scholarly journals Long-lasting rescue of schizophrenia-relevant cognitive impairments via risperidone-loaded microPlates

2022 ◽  
Author(s):  
Elena Bellotti ◽  
Gabriella Contarini ◽  
Federica Geraci ◽  
Sebastiano Alfio Torrisi ◽  
Cateno Piazza ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mouse Model ◽  
Sustained Release ◽  
Temporal Order ◽  
Single Injection ◽  
Chronic Administration ◽  
Psychotic Symptoms ◽  
Residual Rate ◽  
Long Acting

AbstractSchizophrenia is a disorder characterized by cognitive impairment and psychotic symptoms that fluctuate over time and can only be mitigated with the chronic administration of antipsychotics. Here, we propose biodegradable microPlates made of PLGA for the sustained release of risperidone over several weeks. Two microPlate configurations – short: 20 × 20 × 10 μm; tall: 20 × 20 × 20 μm – are engineered and compared to conventional ~ 10 μm PLGA microspheres in terms of risperidone loading and release. Tall microPlates realize the slowest release documenting a 35% risperidone delivery at 100 days with a residual rate of 30 ng/ml. Short microPlates and microspheres present similar release profiles with over 50% of the loaded risperidone delivered within the first 40 days. Then, the therapeutic efficacy of one single intraperitoneal injection of risperidone microPlates is compared to the daily administration of free risperidone in heterozygous knockout mice for dysbindin-1, a clinically relevant mouse model of cognitive and psychiatric liability. In temporal order object recognition tasks, mice treated with risperidone microPlates outperform those receiving free risperidone up to 2, 4, 8, and 12 weeks of observation. This suggests that the sustained release of antipsychotics from one-time microPlate deposition can rescue cognitive impairment in dysbindin mice for up to several weeks. Overall, these results demonstrate that risperidone-loaded microPlates are a promising platform for improving cognitive symptoms associated to schizophrenia. Moreover, the long-term efficacy with one single administration could be of clinical relevance in terms of patient’s compliance and adherence to the treatment regimen. Graphical abstract Single injection of long-acting risperidone-loaded µPL ameliorates the dysbindin-induced deficit in a clinically relevant mouse model of cognitive and psychiatric liability for up to 12 weeks

scholarly journals Age-related cognitive impairment is associated with long-term neuroinflammation and oxidative stress in a mouse model of episodic systemic inflammation

2018 ◽  
Vol 15 (1) ◽  
Author(s):  
Joana Costa d’Avila ◽  
Luciana Domett Siqueira ◽  
Aurélien Mazeraud ◽  
Estefania Pereira Azevedo ◽  
Debora Foguel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Impairment ◽  
Mouse Model ◽  
Systemic Inflammation ◽  
Age Related ◽  
And Oxidative Stress

scholarly journals A Case Report of Severe Delirium after Amantadine Withdrawal

2017 ◽  
Vol 9 (1) ◽  
pp. 44-48 ◽  
Author(s):  
Franz Marxreiter ◽  
Jürgen Winkler ◽  
Martin Uhl ◽  
Dominik Madžar
Keyword(s):  
Cognitive Impairment ◽  
Case Report ◽  
Withdrawal Syndrome ◽  
Dopamine Agonists ◽  
Psychotic Symptoms ◽  
Drug Induced ◽  
Comt Inhibitors ◽  
Mao B ◽  
Psychotropic Substance

Amantadine is frequently used in addition to dopaminergic substances like dopamine agonists or L-Dopa in advanced Parkinson disease (PD). However, adverse effects like hallucinations limit its use. PD patients developing severe psychotic symptoms upon treatment with either dopaminergic substances and/or amantadine need to stop intake of any psychotropic substance. Here, we report the case of a 71-year-old PD patient without previously known cognitive impairment. He presented with drug-induced psychotic symptoms due to changes in his therapeutic regimen (increase in COMT inhibitors, newly introduced MAO B inhibitors). Also, amantadine had been part of his long-term medication for more than 2 years. The severity of his psychotic symptoms required a L-Dopa monotherapy. After changing his medication, the patient developed severe delirium that resolved rapidly after i.v. amantadine infusion, suggesting an amantadine withdrawal syndrome. Amantadine withdrawal syndrome is a rare adverse event that may present even in PD patients without cognitive impairment. This case report highlights the need for a gradual withdrawal of amantadine even if acute and severe psychotic symptoms are present. Moreover, this is the first report of a cognitively unimpaired patient developing an amantadine withdrawal syndrome.

scholarly journals The effectiveness of long-term aripiprazole injections to a patient with paranoid schizophrenia: a case report

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Anna Maria Szota ◽  
Aleksander Araszkiewicz
Keyword(s):  
Case Report ◽  
Negative Symptoms ◽  
Social Withdrawal ◽  
Paranoid Schizophrenia ◽  
Psychotic Symptoms ◽  
Suicidal Thoughts ◽  
Duration Of Hospitalization ◽  
History Of ◽  
Long Acting

AbstractParanoid schizophrenia is a chronic, psychotic disorder which can be treated with long-acting injectable (LAI) antipsychotic drugs. There are risperidone (Risperdal Consta®), olanzapine (Zypadhera®), paliperidone (Xepilon®) and aripiprazole (Abilify Maintena®) currently available.The aim of this study was to present a case history of the patient to whom monthly injections of aripiprazole effectively prevented both relapses of psychotic symptoms and hospitalizations.Case report: A 55-year-old male patient with a 13-year history of paranoid schizophrenia has been effectively treated with aripiprazole (LAI) (400mg, every 4 weeks). During the last 8 years of treatment his mental state has been stabilized, without any acute psychotic symptoms and without any anxiety, or violent behaviours. Moreover, there have been no psychotic symptoms, or suicidal thoughts, or tendencies recordered. Therefore, no hospitalization has been required. However, despite the treatment, negative symptoms such as blunted affect, cognitive dysfunction and social withdrawal have been sustained.Discussion: The available articles on aripiprazole (LAI) treatment indicate that it was effective in reducing the positive and negative symptoms of schizophrenia, as well as reducing the frequency and duration of hospitalization. However, the case report of a patient who has not had relapses of psychotic symptoms and suicidal thoughts and has not been hospitalized during 8 years of treatment with aripiprazole (LAI) has not yet been reported.Conclusions: Regular, long-term injections of aripiprazole (LAI) are very effective at preventing positive symptoms of schizophrenia development and preventing both suicidal thoughts and hospitalizations. Therefore, treatment with this drug in everyday practice should be increased.

scholarly journals Fluoxetine reverses brain radiation and temozolomide-induced anxiety and spatial learning and memory defect in mice

2019 ◽  
Vol 121 (1) ◽  
pp. 298-305 ◽  
Author(s):  
Huaiyong Gan ◽  
Qiong Zhang ◽  
Bo Zhu ◽  
Shiwu Wu ◽  
Damin Chai
Keyword(s):  
Cognitive Impairment ◽  
Chronic Administration ◽  
Long Term Potentiation ◽  
Spatial Learning And Memory ◽  
Behavioral Dysfunction ◽  
Term Potentiation ◽  
Chronic Fluoxetine ◽  
Behavioral Impairments ◽  
Brain Radiation

Radiation therapy and concomitant temozolomide chemotherapy are commonly used in treatment of brain tumors, but they may also result in behavioral impairments such as anxiety and cognitive deficit. The present study sought to investigate the effect of fluoxetine on the behavioral impairments caused by radiation and temozolomide treatment. C57BL/6J mice were subjected to a single cranial radiation followed by 6-wk cyclic temozolomide administration and were then treated with chronic administration of fluoxetine. Behavioral tests were carried out to determine the anxiety-like behavior and cognition function of these animals. Long-term potentiation (LTP) in the hippocampus was measured by electrophysiology, and neurogenesis in the dentate gyrus was evaluated by immunohistochemistry. Mice treated with radiation and temozolomide showed increased anxiety-like behavior and cognitive impairment, along with LTP impairment and neurogenesis deficit. Chronic fluoxetine administration could reverse the behavioral dysfunction, enhance LTP, and increase neurogenesis in the hippocampus. NEW & NOTEWORTHY Mice treated with radiation and temozolomide showed increased anxiety-like behavior and cognitive impairment. Chronic fluoxetine administration could reverse the behavioral dysfunction. The effect of fluoxetine might be via rescuing the neurogenesis deficit caused by radiation and temozolomide treatment.

scholarly journals Prediction of disability in schizophrenia: Symptoms, cognition, and self-assessment

2019 ◽  
Vol 10 (3) ◽  
pp. 204380871986569 ◽  
Author(s):  
Philip D. Harvey ◽  
Martin T. Strassnig ◽  
Juliet Silberstein
Keyword(s):  
Negative Symptoms ◽  
Social Cognitive ◽  
Global Dimension ◽  
Psychotic Symptoms ◽  
Self Assessment ◽  
Everyday Functioning ◽  
Cross Sectional ◽  
Long Acting ◽  
Clinical Stability

Schizophrenia is associated with wide-ranging disability across multiple functional domains. There are several determinants of disability that have been identified to date, including cognitive and social cognitive impairments, impairments in everyday functional skills and social skills, difficulties in self-assessment of abilities, and negative symptoms. These impairments are related to different elements of disability, and disability and its predictors are not a single global dimension. Further, although psychotic symptoms have limited cross-sectional correlations with everyday functioning, emerging evidence suggests that long-term clinical stability, often induced through treatment with long-acting antipsychotic medications, is also associated with improvements in everyday functioning. This review addresses the characteristics and origins of disability, with treatment implications noted in each disability domains.

scholarly journals The long-term actions of etonogestrel and levonorgestrel on decidualized and non-decidualized endometrium in a mouse model mimic some effects of progestogen-only contraceptives in women

Reproduction ◽  
2007 ◽  
Vol 133 (1) ◽  
pp. 309-321 ◽  
Author(s):  
Naomi B Morison ◽  
Jin Zhang ◽  
Tu’uhevaha J Kaitu’u-Lino ◽  
Ian S Fraser ◽  
Lois A Salamonsen
Keyword(s):  
Mouse Model ◽  
Morphological Changes ◽  
Luminal Epithelium ◽  
Tissue Remodelling ◽  
Breakthrough Bleeding ◽  
Functional Studies ◽  
Tissue Integrity ◽  
Uterine Natural Killer Cells ◽  
Long Acting

Breakthrough bleeding (BTB), a major side effect of long-acting progestogen (p)-only contraceptives in women, is the main reason for discontinuation of their use. To understand the mechanisms of BTB, a mouse model of endometrial breakdown and repair was adapted to evaluate the effects of long-term progestogens on the endometrium. Appropriately prepared mice received either an etonogestrel (ENG)- or levonorgestrel (LNG)-releasing subdermal implant. Forty eight hours after decidualization was induced in one uterine horn the majority of tissues were highly decidualized, designated 0 day (0d). Uteri were collected subsequently at 5-day intervals (to 45d) and both decidualized and non-decidualized horns were analysed for morphological changes, leukocyte infiltration and matrix metalloproteinase expression (MMP). In decidualized horns, large blood vessels (BV) developed and disturbance of tissue integrity was observed at 5d with substantial stromal breakdown by 10d, progressing until 25d when re-epithelialization was initiated. By 45d, the tissue was restored to its pre-decidualized state but with considerable tortuosity of the luminal epithelium. Tissue remodelling was not apparent in the non-decidualized horns before 35d, when hyperproliferation of the luminal epithelium resulted in tortuosity. Changes in morphology were similar with the two progestogens, but occurred more rapidly with LNG. Apart from macrophages, few leukocytes were present in non-decidualized horns but large infiltrates of neutrophils and uterine natural killer cells (uNK) were associated with tissue breakdown in decidualized tissue, many of these cells were MMP9-positive. MMP7 was primarily associated with tissue repair. Therefore, this model mimics some of the changes observed in endometria of women using p-only contraceptives and provides an opportunity for functional studies.

Prevalence of paranoid symptomatology in the elderly and relationship to organic brain factors

2011 ◽  
Vol 26 (S2) ◽  
pp. 853-853
Author(s):  
M. Serrano Díaz de Otálora ◽  
J. Gómez-Arnau Ramírez ◽  
R. Martínez de Velasco ◽  
P. Artieda Urrutia
Keyword(s):  
Cognitive Impairment ◽  
Black People ◽  
The Elderly ◽  
Delusional Disorder ◽  
Psychotic Symptoms ◽  
Medical Conditions ◽  
Paranoid Symptoms ◽  
Organic Brain ◽  
The Many

IntroductionPsychotic diseases in the elderly are underdiagnosed due to the limited use of medical resources. Advanced age makes psychoses of any cause less pure and differentiated, since old age adds a cognitive-impairment component to the basal psychotic defect.ObjectivesWe intend to estimate the prevalence of paranoid symptoms in older patients, and to study the many medical conditions associated with psychosis.MethodsWe conducted a literature review and we have performed a review of several clinical trials.ResultsWe found 12.1% of paranoid symptoms in the elderly with cognitive impairment. In absence of this factor, we found a prevalence of 14.1% for suspicion tendencies, 6.9% for paranoid thoughts and 5.5% for evident delusions. These figures were significantly higher in old black people.We present a table of the main medical conditions that can produce psychotic symptoms. Some cases of apparently typical delusional disorder can appear as a long-term complication of some of these diseases. If organic factors are subtle and long lasting, the clinical may reproduce a fairly typical delusional disorder and may respond to treatment with neuroleptic drugs.ConclusionsIt seems possible that organic brain factors are more common that we believe, becoming essential a comprehensive study of the old psychotic patient. We should pay more attention to psychotic symptoms in elderly patients and avoid conclusions based on cross-evaluations. Diagnosis will be defined by evolution in most of the cases.

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