Psychiatric Alterations Research Articles

Turner syndrome and neuropsychological abnormalities: a review and case series.

The objective of this study was to establish the genotype-phenotype correlation between karyotype results and the neurological and psychiatric alterations presented in patients with Turner syndrome (TS). A retrospective study was conducted on the medical records of 10/140 patients with TS and neurophysiological abnormalities seen at a university hospital in southern Brazil. In addition, a literature review spanning the period from January 1, 2012 to January 1, 2023 was carried out using the PubMed and Virtual Health Library databases. Our study showed a potential correlation between neurological and psychiatric alterations in patients with TS. These findings are in accordance with those described in literature such as a high prevalence of learning or intellectual disabilities. However, our sample found more seizure episodes than those reported in other studies. The correlation established could be due to X chromosome dose-effect, as the review suggests that sex chromosome number and hormonal development can be associated with verbal, social, and cognitive skills or impairments.

Neuroplasticity Alterations Induced by Isotretinoin use in RARA Gene Polymorphism is Associated with Increased Risk of Depression and Suicidal Ideation in Patients with Vitamin D Deficiency: A Systematic Review and Meta-Analysis

Rationale: Isotretinoin is widely used for severe acne treatment, but concerns have emerged regarding its potential association with depression and suicidal ideation. Previous studies have produced mixed findings, necessitating a comprehensive evaluation of the evidence. This systematic review and meta-analysis aim to clarify the association between isotretinoin use and the onset of depression or suicidal ideation, focusing on genetic predispositions, particularly in patients with vitamin D deficiency. Objectives: This review assesses the risk of depression and suicidal ideation in patients treated with isotretinoin for severe acne compared to those not using isotretinoin. A secondary focus is placed on identifying specific genetic factors, such as polymorphisms in the RARA and LEP genes, that may predispose patients to these psychiatric side effects. Eligibility Criteria: Randomized controlled trials (RCTs), cohort studies, and case-control studies comparing isotretinoin users to non-users were included. Exclusion criteria included studies that lacked a comparator group or did not report psychiatric outcomes (depression or suicidal ideation). Outcomes: The primary outcome was the incidence of depression or suicidal ideation among isotretinoin users compared to non-users. Secondary outcomes examined the influence of genetic polymorphisms, specifically in the RARA and LEP genes, on the risk of developing psychiatric side effects. Risk of Bias: Risk of bias was assessed using the Cochrane Risk of Bias tool for randomized trials and the Newcastle-Ottawa Scale for observational studies. The overall quality of the included studies was moderate to high. Synthesis Methods: A random-effects meta-analysis was performed to pool odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I² statistic, and sensitivity analyses were conducted to ensure the robustness of the findings. Included Studies: Fifteen studies were included, comprising 3 randomized controlled trials, 7 cohort studies, and 5 case-control studies, with a total of 8,000 isotretinoin users and 10,000 non-users. The studies were conducted in diverse clinical settings with a follow-up range of 6 months to 5 years. Synthesis of Results: The pooled analysis demonstrated a significant association between isotretinoin use and an increased risk of depression (OR: 1.3, 95% CI: 1.1–1.5, p < 0.05). Specific genetic polymorphisms, particularly in the RARA and LEP genes, were identified as potential risk factors for developing depression among isotretinoin users, particularly in patients with concurrent vitamin D deficiency. Conclusions: Isotretinoin use is associated with an increased risk of depression, particularly in individuals with specific genetic polymorphisms such as RARA and LEP. Clinicians should consider conduct precision medicine genetic testing testing for these polymorphisms before initiating isotretinoin treatment and closely monitor patients for psychiatric alterations, mood changes, especially those with with vitamin D deficiency or genetic predisposition to depression

Enhanced mGluR5 intracellular activity causes psychiatric alterations in Niemann Pick type C disease

Niemann-Pick disease Type C (NPC) is caused by mutations in the cholesterol transport protein NPC1 leading to the endolysosomal accumulation of the lipid and to psychiatric alterations. Using an NPC mouse model (Npc1nmf164) we show aberrant mGluR5 lysosomal accumulation and reduction at plasma membrane in NPC1 deficient neurons. This phenotype was induced in wild-type (wt) neurons by genetic and pharmacological NPC1 silencing. Extraction of cholesterol normalized mGluR5 distribution in NPC1-deficient neurons. Intracellular accumulation of mGluR5 was functionally active leading to enhanced mGluR-dependent long-term depression (mGluR-LTD) in Npc1nmf164 hippocampal slices. mGluR-LTD was lower or higher in Npc1nmf164 slices compared with wt when stimulated with non-membrane-permeable or membrane-permeable mGluR5 agonists, respectively. Oral treatment with the mGluR5 antagonist 2-chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine (CTEP) reduced mGluR-LTD and ameliorated psychiatric anomalies in the Npc1nmf164 mice. Increased neuronal mGluR5 levels were found in an NPC patient. These results implicate mGluR5 alterations in NPC psychiatric condition and provide a new therapeutic strategy that might help patients suffering from this devastating disease.

Autistic Children/Adolescents Have Lower Adherence to the Mediterranean Diet and Higher Salivary IL-6 Concentration: Potential Diet-Inflammation Links?

Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders. Many patients with ASD often show behavioral problems at mealtimes, including food selectivity and atypical feeding behaviors. The Mediterranean diet (MD) has a beneficial effect on mental health for the general population across different ages. There is evidence that good adherence to the MD is effective in reducing peripheral inflammatory markers, such as the cytokine interleukin-6 (IL-6). The present study was designed to evaluate adherence to the MD in children with ASD using age- and sex-matched, typically developing individuals (TDs) as a control group and to determine whether differences in adherence to the MD are associated with salivary IL-6 and IL-6 receptor concentration. Twenty children and adolescents with ASD (mean age 9.95 ± 0.65 years) and twenty TDs (mean age: 9.85 ± 0.59 years) participated in this study (N = 16 males and N = 4 females in each group). Participants with ASD were enrolled in a psychiatric consultation in Valencia (Spain), and TDs were recruited from two public schools in Valencia. The parents of both ASD and TD groups answered the items in a validated Mediterranean Diet Quality Index for children and adolescents (KIDMED) questionnaire on their children's adherence to the MD. The mean adherence to MD score was significantly lower in the ASD group (9.10 ± 0.42) (range 6-12) than in the TD group (10.35 ± 0.31) (range 8-12) (p = 0.02, Mann-Whitney U test). There was no statistically significant association between adherence to the MD and age or sex in both groups, but there was a significant correlation between the total KIDMED score and body mass index (BMI) in the ASD group. Regarding the concentration of Il-6 and the Il-6 receptor in saliva samples, there were no significant differences between the two groups; however, linear regression analysis by group revealed significant associations between the adherence to MD score and the concentration of IL-6 and its receptor in saliva in the ASD group (p = 0.003, OR = 0.68, 95% CI 0.007 to -0.02; p = 0.009, OR = -0.64, 95% CI -0.01 to -0.00). In contrast, no significant associations were observed between the adherence to MD score and the concentration of IL-6 and its receptor in saliva in the TD group. Children and adolescents with ASD showed significantly lower adherence to the MD, which can contribute to nutritional deficits described in ASD, and the role of BMI composition (fat versus lean mass) needs to be further investigated in this group. The concentration of IL-6 and its receptor in saliva is associated with adherence to the MD, suggesting a possible link between IL-6 and diet in ASD. Further studies to clarify the associations between IL-6, psychiatric alterations, and diet in ASD are needed.

Bipolar Disorder due to Cushing’s Disease, with manic characteristics. Regarding a clinical case.

IntroductionThe increase in cortisol can be exogenous or endogenous. As etiologies of endogenous increase we find: Cushing’s disease, 68% of cases, generally due to an ACTH-producing pituitary tumor; Adrenal Cushing syndrome (17%); Ectopic Cushing syndrome (15%) due to lung tumor most frequently. It is relevant since among its symptoms one of the most notable are the psychiatric alterations it produces, among them mood disorders, depression being the most common, as well as psychotic symptoms, delirium and anxiety disorder.ObjectivesTo carry out a correct differential diagnosis of the pathologies that could present with symptoms of a manic episode.MethodsClinical case description of a 52-year-old woman, who presented with manic symptoms in 2020, requiring hospitalization. Upon discharge from the acute care unit, she consulted with the endocrinologist due to weight gain, revealing an increase in abdominal diameter, hyperpigmentation, a moon-like face, and a hump. Free cortisol was measured in 24-hour urine, with a high result, followed by brain MRI, and pituitary microadenoma was confirmed.ResultsThe patient underwent surgical resection of the microadenoma, which was partially effective, so she maintained high cortisol levels, even despite oral retreatment. In 2023 she had a new manic episode, with a cortisol value of approximately 300 nmol/day.ConclusionsThe importance lies in the correct diagnosis to provide appropriate treatment and avoid the chronicity of the disease and the patient psychiatrization. In this case and as in many other diseases, which present with psychiatric symptoms, it is important to differentiate whether it is a primary psychiatric disorder or are component symptoms of another disease that, upon receiving treatment, would resolve the psychiatric symptoms.Disclosure of InterestNone Declared

Wolfram Syndrome; Case Series Report at the “National Medical Center 20 De Noviembre ISSSTE”

Wolfram syndrome it’s a rare autosomal genetic disease. Also, kwon as DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness). Its classified as one of infancy onset diabetes mellitus non autoimmune causes, its presentation generally happens at an early age; other characteristics of the disease are insipidus diabetes, optic atrophy, neurosensorial deafness, psychiatric alterations and other neurodegenerative disorders.

Caregivers' perception of patients’ interpersonal and psychiatric alterations: What is the impact on their health?

PurposePrevious research conducted among caregivers of patients with cancer revealed a poor Quality of Life (QoL) and high levels of distress. In addition to the influence of patients' clinical state, caregivers' appraisals of patients' difficulties should be considered as another predictor of poor caregiver health. This study aims to test the association between caregivers' health (i.e., QoL, depression and anxiety) and their perception of patients’ difficulties. Methods199 caregivers of patients with cancer completed an online survey based on questionnaires measuring their QoL, depression and anxiety, as well as their perception of patients’ cognitive, emotional, functional, psychiatric and interpersonal difficulties. ResultsIt was found that the appraisal of patients' impairments in all domains was mainly correlated with poor caregivers' QoL (Pearson correlations ranged from 0.14 to 0.45; p ≤ .05). Furthermore, linear regression analyses showed that, after controlling for age, sex education level, professional activity and living with or without the patient, the appraisal of patients' interpersonal abilities (β = 0.25, p ≤ .05), psychiatric difficulties (β = −0.25, p ≤ .01) and living with the patient were the main predictors of caregivers’ QoL. ConclusionThis study highlights the importance of better understanding the role of patients' social and psychiatric difficulties when examining caregivers' health. This indicates the importance of providing support and offering information to caregivers to alert them to the role of patients' social and psychiatric difficulties on their own health. Future studies should better understand how these difficulties are associated with caregivers’ perception of identity/sociability alterations in patients and how caregivers cope with these changes.

Bile duct ligation increased dopamine levels in the cerebral cortex of rats partly due to induction of tyrosine hydroxylase.

Liver failure is associated with psychiatric alterations, partly resulting from the increased brain dopamine levels. We investigated the relationship between increased dopamine levels and mental abnormalities using bile duct ligation (BDL) rats and the mechanism by which liver failure increased dopamine levels in SH-SY5Y cells. Behavioural tests were carried out on day 13 and 27 following BDL, along with measurements of dopamine and metabolites, expressions of enzymes and transporters related to dopamine metabolism, and its transport into the cortex and the hippocampus. SH-SY5Y cells were used to investigate whether NH4 Cl, bile acids and bilirubin affected expression of tyrosine hydroxylase or not. Tyrosine hydroxylase (TH) expression in SH-SY5Y cells co-incubated with bilirubin and signal pathway inhibitors was measured. Open-field test results demonstrated BDL rats showed anxiety-like behaviour, accompanied by increased dopamine levels and expression of TH protein in the cortex. Membrane bound long form (MB)-COMT, slightly but significantly decreased. SH-SY5Y cells indicated that increased bilirubin levels was a factor in inducing TH expression. Both inhibitor of NF-κB pathway BAY 11-7082 and silencing NF-κB p65 reversed bilirubin-induced upregulation of TH protein. NF-κB activator TNF-α increased expression of TH protein. Roles of bilirubin in increases of TH protein expressions and dopamine levels were measured using hyperbilirubinemia rats. Anxiety-like behaviour, was associated with increased dopamine levels and TH protein expressions in hyperbilirubinemia rats. BDL significantly increased dopamine levels in rat cortex partly due to bilirubin-mediated TH induction. Increased bilirubin induced TH expression via activating NF-κB signalling pathway.

A Systematic Review and Quality Evaluation of Studies on Long-Term Sequelae of COVID-19.

COVID-19 made its debut as a pandemic in 2020; since then, more than 607 million cases and at least 6.5 million deaths have been reported worldwide. While the burden of disease has been described, the long-term effects or chronic sequelae are still being clarified. The aim of this study was to present an overview of the information available on the sequelae of COVID-19 in people who have suffered from the infection. A systematic review was carried out in which cohort studies, case series, and clinical case reports were included, and the PubMed, Scielo, SCOPUS, and Web of Science databases were extracted. Information was published from 2020 to 1 June 2022, and we included 26 manuscripts: 9 for pulmonary, 6 for cardiac, 2 for renal, 8 for neurological and psychiatric, and 6 for cutaneous sequelae. Studies showed that the most common sequelae were those linked to the lungs, followed by skin, cutaneous, and psychiatric alterations. Women reported a higher incidence of the sequelae, as well as those with comorbidities and more severe COVID-19 history. The COVID-19 pandemic has not only caused death and disease since its appearance, but it has also sickened millions of people around the globe who potentially suffer from serious illnesses that will continue to add to the list of health problems, and further burden healthcare systems around the world.

Functional neurologic disorders in an adult with propionic acidemia: a case report

BackgroundInborn errors of metabolism are often characterized by various psychiatric syndromes. Previous studies tend to classify psychiatric manifestations into clinical entities. Among inborn errors of metabolism, propionic acidemia (PA) is a rare inherited organic aciduria that leads to neurologic disabilities. Several studies in children with PA demonstrated that psychiatric disorders are associated to neurological symptoms. To our knowledge, no psychopathological description in adult with propionic acidemia is available.Case presentationWe aimed to compare the case of a 53-year-old woman with PA, to the previous psychiatric descriptions in children with PA and in adults with other inborn errors of metabolism. Our patient presented a large variety of signs: functional neurologic disorders, borderline personality traits (emotional dyregulation, dissociative and alexithymic trends, obsessive-compulsive disorders), occurring in a context of neurodevelopmental disorder.ConclusionClinical and paraclinical examinations are in favor of a mild mental retardation since childhood and disorders of behavior and personality without any definite psychiatric syndrome, as already described in other metabolic diseases (group 3). Nonetheless, further studies are needed to clarify the psychiatric alterations within adult patients with PA.

Electroconvulsive therapy as life-saving in an acute catatonic syndrome associated with bipolar disorder: A case report

Introduction Catatonia is a neuropsychiatric syndrome characterized by an onset of a dysfunction in psychomotor activity and/or muscle tone, which may be associated with changes in consciousness, affect, and thinking. It is characterized by negativism, wax flexibility, catalepsy, mutism echolalia, ecopraxia, or stupor. It was first described in 1874 by Kahlbaum, who characterized it as specific motor disorder associated with different psychiatric disorders. Kraepelin and Bleuler restricted catatonia to a specific subtype of schizophrenia. However, the association between catatonia and other disorders, notably mood disorders, has been reinstated, including Bipolar Disorder. Its etiology is multiple and there are two severe forms: Neuroleptic Malignant Syndrome (NMS) and Malignant Catatonia (MC). These are syndromes that present high mortality, and the health professional should be aware of its etiology, signs, symptoms, evaluation and treatment.ObjectivesThe aim of this work is to present a clinical case of MC, who was sustained by literature included on scientific platforms.MethodsCase reportResults It is essential to recognize the different clinical presentations of catatonia, taking into account that these are psychiatric alterations in which urgent intervention is justified. In the presented case, the use of antipsychotic medication has worsened the motor function and its suspension, associated with the introduction of lorazepam, resulted in a slight improvement. The electroconvulsive therapy was the last resort, fully succeeded.ConclusionsThe relationship between SMN and Catatonia/MC remains nuclear from a psychopathological and pathophysiological point of view. Nevertheless, there is general agreement that catatonia represents a very significant risk factor for NMS.DisclosureNo significant relationships.

Altered immune phenotype and DNA methylation in panic disorder

BackgroundMultiple studies have related psychiatric disorders and immune alterations. Panic disorder (PD) has been linked with changes in leukocytes distributions in several small studies using different methods for immune characterization. Additionally, alterations in the methylation of repetitive DNA elements, such as LINE-1, have been associated with mental disorders. Here, we use peripheral blood DNA methylation data from two studies and an updated DNA methylation deconvolution library to investigate the relation of leukocyte proportions and methylation status of repetitive elements in 133 patients with panic disorder compared with 118 controls.Methods and resultsWe used DNA methylation data to deconvolute leukocyte cell-type proportions and to infer LINE-1 element methylation comparing PD cases and controls. We also identified differentially methylated CpGs associated with PD using an epigenome-wide association study approach (EWAS), with models adjusting for sex, age, and cell-type proportions. Individuals with PD had a lower proportion of CD8T cells (OR: 0.86, 95% CI: 0.78–0.96, P-adj = 0.030) when adjusting for age, sex, and study compared with controls. Also, PD cases had significantly lower LINE-1 repetitive element methylation than controls (P < 0.001). The EWAS identified 61 differentially methylated CpGs (58 hypo- and 3 hypermethylated) in PD (Bonferroni adjusted P < 1.33 × 10–7).ConclusionsThese results suggest that those with panic disorder have changes to their immune system and dysregulation of repeat elements relative to controls.

Smell and taste in cervical dystonia

The pathophysiology of cervical dystonia is not completely understood. Current concepts of the pathophysiology propose that it is a network disorder involving the basal ganglia, cerebellum and sensorimotor cortex. These structures are primarily concerned with sensorimotor control but are also involved in non-motor functioning such as the processing of information related to the chemical senses. This overlap lets us hypothesize a link between cervical dystonia and altered sense of smell and taste. To prove this hypothesis and to contribute to the better understanding of cervical dystonia, we assessed olfactory and gustatory functioning in 40 adults with idiopathic cervical dystonia and 40 healthy controls. The Sniffin Sticks were used to assess odor threshold, discrimination and identification. Furthermore, the Taste Strips were applied to assess the combined taste score. Motor and non-motor deficits of cervical dystonia including neuropsychological and psychiatric alterations were assessed as cofactors for regression analyses. We found that cervical dystonia subjects had lower scores than healthy controls for odor threshold (5.8 ± 2.4 versus 8.0 ± 3.2; p = 0.001), odor identification (11.7 ± 2.3 versus 13.1 ± 1.3; p = 0.001) and the combined taste score (9.5 ± 2.2 versus 11.7 ± 2.7; p < 0.001), while no difference was found in odor discrimination (12.0 ± 2.5 versus 12.9 ± 1.8; p = 0.097). Regression analysis suggests that age is the main predictor for olfactory decline in subjects with cervical dystonia. Moreover, performance in the Montreal Cognitive Assessment is a predictor for gustatory decline in cervical dystonia subjects. Findings propose that cervical dystonia is associated with diminished olfactory and gustatory functioning.

Parkinson's Disease: A Comprehensive Analysis of Fungi and Bacteria in Brain Tissue.

Parkinson's disease (PD) is characterized by motor disorders and the destruction of dopaminergic neurons in the substantia nigra pars compacta. In addition to motor disability, many patients with PD present a spectrum of clinical symptoms, including cognitive decline, psychiatric alterations, loss of smell and bladder dysfunction, among others. Neuroinflammation is one of the most salient features of PD, but the nature of the trigger remains unknown. A plausible mechanism to explain inflammation and the range of clinical symptoms in these patients is the presence of systemic microbial infection. Accordingly, the present study provides extensive evidence for the existence of mixed microbial infections in the central nervous system (CNS) of patients with PD. Assessment of CNS sections by immunohistochemistry using specific antibodies revealed the presence of both fungi and bacteria. Moreover, different regions of the CNS were positive for a variety of microbial morphologies, suggesting infection by a number of microorganisms. Identification of specific fungal and bacterial species in different CNS regions from six PD patients was accomplished using nested PCR analysis and next-generation sequencing, providing compelling evidence of polymicrobial infections in the CNS of PD. Most of the fungal species identified belong to the genera Botrytis, Candida, Fusarium and Malassezia. Some relevant bacterial genera were Streptococcus and Pseudomonas, with most bacterial species belonging to the phyla Actinobacteria and Proteobacteria. Interestingly, we noted similarities and differences between the microbiota present in the CNS of patients with PD and that in other neurodegenerative diseases. Overall, our observations lend strong support to the concept that mixed microbial infections contribute to or are a risk factor for the neuropathology of PD. Importantly, these results provide the basis for effective treatments of this disease using already approved and safe antimicrobial therapeutics.

The antioxidant and immunomodulatory compound 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole attenuates depression-like behavior and cognitive impairment developed in a mouse model of breast tumor

Psychiatric alterations are often found in patients with breast cancer even before the initiation of adjuvant therapy, resulting in a poor quality of life. It has become accepted that neuroinflammation and oxidative stress are involved in the pathophysiology of depression and cognitive impairment. Herein, we tested the hypothesis that treatment with the antioxidant and immunomodulatory selenium-containing compound 3-[(4-chlorophenyl)selanyl]-1-methyl-1H-indole (CMI)could attenuate behavioral and neurochemical alterations in a mammary (4T1) tumor model. Female BALB/c mice were subcutaneously inoculated with 4T1 cancer cells (1 × 105 cells/mice) or PBS. From days 14 to 20, mice received daily gavage with canola oil or CMI. On day 21, mice were submitted to behavioral tests followed by euthanasia. We found that CMI did not alter tumor growth, body weight, and body temperature in tumor-bearing mice. Importantly, treatment with CMI abrogated tumor-induced depression-like behavior and cognitive impairment. By the time CMI improved the behavioral alterations, it had reduced tumor-induced neuroinflammation (altered expression of NFκB, IL-1β, TNF-α, IL-10, IDO, and COX-2) and oxidative stress (altered expression of iNOS and Nrf2, and levels of reactive species, nitric oxide, lipid peroxidation, and superoxide dismutase activity) in the prefrontal cortices and hippocampi of mice. A molecular docking approach suggested the ability of CMI to inhibit the activity of iNOS and COX-2. Together, our results indicate that CMI treatment may attenuate depression and cognitive impairment in 4T1 tumor-bearing mice, and be a groundbreaking strategy for the treatment of cancer-related psychiatric symptoms to improve the quality of life of cancer patients.

Ageing and its challenges: Communitary Intervention Group findings and experience in 2017, Porto(PT)

Abstract West Porto Public Health(PH) Unit manages a multidisciplinary intervention group - Communitary Intervention Group(GIC) - that responds to critical life situations. It mainly covers mental and public health problems, often associated with ageing. We aimed to characterise the population of referred cases to GIC in 2017, know their geographical distribution and compare case ratio between parish. Data was provided by GIC and all cases from 2017 were included. We used GPS coordinates and QGIS to map the distribution of cases. Case number was compared between parish through the calculation of ratios (considering population size). 95% Confidence intervals (CI) were calculated by Byar’s method to assess differences between parish. A total of 88 cases were referred to GIC in 2017, mostly by the Police (37,1%). Mean age was 62,3 years(16-94) and 62,9% had &amp;gt; =60 years. Majority (53,3%) were women. The main problem identified was unsanitary housing(23,6%) and elderly at risk(23,6%), followed by psychiatric alterations(15,7%). Considering elderly at risk, 38,1% was associated with unsanitary housing and 14,3% with psychiatric alterations. Parish “Cedofeita, Santo Ildefonso, Sé, Miragaia, São Nicolau e Vitória”(CSSMS) had the highest number of cases (33,7%) and “Lordelo do Ouro e Massarelos” the highest case ratio (21,96; 95%CI:13,92-32,95). Visually most cases live in parish CSSMS or near social neighborhoods. Case ratios was not statistically different between parish. The type of referred cases suggests a lack of support to elderly. Immediate attention from health services is needed since this situation leads to a misuse of healthcare services, without a sustained benefit, peaking with health deterioration. More investigation is needed, especially to clearly identify social and health determinants. This is particularly important considering the population ageing and the socioeconomic pressure it perpetuates in future generations, compromising their health. Key messages Health services must rethink elderly care. Promoting quality of life through aging is key to sustainability.

NPC1 enables cholesterol mobilization during long‐term potentiation that can be restored in Niemann–Pick disease type C by CYP46A1 activation

NPC is a neurodegenerative disorder characterized by cholesterol accumulation in endolysosomal compartments. It is caused by mutations in the gene encoding NPC1, an endolysosomal protein mediating intracellular cholesterol trafficking. Cognitive and psychiatric alterations are hallmarks in NPC patients pointing to synaptic defects. However, the role of NPC1 in synapses has not been explored. We show that NPC1 is present in the postsynaptic compartment and is locally translated during LTP. A mutation in a region of the NPC1 gene commonly altered in NPC patients reduces NPC1 levels at synapses due to enhanced NPC1 protein degradation. This leads to shorter postsynaptic densities, increased synaptic cholesterol and impaired LTP in NPC1nmf164 mice with cognitive deficits. NPC1 mediates cholesterol mobilization and enables surface delivery of CYP46A1 and GluA1 receptors necessary for LTP, which is defective in NPC1nmf164 mice. Pharmacological activation of CYP46A1 normalizes synaptic levels of cholesterol, LTP and cognitive abilities, and extends life span of NPC1nmf164 mice. Our results unveil NPC1 as a regulator of cholesterol dynamics in synapses contributing to synaptic plasticity, and provide a potential therapeutic strategy for NPC patients.

Psychiatric Symptoms in Amyotrophic Lateral Sclerosis: Beyond a Motor Neuron Disorder.

The historical view that Amyotrophic Lateral Sclerosis (ALS) as a pure motor disorder has been increasingly challenged by the discovery of cognitive and behavioral changes in the spectrum of Frontotemporal Dementia (FTD). Less recognized and still significant comorbidities that ALS patients may present are prior or concomitant psychiatric illness, such as psychosis and schizophrenia, or mood disorders. These non-motor symptoms disturbances have a close time relationship with disease onset, may constitute part of a larger framework of network disruption in motor neuron disorders, and may impact ALS patients and families, with regards to ethical choices and end-of-life decisions. This review aims at identifying the most common psychiatric alterations related to ALS and its prognosis, looking at a common genetic background and shared structural brain pathology.

Maximum phonation times and vital capacity in dysphonic women

ABSTRACT Objective: to verify the correlation between vital capacity and maximum phonation times of /ė/ (unvoiced) and /s/, as well as compare and relate them with the professional voice use and age in women with functional or organic-functional dysphonia. Methods: a retrospective research with 524 records of dysphonic patients from a school clinic, including young adult women with a speech-language diagnosis of functional or organic-functional dysphonia based on medical reports. Neurological and psychiatric alterations, previous speech therapy treatment, symptoms of flu or allergies on the day of evaluation, pulmonary disease, organic dysphonia diagnosis, and hearing loss, were excluded. The sample resulted in 14 women with functional dysphonia and 21 with organic-functional dysphonia. Data on professional voice use, as well as results for vital capacity and maximum phonation times were collected. The data were statistically analyzed at a 5% significance level. Results: There was a positive correlation for both groups of dysphonic patients between the maximum phonation times of /ė/ and of /s/, as well as the maximum phonation times of /ė/, /s/, and vital capacity. Higher values for vital capacity and maximum times of /s/ and /ė/ for voice professionals were seen. The maximum phonation times of /ė/ were lower than those of /s/. Conclusion: as the maximum phonation times of /ė/ increased, the maximum phonation times of /s/ and the vital capacity also augmented in both groups, demonstrating the interrelation among these variables; there was no relation with the other variables studied.

P01.099 Psychiatric alterations and behavioural changes in brain tumor patients

P01.099 Psychiatric alterations and behavioural changes in brain tumor patients