Resumen:

Las nuevas tecnologías de imaginología cerebral han contribuido con información reciente sobre las anomalías en pacientes con diversos trastornos psiquiátricos. Ejemplos de estas tecnologías son la resonancia magnética (RM), la tomografía por emisión de positrones (PET), la tomografía por emisión de fotón único (SPECT) y la resonancia magnética funcional (RMf), entre otras. Enfermedades tales como trastornos por ansiedad, depresión, demencias, trastorno obsesivo compulsivo, esquizofrenia, enfermedad bipolar, trastornos del aprendizaje y trastorno por déficit de la atención con hiperactividad (TDAH), actualmente se conceptualizan como enfermedades que implican una interacción entre las anormalías en el funcionamiento cerebral y/o en la estructura neuroanatómica y las influencias ambientales.

Los estudios genéticos apoyan la hipótesis de que el TDAH tiene una base biológica, y la aplicación de las nuevas técnicas de imagenología cerebral ha permitido la identificación de los sustratos neuroanatómicos de esta patología. Inicialmente se propuso que existía una alteración en el funcionamiento de algunas estructuras entre las que se cuentan los circuitos frontales y límbicos de los pacientes con TDAH, la que se denominó "hipótesis fronto-límbica del TDAH". No obstante, los estudios realizados desde el punto de vista de diferentes disciplinas, tales como la neuropsicología, la neuroimagen y los estudios neuroquímicos, sugieren que aunque la "hipótesis fronto-límbica del TDAH" sea la correcta, la neurobiología de este padecimiento es aún más compleja. Dada la complejidad de los circuitos prefrontales, aún no ha quedado claro sí las anomalías prefrontales del TDAH se deben a "lesiones" en la neocorteza prefrontal y/o en las estructuras subcorticales (por ejemplo, el cuerpo estriado, el tálamo, y los núcleos subtalámicos) que están interconectadas con esta. Por esta razón, es más apropiado referirnos a la alteración funcional del TDAH como a una alteración de las estructuras "fronto-subcorticales".

Las técnicas de imagenología cerebral permiten hacer evaluaciones directas de la estructura y de la función cerebral, por lo que son ideales para poner a prueba las hipótesis acerca de la localización de las anomalías cerebrales del TDHA. Sin embargo, dado que éstas técnicas de neuroimagen son caras e invasivas, se aplican comúnmente a muestras pequeñas de pacientes y de controles sanos, lo cual produce dudas acerca de la validez externa y del poder estadístico de los estudios que utilizan estas técnicas. Los primeros estudios realizados en sujetos con TDAH utilizaron la tomografía axial computarizada (TAC) pero desafortunadamente problemas metodológicos tales como la pobre resolución espacial de la TAC, la falta de mediciones cuantitativas y las muestras pequeñas de sujetos inadecuadamente diagnosticados, hicieron que los resultados de esos estudios no fueran congruentes. Los hallazgos de dichos estudios oscilan desde ninguna anomalía hasta atrofia frontal y cerebelosa en pacientes con TDAH. Con el advenimiento de la RM que permite una evaluación anatómica detallada y precisa, ésta se convirtió en la técnica de elección utilizada en poblaciones pediátricas.

La utilización de criterios diagnósticos válidos y confiables así como la inclusión de grupos controles, mejoró las deficiencias metodológicas observadas en los estudios realizados con TAC.

Los estudios anatómicos con RM en poblaciones de sujetos con TDAH, han demostrado disminución del tamaño del cuerpo calloso, del globo pálido izquierdo, y del cerebelo, así como de la corteza frontal derecha y del volumen cerebral total, comparados con los controles sanos.

Las técnicas de imagenología funcional, que incluyen PET, SPECT y la RM, en general apoyan la hipótesis del mal funcionamiento de los circuitos neurales entre los lóbulos frontales, el cuerpo estriado y el cerebelo, en el mecanismo fisiopatológico del TDAH.

Los estudios con SPECT han demostrado la presencia de hipoperfusión de la corteza frontal, del núcleo caudado e hiperperfusión en las cortezas occipitales, auditivas primarias y sensoriales izquierdas en los sujetos con TDAH. Con la utilización de PET en adultos con TDAH, se visualiza una disminución del metabolismo en la corteza frontal. La RM con pruebas de activación cerebral, indica que los circuitos frontoestriatales funcionan de manera diferente en los sujetos con TDAH en comparación con los sujetos normales.

Palabras clave: TDAH; alteraciones anatómicas y funcionales

Abstract:

The most recent technologies of cerebral imaging provide new data about cerebral abnormalities in patients with diverse psychiatric disorders.

These methods include computed tomography (CT), magnetic resonance (MRI), electro magnetic (EMEKG), functional magnetic resonance (MRIf), positron emission tomography (PET), single photon emission computed tomography (SPECT), quantitative electroencephalography (QEEG), and evoked potentials (Eps), among others.

Illnesses such as anxiety disorders, depressive disorders, dementing disorders, obsessive compulsive disorder, schizophrenia, bipolar disorder, learning disorders, and attention-deficit/ hyperactivity disorder (ADHD), are now considered the result of an interaction between environmental factors and abnormal function and structure of the brain.

Data obtained from studies in ADHD subjects indicate a biological basis for this disorder. The specific anatomical and functional alterations of the brain in these patients, has been possible thanks to neuro-imaging.

Satterfield & Dawson, in 1971, were pioneers proposing that the ADHD symptoms were related to a malfunction of the fronto-limbic circuits. They said that the normal fronto- cortical inhibitory control exerted over the limbic system is weak in patients with ADHD. This hypothesis was known as the "fronto limbic hypothesis of ADHD"; although, the results of the research derived from diverse disciplines such as neuropsychology, neuro-imaging, and neuro biochemistry, suggest that Satterfield & Dawson were partially right, in fact the neurobiology of ADHD would be more complex than they originally supposed.

Almost every research done with neuropsychological methods in ADHD patients points to the same results: a malfunction in the frontal cortex.

Damage in the orbital area of the human frontal cortex produ ces social disinhibition and impulsivity; also injury to dorsolateral prefrontal cortex (DLPFC), causes deficit in the ability of behavioral organization, planning, working memory and attention. The findings of neuropsychological research point toward dysfunction to the orbito frontal cortex and DLPFC in subjects with ADHD.

With the advance of the new neuroimaging techniques, the results delivered from the clinical and neuropsychological observations can be validated; when used in combination they can give us detailed information about the anatomic areas involved.

The early structural studies made in subjects with ADHD were done using CT. Unfortunately the poor resolution and the lack of quantitative measurement of the CT, besides of the small sample size of subjects using diverse methods of clinical diagnosis, and the difficulty to find healthy controls; made the results of these early studies with CT inconsistent.

The results reported by different authors were contradictory, since some of them reported no abnormality at all in subjects with ADHD, and some others found frontal and cerebellar atrophy in patients with ADHD.

The studies made with MRI improved the quality of the structural studies done in subjects with ADHD. At the same time, the improvement of the diagnostic tools in regard to validity and reliability, and the inclusion of adequate control groups; made the results obtained from these new studies to overcome the deficits of the studies that were made with CT.

The studies made with MRI found a decrease in the size of corpus callosum, basal ganglia, particularly in left globus pallidus, and cerebellum; and atrophy of the right frontal cortex and a change in the total cerebral volume.

On the other hand the studies made with techniques such as PET, SPECT and functional magnetic resonance, have found a decrease in cerebral blood flow (CBF) in the frontal lobes, striatum and cerebellum in subjects with ADHD.

The studies with SPECT made by several groups of researchers have shown increase of the CBF frontal cortex and the caudate nucleus, and decrease of the CBF of the occipital cortex; however, almost all these studies included small sample sizes and used inadequate control groups.

Other studies made with PET in adults with ADHD have shown a decrease of the metabolism of the frontal cortex; however, different groups of researchers have reported different findings, possibly due to methodological variations across the studies. Again the majority of these studies used small sample sizes.

The studies made with MRIf show that the fronto-stratial circuits work differently in subjects with ADHD when they are compared with controls. Again almost all the published studies included a small sample size.

In particular, the results from the studies done by Bush C. et al in 1999 using MRIf combined with a neuropsychological test named "Counting Stroop", showed a lack of activation of the anterior cingulate gyrus in subjects with ADHD compared with controls.

The PET technology can study the brain chemistry invivo. Some researchers have found a decrease ofdopamine reuptake in the prefrontal and medial cortex and an increase in the mesencephalon in patients with ADHD. Some studies have found an increase of the dopamine transporter density in the striatum in subjects with ADHD.

In conclusion: the neuropsychological studies and the studies of neuroimaging, suggest that the fronto-stratial circuit in the right side plus the cerebellar influence are involved in the neurobiology of ADHD. The cortex-striatum-thalamic circuit selects, starts and executes cognitive and motor complex responses, and the cerebellar circuits provide the guide for these functions.

The hypothetical implications of the data contributed by the findings with neuroimaging techniques in ADAH are at this time only tentative. Reproduction of this data for independent researchers is needed. Besides, it is necessary to perform more detailed subdivisions of the brain areas implicated in ADHD.

The low statistical power due to the cohort small size included in almost all of these studies is an important problem because of the high anatomical variability of brain measurements.

Besides just a few of the published studies controlled the previous exposure to medications for ADHD. Finally, there are no studies in other circuits that play a role in the attention such as those formed by the thalamic pulvinar, the parietal inferior cortex, the primary sensory area, and the postero-inferior parietal cortex.

However, the research using methods of structural and functional imaging surely will be valuable in the future, in order to improve our understanding of the anatomical and functional physiopathology ofADHD and ofthe other psychiatric disorders.

Keywords: ADHD; anatomic and functional alterations