Anomalías físicas menores y esquizofrenia

• Autores: Francisco Caballero, Ana Fresán Orellana, Juan Jorge Palacios, M. Soledad Rodríguez Verdugo
• Localización: Salud mental, ISSN 0185-3325, Vol. 30, Nº. 5, 2007, págs. 12-19
• Idioma: español
• Enlaces
  • Texto completo (pdf)
• Resumen
  • español

    La hipótesis del papel que desempeña el neurodesarrollo en la génesis de la esquizofrenia es un constructo teórico que intenta explicar, al menos en parte, la etiopatogenia de esta entidad. Desde sus primeras descripciones se ha sugerido la idea de que la esquizofrenia es una enfermedad relacionada con la estructura del Sistema Nervioso y desde entonces hasta la fecha se ha intentado demostrar la existencia de marcadores biológicos.

    Las anomalías físicas menores (AFM) son ligeras desviaciones de algunas de las características físicas externas de los individuos, que no representan una consecuencia médica seria ni un conflicto estético. Si se entiende a la esquizofrenia como una enfermedad que tiene su origen en una alteración del neurodesarrollo en los primeros meses de vida intrauterina, las AFM pueden ser consideradas como un marcador biológico válido en su evaluación, y al igual que los dermatoglifos, ser vistos como indicios "fósiles" que reflejarían el ambiente in utero. Podrían servir como una medida indirecta de la existencia de una alteración de las estructuras que se relacionan en su origen embriológico con el Sistema Nervioso Central, o bien con aquellas que pertenecen a campos de desarrollo embrionario adyacentes a las estructuras cerebrales.

    Se ha especulado acerca de la existencia de un subtipo de esquizofrenia llamado «congénita» y que estaría asociado con una serie de características clínicas en las que el factor de las alteraciones del neurodesarrollo tendría una importancia prevalente dentro de la etiopatogenia de la enfermedad.

    El instrumento más utilizado para la medición de estas anomalías es la escala de Waldrop, a la que se le han hecho múltiples modificaciones. Aunque se considera confiable y con buena consistencia interna, hay muchas limitaciones en la interpretación de los resultados. En los estudios clínicos realizados se ha encontrado una mayor prevalencia de AFM en pacientes con esquizofrenia comparados con grupos de control. Estas alteraciones se observan igualmente en pacientes con otros trastornos como retraso mental, autismo, déficit de atención y conducta violenta en la adolescencia, por lo que no se considera que haya una especificidad para la esquizofrenia. Sin embargo, entre los pocos datos sólidos obtenidos que se correlacionan con un mayor número de AFM están: correlación positiva con el sexo masculino, alteraciones cerebrales en neuroimagen, carga genética para esquizofrenia, mayor frecuencia de complicaciones obstétricas y deterioro cognitivo más notable. Otros estudios informan sobre una correlación positiva con un bajo ajuste premórbido, un inicio más temprano, predominio de síntomas negativos y mayor tendencia para desarrollar discinesia tardía, pero estos datos han tenido resultados que parecen ser contradictorios. Aunque las variantes fenotípicas de los diversos grupos étnicos limitan la interpretación de la presencia de una u otra anomalía física menor, la mayoría han encontrado un predominio de éstas en el área cráneo facial, principalmente en orejas y boca.

    Se puede concluir que las AFM pueden ser un marcador biológico de rasgo que nos ayude a caracterizar al menos a un subgrupo de pacientes con esquizofrenia o que tienen predisposición a presentar ciertas características clínicas relacionadas, pero se precisa desarrollar un instrumento de medición que incluya medidas antropométricas objetivas para poder compararlas con las variantes fenotípicas de cada grupo étnico, además de realizar estudios de genética para tratar de determinar cuáles de esas variantes son determinadas genéticamente y cuales se han visto influidas por un factor ambiental o por la interacción de estos dos factores. La existencia de un tipo de esquizofrenia clínicamente reconocible y para el que se cuenta con una hipótesis etiopatogénica es un asunto aún en discusión que amerita mayores esfuerzos en su investigación y que nos puede ayudar eventualmente a replantear el concepto mismo de esquizofrenia.

  • English

    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, brain abnormalities 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 male gender, neuroimaging brain 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.