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(PSYCHIATRIC TIMES) - This statistic is as familiar as it is startling. According to the National Comorbidity Survey-Replication (NCS-R), the peak age of onset for any disease involving mental health is 14 years. True for bipolar disorder. True for anxiety. True for schizophrenia and substance abuse and eating disorders. The data suggest that most mental health challenges emerge during adolescence. If true, this brings to mind an important developmental question:

What is up with adolescence?

The teenaged years are chock-full of byzantine, intricately timed, molecular processes that have to be closely choreographed and deployed in a specific sequence to accomplish their sexual mission. Do these extraordinarily complex developmental processes go awry in some children as they evolve through adolescence? Do these changes create, or at least contribute, to future mental disorders? Is this one way to get at what are sometimes called genetic “trapdoors”—DNA-based psychopathologies that do not show up until a certain developmental milestone is reached?

These are important issues. Most of the mental health challenges that emerge during puberty have real staying power. The symptoms tend to be more severe. Many go undetected in the early formative stages of the illness and comorbid disorders often develop. These complications can create problems in determining the correct diagnosis, and make it difficult for the clinician to select the treatment strategies with the greatest probability of success.

Researchers face similar daunting challenges in attempting to understand the cellular and molecular basis for such disorders. Fortunately, fairly recent findings have provided a ray of hope—potential illumination for both clinician and scientist. From gene to cell, we are beginning to learn more and more about the neurobiological maturation of the brain transiting through adolescence. The question is, Does any of this knowledge help us understand the NCS-R data?

In this column and the next, we will explore the developmental biology of the so-called teenaged brain, focusing first on cellular studies, then on behavioral ones. In this first installment, we will address specific aspects of the brain’s developmental trajectory. We’ll look initially at structural changes and then focus on the notion of the canonical “teenage brain” behaviors.

In the second installment, we will discuss how changes in these developmental processes may contribute to the emergence of mental disorders.

Alterations in Brain Structure

The past 20 years have witnessed extraordinary progress in our understanding of the functional and structural development of the human brain. Some of the best stuff has been obtained using noninvasive brain imaging technologies, such as fMRI. Though fraught with the potential for misinterpretation (please see my 2 articles online, and, even the most conservative interpretations reveal a fantastic world of molecular and cellular activities during development. Efforts examining how the volume of gray matter changes over time has been particularly fruitful, and is explained below.

Initial evidence demonstrating volumetric gray matter changes focused on 2 temporal processes. The first efforts appeared to detect a gradual increase in gray matter volume during the elementary years that reached its peak at puberty. The second effort showed that the volumes appeared to gradually decline after this peak. The “final” adult form of the brain was fully formed by the time students were ready for college.

The problem with this standard model is that it was oversimplified. Closer inspection of brains developing in the elementary years revealed a much more complex picture. Volumetric increases of gray matter followed by a tailing off only occurred for certain cortical regions, such as the frontal and parietal lobes. The temporal lobes didn’t follow this trajectory at all. Actually, the volume of some cortical regions (such as the superior temporal gyrus) was shown to decline during the elementary years.

The picture that emerged was far more complex than previously supposed. It is now apparent that different parts of the preadolescent brain undergo developmental changes at different times—and at surprisingly different rates.

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