Adrenarche – that other puberty

Most of us are familiar with a stage of puberty (that we probably hope we can forever push to the back of our minds and never re-live ever again, and desperately hope that when our own children reach that stage, that our partner will take over parenting duties for a few years…) called gonadarche. This is the more obvious phase of puberty where secondary sex characteristics appear and hormones that are released from the gonads (testosterone for boys, estradiol for girls) start to increase. For girls, these are responsible for the start of menstruation. Chronological ages for the start of this phase vary a lot (and interestingly, for girls, where the start of menstruation is an easy way to mark this onset, ages have been getting increasingly younger over the past century!), but most would place this in the beginning of the teenage years.

What a lot of people don’t know is that there another, earlier phase of puberty that everyone goes through, when hormones from the adrenal gland such as DHEA are released, that is aptly named adrenarche. Again, ages vary, but we think kids around 6-10 (maybe as early as 5!) are going through this development. There are some physical changes that go along with with this phase of puberty too, like an increase in body and pubic hair.

My colleagues and I are especially interested in this phase of puberty, partly because we know less about it than gonadarche, but also because there is some evidence to suggest that the timing of it (i.e., when kids go through this phase compared to their same sex and chronological aged peers) is associated with mental health problems. We also think  that this might be due to important changes in brain development during this time of life, but we need more research to test this. The bottom line is that we need to better understand this phase of life for kids because it could have really important implications for their brain and mental health later in life.sagittal_brain_mri

We’ve written a review paper that systematically goes through all the literature on adrenarche, mental health, and brain development. Then we propose a model for future research to test if adrenarche is a particularly sensitive time of neurobiological and mental health development for kids. It’s just been published in the excellent journal* Developmental Cognitive Neuroscience. It is an open access journal, meaning that anyone can see the full text (BIG CHEERS FOR THAT!). I hope you enjoy reading it.

*Also be on the lookout for a special issue in DCN coming out later this year, on methodological challenges in developmental neuroimaging, that I am helping to guest edit.

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When was the last time your doctor asked about your mental health?

Those of you that have read a few of my posts on this site understand that I believe your mental and physical health are intricately linked together and what affects one will undoubtedly affect the other.

So I want to ask you all this question: The last time you saw your GP, did s/he ask how you were handling stress? Did they ask how your mood was lately? Did they ask if you were going through any tough times, feeling bluer than usual, experiencing a major life change? No? Did they weigh you and tell you what your BMI was, and if it was too high, did they recommend any diet changes? Something tells me the latter is probably more common.

Here’s a study published last week in Molecular Psychiatry suggesting that stress and mental health are not just as important, but maybe even more important than diet when it comes to our metabolism and inflammatory responses to meals. In this randomized control trial, the authors studied a group of women and gave some a high saturated fat meal (let’s call it the fat meal) and others a high oleic sunflower oil meal (let’s call that the hippie meal), which is supposed to be healthier. First they looked at the women that hadn’t reported any significant stress the day before. As you’d expect, their levels of inflammation increased more after the fat meal than the hippie meal. But for the women that had reported stress the day before, their levels of inflammation increased just as much if they ate the fat meal or the hippie meal.

When was the last time you read diet advice that really focused on reducing stress or getting treatment for underlying mental health problems? Does the South Beach/Atkins/(enter fad of choice) diet casually mention going to a regular guided meditation class? Checking in with a psychologist or counselor if you are going through a difficult time? No?

Now, the study mentioned above included a group of women who had either experienced breast cancer and group who had not (but didn’t look at differences between groups), so it would be interesting to see if the results are consistent across healthy and patient groups of all kinds, and across age and sex.

So, here’s my next question for future research: How much does stress and mental health affect obesity, and could inflammation be a mechanism? What do you all suspect?

The Mindful Brain: Q and A with Stefan Friedel

A few years ago on this blog, I presented a series on meditation (Here are links to parts one, two, three, and four). Research has shown effects of meditation on our physiology and mental health, and there has been limited research suggesting that it may be a viable option for treatment (or prevention) of mental illness.

One thing that scientists are working hard to figure out is how mindfulness, a trait that is related to meditation, is associated with neural changes. That is, we want to know if there are changes in brain structure and function in people who have this trait compared to people who do not. This is especially important to examine in young people whose brains are rapidly changing and developing. A recent study from our lab, published in Developmental Cognitive Neuroscience, showed that there were changes in brain development over time between adolescents who scored high vs. low on dispositional mindfulness.

I had a chat with Stefan Friedel, the lead scientist on this study, to talk all things mindfulness and brainy in teenagers.stefan

Q: Your study showed that “dispositional mindfulness” was associated with differences in brain development in teenagers. What is dispositional mindfulness and why is it important?

A: Dispositional mindfulness is a quality of consciousness related to present-moment awareness. So people that are high in mindfulness live life in ‘the moment’, without undue thoughts or anxieties about the past or future.  While dispositional mindfulness can be cultivated by meditation, it is also a dispositiona
l trait that all people have to varying degrees. There are many associated psychological benefits with high levels of mindfulness, including enhanced self-regulation and improved health and well-being.

Q: Can you explain why adolescents of this age (16-19) were a perfect group of people for you to study how brain development and mindfulness are related? What is happening in these kids at this time that is so important for mindfulness skills?

A: Kids aged 16-19 are transitioning to adult independence and therefore learning to negotiate relationships and the environment around them without adult supervision. Good self-regulation is vital in this process, allowing adolescents to stick to a task without distraction, cope with strong emotions (that adolescents’ brains are hard-wired for) as well as help mitigate risky peer-pressured behaviours such as drug-use and unsafe sex. So, while mindfulness helps self-regulation in people of all ages, it might be of most benefit during adolescence where acquiring self-regulation is critical.

Q: The part of the brain that you found was related to mindfulness was the insula. Do you think this area is especially activated when people are practicing mindfulness or meditation, and why?

A: Long-term meditation practice has been associated with change within the insula in adults; also, research has shown that the insula is activated when ‘interoceptive awareness’ occurs, which is awareness directed towards the body. Given that mindfulness meditation practices deliberately cultivate interoceptive awareness, the fact that meditation activates the insula is not surprising. In our adolescent study, observing significant insula developmental changes occurring in association with higher levels of mindfulness is very satisfying as it bolsters, from a unique developmental perspective, the adult studies demonstrating insula involvement  in mindfulness.

Q: Can your study tell us if we should be screening teenagers using MRI to see if they are at-risk for self-regulation disorders?

A: Good question, and probably too early to say. Though MRI technology is becoming increasingly accessible and affordable, I think that outward behavioural signs, such as ADHD symptoms in childhood and adolescence are still the most practical way to determine if self-regulation might be a problem later in life.

Q: Based on your results and other studies, what kind of intervention programs do you think would be helpful for teenagers at-risk for self-regulation disorders? 

A: Personally, I think that a school-based approach is the way to go. Kids have so much to do nowadays, so many activities and commitments – so if you really want to encourage something, even an easy practice like mindfulness meditation it needs to be available in a timetabled format for them. School is the perfect place to do this. There have already been reports of successful results with school-based meditation practice, for example the Quiet Time program using transcendental meditation has been shown to be effective in reducing stress and violence as well as improving academic performance in low income US schools.

For individuals that struggle and need specific targeted help, there are short-term intensive mindfulness programs available. For example, mindfulness-based interventions (MBIs) combine mindfulness meditation with psychotherapy over a month or two, which has been shown to be a highly effective therapeutic combination to help adolescents learn to self-regulate, with improved outcomes in mental and physical well-being following MBIs.

Q: Do you think practicing mindfulness would be beneficial for everyone? Why?

A: Mindfulness and meditation practice can benefit all ages. We live in a culture of go-go-go, a society that values high achievement and encourages long working hours. There is often little opportunity to take it down a gear and enjoy the moment. There’s an old adage that before you fire the arrow (activity), you need to pull back the bow (rest and relaxation). Meditation and mindfulness practice allow individuals to wind down quickly resulting in a calmer present-moment awareness. With a rested mind and less distracting thoughts, activity becomes better regulated and vital and therefore more effective and enjoyable.

Thank you to Stefan for taking part in this Q & A! A link to the article can be found here:

http://www.sciencedirect.com/science/article/pii/S1878929315000663

What I learned at PNIRS

I’ve been in Seattle this week at the 22nd Annual Scientific Meeting of the Psychoneuroimmunology Research Society. It’s been a great conference, and here are some interesting things I have learned so far:

– Sleep is important. Ok, I already knew this, but I have been learning that good and poor sleep have more effects than I ever knew. For example, Dr. Illiff gave a great talk on how, in rats, sleep improves how brain fluid clears plaque that has been implicated in Alzheimer’s. So I’m keen to see if sleep interventions are in the near future of Alzheimer’s research in humans.

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Dr. Jeffrey Illiff, Oregon Health and Science University

– Peripheral inflammation (what you see in circulation), can be quite different to neuroinflammation. Activation (or dysregulation) of microglia, which are immune cells in the brain, can have implications for neurodegenerative diseases like Alzheimer’s and even depression. So it’s important for researchers like myself, who mainly measure peripheral inflammation, to know where our limitations are. However, there are imaging methods that can examine inflammation in the brain in humans.

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Dr. Haroon speaking about inflammation in the brain in people with depression

– That said, I have also learned that animal research, while interesting, needs to do a much better job of translating. Most of the research at this meeting has been animal, which is fine, but for example, while it is great that some research has identified inflammatory changes in the brains of pregnant rats, can we really make conclusions about postnatal depression in humans based on that? What are the next steps?

– Always have a backup laser pointer. The one here didn’t work, and while it’s fun to see how many stand up jokes academics can make about how they can operate a million dollar microscope but not a laser pointer, part of running a conference includes mundane items such as having IT equipment that, you know, works. But overall, the conference has been very well organized.

– Finally, I learned that I can attend a scientific conference and bring my infant son (thanks to our amazing nanny, Shannon; I recommend ANI nannies if you need a hotel nanny in Seattle). Personally, this means a lot to me, because it’s given me confidence to know that I can make my family and professional life work together. I know there are more challenges ahead, but I feel optimistic about the future in this regard.

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It also helps that Simon happens to be a good flyer. Thanks for the souvenir, Alaska Airlines!

Babies are cute little disease vectors

For the first 6 months of my little one’s life, I enjoyed the luxury of spending almost every waking moment with him, thanks to Australia’s generous maternity leave laws. I was also lucky enough to be able to breastfeed him – a feat which, while challenging at first, proved invaluable the first time I got a cold after he was born. He was about 8 weeks old and I woke up with a sore throat. I woke my husband up and told him, in a solemn voice, “I’m sick”. We prepared for the worst. We stocked up on a vaporizer, saline nose spray, baby chest rub, and bunkered down.

He didn’t get sick. He stayed jolly and healthy through my cold, and the next one, and the next one. Suddenly the sore nipples and leaking milk didn’t seem quite so bad. Breastfeeding was a miracle! We realized that, as long as I got sick first, our little one was less likely to get sick because he was getting antibodies through my breast milk.

Fast forward to last week. I have been at work for just over a month and, luckily, I am still able to express milk for him to drink. But, because I’m not with him all the time, he caught a cold before I could take the bullet for him. And then, because babies have no manners, and like to do things like jam their snot-covered fists into your mouth and laugh, both my husband and I caught it. I don’t think there’s any argument over how we got sick this time.

But I have been rather annoyed at the number of times I have been gotten a cold since the baby was born – probably 4 or 5 – that I have obviously caught from people who weren’t coughing directly into my face as I swung them over my head singing, “Wheee!”. And I’m someone who never really used to get sick. I used to brag about my immune system of steel.

This got me thinking about a body of literature on stress and disease and, in particular, Sheldon Cohen’s work on susceptibility to the common cold and other infectious diseases.

In one of his most famous studies, the researchers asked participants how much psychological stress that had recently experienced, and then gave them nasal drops with various forms of the common cold (or saline, to have a control condition). The more stress that someone had experienced increased the likelihood of infection and cold symptoms.

Could one reason I am getting sick more often be due to a general increase in psychological stress? Taking care of a baby is hard. They’re cute but they’re awfully demanding. On top of that, after he was born I was spending a lot of time dealing with immigration issues for my husband and just generally moving our entire household overseas. And worrying a lot.

This seems a likely culprit, but I’d also like to pinpoint one particular thing that I believe may have affected me the most – sleep, or rather, lack of it. Anyone who has had a baby knows that you pretty much never sleep again. Ever. At least, that’s the way it’s looking right now. In particular, it’s the uninterrupted sleep, rather than the total number of hours, that I think I am most nostalgic for.

Indeed, another study of Cohen’s (using the same method of subjecting people to the common cold virus; I’m sure they got paid for it) showed that people who normally slept better (for my sleep-research friends, longer sleep duration and better sleep efficiency), were less likely to get sick.

coldsThe final thing that seems to play a role in being resistant to getting sick is social connections. Cohen’s earlier work has shown that the more social roles you have, the less likely you are to get colds. And other research has found that social support helps you to not die from illnesses like heart disease and cancer.

So while there are some things about stress that we can’t control, like when my baby wants to wake up every hour at night and play a fun game where he grabs my nose and sticks his fingers up my nostrils, we can remember to keep good friends and family around us for support, and to take care of ourselves both physically and mentally.

I’m back. Was just busy having a baby.

Since last posting on TDAP, I’ve been busy with a number of things, but giving birth and starting to raise a new human being is probably top of the list. Now my little one is seven months old and my family and I have uprooted from Melbourne so I can take up a postdoctoral position at The University of Oregon in the US. It’s a very exciting time for me because I am going to have lots of new opportunities – I’ve already been busy hitting up funding bodies for moolah. I’m also getting a chance to work with new researchers and collaborate on lots of interesting projects and sharing ideas. It’s all happening.

Another thing that I’ll be getting back to is posting on here. So keep an eye out.

In the meantime, read this article about Twitter: This is Your Brain on Twitter.

Big ass Scandinavian health study is big

Age-standardised disability-adjusted life year...

Depression takes a huge toll on society: Age-standardised disability-adjusted life year (DALY) rates from Unipolar depressive disorders by country (per 100,000 inhabitants). (Photo credit: Wikipedia)

A friend of mine passed on a new study published this month in JAMA Psychiatry he thought I’d find interesting. It’s one of those really big studies they can only do in Scandinavian countries like Denmark where healthcare is truly socialised and researchers can have access to every single person’s medical file (before anyone freaks out, this data is deidentified. I think.). The result? N’s bigger than your mom.

For example, this study found that out of 3.56 million people, over 91,000 had hospital contact for a mood disorder (depression, bipolar, etc). Previous hospital contact for an autoimmune disease increased risk for later contact due to a mood disorder by 45%.

The justification for this study was that a) medical illness and mood disorders are associated (true), b) immune processes affect the brain and could influence mood and mood disorders (also plenty of evidence for this, especially from animal studies, but human ones as well), and c) longitudinal studies are needed to demonstrate this model and there aren’t enough of them (also true, but there have been a few).

Unfortunately this study doesn’t contribute to c). Why? We’re pretty sure that inflammation affects mood and can increase depressive symptoms in some people. But depressive symptoms are different to a diagnosed depressive disorder – especially one that would require someone to make hospital contact. People with clinical depression don’t just wake up one day and have it, despite feeling fine the day before. And this study had no way of measuring, and therefore controlling for, the level of depressive symptoms at the time that they came in to hospital with their autoimmune disease problems. So how can we say that the autoimmune disease occurred before depression, let alone suggest that the autoimmune disease caused the depression?

It’s not to say that these large scale national studies with a bajillion people don’t have their place. They are a good justification for conducting further research with smaller sample sizes that might be able to more closely examine the specific mechanisms in the inflammation-mood relationship. But the thing is, we’ve already had lots of these large scale studies looking at other medical illnesses that involve inflammatory processes like heart disease, arthritis, and diabetes, and a lot of them show that depression may actually precede medical illness. Furthermore, there are smaller longitudinal studies looking at actual levels of inflammation and depressive symptoms, although results on which precedes which are still conflicting.

So the next thing I’d like to say about longitudinal research is that it can really only tell us about temporal relationships – it can only say that x happened before y. And that’s a very good thing, don’t get me wrong. It helps us to identify people early on that might be a risk for developing certain disorders and diseases and get them treatment or prevention as early as possible. But it can’t necessarily pin down causality. For example, even if the above study had controlled for mood symptoms at baseline, and found that autoimmune diseases truly manifested well before any signs of depression, that’s all it can tell us – about when each disease manifested. It doesn’t rule out the possibility that autoimmune diseases and mood disorders are both attributable to some other heritable phenotype that causes each to emerge at different points over the lifetime.

So what’s the best study? A randomised control trial testing an intervention with a longitudinal follow-up. For example, you take two groups and reduce inflammation in one, and follow them up to see who develops depression.

Expensive? Yes. A nightmare to manage? Yes. Somewhat difficult to get through ethics? I would think so. But you don’t need 3.56 million people to take part in it.