Risk factors of deficit and non-deficit schizophrenia: Results from a cross-sectional study / Factores de riesgo para la esquizofrenia deficitaria y no deficitaria: resultados de un estudio transversal

Aim: It has been observed that deficit and non-deficit schizophrenia (SCZ-D and SCZ-ND) might be characterized by different risk factors. Therefore, the present study aimed to assess as to whether previously reported risk factors of schizophrenia are specifically associated with SCZ-D and SCZ-ND. Method: This study was based on a cohort of 118 stable outpatients with schizophrenia. A diagnosis of SCZ-D was established using the Schedule for the Deficit Syndrome (SDS). Risk factors were recorded using structured interview, the Operational Criteria for Psychotic Illness (OPCRIT) checklist and the Traumatic Experience Checklist (TEC). The following risk factors were explored: male sex, a history of schizophrenia in first-degree relatives, seasonality of birth, birth weight <3000g, delivery by cesarean section, a history of childhood trauma (emotional abuse, emotional neglect, physical abuse and sexual abuse) as well as substance abuse (other than nicotine) and cigarette smoking at psychosis onset. Results: Individuals with SCZ-D were more likely to be males as well as reported higher rates of birth weight <3000g and any categories of childhood trauma. In turn, substance abuse (other than nicotine) at psychosis onset was significantly more frequent in patients with SCZ-ND. Binary logistic regression, controlling for multiple comparisons, revealed similar findings, except for the association with any categories of childhood trauma that appeared to be not significant. Conclusion: Our findings partially replicate differential patterns of risk factors for SCZ-D (male sex and birth weight <3000g) and SCZ-ND (substance abuse at psychosis onset), likely attributable to the effects of timing of exposure. (AU)

Objetivo: Se ha observado que la esquizofrenia deficitaria y no deficitaria (ES-D y ES-ND) pueden caracterizarse por diferentes factores de riesgo. El presente estudio tuvo como objetivo evaluar si los factores de riesgo de esquizofrenia previamente informados están específicamente asociados con ES-D y ES-ND. Método: Este estudio se basó en una cohorte de 118 pacientes ambulatorios. Se estableció el diagnóstico de ES-D mediante el Inventario para la Esquizofrenia Deficitaria. Los factores de riesgo se registraron mediante entrevista estructurada, la lista de verificación de Criterios Operativos para Enfermedades Psicóticas y la Lista de Verificación de Experiencia Traumática. Se exploraron los siguientes factores de riesgo: sexo masculino, antecedentes de esquizofrenia en familiares de primer grado, estacionalidad del nacimiento, peso al nacer <3.000g, parto por cesárea, antecedentes de trauma infantil, así como el abuso de sustancias (aparte de la nicotina) y el tabaquismo al inicio de la psicosis. Resultados: Las personas con ES-D tenían más probabilidades de ser varones y también informaron de tasas más altas de peso al nacer <3.000g y cualquier categoría de trauma infantil. A su vez, el abuso de sustancias (diferentes a la nicotina) al inicio de la psicosis fue significativamente más frecuente en pacientes con ES-ND. La regresión logística binaria, controlando comparaciones múltiples, reveló hallazgos similares, excepto por la asociación con cualquier categoría de trauma infantil que pareció no ser significativa. Conclusión: Nuestros resultados replican parcialmente los patrones diferenciales de los factores de riesgo para ES-D (sexo masculino y peso al nacer <3.000g) y ES-ND (abuso de sustancias al inicio de la psicosis), probablemente atribuibles a los efectos del momento de la exposición. (AU)

A novel p.E311K mutation of thyroid receptor beta gene in resistance to thyroid hormone syndrome, inherited in autosomal recessive trait.

Resistance to thyroid hormone (RTH) syndrome is caused by mutations in THRB gene and is inherited mainly as an autosomal dominant trait with dominant negative effect. Most of up-to-now described RTH cases were heterozygous. We studied a 19-year-old woman presenting severe mental impairment, hyperkinetic behavior, learning disability, hearing loss, tachycardia, goiter, strabismus, nystagmus, and normal stature. The laboratory findings revealed elevated TSH, T3, and T4 serum levels. Her parents were healthy with normal serum level of TSH, fT3, and fT4. Sequence based prediction of a substitution was analyzed by SDM, PolPhen, and SNAP software whereas structural visualizations were performed in UCSF Chimera. We found a novel mutation in THRB gene in position 1216 (G to A transition, codon 311) resulting in novel Glu-311-Lys (p.E311K) substitution, homozygous in proband presenting with severe symptoms of RTH and heterozygous in both of her healthy parents, thus suggesting autosomal recessive mode of inheritance. p.E311K substitution was not found in 50 healthy, unrelated individuals. p.E311K was shown to be deleterious by SDM, PolPhen, and SNAP software. Structural visualizations of mutated protein performed by UCSF Chimera software disclosed a loss of hydrogen bonds between E311, R383, and R429 along with abnormal residue-residue contact between K311 and L377. This is a very rare case of a homozygous mutation in a patient with severe symptoms of RTH and lack of symptoms in both heterozygous parents. Although, computational analyses have provided the evidence that p.E311K substitution may affect THRB function, lack of dominant negative effect typical for THRB mutations could not be explained by structure-based modeling. Further in vitro analysis is required to assess the functional consequences of this substitution.