made prior suicide attempts. But here we looked at whether participants made an attempt in the future and that can provide very important information for prevention.

[00:04:06.689] Jo Carlowe: That’s really clear, thank you. Can you tell us a little about the methodology that you used for the study?

[00:04:13.270] Lejla Colic: So, as Hilary mentioned, we really focussed on this dynamic age period, so adolescents and young adulthood, and we focused on participants with mood disorders. So, participants who had either diagnosis of bipolar disorder or major depressive disorder. We used magnetic resonance imaging or, as we say, MRI scanning to look at the brain grey matter and white matter tracts. We also completed comprehensive clinical assessments where we looked at not only past suicidal ideation and presence of past suicidal ideation and behaviour, but also we then followed up our participants for at least one year and then we assessed them again, with the same comprehensive questionnaire. And, as Hilary said, this is a really, really unique dataset because not only we targeted this specific age group, but we also used C-SSRS, which is really clear and comprehensive questionnaire looking at these complex constructs.

We then divided our participants into three groups: those who have not had any suicidal ideation or behaviours in this follow-up period, those that showed only suicidal ideation, but not behaviours, and then those participants who had also suicidal behaviour in this follow-up period. We also then looked at the differences between these brain regions and tracts between these groups and then we can move onto the results.

[00:05:37.949] Jo Carlowe: Okay, I’m interested to hear. Can I just check, when you talk about the age group, what was the age range?

[00:05:44.590] Lejla Colic: The age range was between 14 and 25 years. Som we did cover up adolescents and young adulthood just because of the sample characteristics, but also we, kind of, wanted to not look only until age 18 because our brain matures until we’re around 25. So we really wanted to catch up also that period of young adulthood.

[00:06:06.160] Jo Carlowe: Well, let’s turn to the findings, what can you share? If you could perhaps give us an overview of the key findings that emerged?

[00:06:13.259] Lejla Colic: So, the most important finding in our study was that the adolescents who did show suicidal ideation or suicidal behaviour in this follow-up period had decreases in cortical thickness in frontal brain regions, which are involved in emotional regulation and decision- making. And these include, as I said, area – lower cortical thickness in frontal areas and also temporal areas.

There were also decreases in white matter tracts that connect these temporal and frontal areas, which are – also have been previously implicated in emotion regulation and decision- making. And some of these changes that we observed were also previously reported in adults with past suicide ideation and behaviours suggesting that changes in these brain areas really do carry a certain increase for suicidal ideation and behaviours.

[00:07:04.790] Jo Carlowe: As you’ve just described then, the paper finds that females with future suicide ideation and behaviours showed decreases in cortical thickness and some other differences in the brain regions subserving emotional and behavioural regulation. Can you explain the significance of this, buy in lay terms?

[00:07:24.560] Lejla Colic: Absolutely. So, we believe that it is very important that these new findings identified brain differences that may increase risk for future suicide ideation and suicide behaviours as these may be key targets for new suicide prevention strategies and also therapeutical approaches.

[00:07:42.470] Jo Carlowe: And just for the layperson who perhaps doesn’t have that much understanding of the different regions of the brain, can you say about the significance of the cortical thickness?

[00:07:52.400] Lejla Colic: So, cortical thickness is a measure of the structural integrity of our brain. So, although we cannot really measure, for example, how plastic our brain is as we can with animals, cortical thickness does change throughout ageing and during this period. So, we do believe that these also maturation – that the – our findings also indicate certain maturational differences between the participants that showed suicidal ideation and behaviours.

[00:08:21.400] Jo Carlowe: Are these neurobiological differences genetic, environmental or developmental or some combination of all of these? And, depending on your answer, what does this mean in terms of brain plasticity and the reversibility of biomarkers that suggest a young person is at increased risk of suicidal ideation or behaviours?

[00:08:45.010] Dr. Hilary Blumberg: As your question suggests, the possible contributing causes can be complex and multifactorial. We can’t determine the causes from this study, but we’re investigating causes, which is an important aspect of our ongoing work and our planned future work. But, as you say, since the brain is so plastic, especially while it’s maturing in adolescence, in this frontotemporal brain circuitry, there’s great hope that the development of the differences can be halted or if they’ve occurred, potentially reversed. And there is a great deal of research taking place, some at our sites and also at other sites, on genetic, environmental and developmental factors and interactions among them that’s showing that there are multiple ways to increase the health of this brain circuitry.

[00:09:44.630] Jo Carlowe: It’s really positive to know that. You focused on young and adolescent females, what was the reason for that and are the findings relevant for males as well?

[00:09:54.220] Lejla Colic: Well, we definitely noticed from the literature and also, for example, Hilary, from her clinical practice, is that one important aspect in suicidal ideation and behaviours is gender and this aspect also often neglected or not specifically looked at. So, for example, young adult women, there’s a higher chance that they will attempt suicide than males in their age groups. Also, in our sample, more women showed suicidal ideation and behaviours than men. So we, kind of, wanted to focus on them also to be able to have enough power to look at these brain differences and, as you suggested, because we focus only on women, we do really need to replicate our findings also in populations that have all genders included.

[00:10:46.120] Jo Carlowe: In your paper, you suggest the findings may aid targeted interventions through pharmacological, neurostimulation or psychotherapy approaches, can you elaborate on this? How do you envisage your research being translated into practice to better identify and better support adolescents at risk of suicidal ideation and behaviours?

[00:11:07.300] Dr. Hilary Blumberg: Well, the very good news is that there are many potential ways to target the brain circuitry that we observed in the study. This could include medications that target neurotransmitters and other molecular mechanisms acting in this circuitry. Another is to target the anatomical barriers using neurostimulation methods such as rapid transcranial magnetic stimulation and there are other ways to stimulate the brain and many new ones that are emerging.

Talk therapies can also be very helpful. And there are also things that individuals can do for themselves to help their brain health, including increasing the regularity of their sleep and other daily routines, which can actually be robust in helping to strengthen the health of the brain circuitry that’s involved to prevent suicide.

We and others have also observed adverse effects on the brain circuitry of stressors, such as exposure to childhood maltreatment. This is especially an area that Dr Colic is really, you know, a world expert in. And so preventing these types of social stressors that she’s looking at can also be very important in reducing suicide risk. And we and others are finding, in our research, that these types of strategies can actually improve the functioning of the brain circuitry involved and thereby decrease the mood symptoms and suicide risk.

[00:12:45.200] Jo Carlowe: Is there anything else in the paper that you would like to highlight?

[00:12:48.930] Lejla Colic: So, what I can say from me as a non-Clinician, I’m a Neuroscientist and Neurobiologist by training, was extremely striking to me was that 44% of our sample had suicidal behaviour in the follow-up and 36% had suicidal ideations. So that’s over 70% of participants showed some kind of suicidal thoughts and behaviours in this follow-up period. And even though we were expecting and investigating an especially clinically severe population, so adolescents with BD or NDD, still it was really a factor that highlighted the importance of further research and work in this age group to improve suicide prevention. So that’s, kind of, a fact that was really, really striking for me.

[00:13:38.649] Jo Carlowe: Well, you just mentioned future research, so are you planning some follow-up research or is there anything else in the pipeline for either or both of you that you would like to share with us?

[00:13:49.220] Lejla Colic: So, as Hilary mentioned before, I’m really, really interested in looking at the effects of early life stress. So, childhood maltreatment, so I’m following up on that area, investigating the effects in adolescents and as well as in adults. I’m also using magnetic resonance imaging, which allows us to look at the levels of different neurometabolites. So, I’m interested to look at contributions of GABAergic system in these interaction between early life stress and clinical severity.

[00:14:16.670] Dr. Hilary Blumberg: In our group at Yale, we are also continuing the brain scanning work and we’re looking at mechanisms that may be contributing to the brain differences and neurodevelopmental differences through genetic and stem cell research, and we’re studying the effects of talk therapies. And we’re especially excited about emerging findings that if adolescents and young adults improve the regularity of their sleep and other routines, that can be robust in improving the health of their brain circuitry and in reducing suicide risk. And we’re also performing some research with digital devices, and I think that can gives us really important information in time, and that can be very important because you want to detect suicide risk at its earliest stages to prevent it.

[00:15:08.820] Jo Carlowe: It’s a really exciting area, isn’t it? Finally, Lejla and Hilary, what are your take-home messages for our listeners?

[00:15:15.670] Dr. Hilary Blumberg: I would say that this is one example of research that’s going on across the world that’s advancing in identifying the causes and finding new ways to prevent suicide, so that the future is very hopeful that we will be better able to prevent suicide in the future.

[00:15:38.090] Lejla Colic: I just want to echo what Hilary has said. I think there’s more and more international research dedicated to looking at mechanisms of suicidal ideation and behaviour, not only through imaging, but also through, as Hilary mentioned, stem cell research, genetic research and also using actigraphy and mobile devices. So, I think more international efforts are needed also to look at differences, not only biological, but also cultural and socioeconomic. So, I’m really hopeful in that sense that by increasing our international collaborations, we can really tackle this worldwide phenomena.

[00:16:17.529] Jo Carlowe: Brilliant, thank you both so much. For more details on Dr. Lejla Colic and Professor Hilary Blumberg, 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 enjoyed the podcast, with a rating or review, and do share with friends and colleagues.