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Salud mental

versão impressa ISSN 0185-3325

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ALMEIDA MONTES, Luis Guillermo; RICARDO-GARCELL, Josefina; PRADO ALCANTARA, Hugo  e  MARTINEZ GARCIA, Reyna Beatriz. Structural brain alterations in attention-deficit/hyperactivity disorder: an update. First part. Salud Ment [online]. 2009, vol.32, n.6, pp.503-512. ISSN 0185-3325.

The DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, fourth Edition, text Revision) defines attention-deficit/hyperactivity disorder (ADHD) as a disorder usually first diagnosed during infancy. Its essential feature is a persistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than typically observed in individuals at a comparable level of development. It produces a significant impairment in social, academic, or occupational functioning. The prevalence of ADHD among the general population is between 5-10% in children and adolescents, and 1.2% to 7.3% in adults. In clinical samples, the prevalence in adults is higher: 1 6.80%. Less than 10% of the children diagnosed with ADHD reached a total functional remission when they became adults. Subjects with ADHD have a higher risk of suffering personality disorders and substance abuse. This disorder has a genetic basis. About 80% of the variance is explained by genetics. Some of the genes implied in this disorder are the dopamine transporter, the dopamine receptor 4, the beta-hydroxilase enzyme, the adrenergic receptor α2, the serotonin transporter and the serotonin receptor 1B. Environmental factors such as parental nicotine consumption during pregnancy, low birth weight, perinatal problems, parental psychiatric disorders, social adversity, and low parental education are related to a higher risk for ADHD. Several studies have shown that there are morphological brain abnormalities in subjects with ADHD. Structures like frontal lobe, cerebellar hemispheres and vermis, callosum splenium, cingulate anterior cortex and right caudate, are smaller in subjects with ADHD compared with healthy subjects. On the other hand, regarding the response to stimulants, studies with positron emission tomography (PET), among other techniques, suggest that the dopamine and noradrenergic systems play a role in the pathophysiology of ADHD. From 1990 to date, there are 41 morphological studies in ADHD, published in English, reporting volumetric abnormalities. However, the results are contradictory, so definitive conclusions about the brain structures being involved in ADHD remain unclear. Objective This article reviews the general neurobiology of ADHD providing an updated and comprehensive overview of the brain structural findings. The methodologies of morphological studies using magnetic resonance imaging (MRI) are reviewed in detail so as to find the source of the contradictory findings reported in the published studies. Method A literature search and review of the relevant published articles in MEDLINE and PsycINFO sites was made using the following key words: attention deficit hyperactivity disorder, neurobiology, morphological alteration, and MRI. In general, the literature supports the genetic basis of the disorder as well as the involvement of dopaminergic and noradrenergic systems in the pathophysiology. Nevertheless, regarding the structural abnormalities reported in ADHD, there is an enormously heterogeneous methodology in MRI scan acquisition and processing. Almost every study used a different image analysis to measure brain structures. Some works chose a hand user definition of the region of interest (ROI), which is prone to a user's bias. Other papers used a semi-automated analysis combining a user-defined ROI and segmentation techniques based only in intensity. These methodologies are prone to bias and to a deficient separation of grey and white matter. Finally, the automated methods where there is no user intervention are preferred because they are not a biased in the selection of ROI and use tissue probability maps to improve the segmentation. Unfortunately, none of these methods has been validated against histological and anatomopatological data. So, there is not a measure of validity and reliability of these methods. On the other hand, female subjects are extremely underrepresented in these studies: only around 20% of the individuals studied were females and only 50% of the ADHD samples included female subjects, whereas 95% included males. The number of reports done in ADHD adults is very scarce. Discussion Despite the multiple inconsistencies found in each MRI study as a consequence of limitations such as small samples size, and methodological differences across the studies such as lack of consistency in the acquisition and the image analysis, the structures more frequently and consistently reported to be smaller in ADHD subjects, compared to healthy subjects, are regions of the frontal lobe, the callosum splenium, the anterior cingulate gyrus, the vermis, the cerebral hemispheres and the right caudate. However, these findings are applicable to the most frequently studied samples: male children. Considering the prevalence and lack of complete remission of ADHD symptoms during adulthood, there is a need for structural studies in adults as well as in women. Conclusion The findings and results of MRI studies represent clear but insufficient advances in the knowledge of the anatomical structures involved in ADHD. There is a lack of research on the age-related changes imposed by neurodevelopment. The brain abnormalities and their gender differences in ADHD individual are subjects of future research.

Palavras-chave : ADHD; neurobiology; cerebral morphology.

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