LPS-Induced Systemic Inflammation Affects the Dynamic Interactions of Astrocytes and Microglia with the Vasculature of the Mouse Brain Cortex.

The Neurovascular Unit (NVU), composed of glia (astrocytes, oligodendrocytes, microglia), neurons, pericytes and endothelial cells, is a dynamic interface ensuring the physiological functioning of the central nervous system (CNS), which gets affected and contributes to the pathology of several neurodegenerative diseases. Neuroinflammation is a common feature of neurodegenerative diseases and is primarily related to the activation state of perivascular microglia and astrocytes, which constitute two of its major cellular components. Our studies focus on monitoring in real time the morphological changes of perivascular astrocytes and microglia, as well as their dynamic interactions with the brain vasculature, under physiological conditions and following systemic neuroinflammation triggering both microgliosis and astrogliosis. To this end, we performed 2-photon laser scanning microscopy (2P-LSM) for intravital imaging of the cortex of transgenic mice visualizing the dynamics of microglia and astroglia following neuroinflammation induced by systemic administration of the endotoxin lipopolysaccharide (LPS). Our results indicate that following neuroinflammation the endfeet of activated perivascular astrocytes lose their close proximity and physiological cross-talk with vasculature, an event that most possibly contributes to a loss of blood-brain barrier (BBB) integrity. At the same time, microglial cells become activated and exhibit a higher extent of physical contact with the blood vessels. These dynamic responses of perivascular astrocytes and microglia are peaking at 4 days following LPS administration; however, they still persist at a lower level at 8 days after LPS injection, revealing incomplete reversal of inflammation affecting the glial properties and interactions within the NVU.

A miR-124-mediated post-transcriptional mechanism controlling the cell fate switch of astrocytes to induced neurons.

The microRNA (miRNA) miR-124 has been employed supplementary to neurogenic transcription factors (TFs) and other miRNAs to enhance direct neurogenic conversion. The aim of this study was to investigate whether miR-124 is sufficient to drive direct reprogramming of astrocytes to induced neurons (iNs) on its own and elucidate its independent mechanism of reprogramming action. Our data show that miR-124 is a potent driver of the reprogramming switch of astrocytes toward an immature neuronal fate by directly targeting the RNA-binding protein Zfp36L1 implicated in ARE-mediated mRNA decay and subsequently derepressing Zfp36L1 neurogenic interactome. To this end, miR-124 contribution in iNs' production largely recapitulates endogenous neurogenesis pathways, being further enhanced upon addition of the neurogenic compound ISX9, which greatly improves iNs' differentiation and functional maturation. Importantly, miR-124 is potent in guiding direct conversion of reactive astrocytes to immature iNs in vivo following cortical trauma, while ISX9 supplementation confers a survival advantage to newly produced iNs.

Effectiveness of a Community-Based Crisis Resolution Team for Patients with Severe Mental Illness in Greece: A Prospective Observational Study.

This prospective observational study evaluated the effectiveness of a crisis resolution team (CRT) for outpatient treatment of psychiatric patients experiencing an acute episode of severe mental disorder. The effectiveness of the CRT (n = 65) was assessed against the care-as-usual [CAU group (n = 65)]. Patients' clinical state, overall functioning, quality of life and satisfaction were respectively evaluated at baseline, post intervention and three-month post-intervention.CRT patients compared to the CAU group, had significantly improved outcomes concerning clinical state and patient satisfaction at post intervention phase. Statistically significant improvement was also recorded for the dimensions of environment, physical and psychological health related to quality of life. No significant differences were observed between the two groups regarding overall functioning.On the basis of these results, reforming of existing crisis-management services, in Greece, using the CRT model may improve substantially the services offered to psychiatric patients.

[Crisis intervention for serious mental disorders. The example of the First Department of Psychiatry of Athens University].

We describe the crisis management and resolution service for serious mental disorders established by the First Department of Psychiatry of the National and Kapodistrian University of Athens. The service is intended to meet patients' needs for adequate management of acute mental crisis without hospitalization, while implementing modern standards in mental care and considering existing restrictions in mental health resources and public expenditure. Last decade we witness an increase in demand for psychiatric beds in Psychiatric clinics of General Hospitals resulting in a drastic increase of auxiliary beds that becomes a serious problem in mental health provision. The shutdown of big psychiatric hospitals in the process of psychiatric reform, accompanied by a delay in the establishment of all the anticipated beds in general hospitals together with overloaded and insufficient network of mental health services in the community are the major determinants. Additionally, fiscal economic crisis of the last decade intensified even more the problem by diminishing funding for the recruitment of new personnel and drastically reducing allocated funding for new and old services. In 2016 we set up a crisis intervention service for serious mental disorders within the operational framework of the emergency psychiatric services of the Department of Psychiatry in Eginition Hospital in Athens. The crisis resolution team is composed by two psychiatrists, a psychiatric nurse, social workers, a psychologist, mental health volunteers, and mental health trainees/students. The patient enters the service through the emergency service when an indication for hospitalization is given by the emergency psychiatrist, followed by the clinical estimation of a member of our team. The therapeutic team convenes twice a week for the new entrants and for follow-up sessions with the participation of the patient and the family members whenever feasible. The rest of the therapeutic interventions take place during the week. The work 'with' the person and not 'to' the person encapsulates the philosophy of the service, which is characterized by a holistic treatment approach aiming to empower the individual strengths and sense of control of the patient for crisis resolution on the basis of a safe therapeutic milieu. Therapeutic interventions include family and supportive members, as well as community interventions. In summation, interventions consist of a) comprehensive evaluation (psychiatric/ physical) and therapeutic plan, b) psychopharmacological treatment, c) psychotherapeutic support for the patient and the family for management of the crisis, d) training for the management of future crises and e) referral to appropriate community services for follow up management and treatment. Treatment lasts approximately 6-8 weeks. Initial data of the evaluation study indicate clinical effectiveness and high levels of satisfaction for patients and family. Conclusively, crisis management and resolution services are feasible even in a time of heavy restrictions in recourses, and anticipated benefits are multiple for the economy, mental health provision, the public health system, patients and relatives alike.

[New patients' access to psychiatric treatment services: Improving the quality indicators of mental health services].

Accessibility of patients to the health system as well as the system's rapid and effective response to patients' needs constitute basic quality indices of health services. Major parameter of accessibility is the required waiting time for a new patient to enter the health system. We present the results of the use of an organized system for the management of new requests for psychiatric treatment, which is based on the triage and evaluation of priorities. While taking into consideration the administrative distribution of the health services, our system intervenes in the waiting time by evaluating the requests in terms of medical and moral criteria, via gradual prioritization. Principal aim is waiting time reduction as well as the optimal response of our service to the needs of our patients. This perspective study was based on the new requests. The 1839 (100%) requests for first psychiatric evaluation at the outpatient clinic of Eginition University Hospital in 2019 were studied in relation to different parameters, as well as the efficacy of the system in terms of waiting-time management. Mean age of the petitioners was 45.8 (± 16.8), with statistically significant rate of women over men (N=1062, 59.1%, p˂0.05). The initial communication with the petitioners and the evaluation of the requests rendered the correct management feasible via immediate referrals to special psychiatric services depending on the nature of the cases, as well as redirection to their local psychiatric services for 1057 (57,5%) of the requests, where needed. The remaining 595 (33,4%) requests, after their assortment into three categories of graded prioritization, were placed in outpatient psychiatric clinics after waiting time of 25 days, 50 days and 76 days, respectively. In conclusion, the results of the study show that the systematic management of psychiatric treatment requests, when scientifically and ethically substantiated, may provide mental health services with manifold benefits.Accessibility of patients to the health system as well as the system's rapid and effective response to patients' needs constitute basic quality indices of health services. Major parameter of accessibility is the required waiting time for a new patient to enter the health system. We present the results of the use of an organized system for the management of new requests for psychiatric treatment, which is based on the triage and evaluation of priorities. While taking into consideration the administrative distribution of the health services, our system intervenes in the waiting time by evaluating the requests in terms of medical and moral criteria, via gradual prioritization. Principal aim is waiting time reduction as well as the optimal response of our service to the needs of our patients. This perspective study was based on the new requests. The 1839 (100%) requests for first psychiatric evaluation at the outpatient clinic of Eginition University Hospital in 2019 were studied in relation to different parameters, as well as the efficacy of the system in terms of waiting-time management. Mean age of the petitioners was 45.8 (± 16.8), with statistically significant rate of women over men (N=1062, 59.1%, p<0.05). The initial communication with the petitioners and the evaluation of the requests rendered the correct management feasible via immediate referrals to special psychiatric services depending on the nature of the cases, as well as redirection to their local psychiatric services for 1057 (57,5%) of the requests, where needed. The remaining 595 (33,4%) requests, after their assortment into three categories of graded prioritization, were placed in outpatient psychiatric clinics after waiting time of 25 days, 50 days and 76 days, respectively. In conclusion, the results of the study show that the systematic management of psychiatric treatment requests, when scientifically and ethically substantiated, may provide mental health services with manifold benefits.

Neurobiological Trajectories Involving Social Isolation in PTSD: A Systematic Review.

Social isolation (SI) stress has been recognized as a major risk factor of morbidity in humans and animals, exerting damaging effects at the physical and mental health levels. Posttraumatic stress disorder (PTSD), on the other hand, occurs as a result of experiencing serious, life-threatening, traumatic events and involves involuntary re-experiencing trauma (intrusion), avoidance symptoms, and distortions of cognition and emotional arousal. The literature shows that PTSD is affected by genetic predisposition and triggers a large neurocircuitry involving the amygdala, insula, hippocampus, anterior cingulate- and prefrontal-cortex, and affects the function of the neuroendocrine and immune systems. Social isolation seems to influence the predisposition, onset and outcome of PTSD in humans, whereas it constitutes a valid model of the disorder in animals. According to the PRISMA (preferred reporting items for systematic reviews and meta-analyses) protocol, we systematically reviewed all original studies involving the neurobiological trajectories between SI and PTSD published till July 2019 (database: PubMed/Medline). Out of 274 studies, 10 met the inclusion criteria. We present the results of the retrieved studies in terms of hypothalamic-pituitary-adrenal (HPA)-axis and endocannabinoid system function, immune reactions, neuroplasticity, novel pharmacological targets, and shortening of telomere length, which confirm a synergistic effect on a neurobiological level between the two entities.

1st International Experts' Meeting on Agitation: Conclusions Regarding the Current and Ideal Management Paradigm of Agitation.

Agitation is a heterogeneous concept without a uniformly accepted definition, however, it is generally considered as a state of cognitive and motor hyperactivity characterized by excessive or inappropriate motor or verbal activity with marked emotional arousal. Not only the definition but also other aspects of agitated patients' care are still unsolved and need consensus and improvement. To help the discussion about agitation among experts and improve the identification, management, and treatment of agitation, the 1st International Experts' Meeting on Agitation was held in October 2016 in Madrid. It was attended by 20 experts from Europe and Latin America with broad experience in the clinical management of agitated patients. The present document summarizes the key conclusions of this meeting and highlights the need for an updated protocol of agitation management and treatment, the promotion of education and training among healthcare professionals to improve the care of these patients and the necessity to generate clinical data of agitated episodes.

FEMALE SEXUAL DYSFUNCTION (FSD) IN WOMEN HEALTH CARE WORKERS.

PURPOSE: The main aim of this study is to investigate the occurrence and severity of FSD in women working in tertiary hospitals. MATERIAL AND METHODS: The study sample was drawn from health care women between the ages of 20 and 65 years, working in two hospitals in Greece. This descriptive study used a structured Greek questionnaire and sexual function screener and quality of life sectors were consisted of rated scale questions. Eighty eight questionnaires were returned properly completed. The statistical analysis used the SPSS statistical program. RESULTS: Female sexual dysfunction is a highly prevalent health issue whose exact incidence is not well defined. Factors that can contribute to female sexual dysfunction may be psychogenic, physical, mixed or unknown. Each of these factors consists of individual components that influence the sexual response; however their precise impact in FSD development and progression is unknown. Moreover, the role of circadian rhythm disorders (especially that of shift work sleep disorder) to the development and progression of FSD has been poorly investigated. CONCLUSION: Working environment and patterns of work schedules may play a role in FSD however it has been difficult to specify in what extent they contribute to FSD development.

Quality of life in schizophrenia spectrum disorders: associations with insight and psychopathology.

Therapeutic interventions in chronic mental illness face the important challenge to pursuit the quality of life (QOL) of patients. Insight into chronic mental illness, though a prerequisite for treatment adherence and a positive therapeutic outcome, has shown adverse associations with subjective QOL. This study aims to explore the contribution of psychopathological symptoms on the ambiguous role of insight on QOL. Seventy-two outpatients with schizophrenia spectrum disorders were assessed using the positive and negative syndrome scale, the scale to assess unawareness of mental disorder, and the WHOQOL-100 instrument for the assessment of quality of life. Insight was found to associate inversely with quality of life. Among psychopathological symptoms, depressive symptoms were the strongest negative contributor on QOL. Mediation analysis revealed that the effects of awareness of the consequences of illness on QOL were largely mediated by depressive symptoms (full mediation for the effect on physical and psychological domain and partial mediation for the effect on independence and environment domain of the QOL). Our results suggest that the inverse relationship between insight and subjective quality of life is partially mediated by depressive symptoms. We discuss theoretical and therapeutic implications of the findings, in conjunction with similar recent research data.

Assessment of long-term subacute exposure to dimethoate by hair analysis of dialkyl phosphates DMP and DMTP in exposed rabbits: The effects of dose, dose duration and hair colour.

Hair analysis for dialkyl phosphates' (DAPs) residues could provide a measure of chronic exposure to organophosphate pesticides (OPs). The aim of this study was to determine whether these metabolites can be internally incorporated into the hair of rabbits exposed to dimethoate and also to investigate the influence of dose and dose duration of this OP, as well as the effect of hair colour on the concentrations of its DAPs in hair. Two-coloured rabbits were daily exposed to dimethoate (0, 12 or 24mgkg(-1) body weight) via their drinking water. Hair samples of both colours were obtained 4 and 6 months after the beginning of exposure from the back of all treated rabbits, and each hair colour sample was analyzed for dimethyl phosphate (DMP) and dimethyl thiophosphate (DMTP) by gas chromatography-mass spectrometry (GC-MS). Analysis revealed the incorporation of these metabolites into the rabbit hair in a dose-dependent manner. The mean concentrations found ranged from 0.18 to 0.77ngmg(-1) for DMP and from 0.43 to 1.53ngmg(-1) for DMTP. Mixed results for the significance of the relationship between dose duration and the levels of the two DAPs in hair are observed. Hair pigmentation does not appear to affect the concentration values of DMTP, whereas it seems to be a critical factor in the incorporation of DMP into hair. These data confirm the ability of hair testing to assess chronic OP exposure by the detection of DAPs.

The delusional misidentification syndromes: strange, fascinating, and instructive.

The delusional misidentification syndromes (Capgras' syndrome, Frégoli syndrome, intermetamorphosis syndrome, syndrome of subjective doubles) are rare psychopathologic phenomena that occur primarily in the setting of schizophrenic illness, affective disorder, and organic illness. They are grouped together because they often co-occur and interchange, and their basic theme is the concept of the double (sosie). They are distinguished as hypoidentifications (Capgras' syndrome) and hyperidentifications (the other three syndromes). In this review, we present the basic hypotheses that have been put forward to explain these syndromes and propose that the appearance of these syndromes must alert physicians to investigate the existence of possible organic contributions.

Analysis of dialkyl phosphate metabolites in hair using gas chromatography-mass spectrometry: a biomarker of chronic exposure to organophosphate pesticides.

The aim of our study was to develop and validate an analytical approach for the quantitative determination of three dialkyl phosphate (DAP) metabolites, dimethyl phosphate (DMP), dimethyl thiophosphate (DMTP) and diethyl phosphate (DEP), of organophosphate pesticides (OPs) in hair samples. The proposed methodology comprises a decontamination step, solid-liquid extraction, followed by liquid-liquid extraction, pentafluorobenzyl bromide derivatization, clean-up on Florisil/PSA column and analysis by gas chromatography-mass spectrometry (GC-MS). Extraction recovery, obtained from 50 mg hair samples spiked at two concentration levels, ranged from 56.1 to 107.9% and the within-day precision ranged from 13.5 to 17.5%. Limits of detection (LODs) ranged from 0.02 to 0.10 ng mg(-1). The results obtained from the analysis of hair samples of 30 agricultural workers show the suitability of the proposed method for monitoring people occupationally exposed to OPs. The most frequently detected compound was DEP followed by DMP. This is the first report on the detection of dialkyl phosphates in human hair which reflects the ability of hair testing to assess chronic exposure to OPs.

Association of physical and social anhedonia with depression in the acute phase of schizophrenia.

BACKGROUND/AIMS: Researchers have shown interest in the association between anhedonia and depression in schizophrenia. The aim of the current study was to investigate the relationship between physical and social anhedonia with depression in a sample of inpatients with schizophrenia in the acute phase of their illness. METHODS: Sixty-two patients with acute schizophrenia consecutively admitted at the Eginition Hospital, Department of Psychiatry, University of Athens were assessed using the revised Physical Anhedonia Scale, the revised Social Anhedonia Scale and the Calgary Depression Scale for Schizophrenia. RESULTS: The Calgary Depression Scale for Schizophrenia score correlated with both physical anhedonia and social anhedonia ratings. The revised Social Anhedonia Scale score significantly correlated to self-depreciation, guilty ideas of reference, pathological guilt, early wakening, suicidality and observed depression. The revised Physical Anhedonia Scale score significantly correlated with depressive mood, self-depreciation, pathological guilt and observed depression. Self-depreciation, pathological guilt and observed depression were correlated with both social and physical anhedonia. CONCLUSION: Depression in schizophrenia and anhedonia may overlap, and it could therefore be difficult to clinically differentiate them, especially in acute schizophrenia patients.

Cytogenetic effects of grape extracts (Vitis vinifera) and polyphenols on mitomycin C-induced sister chromatid exchanges (SCEs) in human blood lymphocytes.

In the present study, the effects of extracts and polyphenol-rich fractions as well as monomer polyphenols identified in them, from both red and white grapes, on mitomycin C (MMC) induced sister chromatid exchanges (SCEs) in human peripheral blood lymphocytes were investigated. The grape extracts and two of the three polyphenol-rich fractions promoted MMC-induced SCEs at concentrations from 75 to 300 microg/mL. However, none of the extracts or fractions alone induced SCEs. Thus, these results suggest caution especially with regard to the use of grape extracts as dietary supplements. On the other hand, the fact that these extracts were not genotoxic alone may indicate a selective activity against genetically damaged cells. This is the first study regarding the clastogenic effects of grape extracts in human cells. Moreover, from the tested polyphenols, caffeic acid, gallic acid, and rutin hydrate enhanced MMC-induced clastogenicity, whereas ferulic acid, protocatechuic acid, (+)-catechin, (-)-epicatechin, and trans-resveratrol had no effect at concentrations between 5 and 100 microM. The differences in the chemical structures of the tested polyphenols may account for their differential effects on MMC clastogenicity.

Analytical methods of biological monitoring for exposure to pesticides: recent update.

Extensive use of synthetic pesticides for agricultural and nonagricultural purposes began in the past 50 years. As a result of their wide and extensive application, exposure to hazardous pesticides is a concern to the general population and occupationally exposed persons. Robust methods are therefore needed for measuring markers of pesticide exposure. This article presents a review of the most recently published analytical methodologies and instrumentations developed for and applied to biological monitoring of exposure to pesticides of various classes. Most of the methods reviewed here are based on chromatography combined with mass spectrometry detection. This work clearly demonstrates that although gas chromatography still appears to be the most widely employed technique for pesticide analysis in various biological samples, recently a trend has been observed toward the use of liquid chromatography coupled with tandem mass spectrometry.

Approaching delusional misidentification syndromes as a disorder of the sense of uniqueness.

Co-occurrence of the different types of delusional misidentification syndromes (DMS) implies a common pathogenetic substrate. Until now, theoretical explanations have strained to produce a collective approach, but have been trammeled by the initial definition of the syndromes (Capgras/Fregoli) that originated from the attribution of causal significance to the element of familiarity towards the misidentified object. In this article, we present two cases illustrating the co-occurrence of the syndromes and we attempt to propose a new approach to DMS. We hypothesize that a common potential pathogenetic factor underlying DMS could be a disorder of the sense of uniqueness. The ability to attribute uniqueness to the self and to surrounding people, objects, or places is a principal property of the adaptable mind that acts as a matrix for the identification process. We propose that although the term 'identity' encompasses the concept of uniqueness, this must be accomplished somewhere in a model of semantic processing of identity. Our approach is questioning the current view that this sequential stage is the PIN stage in the functional model of face recognition by Bruce and Young, and we attempt to see the disordered sense of uniqueness within the evolved form of the model of face recognition and delusional misidentification introduced by Ellis and Lewis. We propose that such a disturbance could result in an unstable identification process, vulnerable to discrepancies in perceptual, emotional, or memory input caused by psychotic or organic mental states, thus resulting in a breakdown of the identification process that inevitably leads to a delusion of denial of identity, or to a delusion of 'doubles'.

Physical anhedonia in the acute phase of schizophrenia.

BACKGROUND: The aim of the current study is to investigate the relationship between physical anhedonia and psychopathological parameters, pharmacological parameters or motor side-effects in a sample of inpatients with schizophrenia in an acute episode of their illness. METHOD: Eighty one patients with schizophrenia, consecutively admitted, with an acute episode of their illness, at the Eginition Hospital, Department of Psychiatry, University of Athens, during a one-year period were investigated regarding possible relationships between physical anhedonia, social-demographic data and clinical parameters as well as motor side-effects, induced by antipsychotic agents. All patients were assessed using the Chapman Revised Physical Anhedonia Scale (RPAS), the Positive and Negative Syndrome Scale (PANSS), the Rating Scale for Extrapyramidal Side-Effects (EPSE), the Barnes Akathisia Rating Scale (BARS) and the Abnormal Involuntary Movement Scale (AIMS). Simple cross tabulations were initially employed. Subsequently, multiple regression analysis was performed. RESULTS: Both positive and negative symptoms were associated with physical anhedonia. A positive association between physical anhedonia and the non-paranoid sub-category of schizophrenia was also proved. CONCLUSION: According to these results, it seems that in the acute phase of schizophrenia, physical anhedonia may be a contributing factor to patient's psychopathology.

Suicidal ideation in inpatients with acute schizophrenia.

OBJECTIVE: Schizophrenia has been associated with a high rate of suicide. This study investigates the prevalence of suicidal ideation in a population of inpatients with acute schizophrenia, together with the clinical parameters associated with suicidal thoughts. METHOD: We assessed 93 schizophrenia patients. We matched subjects for age and sex and compared subjects with and without suicidal thoughts. We performed stepwise multiple regression analysis to assess the association between specific clinical symptoms and suicidal ideation. RESULTS: Of the patients, 20.4% reported suicidal thoughts during the last 15 days. Severity of depressive symptoms, motor retardation, guilt feelings, pathological guilt, and self-depreciation predicted the patients' suicidal ideation. CONCLUSIONS: Suicidal thoughts are frequent among inpatients with acute schizophrenia. Prevention of suicidal behaviour should include helping patients improve their self-esteem and reducing depression and guilt feelings.

Treatment of severe neuroleptic-induced tardive torticollis.

BACKGROUND: The aim of this paper is to describe a case of severe neuroleptic-induced tardive torticollis successfully treated with a combination of clozapine, clonazepam and botulinum toxin-A. CASE REPORT: The patient, a 30-year old man with a seven-year history of delusional disorder experienced severe right torticollis with painful tightness of the neck and elevation of the shoulder. At this time he was receiving haloperidol 20 mg, trifluoperazine 5 mg, zuclopenthixol 20 mg and biperidine 4 mg daily. The combination therapy with clozapine and clonazepam and the long-term use of botulinum toxin-A resulted in a complete remission of dystonic movements. CONCLUSIONS: The present observations provide evidence indicating that this combination therapy may be of benefit in patients with severe neuroleptic-induced tardive torticollis.