Spectrum of Clinical Signs and Genetic Characterization of Gelatinous Drop-Like Corneal Dystrophy in a Colombian Family.

PURPOSE: To describe the clinical signs of gelatinous drop-like corneal dystrophy (GDLD) in a consanguineous Colombian family and determine the underlying genetic cause. METHODS: We performed ocular examination of available family members and bidirectionally Sanger sequenced the GDLD-associated gene, TACSTD2. In one individual, the presence of subepithelial amyloid was confirmed with biopsy. RESULTS: The parents were consanguineous and 5 of their 10 children had GDLD. Typical mulberry subepithelial deposits with subepithelial vascularization were present in 3 individuals; 2 individuals only had mild polymorphic anterior stromal opacity. We identified a homozygous TACSTD2 missense mutation, c.551A>G, p.(Tyr184Cys), in the affected family members. Both parents were heterozygous for the mutation, and unaffected siblings were either heterozygous or homozygous wild-type for this allele. In the Colombian population, this mutation has a minor allele frequency of 0.53%. CONCLUSION: The clinical presentation of GDLD in this family was variable and does not solely support an age-dependent progression of the phenotype, suggesting that environmental or other genetic factors can modify phenotypic expression. The relatively high prevalence of this mutation in the Colombian population suggests that other individuals may have undiagnosed subclinical disease.

Subtipos neurocognitivos de esquizofrenia / Neurocognitive Subtypes of Schizophrenia

Objetivo. Identificar empíricamente subtipos neurocognitivos de esquizofrenia y establecer la asociación de estos con características clínicas. Métodos. Se aplicaron pruebas de atención sostenida, función ejecutiva, reconocimiento facial de emociones, memoria verbal y de trabajo a 253 sujetos con esquizofrenia. A partir de los resultados de estas pruebas se identificaron los subtipos mediante análisis de clases latentes. Posteriormente, se evaluó la asociación de cada subtipo con características clínicas. Resultados. Se identificaron cuatro subtipos: 1) déficit cognitivo global, 2) déficit de memoria y función ejecutiva, 3) déficit de memoria y reconocimiento de emociones y 4) sin déficit cognitivo. Al comparar con el subtipo sin déficit cognitivo, se observó que tanto el de déficit de memoria y función ejecutiva como el de déficit cognitivo global tenían mayor frecuencia individuos de sexo masculino, desempleados, con deterioro grave y adherentes al tratamiento. Sin embargo, en el subtipo con déficit cognitivo global la diferencia fue más alta y presentaron una frecuencia más baja de antecedentes de episodios depresivos (OR 0,39; IC95%: 0,16 a 0,97). El subtipo de déficit de memoria y reconocimiento emocional tenía más sujetos con deterioro grave (OR 5,52; IC95%: 1,89 a 16,14) y desempleo (OR 2,43; IC95%: 1,06 a 5,55), pero menos con antecedentes de episodios depresivos (OR 0,21; IC95%: 0,07 a 0,66). Conclusión. Los resultados muestran cuatro subtipos neurocognitivos de esquizofrenia con un posible espectro de severidad, asociándose en un extremo con mayor disfunción, y en el otro con mayor psicopatología afectiva y menor adherencia al tratamiento

Objective. To empirically identify schizophrenia neurocognitive subtypes and establish their association with clinical characteristics. Methods. Sustained attention, executive function, facial emotion recognition, verbal learning, and working memory tests were applied to 253 subjects with schizophrenia. We identified neurocognitive subtypes by a latent class analysis of the tests results. After, we made a search for the association of these subtypes with clinic characteristics. Results. We identified four neurocognitive subtypes: 1) 'Global cognitive deficit', 2) 'Memory and executive function deficit', 3) 'Memory and facial emotion recognition deficit,' and 4) 'Without cognitive deficit.' In comparison with the subtype 'without cognitive deficit,' we found that the 'memory and executive function deficit subtype' and the 'global cognitive deficit subtype' had a higher frequency of male, unemployed, severe impairment, and adherence to treatment participants. However, in the 'global cognitive deficit subtype' the differences were higher and there was also a lower frequency of past major depressive episodes (OR 0.39; 95%CI: 0.16 to 0.97). The 'memory and facial recognition deficit subtype' had a higher probability of severe impairment (OR 5.52; 95%CI: 1.89 to 16.14) and unemployed (OR 2.43; 95%CI: 1.06 to 5.55) participants, but also a lower probability of past depressive episodes (OR 0.21; 95%CI: 0.07 to 0.66). Conclusion. Our results suggest the existence of four neurocognitive subtypes in schizophrenia with a spectrum of dysfunction and severity. We found higher dysfunction in those with worse cognitive dysfunction, and higher affective psychopathology and less treatment adherence in those with less cognitive dysfunction

Neurocognitive subtypes of schizophrenia.

OBJECTIVE: To empirically identify schizophrenia neurocognitive subtypes and establish their association with clinical characteristics. METHODS: Sustained attention, executive function, facial emotion recognition, verbal learning, and working memory tests were applied to 253 subjects with schizophrenia. We identified neurocognitive subtypes by a latent class analysis of the tests results. After, we made a search for the association of these subtypes with clinic characteristics. RESULTS: We identified four neurocognitive subtypes: 1) “Global cognitive deficit”, 2) “Memory and executive function deficit”, 3) “Memory and facial emotion recognition deficit,” and 4) “Without cognitive deficit.” In comparison with the subtype “without cognitive deficit,” we found that the “memory and executive function deficit subtype” and the “global cognitive deficit subtype” had a higher frequency of male, unemployed, severe impairment, and adherence to treatment participants. However, in the “global cognitive deficit subtype” the differences were higher and there was also a lower frequency of past major depressive episodes (OR 0.39; 95%CI: 0.16 to 0.97). The “memory and facial recognition deficit subtype” had a higher probability of severe impairment (OR 5.52; 95%CI: 1.89 to 16.14) and unemployed (OR 2.43; 95%CI: 1.06 to 5.55) participants, but also a lower probability of past depressive episodes (OR 0.21; 95%CI: 0.07 to 0.66). CONCLUSION: Our results suggest the existence of four neurocognitive subtypes in schizophrenia with a spectrum of dysfunction and severity. We found higher dysfunction in those with worse cognitive dysfunction, and higher affective psychopathology and less treatment adherence in those with less cognitive dysfunction.

Verbal working memory in individuals with schizophrenia and their first degree relatives: relationship with negative and disorganized symptoms.

OBJECTIVE: To determine whether there are differences in verbal working memory amongst subjects with schizophrenia, their first degree relatives and controls, and to evaluate the influence of symptoms on these differences, as an initial step to assess whether this cognitive function is an endophenotype. METHODS: We examined 197 cases with schizophrenia, 197 first degree relatives and 200 controls through psychiatric interviews and the Letters and Numbers Sequencing test (LNS). Performance was compared among the three groups adjusting for age, sex and education level. Adjustment for "negative symptoms" and "disorganization" was performed afterwards. RESULTS: Subjects with schizophrenia showed lower performance in the LNS than their first degree relatives and the healthy controls; the effect sizes were 0.75 and 1.18 respectively. There was a small difference between relatives and controls (effect size =0.38). These differences were significant after adjustment for negative and disorganized symptoms, but the effect sizes became smaller: 0.26 for relatives vs. subjects with schizophrenia, 0.56 for controls vs. subjects with schizophrenia and 0.33 for relatives vs. controls. Among individuals with schizophrenia, performance in the LNS was not associated with disorder duration, disease onset age, antipsychotics, history of depressive episodes or substance use disorders. CONCLUSION: Results suggest verbal working memory may be considered as an endophenotype in schizophrenia.

Memoria de trabajo verbal en individuos con esquizofrenia y sus familiares de primer grado: Relación con los sintomas negativos y desorganizados / Verbal working memory in individuals with schizophrenia and their first degree relatives: relationship with negative and disorganized symptoms

Objetivo: Determinar si hay diferencias en la memoria de trabajo verbal entre sujetos con esquizofrenia, familiares de primer grado y controles, y evaluar la influencia que pueden tener en estas diferencias los síntomas del trastorno, como un paso para establecer si esta función cognitiva es un endofenotipo. Métodos: A 197 sujetos con esquizofrenia, 197 familiares de primer grado y 200 controles comunitarios, se les hizo evaluación psiquiátrica y se les aplicó la prueba sucesión de letras y números (SLN). Se comparó el desempeño de los tres grupos ajustando por edad, sexo y escolaridad, y luego se ajustó también por síntomas negativos y desorganizados. Resultados: Los sujetos con esquizofrenia mostraron un menor desempeño en la SLN con respecto a sus familiares de primer grado no-afectados y los controles, con tamaños de efecto de 0,75 y 1,18 respectivamente. Hubo una diferencia pequeña pero significativa entre familiares y controles (tamaño de efecto =0,38). Estas diferencias siguieron siendo significativas después de ajustar por síntomas negativos y desorganizados, pero los tamaños de efecto disminuyeron a: 0,26 para familiares vs sujetos con esquizofrenia, 0,56para controles vs sujetos con esquizofrenia y 0,33 para familiares vs controles. Entre los sujetos con esquizofrenia, el desempeño en la SLN no se asoció significativamente con duración del trastorno, edad de inicio, uso de antipsicóticos, ni historia de episodios depresivos o trastornos por uso de sustancias. Conclusión: Los resultados sugieren que la memoria de trabajo verbal puede ser considerada un endofenotipo de la esquizofrenia (AU)

Objective: To determine whether there are differences in verbal working memory amongst subjects with schizophrenia, their first degree relatives and controls, and to evaluate the influence of symptoms on these differences, as an initial step to assess whether this cognitive function is an endophenotype. Methods: We examined 197 cases with schizophrenia, 197 first degree relatives and 200 controls through psychiatric interviews and the Letters and Numbers Sequencing test (LNS). Performance was compared among the three groups adjusting for age, sex and education level. Adjustment for “negative symptoms” and “disorganization” was performed afterwards. Results: Subjects with schizophrenia showed lower performance in the LNS than their first degree relatives and the healthy controls; the effect sizes were 0.75 and 1.18 respectively. There was a small difference between relatives and controls (effect size =0.38). These differences were significant after adjustment for negative and disorganized symptoms, but the effect sizes became smaller: 0.26 for relatives vs. subjects with schizophrenia, 0.56 for controls vs. subjects with schizophrenia and 0.33 for relatives vs. controls. Among individuals with schizophrenia, performance in the LNS was not associated with disorder duration, disease onset age, antipsychotics, history of depressive episodes or substance use disorders. Conclusion: Results suggest verbal working memory may be considered as an endophenotype in schizophrenia (AU)