Tuesday, June 17, 2014

MRI technique may help prevent ADHD misdiagnosis

This shows subgroup averages of parametric maps of MRI brain iron indices: magnetic field correlation (MFC: top row) and relaxation rates R2 (second row), R2*(third row), and R2' (bottom row). 

Parametric maps, masked for regions of interests (green): caudate nucleus (CN), putamen (PUT), globus pallidus (GP) and thalamus (THL), are shown for controls (n = 27), medication-naïve ADHD patients (ADHD-non-medicated; n = 12) and ADHD patients with a history of psychostimulant treatment (ADHD-medicated; n = 10). 

The ADHD-non-medicated subgroup displayed significantly reduced striatal (CN, PUT) and thalamic MFC compared to both controls and the ADHD-medicated subgroup. 

No significant differences were detected between the latter two groups. 

Credit: Radiological Society of North America 

Brain iron levels offer a potential biomarker in the diagnosis of attention deficit hyperactivity disorder (ADHD) and may help physicians and parents make better informed treatment decisions, according to new research published online in the journal Radiology.

ADHD is a common disorder in children and adolescents that can continue into adulthood. Symptoms include hyperactivity and difficulty staying focused, paying attention and controlling behavior. The American Psychiatric Association reports that ADHD affects 3 to 7 percent of school-age children.

Psychostimulant medications such as Ritalin are among the drugs commonly used to reduce ADHD symptoms.

Psychostimulants affect levels of dopamine, a neurotransmitter in the brain associated with addiction.

"Much debate and concern has emerged regarding the continual rise of ADHD diagnosis in the U.S. given that two-thirds of those diagnosed receive psychostimulant medications," said Vitria Adisetiyo, Ph.D., postdoctoral research fellow at the Medical University of South Carolina in Charleston, S.C.

"We wanted to see if we could identify brain iron as a potential noninvasive biomarker for medication-naïve ADHD to prevent misdiagnosis."

For the study, the research team measured brain iron levels in 22 children and adolescents with ADHD, 12 of whom had never been on medication for their condition (medication naïve), and 27 healthy control children and adolescents using a magnetic resonance imaging (MRI) technique called magnetic field correlation imaging.

The technique was introduced in 2006 by study co-authors and faculty members Joseph A. Helpern, Ph.D., and Jens H. Jensen, Ph.D. No contrast agents were used, and blood iron levels in the body were measured using a blood draw.

The results showed that the 12 ADHD medication-naïve patients had significantly lower brain iron levels than the 10 ADHD patients who had been on psychostimulant medication and the 27 children and adolescents in the control group.

In contrast, ADHD patients with a history of psychostimulant medication treatment had brain iron levels comparable to controls, suggesting that brain iron may increase to normal levels with psychostimulant treatment.

"Our research suggests that iron absorption into the brain may be abnormal in ADHD given that atypical brain iron levels are found even when blood iron levels in the body are normal," Dr. Adisetiyo said.

"We found no differences in blood iron measures between controls, medication-naïve ADHD patients or pscyhostimulant-medicated ADHD patients."

If the results can be replicated in larger studies, magnetic field correlation might have a future role in determining which patients would benefit from psychostimulants—an important consideration because the drugs can become addictive if taken inappropriately and lead to abuse of other drugs like cocaine.

"We want the public to know that progress is being made in identifying potential noninvasive biological biomarkers of ADHD which may help to prevent misdiagnosis," Dr. Adisetiyo said.

"We are currently testing our findings in a larger cohort to confirm that measuring brain iron levels in ADHD is indeed a reliable and clinically feasible biomarker."

More information: "Multimodal MR Imaging of Brain Iron in Attention Deficit Hyperactivity Disorder: A Non-invasive Biomarker that Responds to Psychostimulant Treatment?" Radiology, 2014.

Tuesday, June 3, 2014

Children with autism have elevated levels of steroid hormones in the womb

Scientists from the University of Cambridge and the Statens Serum Institute in Copenhagen, Denmark have discovered that children who later develop autism are exposed to elevated levels of steroid hormones (for example testosterone, progesterone and cortisol) in the womb.

The finding may help explain why autism is more common in males than females, but should not be used to screen for the condition.

Funded by the Medical Research Council (MRC), the results are published today in the journal Molecular Psychiatry.

The team, led by Professor Simon Baron-Cohen and Dr Michael Lombardo in Cambridge and Professor Bent Nørgaard-Pedersen in Denmark, utilized approximately 19,500 amniotic fluid samples stored in a Danish biobank from individuals born between 1993-1999.

Amniotic fluid surrounds the baby in the womb during pregnancy and is collected when some women choose to have an amniocentesis around 15-16 weeks of pregnancy.

This coincides with a critical period for early brain development and sexual differentiation, and thus allows scientists access into this important window in fetal development.

The researchers identified amniotic fluid samples from 128 males later diagnosed with an autism spectrum condition and matched these up with information from a central register of all psychiatric diagnoses in Denmark.

Within the amniotic fluid the researchers looked at 4 key 'sex steroid' hormones that are each synthesized, step-by-step from the preceding one, in the 'Δ4 sex steroid' pathway: progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone.

They also tested the steroid hormone cortisol that lies outside this pathway. The researchers found that levels of all steroid hormones were highly associated with each other and most importantly, that the autism group on average had higher levels of all steroid hormones, compared to a typically developing male comparison group.

Professor Baron-Cohen said: "This is one of the earliest non-genetic biomarkers that has been identified in children who go on to develop autism."

"We previously knew that elevated prenatal testosterone is associated with slower social and language development, better attention to detail, and more autistic traits."

"Now, for the first time, we have also shown that these steroid hormones are elevated in children clinically diagnosed with autism."

"Because some of these hormones are produced in much higher quantities in males than in females, this may help us explain why autism is more common in males."

He added: "These new results are particularly striking because they are found across all the subgroups on the autism spectrum, for the first time uniting those with Asperger Syndrome, classic autism, or Pervasive Developmental Disorder Not-Otherwise-Specified. We now want to test if the same finding is found in females with autism."

Dr Michael Lombardo said: "This result potentially has very important implications about the early biological mechanisms that alter brain development in autism and also pinpoints an important window in fetal development when such mechanisms exert their effects."

Steroid hormones are particularly important because they exert influence on the process of how instructions in the genetic code are translated into building proteins.

The researchers believe that altering this process during periods when the building blocks for the brain are being laid down may be particularly important in explaining how genetic risk factors for autism get expressed.

Dr Lombardo adds: "Our discovery here meshes nicely with other recent findings that highlight the prenatal period around 15 weeks gestation as a key period when important genetic risk mechanisms for autism are working together to be expressed in the developing brain."

Professor Baron-Cohen said: "These results should not be taken as a reason to jump to steroid hormone blockers as a treatment as this could have unwanted side effects and may have little to no effect in changing the potentially permanent effects that fetal steroid hormones exert during the early foundational stages of brain development."

He cautioned further: "Nor should these results be taken as a promising prenatal screening test. There is considerable overlap between the groups and our findings showed differences found at an average group level, rather than at the level of accurately predicting diagnosis for individuals."

"The value of the new results lies in identifying key biological mechanisms during fetal development that could play important roles in atypical brain development in autism."