Evidence For Monoamine Contributions To Adhdne And 5ht Activity

9.1. Evidence From Group Comparisons

Does the metabolism of NE and 5-HT differ between children with ADHD and those without a psychiatric or medical diagnosis? The question is based on the following assumptions:

1. Pathological-developmental factors affecting transmitters in the body will affect peripheral and central metabolism similarly.

2. Transmitter metabolism underlies the expression of the behavioral and cognitive measures typical of ADHD.

To a degree both assumptions are equivocal. The main limit to interpretation of the answer (apart from the caveat over the sample's source) lies with the knowledge that there are many other factors involved in the efficient coupling of nervous activity to the appropriate postsy-naptic response that have not been studied, and may not necessarily influence the metabolic parameters as currently measured.

Analyses of CSF, blood compartments, and urine (Table 1) indicate that in the ADHD condition MHPG levels (NE metabolite) are usually lower than normal; less clearly, NE levels may be increased. Overall this suggests a decreased turnover. There is a hint that other catabolic pathways may be differentially affected (NMN levels). The severity of the core symptoms do not influence the results (161,162). But, over the 4-5 yr from pre- to post-puberty when a number of symptoms regress, MHPG levels have been noted to increase or normalize (163). Further, some studies that deliberately contrasted subgroups find that several comorbidities (independent of their nature) appear to counteract the metabolic decrease: e.g., in those with a reading disorder (159), and in 15 subjects with high levels of anxiety (not in table; 103).

The results for the 5-HT system are more limited, reflecting in part the methodological issues (see Section 7). However, if one brings the separate findings together, there is an indication of an increase of 5-HT turnover, largely reflecting decreases in 5-HT levels (Table 1). Nonetheless, as with NE, it must be recognized that there will be subgroups, however defined, for which the effects associated with the core symptoms will be masked by other features. One such example is shown by the contrast between ADHD boys brought up in families with or without alcoholic fathers (164). Those with this experience showed a larger cortisol response to a challenge dose of fenfluramine than those without an alcoholic father. This was interpreted as reflecting increased 5-HT receptor sensitivity.

Another example of the influences of comorbidity on 5-HT activity concerns impulsiv-ity. Impulsive aggression (oppositional behaviors; 30,165) has been associated with low plasma and CSF 5-HIAA and synaptic availability of 5-HT. This contrasts with the generalization noted in the preceding paragraph. Intriguingly, Oades et al. (36) compared the binding characteristics of the platelet 5-HT T with clinical ratings (impulsivity/distractibil-ity, externalizing/ aggression) and the (in)ability to withhold responses on the stop-signal task (cognitive impulsivity). Decreased affinity correlated with poor response inhibition (cognitive impulsiveness) but not clinical ratings, even though the cognitive and clinical indices of impulsivity were related. In contrast, aggressive behavior related to increased 5-HT T affinity (see Subheading 6.2.: genetic control of 5-HT availability by the transporter [HTTLPR]).*

Cognitive impulsivity might be expected to reveal itself on the CPT test of sustained attention in the form of an increased rate of false alarms. However, as yet, both high (blood; 166) and low levels of 5-HT (tryptophan depletion; 167) have been related to more errors of commission. But d' reflecting target sensitivity, was reported to decrease as the excretion of the 5-HT metabolite increased (160), which supports interpretations of the aforementioned platelet study.

'Reductions of binding site affinity should normally be offset by increased receptor capacity. If this does not occur then more 5-HT remains available in the synapse.

Comparisons of Components of NE and 5-HT Metabolism in Urine, Blood, and CSF Samples From ADHD and Controls.






Change vs controls



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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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