The neurodevelopment hypothesis in schizophrenia is a theoretic construction that tries to explain, at least partially, the etiopatho-geny of this disease. Since Kraepelin's early descriptions it has been suggested that schizophrenia is a disease linked to the Central Nervous System structure, and vast efforts have been made to prove the existence of the biological markers of schizophrenia that include clinically distinguishable features (like dermatoglyphs and neuropsychological tests), electrophysiological, endocrine, immunologic and genetic tests, and neuroimaging studies. The Minor Physical Anomalies (MPAs) are slight anatomical deviations of an individual's external physical features, which imply neither a serious medical consequence nor an aesthetic problem. MPAs could be considered a valid biological marker in the evaluation of schizophrenia if we interpret this disease as a disorder originating in the early months of intrauterine life during the first stages of neurodevelopment. Like dermatoglyphs, the MPAs may be seen as "fossil" signs that reflect the intrauterine environment. They could be useful as an indirect measurement of an alteration of structures related to the Central Nervous System in its embryologic origin, or in nervous structures and non-neuronal epidermic and other superficial tissues derived from ectoderm, especially in skin, eyes and ears, or else with those that belong to embrionary developmental fields adjacent to brain structures, that may induce cranial-facial alterations. This developmental fields theory explains the existence of a relationship between tissues or structures that do not have a common embryologic origin. After embryogenesis, they determine topographic zones of development, and the presence of a defect could affect a single structure (monotopic defect), but those that appear earlier would promote several areas in the body (polytopic field defects). Due to these complex interactions, it is not easy to correlate the intensity of the damage with the moment in which this occurred. A minor malformation could even have been generated in blastogenesis and could therefore be related to associated defects. It is not always a 'benign' abnormality. This observation is important if we consider that several genetic syndromes exist that present specific malformations. These are strongly associated with a high risk to develop schizophrenia (around 25 fold), such as the 22qll.2 deletion (velocardiofacial syndrome, DiGeorge syndrome and other variations). There has been speculation around a so-called "congenital" schizophrenia subtype on the basis of an association with several clinical features such as gender, age of onset, positive or negative symptoms, brainabnormalities that show up in MRI scans, additional cognitive impairment and a worse evolution and prognosis in which the neurodevelopmental disturbances factor would have a widespread significance in the etiopathogeny of the disease. The Waldrop's Scale for Minor Physical Anomalies has been the most used tool to measure these abnormalities and has been subject to numerous modifications. Even though it is considered a reliable instrument, with a good internal consistence, numerous limitations in results interpretation have been noted, most of them derived of limited inter-evaluator reliability, lack of consensus about the relative importance of each item and the extensive interracial variability in the presentation of MPAs. In the 1980's, the neurodevelopmental theory emerged as an explanation of the origin of schizophrenia and a number of investigations have been carried out, to measure MPAs and other biologic markers of neurodevelopment (like dermatoglyphs). Most studies have shown a greater prevalence of MPAs in schizophrenic patients compared to control groups, as it has been observed in other disorders like mental retardation, autism, attention-deficit disorder and violent behavior in adolescence. Nevertheless, there are only a few consistent data sets that correlate with an increased number of MPAs, and amongst them we can point out a positive correlation with malegender, neuroimagingbrain alterations, genetic charge for schizophrenia, more frequent obstetric complications and a more perceptible cognitive impairment. Additionally, other investigations draw attention to a positive correlation with a lower premorbid adjustment, an earlier beginning of the disease, a predominance of negative symptoms and a larger tendency to develop late dyskinesia, although these data show contradictory results. Even though the diverse ethnic groups' phenotypic variants tend to limit the interpretation of each minor physical anomaly, most investigations have found a prevalence of these abnormalities in the cranial-facial area, most of them in ears and mouth, although the peripheral zones are not unaffected. When we consider those studies, we notice that the diversity of data is predominant. We can explain this if we bear in mind that some of the MPAs can be normal phenotypic features in some ethnic groups, or frequent enough to be a normal variant without discriminative meaning. We must also take into account that different scales have been used for the measurements. For this specific problem it has been suggested to use anthropometric scales, similar to those used by cranial-facial surgeons. The variability of the presentation of MPAs and the phenotypic variations compel us to conduct local investigations focused on determining which variants are outstanding or not in any ethnic group in relation to neurodevelopment deviations. We can conclude than MPAs might be a biological marker that can help us to characterize at least a subgroup of clinically recognizable schizophrenic patients, or those that have predisposition to present some clinical features, but it is necessary to develop an objective evaluation tool that ideally would incorporate anthropometric measurements in order to compare these MPAs with the phenotypic variants in each ethnic group. It is necessary to design and carry out genetic studies (first among first and second-degree relatives and afterwards in bigger populations and also comparative studies with the general population) with the aim to distinguish between genetically-determined variants and those resulting from environmental factors, as well as establishing the interaction of both types of variants. The existence of a clinically recognizable subtype of schizophrenia on which we can rely on as an etiopathogeny hypothesis is an appreciable area that is still under discussion and which deserves further investigation efforts. This could have implications on our approach to nosologic, diagnostic and even prognostic features of this heterogeneous disorder. Such investigation could help us to reformulate the schizophrenia notion itself.
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