Impact of COVID-19 outbreak on subjective sleep during lockdown: relation with resilience characteristics.

The SARS-CoV-2 pandemic had a considerable impact on both the physical and mental health of people. Resilience is a psychological characteristic reflecting the ability to overcome or adapt to difficulties such as adversity, trauma, or extremely stressful situations. People with high resilience have been shown to exhibit lower levels of anxiety, stress and depression when faced with a stressful event. Sleep is particularly sensitive to anxiety and stress. The aim of this study was to investigate the impact of COVID-19 pandemic on sleep quantity, quality, and habits, while considering resilience as a factor. A total of 1260 individuals were recruited through an online survey. The variables that were assessed were socio-demographic, sleep habits and sleep disorders history, the Athens Insomnia Scale (AIS), the 25-item version of the Connor-Davidson Resilience Scale (CD-RISC), and any work/financial consequences during the first COVID-19 lockdown. The results showed that sleep habits during the lockdown changed for many of the participants. Their sleep schedule moving towards earlier or later for 9% and 67% of them, respectively; 38% of the participants were found to suffer from insomnia, based on the AIS score. A higher score on the CD-RISC was associated with better sleep. In conclusion, our study confirmed previous studies identifying quantitative and qualitative changes in sleep during the COVID-19 lockdown. It also expanded on the previous findings by identifying the correlation between sleep and resilience during the stressful period of the COVID-19 lockdown.

Diminished social motivation in early psychosis is associated with polygenic liability for low vitamin D.

Insufficiency of vitamin D levels often occur in individuals with schizophrenia and first-episode psychosis (FEP). However, it is unknown whether this represents a biological predisposition, or it is essentially driven by illness-related alterations in lifestyle habits. Lower vitamin D has also been associated with adverse neurodevelopmental outcomes and predominant negative psychotic symptoms. This study aimed to investigate the contribution of polygenic risk score for circulating 25-hydroxyvitamin D concentration (PRS-vitD) to symptom presentation among individuals with FEP enrolled in the Athens First-Episode Psychosis Research Study (AthensFEP n = 205) and the Psychosis Incident Cohort Outcome Study (PICOS n = 123). The severity of psychopathology was evaluated using the Positive and Negative Syndrome Scale at baseline and follow-up assessments (AthensFEP: 4-weeks follow-up, PICOS: 1-year follow-up). Premorbid intelligence and adjustment domains were also examined as proxy measures of neurodevelopmental deviations. An inverse association between PRS-vitD and severity of negative symptoms, in particular lack of social motivation, was detected in the AthensFEP at baseline (adjusted R2 = 0.04, p < 0.001) and follow-up (adjusted R2 = 0.03, p < 0.01). The above observation was independently validated in PICOS at follow-up (adjusted R2 = 0.06, p < 0.01). No evidence emerged for a relationship between PRS-vitD and premorbid measures of intelligence and adjustment, likely not supporting an impact of lower PRS-vitD on developmental trajectories related to psychotic illness. These findings suggest that polygenic vulnerability to reduced vitamin D impairs motivation and social interaction in individuals with FEP, thereby interventions that encourage outdoor activities and social engagement in this patient group might attenuate enduring negative symptoms.

The relationship between bullying and symptom presentation in first-episode psychosis.

Multiple recent studies have indicated that adverse psycho-traumatic experiences are particularly significant, if not the most significant, among the environmental factors that participate in the aetiology of schizophrenic spectrum disorders. The prevalence of bullying in the adolescent population has increased dramatically compared to earlier reports. This may be related to the recent development of communication technology and the use of social media, which have expanded the means by which bullying can be practiced. The present study aims to investigate the association between bullying victimisation and psychotic symptoms in First-Episode Psychosis (FEP) patients, hypothesising that patients who have a bullying history may have increased psychotic symptoms and a more unfavourable early trajectory after treatment as usual compared to patients who do not have a bullying history. Research data were collected from a sample of men and women of the Greek general population aged between 16 and 45 (N=225) who experienced a FEP in the context of the Athens First-Episode Psychosis (FEP) Study. The assessment of bullying was performed using the Retrospective Bullying Questionnaire (RBQ). Assessment of positive and negative psychotic symptoms and general psychopathology was performed using the corresponding subscales of the Positive and Negative Syndrome Scale (PANSS) at baseline and after 4 weeks of treatment as usual. Clinical remission was assessed based on the baseline and follow-up values of the PANSS and on Andreasen's symptomatic criteria. Methodologically, Pearson's chi-square test was used to compare the history of bullying between men and women, while linear and logistic regression models were used to check the correlations between history of bullying and symptom severity at baseline and 4-week follow-up, as well as the correlation between history of bullying and remission. The prevalence of bullying history in our sample of patients (N:225) with a FEP was 51.4% (114/225). Bullying was recorded in our study participants with equal frequency in women and men. According to the analysis results, the patients who had experienced bullying did not present at baseline with significantly increased psychotic symptoms compared to the patients who did not have a history of bullying. In addition, bullying was not associated with reduced remission according to Andreasen's criteria. However, the patients who had experienced bullying were found to have significantly increased negative symptoms (B=1.66; SE=0.70; p=0.018) and increased PANSS total score (B=4.81; SE=2.34; p=0.041) at 4-week follow-up. Our results highlight the persistence of negative and overall symptoms as an impact of bullying on the development of the FEP and align with studies that support the consideration of a history of bullying during both the diagnostic and therapeutic processes.

Comprehensive Evaluation of Psychotic Features and Their Clinical Correlates in Early Parkinson's Disease.

BACKGROUND: Some reports suggest that psychotic features may occur in the early stages of Parkinson's disease (PD), but sensitive tools have not been utilized. OBJECTIVE: The aim was to evaluate the presence of psychotic symptoms using detailed scales and to assess the association with clinical characteristics. METHODS: Healthy controls and patients within three years of PD onset were recruited. Participants were examined for psychotic symptoms using two different instruments: the Comprehensive Assessment of At-Risk Mental States (CAARMS) and a 10 question PD specific psychosis severity scale (10PDQ). In the PD group, medication use, motor and non-motor symptoms were documented. RESULTS: Based on CAARMS and 10PDQ scales, psychotic features were present in 39% (27/70) of patients and 4% (3/74) of controls. The prevalence of passage hallucinations and illusions was significantly higher in PD compared to the control group. The presence of PD-associated psychotic features was not significantly affected by medication, motor severity or global cognitive status. Higher prevalence of overall non-motor manifestations, REM sleep behavior disorder (RBD) and depressive symptoms was significantly associated with the manifestation of psychotic features in PD [(adjusted OR:1.3; 95% CI:1.1-1.6; p = 0.003), (adjusted OR:1.3; 95% CI:1.0-1.6; p = 0.023), and (adjusted OR:1.2; 95% CI:1.0-1.4;p = 0.026)]. CONCLUSIONS: Psychotic phenomena mainly of minor nature are highly common in early PD. Cumulative non-motor symptoms, RBD and depressive features are associated with the presence of psychotic symptoms in this non-demented, early-stage PD population. More studies are needed to clarify the mechanisms that contribute to the onset of psychotic features in early PD.

Jumping to conclusions bias, psychosis and impulsivity in early stages of Parkinson's disease.

OBJECTIVES: The aim was to explore the correlations between Jumping to Conclusions (JtC) tendency and neuropsychiatric features in patients with early Parkinson's disease (PD). BACKGROUND: According to few reports, PD patients with impulsive-compulsive behaviors (ICBs) are prone to working memory difficulties including JtC bias. The correlation of psychotic features and JtC tendency remains still unclear. METHODS: Healthy controls and patients within 3 years of PD onset were recruited. Participants were examined for psychotic symptoms using a 10 question PD-specific psychosis severity scale. JtC was measured by a probalistic reasoning scenario (beads task). In PD group, medication use, motor and non-motor symptoms were documented. Impulsivity was evaluated using the Questionnaire for Impulsive-Compulsive Disorders in PD (QUIP). RESULTS: The prevalence of JtC bias was 9% (6/70) in healthy individuals, compared to 32% (22/68) of PD group [p = 0.001]. No association was detected between the presence of JtC tendency and PD-associated psychosis (p = 0.216). Patients with JtC had shorter duration of PD, more tremor-dominant PD subtype and higher QUIP scores, regardless of the dopaminergic therapy (p = 0.043, p = 0.015, p = 0.007, respectively). A trend towards attention and inhibition control deficit was noticed in JtC patients. CONCLUSIONS: We found a high prevalence of JtC bias in early, cognitively intact PD population and a potential link between subthreshold ICBs and poor performance on beads task. Additional studies are needed to confirm our results and elaborate on the mechanisms that correlate impulsivity with JtC tendency, which are likely to be different from those mediating psychotic features in early PD.

Role of Clinical Insight at First Month in Predicting Relapse at the Year in First Episode of Psychosis (FEP) Patients.

INTRODUCTION: Clinical insight constitutes a useful marker of the progress and outcome of the First Episode of Psychosis (FEP), and lack of insight has been associated with more severe psychopathology, treatment non-adherence, and rehospitalization/relapse. In this study, we aimed to further investigate the possible role of insight as a predictor of relapse, its relation to diagnosis, and other parameters of positive psychotic symptomatology (delusions, hallucinations, and suspiciousness). METHODS: The Athens FEP study employed a prospective, longitudinal cohort design in which consecutive newly diagnosed patients with psychosis were interviewed and asked to voluntarily participate after completing informed consent. A total of 88/225 patients were examined at three different time points (baseline, month, and year). Their scores in the relevant items of the Positive and Negative Syndrome Scale (PANSS) were compared (G12 for insight, P1 for delusions, P3 for hallucinations, and P6 for suspiciousness), and they were further associated to diagnosis and the outcome at the end of the year (remission/relapse). RESULTS: In total, 22/88 patients with relapse at the year had greater scores in G12 for both the month and the year, and this finding was corroborated after adjusting the statistical analysis for demographics, diagnosis, social environment, and depression via multiple logistic regression analysis. Moreover, delusions and suspiciousness were significantly higher in patients diagnosed with non-affective psychosis compared to those diagnosed with affective psychosis (p < 0.001) at the first month. CONCLUSIONS: Lack of insight at the first month may serve as a predictor of relapse at the year.

Old-age mental telehealth services at primary healthcare centers in low- resource areas in Greece: design, iterative development and single-site pilot study findings.

BACKGROUND: Even though communities in low-resource areas across the globe are aging, older adult mental and cognitive health services remain mainly embedded in tertiary- or secondary hospital settings, and thus not easily accessible by older adults living in such communities. Here, the iterative development of INTegRated InterveNtion of pSychogerIatric Care (INTRINSIC) services addressing the mental and cognitive healthcare needs of older adults residing in low-resource areas of Greece is depicted. METHODS: INTRINSIC was developed and piloted in three iterative phases: (i) INTRINSIC initial version conceptualization; (ii) A 5-year field testing in Andros island; and (iii) Extending the services. The INTRINSIC initial version relied on a digital platform enabling videoconferencing, a flexible battery of diagnostic tools, pharmacological treatment and psychosocial support and the active involvement of local communities in service shaping. RESULTS: Ιn 61% of the 119 participants of the pilot study, new diagnoses of mental and/or neurocognitive disorders were established. INTRINSIC resulted in a significant reduction in the distance travelled and time spent to visit mental and cognitive healthcare services. Participation was prematurely terminated due to dissatisfaction, lack of interest or insight in 13 cases (11%). Based on feedback and gained experiences, a new digital platform, facilitating e-training of healthcare professionals and public awareness raising, and a risk factor surveillance system were created, while INTRINSIC services were extended to incorporate a standardized sensory assessment and the modified problem adaptation therapy. CONCLUSION: The INTRINSIC model may be a pragmatic strategy to improve access of older adults with mental and cognitive disorders living in low-resource areas to healthcare services.

Association between exposome score for schizophrenia and functioning in first-episode psychosis: results from the Athens first-episode psychosis research study.

BACKGROUND: Evidence suggests that environmental factors not only increase psychosis liability but also influence the prognosis and outcomes of psychotic disorders. We investigated temporal and cross-sectional associations of a weighted score of cumulative environmental liability for schizophrenia - the exposome score for schizophrenia (ES-SCZ) - with functioning in first-episode psychosis (FEP). METHODS: Data were derived from the baseline and 1-month assessments of the Athens FEP Research Study that enrolled 225 individuals with FEP. The Global Assessment of Functioning (GAF) and the Personal and Social Performance Scale (PSP) were used to measure social, occupational, and psychological functioning. The ES-SCZ was calculated based on the previously validated method. RESULTS: ES-SCZ was associated with the total scores of GAF and PSP at baseline and 1-month assessments. These findings remained significant when accounting for several associated alternative explanatory variables, including other environmental factors (obstetric complications, migration, ethnic minority), clinical characteristics (duration of untreated psychosis, symptom severity, previous antipsychotic use), and family history of psychosis, demonstrating that the association between ES-SCZ and functioning is over and above other risk factors and cannot be explained by symptom severity alone. Functioning improved from baseline to 1-month assessment, but no significant ES-SCZ-by-time interaction was found on functioning, indicating that functioning changes were not contingent on ES-SCZ. CONCLUSIONS: Our findings suggest that rather than a predictor of functional improvement, ES-SCZ represents a stable severity indicator that captures poor functioning in early psychosis. Environmental risk loading for schizophrenia (ES-SCZ) can be beneficial for clinical characterization and incorporated into transdiagnostic staging models.

Don't blame psychosis, blame the lack of services: a message for early intervention from the Greek standard care model.

BACKGROUND: Early Intervention Services (EIS) aim to reduce relapse rates and achieve better treatment and functional outcomes for first episode psychosis (FEP) patients. Existing models of services in Greece are still treatment as usual (TAU), however a reform of mental health services is underway and initial steps have been taken to shift standard care towards EIS. The purpose of the study is to address therapeutic gaps by exploring service engagement and relapse rates in the current standard care model for psychosis. METHODS: We examined follow-up and relapse rates one year after initial treatment contact in the first longitudinal FEP study conducted in Greece. 225 patients were enrolled between 2015-2020. Sociodemographic, clinical and functional characteristics were assessed in association with follow-up and relapse rates. RESULTS: Within a TAU follow-up setting, one year attrition rates were high. Only 87 patients (38,7%) retained contact with services after one year and within this time frame, 19 of them (21,8%) experienced a severe relapse requiring rehospitalization. Demographic, clinical and functional contributors failed to predict service engagement and relapse rates, with the exception of treatment adherence. CONCLUSION: Both follow-up and one-year rehospitalization rates in our FEP sample, highlight the need for the implementation of early intervention services, that will aim at engagement maximization and relapse prevention. These indexes also provide a benchmark against which future early intervention services for psychosis in Greece will have to demonstrate superior efficacy.

Cortico-cognition coupling in treatment resistant schizophrenia.

BACKGROUND: Brain structural alterations and cognitive dysfunction are independent predictors for poor clinical outcome in schizophrenia, and the associations between these domains remains unclear. We employed a novel, multiblock partial least squares correlation (MB-PLS-C) technique and investigated multivariate cortico-cognitive patterns in patients with treatment-resistant schizophrenia (TRS) and matched healthy controls (HC). METHOD: Forty-one TRS patients (age 38.5 ± 9.1, 30 males (M)), and 45 HC (age 40.2 ± 10.6, 29 M) underwent 3T structural MRI. Volumes of 68 brain regions and seven variables from CANTAB covering memory and executive domains were included. Univariate group differences were assessed, followed by the MB-PLS-C analyses to identify group-specific multivariate patterns of cortico-cognitive coupling. Supplementary three-group analyses, which included 23 non-affected first-degree relatives (NAR), were also conducted. RESULTS: Univariate tests demonstrated that TRS patients showed impairments in all seven cognitive tasks and volume reductions in 12 cortical regions following Bonferroni correction. The MB-PLS-C analyses revealed two significant latent variables (LVs) explaining > 90% of the sum-of-squares variance. LV1 explained 78.86% of the sum-of-squares variance, describing a shared, widespread structure-cognitive pattern relevant to both TRS patients and HCs. In contrast, LV2 (13.47% of sum-of-squares variance explained) appeared specific to TRS and comprised a differential cortico-cognitive pattern including frontal and temporal lobes as well as paired associates learning (PAL) and intra-extra dimensional set shifting (IED). Three-group analyses also identified two significant LVs, with NARs more closely resembling healthy controls than TRS patients. CONCLUSIONS: MB-PLS-C analyses identified multivariate brain structural-cognitive patterns in the latent space that may provide a TRS signature.

Prediction of Early Symptom Remission in Two Independent Samples of First-Episode Psychosis Patients Using Machine Learning.

BACKGROUND: Validated clinical prediction models of short-term remission in psychosis are lacking. Our aim was to develop a clinical prediction model aimed at predicting 4-6-week remission following a first episode of psychosis. METHOD: Baseline clinical data from the Athens First Episode Research Study was used to develop a Support Vector Machine prediction model of 4-week symptom remission in first-episode psychosis patients using repeated nested cross-validation. This model was further tested to predict 6-week remission in a sample of two independent, consecutive Danish first-episode cohorts. RESULTS: Of the 179 participants in Athens, 120 were male with an average age of 25.8 years and average duration of untreated psychosis of 32.8 weeks. 62.9% were antipsychotic-naïve. Fifty-seven percent attained remission after 4 weeks. In the Danish cohort, 31% attained remission. Eleven clinical scale items were selected in the Athens 4-week remission cohort. These included the Duration of Untreated Psychosis, Personal and Social Performance Scale, Global Assessment of Functioning and eight items from the Positive and Negative Syndrome Scale. This model significantly predicted 4-week remission status (area under the receiver operator characteristic curve (ROC-AUC) = 71.45, P < .0001). It also predicted 6-week remission status in the Danish cohort (ROC-AUC = 67.74, P < .0001), demonstrating reliability. CONCLUSIONS: Using items from common and validated clinical scales, our model significantly predicted early remission in patients with first-episode psychosis. Although replicated in an independent cohort, forward testing between machine learning models and clinicians' assessment should be undertaken to evaluate the possible utility as a routine clinical tool.

Hospital workforce mental reaction to the pandemic in a low COVID-19 burden setting: a cross-sectional clinical study.

Τhe COVID-19 pandemic has mental health implications for both healthcare workforces and general population, particularly in regions heavily hit by the crisis. Τhe study aimed (i) to investigate anxiety- and depression severity differences between staff of a COVID-19 treatment unit (N = 84) and a hospital without such a unit (N = 55) in comparison to participants of a convenience general population online survey (N = 240) and (ii) to explore relations between such symptoms and hospital staff reaction to COVID-19 in a low COVID-19 burden setting. Anxiety was studied with the Generalized Anxiety Disorder 7-Item in hospital workforces and with the Hospital Anxiety Depression Scale (HADS) in online survey participants. Depression symptoms were assessed with the Patient Health Questionnaire-9 in hospital employees and the HADS in the online survey sample. Symptoms were classified as absent/minimal, borderline abnormal or indicating clinical caseness. Staff reaction to COVID-19 was tapped with a 9-item-questionnaire and the 22-item Impact of Event Scale-revised (IES-R). Proper tests for differences and stepwise ordered logistic regression models were employed. Anxiety- and depression severity was higher in hospital workforces than in online survey participants (P < 0.05). Anxiety was more severe in frontline- compared to backstage employees (P < 0.001) was inversely correlated with age (P = 0.011) and positively with avoidance (P = 0.028). Both anxiety and depression symptoms related to intrusion symptoms (P < 0.001). Regarding the relatively long data collection period, an inverse association between crisis duration and depression symptoms was detected (P = 0.025). These observations point to the urgent need for distress-mitigating interventions for hospital workforces even in low COVID-19 burden settings.

The relationship between early symptom severity, improvement and remission in first episode psychosis with jumping to conclusions.

It is suggested that Jumping To Conclusions (JTC) reasoning bias might contribute to the distortion of external reality. However, the association between psychotic manifestations and JTC is obscure, especially if general intelligence is considered as a mediator. The aim of this study is to investigate the relation between severity, early clinical improvement and remission of symptoms in First Episode Psychosis (FEP) with JTC as an explanatory factor. One hundred seventy-one FEP individuals were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and one month after treatment initiation. Clinical improvement was ascribed as symptom change one-month post-baseline measurements. Symptomatic remission was assessed with the Andreasen severity criteria and JTC with the Beads Task, operationalized through Draws To Decision (DTD) (the lower the number of DTD, the higher the JTC bias). Regarding symptoms severity, total psychotic, total positive psychotic, and hallucinations-item PANSS scores showed a negative association with JTC after controlling for IQ. Regarding early clinical improvement, the association with JTC was non-significant. No significant association was detected between one month remission status of FEP and JTC. Our findings indicate that severity of positive symptoms is not associated with hastiness in decision-making, but rather with a heightened conservatism in terms of increased data gathering. Further research is required to replicate the results and clarify the cognitive processes involved.

COVID-19 Crisis Effects on Caregiver Distress in Neurocognitive Disorder.

BACKGROUND: The outbreak of the COVID-19 pandemic seems to have mental health implications for both people with neurocognitive disorder and their caregivers. OBJECTIVE: The study aimed to shed light on relations between caregiver mental reaction to the pandemic and caregiver distress related to neuropsychiatric symptoms, memory impairment progression, and functional impairment of people with neurocognitive disorder during the period of confinement in Greece. METHODS: The study included caregivers of patients with mild (N = 13) and major (N = 54) neurocognitive disorder. The caregiver-based telephone interview was based on items of the neuropsychiatric inventory questionnaire, the AD8 Dementia Screening Instrument, and the Bristol Activities of Daily Living Scale. Regarding the mental impact of the COVID-19 crisis on caregivers, four single questions referring to their worries in the last seven days were posed, in addition to the scales Generalized Anxiety Disorder 7-Item (GAD-7) and the 22-item Impact of Event Scale-revised (IES-R). A stepwise linear regression model was employed for studying the relationship between caregiver distress and demographic and clinical data and caregiver mental reaction to COVID-19 pandemic outbreak. RESULTS: Caregiver distress severity during the confinement period was influenced not only by memory deficits (p = 0.009) and neuropsychiatric symptoms (p < 0.001) of patients, but also by caregiver hyperarousal (p = 0.003) and avoidance symptoms (p = 0.033) and worries directly linked to the COVID-19 crisis (p = 0.022). CONCLUSION: These observations provide further evidence for the urgent need for support of caregivers of patients with neurocognitive disorder during the COVID-19 pandemic.

Familial and socioeconomic contributions to premorbid functioning in psychosis: Impact on age at onset and treatment response.

BACKGROUND: Premorbid adjustment (PA) abnormalities in psychotic disorders are associated with an earlier age at onset (AAO) and unfavorable clinical outcomes, including treatment resistance. Prior family studies suggest that familial liability, likely reflecting increased genetic risk, and socioeconomic status (SES) contribute to premorbid maladjustment. However, their joint effect possibly indicating gene-environment interaction has not been evaluated. METHODS: We examined whether family history of psychosis (FHP) and parental SES may predict PA and AAO in unrelated cases with first-episode psychosis (n = 108) and schizophrenia (n = 104). Premorbid academic and social functioning domains during childhood and early adolescence were retrospectively assessed. Regression analyses were performed to investigate main effects of FHP and parental SES, as well as their interaction. The relationships between PA, AAO, and response to antipsychotic medication were also explored. RESULTS: Positive FHP associated with academic PA difficulties and importantly interacted with parental SES to moderate social PA during childhood (interaction p = 0.024). Positive FHP and parental SES did not predict differences in AAO. Nevertheless, an earlier AAO was observed among cases with worse social PA in childhood (ß = -0.20; p = 0.005) and early adolescence (ß = -0.19; p = 0.007). Further, confirming evidence emerged for an association between deficient childhood social PA and poor treatment response (p = 0.04). CONCLUSIONS: Familial risk for psychosis may interact with parental socioeconomic position influencing social PA in childhood. In addition, this study supports the link between social PA deviations, early psychosis onset, and treatment resistance, which highlights premorbid social functioning as a promising clinical indicator.

Organization framework and preliminary findings from the Athens First-Episode Psychosis Research Study.

AIMS: Athens First-Episode Psychosis (FEP) Research study, aims to explore the potential associations between multiple genetic, environmental and neurometabolic risk factors of psychotic disorders, through the clinical management of FEP patients with minimal exposure (<2 weeks) to antipsychotic treatment at entry. The goal of this paper is to introduce the background, rationale and design of the study and present its preliminary findings. METHODS: We developed a longitudinal cohort study of FEP patients 16-45 years old, presenting at the emergency units of five psychiatric hospitals across Athens, Greece. Research timeline includes baseline, 1-month and 1-year follow-up. Clinical, genetic, environmental, cognitive and biochemical parameters are measured, using psychometric tools, clinical interviews and laboratory tests. A descriptive analysis of baseline and 1-month assessments was performed including demographic characteristics, family history, medication, clinical picture, traumatic experiences, drug use and cognitive functioning. RESULTS: During the last 3 years, 130 subjects have been enrolled in the study. Data so far reveal that, despite the severity of baseline presentation, at 1-month the majority (57.4%) met the Andreasen symptom severity criteria for remission, without the time criterion and showed mild functional improvement. Several environmental adversities and poor cognitive performance were identified, which need to be further elaborated. CONCLUSIONS: Athens FEP Research study is the first gene-environment interaction study in Greece. In this article we introduce the organization and methodological framework of the project, along with its basic initial findings. Future analysis will allow the validation of tractable predictors and risk factors implicated in the development and outcome of psychosis.

Complex interactions between the components of the PI3K/AKT/mTOR pathway, and with components of MAPK, JAK/STAT and Notch-1 pathways, indicate their involvement in meningioma development.

We investigated the significance of PI3K/AKT/mTOR pathway and its interactions with MAPK, JAK/STAT and Notch pathways in meningioma progression. Paraffin-embedded tissue from 108 meningioma patients was analysed for the presence of mutations in PIK3CA and AKT1. These were correlated with the expression status of components of the PI3K/AKT/mTOR pathway, including p85α and p110γ subunits of PI3K, phosphorylated (p)-AKT, p-mTOR, p-p70S6K and p-4E-BP1, as well as of p-ERK1/2, p-STAT3 and Notch-1, clinicopathological data and patient survival. A mutation in PIK3CA or AKT1 was found in around 9 % of the cases. Higher grade meningiomas displayed higher nuclear expression of p-p70S6K; higher nuclear and cytoplasmic expression of p-4E-BP1 and of Notch-1; lower cytoplasmic expression of p85αPI3K, p-p70S6K and p-ERK1/2; and lower PTEN Histo-scores (H-scores). PTEN H-score was inversely correlated with recurrence probability. In univariate survival analysis, nuclear expression of p-4E-BP1 and absence of p-ERK1/2 expression portended adverse prognosis, whereas in multivariate survival analysis, p-ERK1/2 expression emerged as an independent favourable prognostic factor. Treatment of the human meningioma cell line HBL-52 with the PI3K inhibitor LY294002 resulted in reduction of p-AKT, p-p70S6K and p-ERK1/2 protein levels. The complex interactions established between components of the PI3K/AKT/mTOR pathway, or with components of the MAPK, JAK/STAT and Notch-1 pathways, appear to be essential for facilitating and fuelling meningioma progression.

Mortality in diabetic and nondiabetic patients after amputations performed from 1996 to 2005 in a tertiary hospital population: a 3-year follow-up study.

AIMS: Diabetes is the leading cause of lower-extremity amputations worldwide. The objective of this study was to look at the survival after first amputation between subjects with and without diabetes in a sample of Greek population. METHOD: We performed a retrospective study of all nontrauma, nonneoplasm-related amputations performed in a tertiary centre during the years 1996-2005 in diabetic (n=183) and nondiabetic patients (n=75). Survival status was assessed from the first amputation until December 31, 2005. RESULTS: A total of 54.6% of amputees with diabetes and 51.6% of those without diabetes died in a mean [95% confidence interval (CI)] time of 4.3 (3.5-5.1) and 6.6 (4.6-8.6) years after the first amputation, respectively (P=.65). Diabetic patients underwent a second amputation (P=.003) and contralateral amputations (P=.02) more often in comparison with nondiabetic subjects. Predictors of all-cause mortality in the diabetic group, after adjustment for sex, were age [hazard ratio (HR) (95% CI), 1.04 (1.02-1.06); P<.001] and the level of amputation (major vs. minor) [HR, 1.55 (1.00-2.40), P=.05]. The respective values in the nondiabetic patients were HR of 1.06 (1.03-1.08; P<.001) and HR of 3.12 (1.27-7.64; P=.01). Median length of hospital stay was comparable between the two groups. CONCLUSION: Mortality rates after amputation were high in both patients with and without diabetes. Older age and a higher level of amputation were associated with poorer survival. Diabetic patients more often underwent a second amputation to the same and the contralateral limb. Additionally, mortality rates, length of hospital stay, and perioperative mortality were not different between patients with and without diabetes.

Components of the metabolic syndrome, but not the metabolic syndrome per se, are associated with aortic distensibility.

BACKGROUND AND AIM: Reduction in aortic distensibility occurs early in the atherosclerosis process and carries a poor prognosis. Metabolic syndrome is common and it is associated with increased cardiovascular mortality. The aim of this cross-sectional study was to investigate the association between metabolic syndrome and aortic distensibility. METHODS AND RESULTS: A total of 135 subjects without diabetes were studied. Metabolic syndrome was diagnosed using the NCEP-ATP-III criteria. Aortic distensibility was assessed non-invasively by ultrasonography. Multivariate analysis, after controlling for the components of the metabolic syndrome, and, additionally, for body mass index, pulse pressure, presence of coronary artery disease, use of statins and use of angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers, demonstrated an independent association between aortic distensibility and age (p<0.001), systolic blood pressure, (p=0.02), diastolic blood pressure (p=0.005), and history of hypertension (p<0.001), but not metabolic syndrome status. Moreover, there was a suggestive association with albumin-to-creatinine ratio (p=0.06). CONCLUSIONS: Metabolic syndrome per se is not associated with reduction in aortic distensibility. From the components of the metabolic syndrome, only blood pressure is a strong predictor of aortic distensibility. In addition, ageing and higher values of albumin-to-creatinine ratio are also associated with low aortic distensibility.