Phytochemical Extract from Carica papaya Leaves and Punica granatum Seeds as Therapy Against Cognitive Impairment in a Murine Model.

Mild cognitive impairment (MCI) is defined as inter-stage between normal cognitive aging and major neurocognitive disorder (MND). This state of decay is a crucial factor in treatment to prevent the progression to MND. In this study, our group developed a virtual screening process to evaluate 2568 phytochemical compounds against 5 key proteins associated with MCI and MND. As a result, two potential candidates were identified: carpaine, found in Carica papaya leaves, and punicalagin, present in Punica granatum. A model of cognitive impairment (CI) was developed in 10-month-old male Sprague Dawley rats by administering aluminum chloride (AlCl3) at a dose of 100 mg/kg/day for 30 days. After AlCl3 administration period, one of the groups received carpaine and punicalagin in a phytochemical extract (PE) by oral gavage for 30 days. Novel object recognition test (NOR) was assessed at three different time points (T1 - before CI, T2 - after CI, and T3 - after PE treatment). Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were identified in the hippocampus of rats at the end of the study period. After administration of AlCl3, a reduction in discrimination index vs control rats (CI = 0.012 ± 0.08 vs Control = 0.076 ± 0.03), was observed. After phytochemical extract treatment, a significant increase in discrimination index values was observed in the PE group 0.4643 ± 0.13 vs CI group 0.012 ± 0.08. Additionally, the evaluation of immunohistochemistry showed an increase in GFAP positivity in the hippocampus of the CI groups, while a slight decrease was observed in the PE group. This work addressed a comprehensive methodology that utilized in silico tools to identify phytochemical compounds (carpaine and punicalagin) as potential candidates for affecting key proteins in CI. The phytochemical extract containing carpaine and punicalagin resulted in a trend in the decrease of GFAP expression in the hippocampus and improved recognition memory in rats with CI induced by age and AlCl3 administration.

Cognitive impairment in the co-occurrence of alcohol dependence and major depression: neuropsychological assessment and event-related potentials analyses.

To evaluate the putative detrimental effect of Major Depressive Disorder (MDD) on the cognitive impairment associated with Alcohol Dependence (AD), we contrasted the neuropsychological profile and behavioral responses of AD subjects, MDD individuals, and in those with a co-occurring AD-MDD diagnosis (DD). Patients and healthy subjects completed a comprehensive neuropsychological battery and were recorded for P200, P300, and N450 event-related potentials during memory and Stroop tasks. AD subjects exhibited a generalized detrimental neuropsychological performance; in contrast, in MDD individuals, impairment was limited to discrete domains. Notably, the deficits were distinctive in DD cases. A P200 increased amplitude in MDD, a decrease in P300 amplitude in AD, and increased latency of P300 in DD patients were the overt electrophysiological abnormalities identified. Dual patients also exhibited a distinct pattern of behavioral responses, particularly apparent during high-demand cognitive tasks. Specific ERP adjustments were associated with the short-term fluoxetine treatment in DD and MDD subjects; the SSRI also improved altered baseline performance in learning and cognitive flexibility in DD subjects. In conclusion, the neuropsychological and behavioral alterations detected in the co-occurrence of AD-MDD did not seem to be merely the sum of the negative contributions of the independent disorders.

El efecto aditivo en el diagnóstico dual: una revisión del funcionamiento cognitivo de pacientes con depresión mayor y alcoholismo / The additive effect in dual diagnosis. A review of cognitive functioning of patients with major depression and alcoholism

La comorbilidad entre el trastorno depresivo mayor (TDM) y dependencia de alcohol (DA) se conoce como diagnóstico dual (DD). Se ha sugerido que los pacientes con esta comorbilidad presentan síntomas anímicos y neurovegetativos de mayor gravedad en comparación con los pacientes de diagnóstico único. Sin embargo, el efecto aditivo de los déficits cognitivos en esta población ha sido escasamente explorado. El objetivo de este trabajo fue sintetizar la información existente hasta la fecha sobre las alteraciones neurocognitivas en pacientes con DD (TDM-DA). La búsqueda de artículos se realizó en las bases de datos ScienceDirect y PubMed con las palabras clave: diagnóstico dual, depresión, alcoholismo, funcionamiento cognitivo, desempeño neuropsicológico, déficit cognitivo y alteraciones cognitivas. Los hallazgos de los estudios referidos en este artículo sugieren que los pacientes con DD muestran alteraciones en dominios cognitivos específicos y que sus déficits no parecen mostrar un efecto aditivo de 2 trastornos independientes (AU)

The comorbidity between major depressive disorder (MDD) and alcohol dependence (AD) is known as dual diagnosis (DD). It has been suggested that patients with this comorbidity display a more severe autonomic and mood symptoms compared to patients with a single diagnosis. However, the additive effect of cognitive deficits in this population has hardly been studied. The objective of this study was to present a summary of the current information on neurocognitive alterations in patients with DD (MDD-AD). The search was conducted using ScienceDirect and PubMed with the keywords: dual diagnosis; depression; alcoholism; cognitive functioning; neuropsychological performance; cognitive impairment; cognitive impairment and neuropsychology. The findings of the studies reported in this paper suggest that patients with DD show impairment in specific cognitive domains; and that their deficits do not seem to show an additive effect of two separate disorders (AU)

Reduced P3a amplitudes in antipsychotic naïve first-episode psychosis patients and individuals at clinical high-risk for psychosis.

Event related potentials (ERP) associated with early sensory information processing have been proposed as possible vulnerability markers for psychosis. Compared to other ERPs reported in schizophrenia research, like Mismatch Negativity (MMN), little is known about P3a, an ERP related to novelty detection. The aim of this study was to analyze the MMN-P3a complex in 20 antipsychotic naïve first-episode psychosis patients (FEP), 23 antipsychotic naïve individuals at clinical high-risk for psychosis (CHR) and 24 healthy controls. The MMN-P3a amplitudes and latencies were obtained during a passive auditory mismatch frequency deviant ERP paradigm and analyzed in frontal and central scalp regions. There were no significant differences in MMN amplitude between groups. There was a significant group difference in P3a due to reduced amplitude (F[2,64] = 3.7, p = 0.03) in both CHR and FEP groups (Mean difference (MD) = 0.39, p = 0.04 and MD = 0.49, p = 0.02, respectively) compared to the control group and this effect was most prominent on the right side (Group × laterality effect: MD = 0.57, p < 0.01 and MD = 0.58, p < 0.01, respectively). No significant differences were observed for MMN or P3a latencies between groups. Although a P3a decrement in chronic schizophrenia and FEP has been previously reported, our results suggest that this novelty detection impairment is present even in pre-psychosis stages in antipsychotic naïve subjects. This study supports the evidence that P3a could represent a neurophysiological vulnerability marker for the development of psychosis.

Funciones cognoscitivas y ejecutivas en el TDAH / Cognitive and executive functions in ADHD

Introducción. Se han observado alteraciones en diferentes funciones cognoscitivas en niños con Trastorno por Déficit de Atención con Hiperactividad (TDAH) y recientemente se ha propuesto que la causa que subyace a toda la sintomatología es una deficiencia en las funciones ejecutivas (FE), no obstante, existen muchas discrepancias en los hallazgos. Objetivo. Realizar una evaluación amplia de las funciones cognoscitivas y FE en niños con TDAH tipos hiperactivo impulsivo y combinado (TDAH/HI-C) para conocer sus características neuropsicológicas y analizar que funciones pueden relacionarse con su conducta hiperactivo-impulsiva. Metodología. Se aplicó una Batería Neuropsicológica y los Test de Stroop, de Clasificación de tarjetas de Wisconsin (WCST) y Torre de Londres a 51 niños de 7 a12 años de edad (25 control y 26 con TDAH). Resultados. El grupo TDAH/HI-C tuvo peor resultado en atención sostenida, denominación serial rápida de figuras y colores, comprensión de órdenes escritas, dictado de palabras, comparación de números, problemas aritméticos, memoria de trabajo visual y de largo plazo y en el WCST. Los errores y velocidad en denominación serial rápida de colores y figuras, comprensión de órdenes escritas, problemas aritméticos, y del WCST errores totales, perseverativos y respuestas perseverativas, fueron las variables que se relacionaron con la hiperactividad-impulsividad. Conclusiones. Los niños con TDAH/HI-C tienen una gran variedad de deficiencias cognoscitivas y solamente en algunas áreas de las FE. Estas deficiencias explican en alguna medida el comportamiento hiperactivo-impulsivo (AU)

Introduction. Some studies have reported that attention-deficit/hyperactivity disorder (ADHD) children show alterations in different cognitive functions. Recently, a deficiency in the executive functions (EF) is proposed as the cause underlying all of these symptoms. However discrepancies exist about these findings. Objective. Assessment of cognitive and executive functions of subjects with both ADHD hyperactive-impulsive type and combined type, in order to reveal their neuropsychological characteristics and analyze if those functions are related to hyperactive-impulsive behavior. Method. Neuropsychological Battery, Stroop test, Wisconsin Card Sorting test and London Tower test were applied to 51children between 7 and 12 years old (25 controls and 26ADHD). Results. ADHD children showed worst performance in sustained attention, rapid serial naming of figures and colors, comprehension of written instructions, word dictation, number comparison, arithmetical problems, visual working memory, long term memory and the scores of WCST. Variables related to hyperactivity-impulsivity were: errors and decreased velocity in rapid serial naming of colors and figures, comprehension of written instructions, arithmetical problems and the scores of total errors, perseverating errorsand perseverating responses of WCST. Conclusion. ADHD children show a great variety of cognitive deficiencies and had deficit only in some domains of executive functions. These deficiencies could explain to some extent the hyperactive and impulsive behavior (AU)

Cognitive and executive functions in ADHD.

INTRODUCTION: Some studies have reported that attention-deficit/hyperactivity disorder (ADHD) children show alterations in different cognitive functions. Recently, a deficiency in the executive functions (EF) is proposed as the cause underlying all of these symptoms. However discrepancies exist about these findings. OBJECTIVE: Assessment of cognitive and executive functions of subjects with both ADHD hyperactive-impulsive type and combined type, in order to reveal their neuropsychological characteristics and analyze if those functions are related to hyperactive-impulsive behavior. METHOD: Neuropsychological Battery, Stroop test, Wisconsin Card Sorting test and London Tower test were applied to 51 children between 7 and 12 years old (25 controls and 26 ADHD). RESULTS: ADHD children showed worst performance in sustained attention, rapid serial naming of figures and colors, comprehension of written instructions, word dictation, number comparison, arithmetical problems, visual working memory, long term memory and the scores of WCST. Variables related to hyperactivity-impulsivity were: errors and decreased velocity in rapid serial naming of colors and figures, comprehension of written instructions, arithmetical problems and the scores of total errors, perseverating errors and perseverating responses of WCST. CONCLUSION: ADHD children show a great variety of cognitive deficiencies and had deficit only in some domains of executive functions. These deficiencies could explain to some extent the hyperactive and impulsive behavior.

[Mismatch Negativity (MMN) and schizophrenia: a revision]. / Mismatch Negativity (MMN) y esquizofrenia: una revisión.

The Mismatch Negativity (MMN) is an auditory Event- Related Potential which is generated as an automatic cerebral response to any change in the auditory stimulation that exceeds a limit corresponding to the discrimination threshold. It has been widely and consistently reported that patients with recent and chronic schizophrenia display smaller MMN amplitudes, suggesting that this component may be related with alteration in sensory memory and stimuli integration capacities, which seem to increase with the disease progression. Recently, new research areas have emerged, and studies of MMN of relatives of patients with schizophrenia have been conducted in order to assess the MMN efficacy as an endophenotype. Likewise, there have been MMN studies in schizophrenia prodromes or clinical high risk subjects, aiming to know if there are cerebral processing disturbances prior to the onset of the disease. The results of these studies have been promising, suggesting the presence of auditory stimuli processing disturbances in this population. These disturbances are subtle and seem to increase as the disease appears. The MMN component may be a very effective electrophysiological tool that provides information about the automatic auditory processing in schizophrenia related to its chronicity. It may also be a relative reliable index of genetic vulnerability and clinical risk for developing schizophrenia. Nevertheless, it is necessary to continue performing studies to get comparable and replicable studies in the future that could confirm the information about MMN utility.

Mismatch Negativity (MMN) y esquizofrenia: Una revisión / Mismatch Negativity (MMN) and schizophrenia: A revision

El componente Mismatch Negativity (MMN) es un Potencial Relacionado con Eventos (PRE) de tipo auditivo, que es generado por la respuesta cerebral automática a cualquier cambio en la estimulación auditiva que excede un límite correspondiente al umbral de discriminación. Se ha reportado amplia y consistentemente menor amplitud de MMN en pacientes con esquizofrenia reciente y crónica, por lo que se ha propuesto que este componente se relaciona con alteraciones en la memoria sensorial y en las capacidades de integración del estímulo, las cuales parecen progresara lo largo de la enfermedad. Recientemente se han abierto nuevas líneas de investigación al respecto, y se han realizado estudios con familiares de pacientes con esquizofrenia para evaluar la eficacia de la MMN como endofenotipo. Asimismo, se han llevado a cabo estudios de MMN en pródromos o sujetos en riesgo clínico de desarrollar esquizofrenia, con la finalidad de conocer si existen alteraciones en el procesamiento cerebral previas al inicio de la enfermedad. Los resultados de estos trabajos han arrojado resultados prometedores, que sugieren la presencia de alteraciones sutiles en el procesamiento de estímulos auditivos en esta población, las cuales parecen aumentar con la aparición de la enfermedad. Es así como el componente MMN puede ser una herramienta electrofisiológica eficaz para proporcionar información sobre el procesamiento automático auditivo relacionado con la esquizofrenia y su cronicidad, así como para indicar la vulnerabilidad genética y riesgo clínico para desarrollarla. Sin embargo, es necesario realizar estudios futuros comparables y replicables que permitan confirmar tales hallazgos (AU)

The Mismatch Negativity (MMN) is an auditory Event-Related Potential which is generated as an automatic cerebral response to any change in the auditory stimulation that exceeds a limit corresponding to the discrimination threshold. It has been widely and consistently reported that patients with recent and chronic schizophrenia display smaller MMN amplitudes, suggesting that this component may be related with alteration in sensory memory and stimuli integration capacities, which seem to increase with the disease progression. Recently, new research areas have emerged, and studies of MMN of relatives of patients with schizophrenia have been conducted in order to assess the MMN efficacy as an endophenotype. Likewise, there have been MMN studies in schizophrenia prodromes or clinical high risk subjects, aiming to know if there are cerebral processing disturbances prior to the onset of the disease. The results of these studies have been promising, suggesting the presence of auditory stimuli processing disturbances in this population. These disturbances are subtle and seem to increase as the disease appears. The MMN component maybe a very effective electrophysiological tool that provides information about the automatic auditory processing in schizophrenia related to its chronicity. It may also be a relative reliable index of genetic vulnerability and clinical risk for developing schizophrenia. Nevertheless, it is necessary to continue performing studies to get comparable and replicable studies in the future that could confirm the information about MMN utility (AU)