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J Neurol Neurosurg Psychiatry 2004;75:370-376 Objectives: Declines in brain glucose metabolism have been described early in Alzheimer's disease (AD), and there is evidence that a genetic predisposition to AD contributes [...]

Introduction: With the rapid changes of attitude, investigation and legislation around cannabis and its subproducts in the Western world, there is a need to profoundly examine the consequences of its use in the general population and, specifically, in people affected by mental disorders. There is a clear relationship between cannabis use and psychosis, but there is also growing evidence of its relationship with manic episodes (Sideli et al, 2019). A systematic review published by the CANMAT Task Force in 2022 examined again the relationship between cannabis use and bipolar disorder (BD), establishing association with worsened course and functioning of BD in frequent users (Tourjman et al., 2023). On the other hand, some recent papers have highlighted the role of the endocannabinoid system (ECS) in BD, suggesting even possible beneficial effects, mainly through the CB2 receptor (Arjmand et al, 2019). Objectives: To describe the impact of cannabis in the psychiatric readmission in BD and to approach the differences in course in cannabis users with regards to non-users. Methods: We conducted a prospective cohort study including the patients admitted to our acute psychiatric unit with the diagnosis of manic or mixed episode during the period between 2015 and 2019 (including patients with one of both final diagnosis: BD or schizoaffective disorder). We established a follow-up of 3 years from the date of admission in which hospital readmissions are examined. Results: The study, which included 309 patients, concluded that cannabis users were admitted and had the first episode at a younger age (p=0.005), a higher percentage of them did not have a previous diagnosis (p=0.026) nor a previous history of mental health issues (p=0.019) and it was more likely to be their first admission (p=0.011) and to suffer psychotic symptoms (p=0.002). As of treatment, the results were statistically significant regarding the fact that a lower proportion of patients had received previous psychiatric treatment (p=0.004) and previous electroconvulsive therapy (p=0.003). There was a higher chance of them being non-adherent with medication (p<0.001) and to be administered extended-release antipsychotic treatment during admission (p<0.001). The study did not find a statistically significant relationship with cannabis use and a higher rate of readmission in the 3 years of follow-up. Conclusions: Although a higher relapse rate could not be proven in our study, other previously identified factors related to a worse illness course (Sajatovic et al., 2009) did show a significant association with cannabis use, which could lead to one suggesting that our results are compatible with the actual evidence and that cannabis products are detrimental to people who suffer from BD and schizoaffective disorder. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: Predicting acute affective episodes in individuals with Bipolar Disorder (BD) remains a clinical challenge. Specific environmental stressors, including air pollution, noise, and temperature variations might worsen affective symptoms or sleep in the general population, but their role in BD relapses is often overlooked. Indeed, they might exacerbate BD by perturbing circadian rhythms – fundamental aspects of BD. Objectives: We thereby present the protocol of this pilot study and future preliminary data. We aim to longitudinally assess sleep alterations, mood fluctuations, and environmental exposure to several factors (air pollutants, climate, noise, artificial light-at-night, green space access) in patients with BD and to check the association of these variables with BD relapses. Methods: In this pilot study, we will recruit 40 patients with BD in a 6-month prospective study. Patients were assessed during baseline, at 3 and 6 months. Data recollected will consist of a subjective (questionnaires) and objective (through meteorological stations) evaluation of physical environmental factors around the home residence; clinical assessment of mood and circadian rhythms, and continuous tracking of sleep-wake patterns, energy, and movement using actigraphy. Results: Expected results will show that exposure to a worse environment (higher pollution, noise, light exposure, climate) will be associated with worse BD outcomes (i.e., relapse, mood symptoms, sleep alterations). Conclusions: We will be sharing preliminary data from our ongoing study, offering insights into early patterns and findings that shed light on our objectives. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: Bipolar disorder (BD) is a multifaceted illness encompassing mood, energy, cognitive and biorhythms alterations. Sleep disturbances are common in prodromic, acute and inter-episodic phases of BD. Suicidality presents a known association with sleep disturbances. However, their interplay in BD remains intricate and not fully elucidated. Objectives: The aim of the present systematic review (SR) and meta-analysis (MA) is to summarise the available evidence and to provide an estimate of the association between sleep disturbances and suicidality, defined as presence of suicide ideation, behaviour and suicide attempts, in patients with BD. Methods: We conducted a comprehensive literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines across PubMed, PsycINFO, and SCOPUS databases. We included all studies reporting an association between sleep problems and suicidal behaviour in BD patients. No language restriction was imposed. Effect sizes were calculated as odds ratio (OR) for dichotomic variables, standard mean difference (SMD) for continuous outcomes, and Spearman's coefficient (r) for correlations. Heterogeneity was assessed using the I2 statistic. Global inconsistency was evaluated using the Q statistics with the corresponding p-value. Results: The initial search yielded 911 unique abstracts, of which 62 underwent full-text screening. Fourteen publications were included, comprising twelve cross-sectional and two longitudinal studies. The total sample consisted of 19,601 subjects diagnosed with BD, of which 51.76% were females and 69.52% had a diagnosis of BD type 1. We found that people with BD and sleep disturbances tend to have higher suicidality, both current (SMD=0.79, 95%CI=0.53, 1.05) and lifetime (OR=1.8; 95%CI=1.41, 2.55), when compared with people with BD and no sleep disturbances. Additionally, patients with BD and a history of suicide attempts tend to have more sleep problems (OR=1.37, 95%CI=1.21, 1.55). Moreover, a positive correlation exists between suicidality and poor sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) (r= 0.24, 95%CI=0.10, 0.36). No heterogeneity was found, except in the subanalysis of correlation (I2=66.67%, Q p-value=0.01). Conclusions: Our SRMA outlines a positive relation between sleep disturbances and suicidality in patients with BD. The small number of included studies and the scarcity of longitudinal studies, preventing the inference of a causal relationship, represent the major limitations of this study. Also, studies with objective measures of sleep alterations are currently lacking. The prompt recognition, objective measurement, and treatment of sleep alterations could be crucial in averting or reducing suicidal attempts in BD. Disclosure of Interest: C. Possidente: None Declared, M. Bort: None Declared, M. De Prisco: None Declared, V. Oliva: None Declared, G. Fico Grant / Research support from: Fellowship from "La Caixa" Foundation (ID 100010434 - fellowship code LCF/BQ/DR21/11880019), L. Bracco: None Declared, C. Sommerhoff: None Declared, L. Montejo: None Declared, A. Murru Grant / Research support from: Spanish Ministry of Science and Innovation (PI19/00672, PI22/00840) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdireccion General de Evaluacio ́n and the Fondo Europeo de Desarrollo Regional (FEDER), E. Vieta Grant / Research support from: Spanish Ministry of Science and Innovation (PI18/ 00805, PI21/00787) integrated into the Plan Nacional de I+D+I and cofinanced by the ISCIII-Subdireccio ́n General de Evaluacio ́n and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357; the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant No 754907 and EU.3.1.3. Treating and managing disease: Grant No 945151). [ABSTRACT FROM AUTHOR]

Background and purpose: CLOCK and PER2 genes have been implicated in sleep–wake cycle alterations and neurodegenerative diseases. Our aim was to evaluate the effect of CLOCK T3111C and PER2 C111G on cognitive functioning in subjective cognitive decline (SCD) patients and mild cognitive impairment (MCI) patients at the baseline of a longitudinal study, and the effect of these two polymorphisms on the progression to Alzheimer's disease (AD) of the two groups. Methods: Sixty‐eight subjects (41 SCD and 27 MCI) who underwent clinical evaluation, neuropsychological assessment, CLOCK and PER2 genotyping at baseline and neuropsychological follow‐up every 2 years for a mean time of 10 years were included. Subjects who developed AD (SCD‐c and MCI‐c) and non‐converters (SCD‐nc, MCI‐nc) were considered. Results: CLOCK T3111C was detected in 47% of cases (21 SCD, 11 MCI) and PER2 C111G in 19% of cases (eight SCD and five MCI). PER2 G carriers presented lower premorbid intelligence score (P = 0.049), fewer years of education (P = 0.007) and a lower frequency of family history of AD (P = 0.04) than G non‐carriers. MCI PER2 G carriers had worse performance in tests assessing memory, executive function, language and visuospatial abilities at baseline. During follow‐up, two SCD and 15 MCI subjects progressed to AD: both of the SCD‐c subjects presented the PER2 G allele, while none of the SCD PER2 G non‐carriers converted to AD (P = 0.003). Conclusion: PER2 seems to have a role in cognitive reserve and cognition in SCD and MCI patients. Nevertheless, further studies are needed to assess the role of PER2 C111G on the risk of progression to AD. [ABSTRACT FROM AUTHOR]

Background and purpose: Subjective cognitive decline (SCD) is a self‐experienced decline in cognitive capacity with normal performance on standardized cognitive tests and has been shown to increase the risk of Alzheimer's disease (AD). SCD could also be related to other conditions such as normal aging, psychiatric, neurological or medical disorders. The SCD Initiative proposed a set of features (SCD‐plus) that increase the likelihood of preclinical AD in individuals with SCD. Our aim was to assess the effect of these features on the risk of conversion from SCD to AD. Methods: In total 150 SCD subjects who underwent extensive neuropsychological investigation, assessment of cognitive complaints and apolipoprotein E (ApoE) genotyping at baseline and clinical‐neuropsychological follow‐up for a mean time of 11 years were included. Results: During the follow‐up, 20 subjects developed AD. Considering SCD‐plus features, age at onset ≥60 years and ApoE ε4 significantly increased the risk of conversion from SCD to AD. When our sample was stratified into three groups (no risk factor, one risk factor, two risk factors), the proportion of conversion was statistically significantly different between the three groups. Conclusions: Our model allows the risk of AD to be stratified in patients experiencing SCD according to age at onset and ApoE genotype. [ABSTRACT FROM AUTHOR]

Introduction: Covid-19 causes neuro/psychiatric problems by cerebral hypoxia. Objectives: My therapy could allow us to cross Covid-19 infection by minimizing both immediate and chronic lung damage and would avoid many deaths and neuro/psychiatric problems from cerebral hypoxia. Methods: In the case of a Covid-19 lung infection, the virus infects type II alveolar cells which consequently reduce the production of pulmonary surfactant. The surfactant has the function of reducing the surface tension of the alveoli. The less pulmonary surfactant there is, the more the alveoli tend to collapse due to the increased surface tension of their surface. Consequently, the lung would tend to collapse, that is, to reduce its volume, but collapse is prevented by the muscular movement of inspiration, which instead increases its volume. This means that a "low-pressure area" is created in the interstitial space which attracts liquid and substances which are often inflammatory and which organize over time, giving rise to interstitial pneumonia. Results: I propose to administer the pulmonary surfactant to the patient Covid-19 in the presence of dyspnea and certainly during assisted ventilation. This technique is routinely used in preterm infants suffering from lack of pulmonary surfactant production due to the immaturity of type II alveolar cells, pending that once matured these cells produce it autonomously. Conclusions: Similarly, the administration of surfactant during Covid-19 lung infection would allow the correct amount of surfactant to be maintained during the acute phase of the infection and would give time for type II alveolar cells to heal and independently resume surfactant production. [ABSTRACT FROM AUTHOR]

BACKGROUND/AIMS: Because of controversial results across studies, we evaluated the predictive value of premorbid intelligence and the apolipoprotein E (ApoE) genotype on baseline and progression of cognitive performance in Alzheimer's disease (AD). METHODS: Eighty-five mild AD cases, ApoE genotyped and included in a longitudinal cliniconeuropsychological-genetic study, underwent a premorbid intelligence test and up to 11 (average 5) neuropsychological assessments. We applied linear- and logistic-regression models for cross-sectional data and mixed models for longitudinal ones. RESULTS: Higher premorbid intelligence was associated with higher global, executive and memory performance, while the ApoE epsilon 4 allele was specifically related to poorer memory performance. The premorbid intelligence-ApoE epsilon 4/epsilon 4 interaction was significant, with higher premorbid intelligence scores reducing the detrimental effect of ApoE epsilon 4 homozygosity on memory performance. Higher premorbid intelligence, but not the ApoE epsilon 4 allele, was related to faster memory deficit progression. CONCLUSION: The association of higher premorbid intelligence with better baseline cognitive performance and faster memory decline, as well as its interaction with the ApoE genotype, strengthens the role of cognitive reserve in shaping the disease's clinical expression. Our findings confirm that the epsilon 4 allele affects memory deficit at baseline but does not exert any influence on the rate of cognitive decline. [ABSTRACT FROM AUTHOR]

This study investigated the contribution that white matter changes (WMCs) make to clinical and cognitive features in Alzheimer's disease (AD), independently of possible confounders such as cortical atrophy and the apolipoprotein E genotype as well as their relationship to vascular risk factors. We semiquantitatively assessed the degree and location of WMCs (global, periventricular and deep white matter), lacunes and global atrophy on brain MRI scans of 86 AD cases, extensively evaluated from a clinical and neuropsychological point of view. Multivariate logistic and linear regression analysis showed that age was the only significant predictor of all WMC measures and revealed a significant association of periventricular WMCs with performance on executive function tasks as well as of deep WMCs with history of mood depression. Our results underline the significance of WMC location over size in the occurrence of specific cognitive deficits in AD. [ABSTRACT FROM AUTHOR]

We report that homeodomain-only protein (HOP) is expressed in the suprabasal layer of normal upper aerodigestive tract epithelium and expression strongly decreases in hypopharyngeal carcinoma. Interestingly, HOP has very recently been shown to be a tumour suppressor involved in differentiation, suggesting that HOP may have a similar role in head and neck squamous cell carcinoma (HNSSC). [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in men with an incidence of about 780000 new cases per year worldwide and a poor rate of survival. There is a need for a better understanding of HNSCC, for the development of rational targeted interventions and to define new prognostic or diagnostic markers. To address these needs, we performed a large-scale differential display comparison of hypopharyngeal HNSCCs against histologically normal tissue from the same patients. We have identified 70 genes that exhibit a striking difference in expression between tumours and normal tissues. There is only a limited overlap with other HNSCC gene expression studies that have used other techniques and more heterogeneous tumour samples. Our results provide new insights into the understanding of HNSCC. At the genome level, a series of differentially expressed genes cluster at 12p12-13 and 1q21, two hotspots of genome disruption. The known genes share functional relationships in keratinocyte differentiation, angiogenesis, immunology, detoxification, and cell surface receptors. Of particular interest are the 13 'unknown' genes that exist only in EST, theoretical cDNA and protein databases, or as chromosomal locations. The differentially expressed genes that we have identified are potential new markers and therapeutic targets. [ABSTRACT FROM AUTHOR]

By the use of discriminant analysis it was possible to obtain from a wide neuropsychological battery a few psychometric tests able to stage five levels of mental impairment in 70 healthy and demented elderly subjects, according to two canonical variables. The tests maximally discriminant among the groups were: Personal Memory items of Blessed Dementia Scale, Five Words Recall after 24h, paired Words Acquisition, Information/Orientation and Mental Ability items of Clifton Assessment Schedule. The accuracy of the prediction rule was evaluated on a validation set of patients. The short battery made it possible to classify correctly 90% of subjects and to follow easily the course of mental decline. The agreement between observed and predicted groups was 0.93 as calculated by the weighted kappa. We emphasize the role of discriminate analysis in the evaluation of neuropsychological batteries for diagnostic purposes. [ABSTRACT FROM AUTHOR]

Introduction: Anorexia of females adolescents has a high mortality rate and heavy health, psychological, family consequences even in case of survival. Objectives: To reduce the mortality rate and the consequences of anorexia by providing a theory that allows us to have early or even predictive diagnosis Methods: 25 years ago I found blood type (O, A, B, AB) difference between an anorexic patient and her mother. Pregnancy had been with placental detachment and birth was traumatic, presumed causes of a mother/daughter blood contact. From that day on, I checked, in the case of Anorexia of the Female Adolescent, the blood types of the anorexic girl and her mother. Results: In my collection of data (more than 100 cases in 25 years): only the girls who have a different blood type (O, A, B, AB) from the mother are anorexic and from the patient's history, we could think of a mother/daughter blood contact during the pregnancy. There are no exceptions in my data. My new theory is that Anorexia of the Female Adolescent, in addition to the girl's psychological causes, needs a "conditio sine qua non" (a necessary but not sufficient condition): Different mother/daughter blood types (O,A,B,AB) and traumatic contact between the two blood types during pregnancy and/or birth". Conclusions: My theory facilitates early diagnosis (Preventive Medicine) by limiting observation, for Anorexia risk, to only daughters with a different blood type than that of the mother. Recognizing this "conditio sine qua non" for Anorexia of the Female Adolescent allows us an early diagnosis and a predictive hypothesis. [ABSTRACT FROM AUTHOR]

Abstract Background Commercially available microarrays have been used in many settings to generate expression profiles for a variety of applications, including target selection for disease detection, classification, profiling for pharmacogenomic response to therapeutics, and potential disease staging. However, many commercially available microarray platforms fail to capture transcript diversity produced by alternative splicing, a major mechanism for driving proteomic diversity through transcript heterogeneity. Results The human Genome-Wide SpliceArray™ (GWSA), a novel microarray platform, utilizes an existing probe design concept to monitor such transcript diversity on a genome scale. The human GWSA allows the detection of alternatively spliced events within the human genome through the use of exon body and exon junction probes to provide a direct measure of each transcript, through simple calculations derived from expression data. This report focuses on the performance and validation of the array when measured against standards recently published by the Microarray Quality Control (MAQC) Project. The array was shown to be highly quantitative, and displayed greater than 85% correlation with the HG-U133 Plus 2.0 array at the gene level while providing more extensive coverage of each gene. Almost 60% of splice events among genes demonstrating differential expression of greater than 3 fold also contained extensive splicing alterations. Importantly, almost 10% of splice events within the gene set displaying constant overall expression values had evidence of transcript diversity. Two examples illustrate the types of events identified: LIM domain 7 showed no differential expression at the gene level, but demonstrated deregulation of an exon skip event, while erythrocyte membrane protein band 4.1 -like 3 was differentially expressed and also displayed deregulation of a skipped exon isoform. Conclusion Significant changes were detected independent of transcriptional activity, indicating that the controls for transcript generation and transcription are distinct, and require novel tools in order to detect changes in specific transcript quantity. Our results demonstrate that the SpliceArray™ design will provide researchers with a robust platform to detect and quantify specific changes not only in overall gene expression, but also at the individual transcript level.