Histogenetic Causes of Mental Retardation: Current State and Future Implications 1,2

Pathogenetically, mental retardation (MR) may be classified into three basic forms, including MR with grossly evident developmental abnormalities of the CNS, MR with encephaloclastic, sclerotic and atrophic change of central nervous tissue, and MR without evident alterations of the CNS at the routine microscopic level [“poor morphology MR (PMMR)”]. The complicated polyetiologic situation of MR will be summarized in a multigraph in order to provide a synopsis of the manifold interrelations and of the general factors involved in the origin and pathogenesis of MR. PMMR is said to comprise about 40% of the observations of MR. However, with special techniques, such as selected silver impregnations, immunocytochemistry, electron microscopy, autoradiography, and others, morphologic correlates may also be demonstrated in PMMR at the fine structural level. Of great importance in this respect are not only factors interfering with intrauterine development, but also mechanisms acting upon postnatal differentiation in the most critical period of brain plasticity. This fact should deserve more attention in future morphologic research into the fine structural and molecular correlates of MR. The same is true for CNS myelination which has only infrequently been considered in former investigations into MR. Further, not only the quality and quantity of changes in the CNS should be regarded, but also their topographic distribution in MR. The reticular formation and the hippocampus (limbic system) will be emphasized as sites of major importance in this respect. Future implications for research into morphologic correlates of PMMR will be discussed. Special emphasis will be put on the importance to take more advance of the results of basic neurobiologic research into the molecular bases of learning and behavior as a guideline for future research into PMMR.