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3 Interesting Characters in ADHD History

April 27, 2012

In the heated climate of today’s discussions on attention deficit hyperactivity disorder (ADHD), one of the areas we sometimes lose sight of is the history of this disorder. Although frequently discussed in the context of our fast-paced, high-tech modern lives, the symptoms of ADHD are by no means unique to our time.

Fidgety Phil, often seen as an allegory for ADHD. Illustration from a book written in 1846 by physician Heinrich Hoffmann. Courtesy of Project Gutenberg.

An ADHD-like disorder was actually described as early as 1798, by Scottish physician Sir Alexander Crichton. Writing a chapter “On Attention and its Diseases” in a three-book series entitled “An inquiry into the nature and origin of mental derangement,” Crichton spoke of a disease characterized by difficulty sustaining focus, a predisposition to distraction, restlessness, and possibly some type of impulsivity—highly reminiscent of the current DSM definition of ADHD (although lacking the hyperactivity component). Crichton even recognized the developmental nature of the disorder and understood that it might be due to neurological dysfunction. Read more…

ADHD & Controversy

April 27, 2012

Attention deficit hyperactivity disorder (ADHD) is one of the most controversial psychiatric diagnoses of our time. Unlike bipolar disorder or schizophrenia, which many accept as ‘real’ mental illnesses, as far as I can tell ADHD gets little respect outside of the scientific literature and community of affected families. Some view it less as a medical condition than an example of the flaws of modern life, with overstimulated children and parents who are too eager to medicate away behavior problems.

So it’s not all that surprising that earlier this year, a NY Times article questioning the value of psychostimulant therapy for ADHD, “Ritalin Gone Wrong” elicited an outpour of public commentary and generated heated discourse, both within and beyond the scientific community. Read more…

Unraveling the Mystery of ADHD

April 27, 2012

Psychiatrist Edward Hallowell, MD, EdD, will be presenting on “The ABCs of ADD” at the April 30 Conte-CBS Colloquium on Mental Health. In honor of his visit, let’s take a look at some common questions about this disorder.

 What is ADHD/ ADD and why it is important?

The acronym ADHD refers to Attention Deficit Disorder with Hyperactivity, and ADD refers to Attention Deficit Disorder. In his book Driven to Distraction (1994), Dr. Edward Hallowell, a Harvard-trained psychiatrist, who himself has both ADHD and dyslexia (a reading disorder), defines ADHD as an early onset biological disorder that is usually characterized by inattention and impulsivity, that may or may not include hyperactivity. He explains that as children who have these characteristics mature, they may be seen as having challenging behaviors or be seen as the “dreamers” in a classroom setting. Ultimately, the characteristics of ADHD and ADD may lead to academic failures, social dysfunction, and skill deficits.  In turn, according to Dr. Hallowell, “Under-achievement can lead to poor self-esteem, which can become the real enemy for those who are struggling to succeed.” Because risk factors associated with ADHD may include high rates of injuries, cigarette smoking, substance abuse, and in some cases delinquency, Dr. Hallowell stresses the importance of education, diagnosis, and treatment, which may or may not include medications, to help those in need turn their lives around.

What is the underlying neurobiology of ADHD/ADD?

According to an article by Thomas Spencer, M.D., and colleagues, “Overview and Neurobiology of Attention-Deficit/Hyperactivity Disorder” in the Journal of Clinical Psychiatry (2002), ADHD is highly heritable and may be associated with deficits in the prefrontal cortex and related subcortical system. Read more…

The Tough Journey “From DSM to DNA”

March 22, 2012

It's a tough trail from the symptom checklists for mental illness in the DSM to the genes that influence susceptibility - and one that requires a lot of teamwork. (Image courtesy of Patsy Annala. Shows the Crag Rat mountain climbing team of Hood River, Oregon on Mt. Hood circa 1926.)

Nineteen countries. Over 60 institutions. More than 200 authors per paper.

The large scale of these numbers gives a clue as to just how hard it is to study the genetics of mental illness. They describe the scope of collaborations conducted by the Psychiatric Genomics Consortium, a group that does meta-analyses of genome-wide association studies (GWAS) focused on psychiatric disorders.

GWAS, first reported in 2002, are a way to comb through the genome in an unbiased fashion, looking for genetic variations—often in the form of single nucleotide polymorphisms, or single-letter differences in the DNA code—associated with a specific trait or medical condition. The Consortium began in 2007 with a teleconference among scientists studying ADHD, bipolar disorder, major depressive disorder, and schizophrenia. Autism researchers joined the team soon after.

A leader in the Consortium, Jordan Smoller, MD, ScD, Director of Psychiatric Genetics and Associate Vice Chair in the Department of Psychiatry at Massachusetts General Hospital and author of the upcoming book The Other Side of Normal, will be speaking in next Tuesday’s Conte-CBS Colloquium on the genetics of mood disorders. Smoller is also an associate professor of psychiatry at Harvard Medical School.

Smoller and his colleagues sometimes describe their work as a journey “from DSM to DNA”— from the symptom checklists for mental illnesses in the Diagnostic and Statistical Manual of Mental Disorders (the holy book of psychiatry) to the genes that influence susceptibility, and may eventually lead us to the biological roots of the disorders. Here we take a look at the role of GWAS in this important journey, the challenges associated with them, and what they’ve taught us so far.

Read more…

Schizophrenia: Stigma, GABA, and MRS

February 26, 2012

Why is it that so many people talk openly about their struggles with diabetes, heart disease, or arthritis, while mental illness is often whispered about or kept hidden within families?

Part of the stigma comes from the obvious fact that mental illnesses affect the brain, which we know a lot less about than the pancreas, heart, bones, or cartilage—and which we associate with our behaviors and personality traits. But brain tumors also damage the brain, and have the potential to impact how we think or act. Yet there’s a lot less secrecy surrounding brain tumors than there is around schizophrenia.

One of the key differences is our ability to see and measure the pathology. Brain tumors are routinely imaged and described in radiology reports, with stats on size and location. With a biopsy, individual tumor cells can be analyzed under a microscope and the type of brain cancer can be determined. By comparison, the structural or biochemical changes in the brain that underlie schizophrenia remain a mystery. There is no biologically-based method of diagnosis.

Fortunately, neurobiologists are hard at work trying to uncover the cellular and molecular pathologies in schizophrenia. An important piece in the puzzle seems to be the dysfunction of the GABA system—the major inhibitory neurotransmitter system of the brain. It is hypothesized that abnormalities in the levels of GABA and the neurons which secrete it contribute to the disease process in schizophrenia.

Magnetic resonance spectroscopy (MRS) is one of the tools allowing researchers to begin testing this, and other hypotheses involving alterations in brain metabolites, in living humans. At Tuesday night’s Conte-CBS Colloquium on Mental Health, Dost Ongür, MD, PhD, Chief of the Psychotic Disorders Division at McLean Hospital, will discuss MRS studies on the neurobiology of schizophrenia.

Read more…

An Elephant Schematic of Schizophrenia Research

February 26, 2012

In an article in Schizophrenia Research, published April 2011, a group of researchers led by Matcheri S. Keshavan, MD, of Beth Israel Deaconess Medical Center and Massachusetts Mental Health Center, liken the current state of schizophrenia research to an ancient Indian fable about Blind Men and an Elephant.

In the fable, six blind men touch different parts of an elephant and come to different conclusions about what the elephant is. While each one is right about his part of the elephant, to figure out what they’re really touching they would have to integrate their observations. Similarly, at present there are many observations of the pathology in schizophrenia that need to be connected.

One unifying idea that’s been proposed is that genetic, environmental, or epigenetic factors lead to changes in the activities of various neurotransmitter systems, including the glutamategric, GABAergic, dopaminergic and cholinergic systems. Ultimately, these changes may alter E/I balance and brain plasticity.

Image modified from Figure 1 in Keshavan MS, Nasrallah HA, Tandon R. Schizophrenia, "Just the Facts" 6. Moving ahead with the schizophrenia concept: from the elephant to the mouse. Schizophr Res. 2011 Apr;127(1-3):3-13.

American Academy of Pediatrics Casts Spotlight on Childhood Adversity

January 30, 2012

How might we improve our nation’s educational achievements, spur economic productivity, cut crime, and lessen inequalities in health?

The Center on the Developing Child at Harvard has an answer: Protect young children from adversity. And the American Academy of Pediatrics (AAP) has taken the challenge.

This month the AAP issued a policy statement, crystallizing decades of scientific research on the damaging effects of early childhood adversity into five formal recommendations for the pediatric community. Key strategies in these recommendations included breaking down the barriers between physical and mental health, training all doctors about the importance of reducing toxic stress in children, and encouraging pediatricians to take the lead in education and advocacy efforts targeting this societal scourge.

Co-authored by Jack P. Shonkoff, MD, Professor of Child Health and Development and Director of the Center on the Developing Child, the AAP’s call to action was accompanied by a technical report describing the myriad lifelong consequences of toxic stress in childhood.

Read more…

What Our Name Means

January 30, 2012

E/I Balance refers to the balance of excitatory (E) and inhibitory (I) activity in the brain.

When neurons communicate with each other, they can secrete excitatory or inhibitory neurotransmitters – chemicals that dial up or down, respectively, the electrical activity (aka “firing”) of other neurons. E/I balance is important for the brain’s plasticity, or capacity for change. Early in brain development, this balance is skewed towards excitation. Over time, neurons that make inhibitory neurotransmitter mature, turning on “critical periods” or “sensitive periods”—time windows when the brain is readily shaped by environmental experience.

Disruptions of E/I balance are thought to underlie several nervous system disorders, including mental disorders such as autism and schizophrenia.

Recently, optogenetic experiments demonstrated that altering E/I balance in the prefrontal cortex of mice interferes with cellular information processing and leads to impairments in social function and cognition reminiscent of those occurring in psychiatric disorders. (Visit Schizophrenia Research Forum for coverage of this work and researchers’ comments on it.)


Welcome to E/I Balance

January 30, 2012

We’re not a sneaker company. And no, we have nothing to do with the latest Apple device or movie on extraterrestrials.

E/I Balance is a community blog on mental health research, set up by the Conte Center at Harvard University. Funded by National Institute of Mental Health, the Conte Center is dedicated to basic neuroscience research that probes the origins of mental illness.

In collaboration with the Center for Brain Science, the Conte Center is debuting a monthly, interdisciplinary lecture series called the Conte-CBS Colloquium on Mental Health. We hope this blog can serve as a place where people who attend these talks share their thoughts, ideas, questions or research findings with each other.

Some Blog Sparkers

Need inspiration? Here are some questions to get your creative juices flowing:

  • What was the most interesting or unexpected piece of data, idea, or comment in the talk you attended? Why did it grab your attention and what questions did it raise?
  • Did the talk make you think of anything interesting you’ve learned in other seminars, in classes, or in the lab? What was the connection?
  • Have you read an exciting article or book related to the talk, or related to mental health research in general?
  • Is there a new trend in thinking or new method of analysis in your field that might impact understanding of mental illness?
  • What do you think is one of the most compelling questions or problems in mental health research? Why?

Read more…