Mental retardation serotonin

Two transmitters have been the subject of most studies in mental retardation serotonin and dopamine and this section focuses on abnormalities in the function of these transmitters, and effects of serotonin- and dopamine-altering drugs. 

Vinar O, Klein DE, Potter WZ, et al A survey of psychotropic medications not available in the United States. Neuropsychopharmacology 5 201-217, 1991 Vitiello B, Spreat S, Behar D Obsessive-compulsive disorder in mentally retarded patients. J Nerv Ment Dis 177 232-236, 1989 Vitiello B, Shimon H, Behar D, et al Platelet imipramine binding and serotonin uptake in OCD patients. Acta Psychiatr Scand 84 29-32, 1991 Vizi ES, Harsing LG, Zsilla G Evidence of the modulatory role of serotonin in acetylcholine release from striatal interneurones. Brain Res 212 89-99, 1981 Vogel GW A review of REM sleep deprivation. Arch Gen Psychiatry 32 749-761, 1975... 

McBride PA, Anderson GM, Hertzig ME, Snow ME, Thompson SM, Khait VD, Shapiro T, Cohen DJ (1998) Effects of diagnosis, race, and puberty on platelet serotonin levels in autism and mental retardation. J Am Acad Child Adolesc Psychiatry 37 767-776... 

Desipramine is a tricyclic antidepressant, inhibits reuptake of norepinephrine and serotonin in CNS, and is indicated in relief of symptoms of depression. Desipramine (75 to 150 mg p.o./day in divided doses) is indicated in endogenous depression major depression with melancholia or psychotic symptoms depression associated with organic brain disease, alcoholism, schizophrenia, or mental retardation and the depressive phase of manic-depressive disorder. Desipramine is absorbed rapidly from the GI tract, distributed widely in the body, and appears also in breast miUc. It is bound to plasma proteins to the extent of 90%, undergoes extensive first-pass metabolism, and its metabolites are excreted in urine. Desipramine strongly blocks the norepinephrine uptake mechanism and has no effect on the uptake of serotonin. Desipramine has weak alpha -adrenergic and... 

Elevated levels of phenylalanine have been shown to inhibit transport of other amino acids besides tyrosine. This might result in an imbalance of amino acids in the brain that could disrupt protein synthesis or control of the synthesis of neurotransmitters. Several enzymes, including tyrosine hydroxylase, tryptophan, and pyruvate kinase, are inhibited in vitro by phenylalanine. Irrespective of such phenomena in a patient who died with PKU, catecholamine concentration and serotonin levels were much lower than those in control brains from patients suffering mental retardation from other causes, a finding consistent with such a possible role in vivo (Ikeda et al., 1967). 

It is often assumed that the accumulation of the amino acid or its derivatives interferes with important metabolic acitivites in the nervous system. At least four different theories have been proposed. The first postulates that phenylalanine metabolism directly affects the molecular system responsible for the maintenance of normal mental performance. However, one should not eliminate the possibility of an indirect effect by which the phenylalanine metabolites interfere with biochemical conversions in other pathways, thereby causing mental deficiency. An example of such an indirect mechanism is the chain reaction that links the distortion of phenylalanine metabolism to that of indole metabolism. Low serotonin levels in phenylke-tonurics could also cause mental retardation, but there is no correlation between serotonin levels and severity of mental retardation. Moreover, the role of serotonin in mental functions is not known. 

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