Methods

Invasive methods for measuring transmitter activity in the CNS in vivo are available in animals (e.g., dialysis probes, electrochemistry) and adult humans (e.g., position emission tomography studies of ligand binding) but are not justified from an ethical standpoint in children. Measures must be conducted peripherally. There are three possible points of access along the route of elimination of excess monoamines and their metabolic products. These are the CSF, blood (including plasma and platelets), and urine. Opinions differ widely on the extent to which these peripheral measures can reflect CNS function. Somatic sources of 5-HT are particularly high. As there is no reason to suspect that in otherwise somatically healthy ADHD children central systems are differentially impaired with respect to peripheral systems, crude indicators may be sought in the comparison of baseline measures between groups. The effects of challenges with monoaminergic drugs or environmental conditions on biochemical measures represent a good method for testing the functionality of NE and 5-HT pathways.

The extracerebral release of transmitters does not interfere with CNS transmission, as there is a blood-brain barrier with a powerful pump that transports them from brain to blood. What can cross the blood-brain barrier out of the brain and influence concentrations measured peripherally? Basically all the monoamines can pass with varying degrees of ease passively or actively out of CNS tissue (review, ref. 101), although as acid metabolites do not equilibrate across the blood-brain membranes, they are sensitive to active transport mechanisms (101). These mechanisms of active clearance may contribute to differences reported between blood or plasma and CSF measures. (Regions where the blood-brain barrier does not so function include the circumventricular and subfornical organs, the choroid plexus, and the area postrema of the medulla.) However, measures derived from venous blood and urine often reflect challenges to the system, at least at a qualitative level. Peripheral and central monoamine activities are often correlated: if the correlations are not good, they are still strong enough to be relevant to the study of behavior (103).

Some limits and influences on the study of monoamine activity from peripheral sources should also be recognized. In most cases changes in a peripheral catchment cannot not be attributed to over-or underactivity in any particular part of the CNS.* Further, it should not be overlooked that just as the processes of synthesis, release, and uptake of transmitters change with age, so do the characteristics of the blood-brain barrier (104). These are poorly

*Usually blood samples for plasma or platelet analyses are collected from the arm. However, a series of studies compared venoarterial gradients form the left/right jugular, hepatosplanchnic, forearm, and cardiac vessels and showed that it is possible to separate the contributions from various somatic organs, as well as cortical vs subcortical contributions (e.g., 101,107-109).

documented. The integrity of the blood-brain membranes may receive insult from illness and their properties may be influenced by drug treatment. For example, it has been suggested that neuroleptic treatment can increase permeability (105).

An alternative approach is with the use of models that represent the specific feature of interest rather than the whole system. Relevant choices here include selection of the platelet fraction from blood to examine receptor function: thus, the binding characteristics of platelet 5-HT transporters model precisely those of the central transporter (106). A rather different type of model involves study of a particular breed of animal whose CNS responsivity resembles in certain ways that of children with ADHD.

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Understanding And Treating ADHD

Understanding And Treating ADHD

Attention Deficit Disorder or ADD is a very complicated, and time and again misinterpreted, disorder. Its beginning is physiological, but it can have a multitude of consequences that come alongside with it. That apart, what is the differentiation between ADHD and ADD ADHD is the abbreviated form of Attention Deficit Hyperactive Disorder, its major indications being noticeable hyperactivity and impulsivity.

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