The brain: For adolescents, a scary path to full development
TheStar.com – Insight/healthzone.ca/health
July 24, 2010. Jennifer Wells, FEATURE WRITER
It is the late morning of an exceptionally pleasant summer Sunday when Aaron Mirkin presents himself for an interview.
Four days prior, he celebrated his 21st birthday.
He is wearing cargo shorts and square-nosed black leather Rockport lace-ups and a grey Aesop Rock T-shirt.
His black hair is long and he has a full moustache and beard, which he frequently strokes, as he does when he mentions the slight anxiety he felt prior to our meeting.
Still, the image of manhood, of grown-up-hood, is ever present. So much so that it seems necessary to point out his current state of brain development.
Reporter: “You know you’re an adolescent.”
Mirkin: “So I’ve heard.”
Walking west along Eglinton Avenue, seeking a leafy knoll sheltered from the hot sun, Mirkin tells his tale. He starts with the issues — undiagnosed — he started to experience at school. He recalls he was in Grade 6 when he felt the first flush of anxiety and depression. He started missing school. By Grade 7 he was seeing a psychiatrist. “Grade 8 was the big, bad year for me,” he says. “I basically stayed home.” That year he was prescribed Fluvoxamine, a selective serotonin reuptake inhibitor to deal with his depression.
Before recounting the seven years that followed, Mirkin reflects thoughtfully: “The main thing I’ve always found is that my anxiety is completely illogical. There was always a logical part of my brain saying there’s nothing to be anxious about. But then my emotions would take over. My emotions dominated my thinking.”
In less than a minute, Mirkin has encapsulated an intriguing puzzle, for what he and the world of neuroscience now know, is that the “adolescent” brain is a work in progress.
At the Brain Imaging Centre at McLean Hospital in Belmont, Mass., Dr. Staci Gruber casts her mind back to a revolutionary moment in brain science.
Gruber, an assistant professor of psychiatry at Harvard Medical School, is the director of the centre’s Cognitive and Clinical Neuroimaging Core. McLean was the first psychiatric hospital in the U.S. to have a dedicated magnetic resonance scanner. Gruber started at McLean in 1989, the year after the hospital started using MRI, or magnetic resonance imaging, to conduct structural brain studies.
“The structural imaging gives us a lovely high-resolution picture of the brain where we can measure things like grey matter, white matter and cerebral spinal fluid and we know from studies that are longitudinal . . . that there are very discreet differences in the distribution of grey matter and white matter over time.”
The revelation was, pardon the term, brain-blowing.
“Previously, people assumed that by the time you hit puberty, well, you were done, and in fact that’s not nearly true,” Gruber continues. “While you have 90 to 95 per cent of your brain volume by age 6, the distribution of grey matter and white matter changes significantly over the next two decades.”
By adding fMRI, or functional magnetic resonance imaging, to the mix, the adolescent brain could be studied not only in structure, but in response to stimuli. “There are changes within the magnetic field between oxygenated and deoxygenated blood while doing a task or looking at images,” Gruber explains. “We can subtract what your brain looks like while you’re doing something versus when you’re not doing something and get a really nice picture.” She cites an example, testing the reaction to faces displaying a range of emotions: anger, happiness etc. “What we found is that adults utilize much more frontal regions of the brain while they’re looking at the faces.”
In contrast, children and adolescents over-activated their limbic system, with, says Gruber, a much larger amygdala response.
In other words, adults were making a stronger cognitive decision, drawing on the region of the brain where decision making and executive function rules, while the younger subjects were expressing more of a gut reaction in the area of the brain where emotion reigns supreme. Only later in maturity does the frontal system come “on line” to exert control over the amygdala and other limbic structures.
The discovery that the brain continues to change through adolescence — an imprecise age band that is now commonly described as continuing into the mid-20s — has proved the motherlode for neuroscientists, not to mention upending years of accepted wisdom ascribing the turmoil of the teen-aged years to little more than hormone-induced risk-taking behaviour. (Or, on its flip side, indolence.)
In this league, Tomáš Paus is world renowned. Last January, the Czech-born Paus arrived in Toronto to co-direct, with his wife Dr. Zdenka Pausova, the Toronto Trans-generational Brain and Body Centre at the Baycrest’s Rotman Research Institute.
On a Friday afternoon in July, still slightly damp from a torrential Toronto rain, Paus neatly explains both the joys and frustrations about what the most current research can tell us about the adolescent brain.
“We know that the brain continues to change, we know parts of the brain are changing more than others, both in terms of the structure and to some extent the function,” Paus says. But — and this is a big ‘but’ — “we have very little knowledge of why that is.”
Last November, Paus and a group of co-researchers released the results of a study examining the effects of prenatal exposure to maternal smoking in adolescents aged 12 to 18. Dragging his mouse across a computerized image of the brain, Paus circles the area known as the orbitofrontal cortex, the part of the brain that is important for evaluating rewards. “What we found was that this part of the cortex was thinner in teenagers whose mothers smoked during pregnancy,” says Paus. Participants — approximately 600 Quebec adolescents, half of whom were exposed in utero to maternal cigarette smoking — were asked to document which substances they had experimented with, from a list of 12 that included alcohol, marijuana and harder drugs. For the “exposed” participants, continues Paus, “We also found that the thinner this part of the cortex was, the more different substances the adolescent experimented with in his or her lifetime.”
Paus is quick to caution that the research shows an association, not causality, though controlled testing in rats bore the same conclusion.
What’s even more interesting, Paus continues, is that those adolescents whose mothers did not smoke shows the orbitofrontal cortex thickening with the number of drugs tried. “The more substances used, the thicker the cortex.”
Whatever does it mean?
Well, if you have heard the term “plasticity” bandied about, this is a good example. “We figured out most likely it’s plasticity,” Paus says. “It’s the experience that is now shaping the brain.”
How that happens is in part due to a molecule called BDNF, or brain derived neurotropic factor, which, says Paus, is very important for structural plasticity. “Essentially it translates change in function to structural change,” Paus says. And, in fact, that’s exactly what the study found. “Looking only at those (non-exposed) kids who have the ‘good’ BDNF, the more substances they try, the thicker the cortex.”
While the consequences of that change are not clear, and while the study focuses on drug experimentation, Paus believes that those adolescents might be at greater risk of developing full-blown drug addiction. Could this “out” an individual at risk of addictive behaviour?
Aaron Mirkin has never done non-prescription drugs. “And that includes pot,” he clarifies. This is not a moral issue. “I felt my mind was messed up enough as it was . . . I’ve always had the fear of losing my mind.”
He believes the Fluvoxamine, which he started taking in Grade 8, may have had some positive effect, and he has good things to say about the care he received through the youth psychiatry group at the Canadian Association for Mental Health. Yet half way through Grade 9, Mirkin found himself struggling. In fact, his anxieties were crippling. “There were instances where I felt so anxious I couldn’t move my legs,” he says
While the vast majority of adolescents make an uninterrupted, if sometimes bumpy, transition to adulthood, it is also the case that these are the peak years for the onset of psychiatric disorders. Tomas Paus rhymes through the list. Substance use disorders: 12 to 25. Mood disorders: typical onset around the age of 13. Schizophrenia: as early as mid-adolescence and typically not much later than the mid-20s. That the adolescent brain is vulnerable to such psychopathologies, it’s little wonder that so much of the current research focus is concentrated in these areas.
A micro-study of a single mood disorder can upend what the new research has only recently concluded.
Take those facial stimuli that McLean’s Staci Gruber referenced, which elicited a heightened response in the amygdala versus the frontal cortex. In adolescents with anxiety and depression the results are quite different. Paus refers to a study out of the U.S. National Institute of Health which showed that in those patients the frontal cortex responded more strongly. “You very often hear that the amygdala and the frontal cortex are kind of disconnected, that they don’t talk to each other,” he says. “In fact, in those patients the connectivity between the two structures is actually stronger than in healthy kids.”
“Yes we know more,” he continues. “We now know better what might be the neural mechanisms that underlie the differences in behaviour. That’s helpful. But we still don’t know why they behave that way.”
Next week, Paus will begin to scan a cohort of 500 18 and 19-year-old males in the U.K, part of a longitudinal study that has followed this group from before puberty. Structurally, scientists now know that there’s a huge increase in the volume of white matter in male adolescents. Even this simple fact has the potential to confuse. “We have to make sure that people don’t misunderstand this fact . . . and interpret it as giving boys an advantage.” Paus believes that’s not the case. “If anything it might be a disadvantgae because it might be making the system less stable.”
Sitting before his computer, Paus pokes his cursor at “those chunks of white matter that contain the fibres, or axons, that transfer information between different cortical regions.”
What Paus wants to know is whether and to what degree those myelin-encased axons grow thicker under the influence of testosterone. The thicker the axon, the faster the transport of information, which sounds positive. Not always. “That increase in the thickness and the caliber of the axon may have dramatic consequences in terms of neurotransmission,” Paus theorizes. Could it be that in some subjects the consequence is an imbalance in neurotransmission leading to different mental health problems? “We know that the males who have very efficient androgen receptors (the main receptor that mediates the effect of testosterone) and have high levels of testosterone are reporting more mood symptoms, more symptoms of depression,” Paus says.
There are so many questions. So many what-ifs. The adolescent brain is today a big, black box into which science has only begun to peek. Paus makes the point that once science unearths a potential mechanism, that mechanism can’t be linked to behaviour without understanding genetics, environment, family composition, peer influences — the whole social and cultural buffet. By conducting longitudinal studies, Paus hopes to push past those barriers. His work at the Baycrest will do just that, recruiting three generations of families from different ethnic groups for a multi-year study into physical and mental health.
“Longitudinal studies are really the holy grail of medical research,” says Staci Gruber. “If you could look at those who are at risk…and follow them, where might you see differences and at what points? What might you be able to do to prevent anything from happening that might lead to the development of a disorder? Early intervention is the key, isn’t it? Because all this information is great to have observationally speaking, but it’s only worth something if you can actually intervene and prevent what for most people is a devastating situation.”
Ron Dahl, who up until this summer directed the Child and Adolescent Neurobehavioural Laboratory at the University of Pittsburgh, says it’s time to “move the level of question from a clinical medical level to prevention and early intervention.”
This week, Dahl was busy unpacking boxes at the University of California, Berkeley, where he is taking up a position as professor of public health. “Though it’s important to frame this as most adolescents do really well, even if you say five to 10 per cent begin to struggle with problems, that’s a lot of youth. And if they start spiralling down with chronic depression, with chronic substance use, if their aggression gets them into trouble and they fall off track with their academics and relationship development, then this can really be a key interval that’s going to impact them for the rest of their lives.”
Dahl has spent much of the past five years focusing on emotional and motivational systems. Examining the circuitry that links cognitive and emotional systems, he says, offers key insights into developmental windows when adolescents are going to be more prone to either a negative spiral or a positive improvement.
“This can be a time when a little bit of scaffolding or a little bit of bridging with support can make a big difference in those kids,” he says, referring to the former group.
Dahl remains co-director of a University of Pittsburgh five-year study that has targeted pre-adolescents — nine, 10 and 11 year olds — with anxiety problems. “We think that improving emotion regulation skills, helping them think in different ways and helping them regularize their sleep in that interval of time will prevent depression in the next phase, the 13 to 18-year-old period of time.”
He later adds that physical activity is another key component and that people in the educational system are increasingly expressing interest. “Education policy people and brain development people are having a dialogue about how do we take what we’re learning from brain science and influence educational policy.” Two large neuroeducational conferences are being launched in the U.S. this year.
Aaron Mirkin remembers that he was 11 when he first started experiencing anxiety. In the decade since, his parents have been as supportive as any parents can be. He has no siblings. For his final years of high school he switched to Inglenook Community School. “I was so happy there,” he says. He signed on to a program at Sunnybrook Hospital that has helped him work on coping mechanisms and there he linked up with a psychiatrist he likes very much. His medication was switched to Effexor. It has been a maze of pushing through systems and bureaucracies that would defeat many families. No small part of the problem has been the “adolescent” label. “Part of the reason I wanted to do this,” he says of his participation in this story, “is because of the stigma of mental illness. I think especially for adolescents, I think they really are not taken seriously. I know I was not.”
Mirkin has finished his second year of film studies at Ryerson University. He’s working on a documentary on Pages, the famed, and now closed, indie Queen Street book store. He still has moments. “Sometimes I have to sit for a moment. Think. Breath. Rationalize . . . I can’t think of the last time I was crippled by my anxiety.”
Ten years is a long time. And that’s with all the supports a society can currently muster.
By going public, Aaron Mirkin helps erase the stigma that still enshrouds mental health. With the help of future scientific exploration of the adolescent brain, we may be able to cut that journey, that pathway, short.
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