Reduced right frontal cortical thickness in children, adolescents and adults with ADHD and its correlation to clinical variables: A cross-sectional study

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Abstract

Objective

Some longitudinal magnetic resonance imaging (MRI) studies have shown reduced volume or cortical thickness (CT) in the frontal cortices of individuals with attention-deficit/hyperactivity disorder (ADHD). These studies indicated that the aforementioned anatomical abnormalities disappear during adolescence. In contrast, cross-sectional studies on adults with ADHD have shown anatomical abnormalities in the frontal lobe region. It is not known whether the anatomical abnormalities in ADHD are a delay or a deviation in the encephalic maturation. The aim of this study was to compare CT in the frontal lobe of children, adolescents and adults of both genders presenting ADHD with that in corresponding healthy controls and to explore its relationship with the severity of the illness.

Method

An MRI scan study was performed on never-medicated ADHD patients. Twenty-one children (6–10 year-olds), twenty adolescents (14–17 year-olds) and twenty adults (25–35 year-olds) were matched with healthy controls according to age and sex. CT measurements were performed using the Freesurfer image analysis suite.

Results

The data showed regions in the right superior frontal gyrus where CT was reduced in children, adolescents and adults with ADHD in contrast to their respective healthy controls. The CT of these regions correlated with the severity of the illness.

Conclusions

In subjects with ADHD, there is a thinning of the cortical surface in the right frontal lobe, which is present in the children, adolescents and in adults.

Introduction

Several published studies have used MRI (magnetic resonance imaging) on subjects with attention-deficit/hyperactivity disorder (ADHD) (Valera et al., 2007). These studies have reported structural abnormalities in individuals with ADHD, such as a decrease in the volume of various encephalic structures or in the cortical thickness (CT) of certain cortical regions, particularly in the frontal lobe.(Hesslinger et al., 2002, Castellanos et al., 2002, Shaw et al., 2007a, Makris et al., 2007). However, most of the studies have been carried out on male children and few works have included adults. Additionally, female subjects have been extremely underrepresented in these studies (Valera et al., 2007, Ellison-Wright et al., 2008). This fact precludes the generalisation of the results derived from those studies to older subjects and females with ADHD. Consequently, further research that includes adults and female individuals is necessary to create a broader picture of the developmental and gender characteristics of subjects with ADHD.(Valera et al., 2007).

Some longitudinal studies have found structural abnormalities, such as a decrease in volume or CT of several brain regions analysed in children with ADHD. Nearly all of these abnormalities persisted through adolescence, at which point they disappeared (Castellanos et al., 2002, Shaw et al., 2006, Shaw et al., 2007a, Shaw et al., 2007b). Nevertheless, these longitudinal studies have several problems: they do not include subjects older than 18 years and they do include subjects medicated with stimulants, which can affect CT measurements (Shaw et al., 2009). Furthermore, for a significant proportion of the subjects, the subsequent CT measurements were predicted based on one MRI study instead of the actual values. This was due to a loss of subjects during the follow-up, a problem inherent in the longitudinal design.

On the other hand, some studies have reported reduced volume or CT in diverse encephalic regions in adults with ADHD (Hesslinger et al., 2002, Seidman et al., 2006, Makris et al., 2007; Biederman et al., 2008). These divergent data raise the question: “Is ADHD a delay or a deviation in encephalic maturation?” Based on these contradictory data, we believe this issue remains unclear and therefore warrants further research. On the other hand, the presence of anatomical abnormalities in adults with ADHD probably underlies the clinical features observed in adults with ADHD (e.g., only 10% of individuals with ADHD reach functional clinical remission at age 20) (Biederman et al., 2000).

We chose to analyse the frontal lobe for several reasons. First, it is one of the cortical regions more frequently found to be smaller or thinner in its CT in subjects with ADHD (Castellanos et al., 2002, Shaw et al., 2006, Shaw et al., 2007a, Shaw et al., 2007b, Valera et al., 2007, Hesslinger et al., 2002, Seidman et al., 2006, Makris et al., 2007; Biederman et al., 2008; Ellison-Wright et al., 2008). The frontal lobe is also one of the cortical regions most related to the physiology of attention (Fan et al., 2005, Halperin and Schulz, 2006, Posner et al., 2006, Stahl, 2008), and it is one of the cortical regions that consistently showed abnormalities in studies using functional magnetic resonance imaging (fMRI) (Rubia et al., 2008, Rubia et al., 2009). Our goal in analysing this cortical region was to determine whether there is a persistent structural abnormality in the different stages of life in individuals with ADHD. Additionally, we opted for a cross-sectional design to avoid the inherent problems of the longitudinal design mentioned above.

Section snippets

Objective

To compare frontal CT between healthy individuals and individuals with ADHD in three different age groups.

Method

This study included three age groups of never-medicated subjects with combined type ADHD: 21 children (6–10 year-olds), 18 adolescents (14–17-year-olds) and 20 adults (25–35-year-olds), as well as three age groups of healthy individuals (22 children, 20 adolescents and 20 adults). ADHD and control participants were matched by age, sex, height, weight, body mass index (BMI) and IQ (intellectual quotient). The diagnosis of ADHD was made according to the DSM-IV-TR (Diagnostic and Statistical

General characteristics of the sample

The characteristics of the subjects in the three age groups are presented in Table 1, Table 2, Table 3. All subjects in all three groups were right-handed (EHI score > +40 points).

Comorbidities

Among the groups of children, the presence of other psychiatric disorders was more frequent in ADHD individuals than in healthy individuals: 13 (61.9%) vs. 2 (9.5%) (X2 = 12.48, df = 1, p = 0.000). Two (9.5%) of the healthy children met the criteria for Separation Anxiety Disorder. Among the children with ADHD, 1

Discussion

This study shows that CT in regions of the right superior frontal area is thinner in children, adolescents and adults with ADHD. Furthermore, findings from the present work indicate that there is a correlation between the CT of these regions and the severity of the disorder. The regression model shows that, in the three age groups, a diagnosis of ADHD predicts CT in the right superior frontal regions, where statistical differences between healthy and ADHD subjects were observed (controlling for

Limitations

In the present study we used a cross-sectional design intended to test the hypothesis that CT alterations persist in ADHD from childhood to adulthood. A longitudinal approach would have been an alternative design since we were comparing CT in different age groups and with different patients in each group, thereby creating a great deal of variability. However, our cross-sectional design allowed us to avoid some of the problems inherent to longitudinal studies (e.g., by including patients older

Role of the funding source

Funding for this study was provided by Servicios de Salud del Estado de Querétaro, México (Department of Public Health).

Servicios de Salud del Estado de Querétaro had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

Contributors

Luis G. Almeida. M.D., MSc, Ph.D. Psychiatry and Neurosciences Address 1: Centro Estatal de Salud Mental, Servicios de Salud del Estado de Querétaro. Avenida 5 de Febrero 105, Los Virreyes. C.P. 76170. Querétaro México. Phone/Fax (52–442) 242–4381. [email protected].

Address 2: Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla. Boulevard Juriquilla 3001. C.P. 76230. Querétaro, México.

Josefina Ricardo-Garcell. Ph.D. Neurosciences and Neurophysiology.

Disclosure of competing interests

Drs. Almeida, Ricardo-Garcell, Prado, Barajas, Fernández, Ávila & Martínez state that: “In the present study there are no competing interests of any kind in the last 10 years.”

Acknowledgements

We thank all the individuals who participated in this study, to the Consejo Nacional de Ciencia y Tecnología (CONACYT), al programa de posgrado en ciencias biomédicas de la Universidad Nacional Autónoma de México y a los servicios de salud del estado de Querétaro (SESEQ)

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