Adult ADHD and Brain White Matter Deficits

In my last post I reviewed a recent diffusion tensor imaging study of ADHD in children. This study found evidence for brain white matter deficits in several ciruitry regions including frontal, temporal and occipital areas.

To follow up on this post, I want to highlight a recent study of DTI in adults with ADHD.

This study from Brazil recruited 22 drug treatment-naive subjects between the ages of 18 and 50 years of age.

This study excluded subjects with a history of substance dependence or other medical or neurological conditions that could confound the findings. However, 7 of the 22 did endorse other axis I mental disorders including 4 with bipolar disorder, 2 with major depression and 1 with anxiety disorder.

These adults subjects reported early onset of ADHD symptoms (before age 7) that persisted into adulthood.

Using all 22 with ADHD the research team reported multiple areas of differences compared to the healthy control group:

• Higher fractional anisotropy in ADHD: bilateral frontal gyrus, right middle frontal gyrus, left postcentral gyrus, bilateral cingulate gyrus, bilateral temporal gyrus and right superior temporal gyrus
• Reduced diffusivity measures in ADHD: fronto-striatal-parieto-occipital circuits, corpus callosum circuits, right superior corona radiata and fronto-occipital circuits

A significant finding in this study was the limited findings for ADHD subjects without an axis I comorbidity.

Using only these relatively "pure" ADHD subjects most of the findings lost statistical significance although a trend remained for several regions and circuits including:

• Reduced gray matter volumes in right superior frontal gyrus, right cingulate gyrus and left postcentral gyrus
• Higher fractional anisotropy in right superior frontal gyrus, right cingulate gyrus and left postcentral gyrus
• Reduced diffusivity in right splenium of the corpus callosum and white matter underlying the right cingulate gyrus

This study highlights some of the research study design problems in adult ADHD. First, many adults with ADHD will have received drug treatment and the effects of drug treatment must be controlled in the analysis. Second, many adults with ADHD will have other significant axis I disorders. These disorders may contribute to white matter deficits found with imaging. It is important to assess for these effects in reporting findings that are felt to be specific to an ADHD diagnosis.

One common comorbidity in childhood ADHD is conduct disorder and this disorder needs to be assessed in both children and adults with ADHD.

It is challenging to find subjects with only an axis I ADHD diagnosis for imaging and other types of research.

The present study supports diffuse white matter deficits in adults with ADHD although the link specifically to an ADHD diagnosis remains unclear.

Readers with more interest in this study can access the free full-text manuscript by clicking on the PMID link below.

Figure demonstrates the anatomy of the corona radiata white matter tracts in the brain and is a screen shot from the iPad app Brain Tutor. The authors found abnormalities in those with ADHD in the right corona radiata although this finding was not found in the "pure" ADHD group.

Follow the author on Twitter @WRY999

Chaim TM, Zhang T, Zanetti MV, da Silva MA, Louzã MR, Doshi J, Serpa MH, Duran FL, Caetano SC, Davatzikos C, & Busatto GF (2014). Multimodal magnetic resonance imaging study of treatment-naïve adults with attention-deficit/hyperactivity disorder. PloS one, 9 (10) PMID: 25310815

Common Neuropsychiatric Problems in Epilepsy

Epilepsy represents a complex neuropsychiatric condition with significant public health impact.  The prevalence estimates of active epilepsy range from about 1 to 4% of the general population.  Like other medical conditions, epilepsy appears to increase the risk for a variety of secondary (or cormorbidity problems).  Understanding these related risks can aid patients, families and clinicians in understanding symptoms, common presentation conundrums and best treatment approaches. A recent epidemiology survey published by Ottman and colleagues of a large sample of the general population in the U.S. provides insight into the range and relative risk for variety of disorders in those with epilepsy.  The key elements of this survey include the following key design items:

• Data part of Epilepsy Comorbidity and Health (EPIC) Survey
• Mail survey to random households in the United States
• Case definition of epilepsy a yes response to the following question: “Have you ever been told you have a seizure disorder or epilepsy?”.
• Those who reported being diagnosed with epilepsy (2.0% of those surveyed) were compared to those without a self-reported diagnosis
• Surveyed other neuropsychiatric, pain and other medical conditions included: anxiety disorder, depression, bipolar affective disorder, ADHD, sleep disorder/apnea, tremor/movement disorder, migraine, fibromyalgia, chronic pain, neuropathic pain, asthma, diabetes, high blood pressure
• Risk ratios controlled for a variety of potential confounding variables including: sex, age, income, population density,census region, prior head injury, and prior stroke

The comorbid conditions with the highest relative risks (that were statistically significant) are shown in the accompanying summary figure.   A prevalence ratio of 2.0 would mean those with epilepsy are twice as likely to have the diagnosis compared to controls without epilepsy. ADHD, bipolar disorder, movement disorder/tremor and fibromyalgia led the rank list of diagnoses.  A significant number of the disorders showed statistically significant associations between a risk of 1.0 to 2.0.   The only disorders that showed no link to a diagnosis of epilepsy were diabetes and high blood pressure.

The primary weaknesses of these types of studies is reliance on self-report diagnosis by a the respondents.  One way to exam the validity of diagnoses is to conduct more detailed direct interviews and examinations of a subset of study participants.  Also the rates of self-reported diagnoses can be compared to known direct interview studies.  Here are the rates of self-reported neuropsychiatric diagnoses in those without epilepsy in the current study: depression 25.6%, anxiety 13.9%, bipolar disorder 6.8%, ADHD 5.5%.   The bipolar disorder self-report rates seem unexpectedly high and the implications for the validity of this study is unclear.

The authors note their study demonstrating a lifetime self-report prevalence rate of 2.0% is consistent with previous other population-based surveys.  Neuropsychiatric comorbidities were common in those reporting epilepsy ranging from a low of 8.7% for neuropathic pain to 32.5% for depression.  The authors note this study will aid those caring for epilepsy and help target comprehensive assessment and managment.

Ottman R, Lipton RB, Ettinger AB, Cramer JA, Reed ML, Morrison A, & Wan GJ (2011). Comorbidities of epilepsy: Results from the Epilepsy Comorbidities and Health (EPIC) Survey. Epilepsia PMID: 21269285