Amygdala levels of the GluA1 subunit of glutamate receptors and its phosphorylation state at serine 845 in the anterior hippocampus are biomarkers of ictal fear but not anxiety.

Fear is a conscious state caused by exposure to real or imagined threats that trigger stress responses that affect the body and brain, particularly limbic structures. A sub-group of patients with mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) have seizures with fear, which is called ictal fear (IF), due to epileptic activity within the brain defensive survival circuit structures. Synaptic transmission efficacy can be bi-directionally modified through potentiation (long-term potentiation (LTP)) or depression (long-term depression (LTD)) as well as the phosphorylation state of Ser831 and Ser845 sites at the GluA1 subunit of the glutamate AMPA receptors, which has been characterized as a critical event for this synaptic plasticity. In this study, GluA1 levels and the phosphorylation at Ser845 and Ser831 in the amygdala (AMY), anterior hippocampus (aHIP) and middle gyrus of temporal neocortex (CX) were determined with western blots and compared between MTLE-HS patients who were showing (n = 06) or not showing (n = 25) IF. Patients with IF had an 11% decrease of AMY levels of the GluA1 subunit (p = 0.05) and a 21.5% decrease of aHIP levels of P-GluA1-Ser845 (p = 0.009) compared to patients not showing IF. The observed associations were not related to imbalances in the distribution of other concomitant types of aura, demographic, clinical or neurosurgical variables. The lower levels of P-GluA1-Ser845 in the aHIP of patients with IF were not related to changes in the levels of the serine/threonine-protein phosphatase PP1-alpha catalytic subunit or protein kinase A activation. Taken together, the GluA1 subunit levels in AMY and P-GluA1-Ser845 levels in the aHIP show an overall accuracy of 89.3% (specificity 95.5% and sensitivity 66.7%) to predict the presence of IF. AMY levels of the GluA1 subunit and aHIP levels of P-GluA1-Ser845 were not associated with the psychiatric diagnosis and symptoms of patients. Taken together with previous findings in MTLE-HS patients with IF who were evaluated by stereotactic implanted depth electrodes, we speculate our findings are consistent with the hypothesis that AMY is not a centre of fear but together with other sub-cortical and cortical structures integrates the defensive circuit that detect and respond to threats. This is the first report to address neuroplasticity features in human limbic structures connected to the defensive survival circuits, which has implications for the comprehension of highly prevalent psychiatric disorders and symptoms.

Behavioral and Neurochemical Consequences of Pentylenetetrazol-Induced Kindling in Young and Middle-Aged Rats.

(1) Objectives: Epilepsy disorder is likely to increase with aging, leading to an increased incidence of comorbidities and mortality. In spite of that, there is a lack of information regarding this issue and little knowledge of cognitive and emotional responses in aging subjects following epileptogenesis. We investigated whether and how aging distress epilepsy-related behavioral and biochemical outcomes are associated with cognition and emotion. (2) Methods: Young and middle-aged Wistar rats (3 or 12 months old) were treated with pentylenetetrazol (PTZ, 35 mg/kg) and injected on alternated days for 20 (young rats) and 32 days (middle-aged rats). Kindling was reached after two consecutive stages 4 plus one stage 5 or 6 in Racine scale. Control and kindled rats were evaluated in the elevated plus-maze (EPM) and object-recognition tests and their hippocampus was collected 24 h later for mitogen-activated protein kinases (MAPK) dosage. (3) Results: Middle-aged rats presented a higher resistance to develop kindling, with a decrease in the seizure severity index observed following the 4th and 9th PTZ injections. Middle-aged rats displayed an increased duration of the first myoclonic seizure and an increased latency to the first generalized seizure when compared to younger rats. The induction of kindling did not impair the animals' performance (regardless of age) in the object-recognition task and the EPM test as well as it did not alter the hippocampal levels of MAPKs. (4) Significance: Our findings reveal that, despite age-related differences during epileptogenesis, middle-aged rats evaluated after kindling performed similarly during discriminative learning and emotional tasks in comparison to young animals, with no alteration of hippocampal MAPKs. Additional investigation must be carried out to explore the electrophysiological mechanisms underlying these responses, as well as the long-term effects displayed after kindling.

Cognitive performance of long-term institutionalized elderly patients with schizophrenia: a case control study / Desempenho cognitivo em pacientes idosos com esquizofrenia: um estudo caso-controle

Cognitive impairment is inherent to the ageing process. Several studies suggest that patients with late-life schizophrenia have more marked cognitive impairment. Objective: The aim of this study was to compare the cognitive performance of elderly institutionalized patients with schizophrenia and institutionalized elderly control patients without neurological or psychiatric diseases, matched for age, educational level and institutionalization time. Methods: The Cambridge Examination for Mental Disorders of the Elderly (CAMCOG) was used to test 10 institutionalized elderly patients with schizophrenia. Results were compared with those of 10 institutionalized control patients with history of Hansens disease. Results: Patients with schizophrenia showed a worse performance in terms of total CAMCOG score and on its subtests of orientation, language, abstraction, and memory. Patients with schizophrenia also disclosed a non-significant trend toward lower scores on the MMSE and on calculus. Conclusion: Findings demonstrated that schizophrenia was associated to worse cognitive impairment in long-term institutionalized elderly patients compared with institutionalized patients without neurological or psychiatric diseases.

Prejuízo cognitivo é inerente ao processo de senescência. Estudos tem sugerido que pacientes idosos com esquizofrenia apresentam esse prejuízo de maneira mais acentuada. Objetivo: O objetivo deste estudo foi comparar o desempenho cognitivo de pacientes idosos com esquizofrenia, institucionalizados, com indivíduos idosos, institucionalizados, sem doenças neurológicas ou psiquiátricas, pareados pela idade, escolaridade e tempo de institucionalização. Métodos: Cambridge Examination for Mental Disorders of the Elderly (CAMCOG) foi aplicado em 10 pacientes, institucionalizados, com esquizofrenia, cujo desempenho cognitivo foi comparado ao de 10 indivíduos, institucionalizados, com história de doença de Hansen. Resultados: Pacientes com esquizofrenia apresentaram um pior desempenho na pontuação total do CAMCOG e em seus subitens orientação, linguagem, abstração e memória. Pacientes com esquizofrenia também apresentaram uma tendência, não significativa, para menor pontuação no MEEM e cálculo. Conclusão: Nossos achados demonstram que a esquizofrenia está associada a piora do comprometimento cognitivo em pacientes idosos com institucionalização de longa permanência comparados a pacientes institucionalizados sem doenças neurológicas ou psiquiátricas.

Cognitive performance of long-term institutionalized elderly patients with schizophrenia: A case control study.

Cognitive impairment is inherent to the ageing process. Several studies suggest that patients with late-life schizophrenia have more marked cognitive impairment. OBJECTIVE: The aim of this study was to compare the cognitive performance of elderly institutionalized patients with schizophrenia and institutionalized elderly control patients without neurological or psychiatric diseases, matched for age, educational level and institutionalization time. METHODS: The Cambridge Examination for Mental Disorders of the Elderly (CAMCOG) was used to test 10 institutionalized elderly patients with schizophrenia. Results were compared with those of 10 institutionalized control patients with history of Hansen's disease. RESULTS: Patients with schizophrenia showed a worse performance in terms of total CAMCOG score and on its subtests of orientation, language, abstraction, and memory (p≤0.05). Patients with schizophrenia also disclosed a non-significant trend toward lower scores on the MMSE and on calculus. CONCLUSION: Findings demonstrated that schizophrenia was associated to worse cognitive impairment in long-term institutionalized elderly patients compared with institutionalized patients without neurological or psychiatric diseases.

Prejuízo cognitivo é inerente ao processo de senescência. Estudos tem sugerido que pacientes idosos com esquizofrenia apresentam esse prejuízo de maneira mais acentuada. OBJETIVO: O objetivo deste estudo foi comparar o desempenho cognitivo de pacientes idosos com esquizofrenia, institucionalizados, com indivíduos idosos, institucionalizados, sem doenças neurológicas ou psiquiátricas, pareados pela idade, escolaridade e tempo de institucionalização. MÉTODOS: "Cambridge Examination for Mental Disorders of the Elderly" (CAMCOG) foi aplicado em 10 pacientes, institucionalizados, com esquizofrenia, cujo desempenho cognitivo foi comparado ao de 10 indivíduos, institucionalizados, com história de doença de Hansen. RESULTADOS: Pacientes com esquizofrenia apresentaram um pior desempenho na pontuação total do CAMCOG e em seus subitens orientação, linguagem, abstração e memória (p≤0.05). Pacientes com esquizofrenia também apresentaram uma tendência, não significativa, para menor pontuação no MEEM e cálculo. CONCLUSÃO: Nossos achados demonstram que a esquizofrenia está associada a piora do comprometimento cognitivo em pacientes idosos com institucionalização de longa permanência comparados a pacientes institucionalizados sem doenças neurológicas ou psiquiátricas.