Serotonergic abnormalities

In order to determine whether there are brain serotonergic abnormalities in children with autism, serotonin synthesis capacity was measured in vivo with PET, using alpha[ C]methyl-L-tryptophan as the tracer. Two different types of serotonergic abnormalities were measured in children with autism (Chugani et al., 1997, 1999 Chandana et al., 2005). The first is a difference in whole brain serotonin... 

The role of serotonin (5-hydroxytryptamine, 5-HT) has also been extensively studied in depressed patients. Whereas the overall psycho-physiological effects of noradrenaline in the CNS appear to be linked to drive and motivation, 5-HT is primarily involved in the expression of mood. It is not surprising therefore to find that the serotonergic system is abnormal in depression. This is indicated by a reduction in the main 5-HT metabolite, 5-hydroxy indole acetic acid (5-HIAA), in the cerebrospinal fluid of severely depressed patients and a reduction in 5-HT and 5-HIAA in the limbic regions of the brain of suicide victims. The 5-HT receptor function also appears to be abnormal in depression. This is indicated by an increase in the density of cortical 5-HT2a receptors in the brains of suicide victims and also on the platelet membrane of depressed patients. Platelets may be considered as accessible models of the nerve terminal. 

Thus when the results of the studies on platelets, lymphocytes, changes in cerebrospinal fluid metabolites of brain monoamines and the post-mortem studies are taken into account it may be concluded that a major abnormality in both noradrenergic and serotonergic function occurs in depression, and that such changes could be causally related to the disease process. 

The causes and mechanisms of chronic pain syndromes are diverse (Lance 8c McLeod, 1981). A similarity with depression has been noted by several authors and it has been suggested that chronic pain syndromes might result from reduced activity in serotonergic systems involved in pain suppression and mood control (Moldofsky, 1982). Other authors have suggested that a causative factor in chronic pain syndromes might be abnormally low concentrations or activity of endogenous opioids, particularly beta-endorphin (Lip-man et al., 1990). 

The nature of the neurochemical impairment underlying depressive illness remains elusive. There is a great deal of evidence supporting roles for the 5-HT system and the HPA axis. However the evidence is less clear that an abnormality in one system alone can explain the full extent of the clinical features of depressive illness. Subtle abnormalities in the interactions between the HPA axis and the serotonergic system may lead to profound alterations in the functioning of both systems, and it may be this that results in the range of symptoms found in mood disorders. 

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