CHARACTERISTICS OF SUICIDE VICTIMS WHO HAD VERBALLY COMMUNICATED SUICIDAL FEELINGS TO THEIR FAMILY MEMBERS

Background: Verbal expression of suicidal feelings has rarely been investigated in the literature, particularly regarding individuals who died by suicide. Subjects and methods: We retrospectively collected data on the suicide cases of the period November 2007-October 2009 from the Athens Greater Area and completed psychological autopsy questionnaires after phone interviews with their family members. The specific question was: “Has your relative expressed to you his/her deep suffering or the intention to end his/her life at any time during the six months prior to the suicide?” Results: Data were collected for 248 individuals who died by suicide out of a total of 335. 121 of them (48.8%) had verbally communicated their intention to die -or their profound suffering- to their family members. Suicide communicators were older (p<0.001), less educated (p=0.04), more frequently divorced or separated and less often single (p<0.01) than non-communicators. They had more often positive psychiatric history (p=0.004) and were less physically well (p=0.005), in comparison to noncommunicators. Differences regarding sex, nationality, previous attempts, suicide note-leaving, completed suicide method and hospitalization either for physical illness or psychiatric disorder the year prior to the suicide were not statistically significant among the two groups. Considered that we interviewed only one relative for every case, the actual number of suicide communicators would be probably higher; the suicidal feelings could have been disclosed to another relative instead. Conclusions: This is the first time that a similar study was carried out in Greece. We found that approximately half of the individuals who died by suicide in our sample had been (verbal) suicide communicators. The latter seem to present distinct characteristics. These findings, coupled with the observation that the relatives are keen observers of the suicidal feelings of their loved ones, could provide new insights to future suicide prevention efforts

Quantitation of endogenous metabolites in mouse tumors using mass-spectrometry imaging

Described is a quantitative-mass-spectrometryimaging (qMSI) methodology for the analysis of lactate and glutamate distributions in order to delineate heterogeneity among mouse tumor models used to support drug-discovery efficacy testing. We evaluate and report on preanalysisstabilization methods aimed at improving the reproducibility and efficiency of quantitative assessments of endogenous molecules in tissues. Stability experiments demonstrate that optimum stabilization protocols consist of frozen-tissue embedding, post-tissue-sectioning desiccation, and storage at −80 °C of tissue sections sealed in vacuum-tight containers. Optimized stabilization protocols are used in combination with qMSI methodology for the absolute quantitation of lactate and glutamate in tumors, incorporating the use of two different stable-isotope-labeled versions of each analyte and spectral-clustering performed on each tissue section using k-means clustering to allow region-specific, pixel-by-pixel quantitation. Region-specific qMSI was used to screen different tumor models and identify a phenotype that has low lactate heterogeneity, which will enable accurate measurements of lactate modulation in future drug-discovery studies. We conclude that using optimized qMSI protocols, it is possible to quantify endogenous metabolites within tumors, and region-specific quantitation can provide valuable insight into tissue heterogeneity and the tumor microenvironment

Ανάπτυξη μεθόδων ολιστικής ανάλυσης για την ανεύρεση βιοδεικτών ασθένειας-αποτελεσματικότητας φαρμάκων σε αυτοάνοσα νοσήματα

Autoimmunity characterises a biological state within which the immune system fails to recognise the host leading to a cascade of self attacks. Rheumatoind Arthritis has been often regarded as a prototype autoimmune disease due to clear role of autoimmunity in disease manifestation. Clinical indications of RA are symmetrical polyarthritis and joint swelling that progressively causes bone erosion and cartilage destruction leaving patients in severe pain and disability. Currently RA diagnostic tools employ radiographic imaging and clinical examinations of immunological markers such as RF and ACPA, fail to provide adequate diagnostic power at early disease onset with inevitable consequences to patients life quality. On this PhD project metabolic profile technologies are employed to study RA biology in the hunt of metabolites with clear association to disease manifestation. Global and targeted LC-MS based metabolite approaches were applied for the analysis of urine, serum, hind limb joint and synovial fibroblasts extracts. All samples were collected from in vivo model TG197 that closely mimics the human TNFa RA expression that could potentially help the translation of the finding into the clinic. For this purpose a targeted LC-MS based analytical platform was successfully developed and validated using an ion pair chromatographic separation that enabled detection of more than a hundred polar metabolic intermediates involved in key metabolic pathways. Dried biofluid spot technology was also investigated as alternative to liquid biofluid storage. Short term stability (24hours) study revealed close proximity of the metabolic phenotype of the DBS samples and those of the protein precipitated samples. However medium (1 week) to long (1 month) term stability at room temperature was found poor but card storage at -20ºC or below can improve stability. Global urine metabolic analysis revealed clear differentiation between TG and WT phenotype across all weeks starting from 6 up to 11 weeks of mouse age. Remicade treatment of TG animals found beneficial in progressive swift of the metabolic phenotype from TG to WT like one. Strong evidence of phenotypic differentiation with steroid related marker was found. On the other hand targeted metabolic analysis identified itaconic acid as a proximal marker to RA expression. Serum global metabolite analysis were also shown clear differentiation between TG and WT phenotype. Targeted metabolic profile provided more easily interpreted data with major metabolic differences corresponding to aminoacids and central carbon metabolism. Similarly to urine, itaconic acid revealed strong correlation with disease expression and with potential of non-invasive marker monitoring capability. On line lithium adduct formation combined with ion mobility separation was investigated and unravelled its potential in enhancing lipid fragmentation data associated with differentiating lipid species between TG and WT organic hind limb extracts. Metabolic changes associated primarily with energy producing metabolic pathways (glycolysis, starch metabolism) were found following targeted analysis of aqueous hind limb extracts. To our best of knowledge this is the first time that LC-MS metabolic profiling approaches was implemented to RA biology on the TG197 in vivo model and its responses to standard of care anti-TNFa (Remicade) treatment.Ως αυτοάνοσα νοσήματα χαρακτηρίζονται παθοφυσιολογικές καταστάσεις στις οποίες το ανοσοποιητικό σύστημα ενός οργανισμού στρέφεται εναντίων του ιδίου του οργανισμού. Μέχρι σήμερα έχουν αναγνωριστεί πάνω από 100 αυτοάνοσες παθήσεις με την ρευματοειδή αρθρίτιδα (ΡΑ) να θεωρείται πρότυπο αυτοάνοσο νόσημα εξαιτίας της ξεκάθαρης συμμετοχής του ανοσοποιητικού συστήματος στην εκδήλωση της ασθένειας. Η ΡΑ εκδηλώνεται με πρήξιμο των αρθρώσεων, ανάπτυξη συμμετρικής πολυαρθρίτιδας που προοδευτικά οδηγεί στην καταστροφή του χόνδρου και της οστικής μάζας της άρθρωσης τα όποια προκαλούν σημαντικά προβλήματα κινητικότητας στους ασθενείς. Η διάγνωση της ΡΑ στηρίζεται στη ραδιογραφική απεικόνιση της άρθρωσης σε συνδυασμό με κλινική διερεύνηση για την ύπαρξη κλινικών δεικτών όπως ο ρευματοειδής παράγοντας (RF) και αντισώματα ACPA. Με τα παραπάνω εργαλεία είναι δύσκολη η διάγνωση της ΡΑ σε πρώιμο στάδιο.Στα πλαίσια αυτής της διδακτορικής διατριβής χρησιμοποιήθηκαν τεχνικές στοχευμένης και ολιστικής ανάλυσης μεταβολιτών σε δείγματα ούρων, ορού αίματος και εκχυλισμάτων αρθριτικής άρθρωσης τα οποία συλλέχθηκαν από το πειραματικό μοντέλο ΤG197 ποντικίων με στόχο την ανεύρεση μεταβολιτών που σχετίζονται με την έκφραση της ΡΑ. Αναπτύχθηκε αναλυτική μεθοδολογία (LC-MS) που επέτρεψε την στοχευμένη ανάλυση περισσοτέρων από 100 μεταβολιτών οι οποίοι μετέχουν σε μεταβολικά μονοπάτια όπως η γλυκολιτική οδός, ο κύκλος του κιτρικού οξέος, ο μεταβολισμός νουκλεοτιδίων κ.α. Διερευνήθηκε επίσης η τεχνολογία απόθεσης κηλίδας βιολογικών δειγμάτων προερχόμενων από αίμα και ούρα. Η μελέτη σταθερότητας της παραπάνω τεχνολογίας σε σχέση με την υγρή αποθήκευση δείγματος έδειξε ότι το μεταβολικό προφίλ δεν μεταβάλλεται σημαντικά εντός 24 ωρών αλλά για μεγαλύτερο διάστημα αποθήκευσης ακόμη και σε θερμοκρασίες χαμηλότερες των -20°C το μεταβολικό προφίλ διαφοροποιείται σηματικά από αυτό των δειγμάτων αναφοράς. Η ολιστική ανάλυση δειγμάτων ούρων έδειξε σημαντική διαφοροποίηση μεταξύ του μεταβολικού προφίλ ασθενών και υγιών ποντικών μεταξύ της 6ης και 11ης εβδομάδος της ηλικίας τους. Η χορήγηση φαρμάκου Remicade μετατόπισε το μεταβολικό προφίλ των δειγμάτων ούρων από αυτό των άρρωστων σε αυτό των υγιών ποντικών μέτά από 3 εβδομάδες θεραπείας. Στεροείδης ενώσεις βρέθηκαν να συμμετέχουν στη διαφοροποίηση του μεταβολικού προφίλ των ομάδων δειγμάτων ούρων ενώ το ιτακονικό όξυ βρέθηκε να σχετίζεται με την έκφραση της ΡΑ μετά από στοχευμένη ανάλυση δειγμάτων ούρων. Ανάλογη διαφοροποίηση του μεταβολικού προφίλ μεταξύ υγιών και ασθενών ποντικών παρατηρήθηκε και στα δείγματα ορού αίματος τόσο στην εβδομάδα 6 όσο και στην εβδομάδα 11 της ηλικίας των ποντικών. Στοχευμένη ανάλυση σε δείγματα ορού αίματος έδειξε αλλαγή των ενδογενών συγκεντρώσεων μεταβολιτών σχετικών με το μεταβολισμό αμινοξέων και του κεντρικού μεταβολισμού άνθρακα. Το ιτακονικό οξύ παρουσίασε ανάλογη μεταβολή με αυτή στα δείγματα ούρων. Προσθήκη ιόντων λιθίου βοήθησε στη καλύτερη θραύση ιόντων λιπιδίων ένω η χρήση της τεχνολογίας κινητικότητος ιόντων βελτίωσε τη χρωματογραφική ικανότητα διαχωρισμού λιπιδίων σε οργανικά εκχυλίσματα αρθριτικής άρθρωσης. Στοχευμένη ανάλυση υδατικών δειγμάτων εκχύλισης της αρθριτικής άρθρωσης ανέδειξε αλλαγές μεταβολιτών σχετιζόμενων με το μηχανισμό την παραγωγή ενέργειας. Από όσο γνωρίζω αύτη είναι η πρώτη φόρα που τεχνολογία στοχευμένης και ολιστικής ανάλυσης μεταβολιτών χρησιμοποιείται στη μελέτη της βιολογίας της ΡΑ όπως αύτη εκφράζεται μέσω το πειραματικού μοντέλου TG197 αλλά και στη μελέτη της απόκρισης του μοντέλου αυτού στην θεραπεία με φάρμακο Remicade

Psychiatric Medication Intake in Suicide Victims: Gender Disparities and Implications for Suicide Prevention

Frequency and gender differences of psychiatric medication intake in a sample of suicide victims from the Athens Greater Area were investigated with a particular focus on the implications for suicide prevention. Data were collected from the toxicological analyses of the suicide cases of the period November 2007-October 2009. Information was available for 262 individuals, 196 men (74.8%) and 66 women (25.2%); 109 of these (41.6%) were receiving psychiatric medication(s). Women were statistically more frequently under treatment: antidepressants (32.8% vs. 11.3%, p &lt; 0.001), antiepileptics (9.1% vs. 0.5%, p = 0.001), antipsychotics (24.2% vs. 9.2%, p = 0.003), and benzodiazepines (16.7% vs. 6.6%, p = 0.024). Campaigns aiming to bring men with psychological difficulties in contact with mental health services and to lessen the stigma of mental illness, together with better training of nonpsychiatrists into “suspecting” “male” depression, could be particularly helpful for decreasing male suicides. More thoughtful choice of psychiatric medication could possibly already prevent a number of female suicides

Characteristics of immigrant suicide completers in a sample of suicide victims from Greece

Background: Immigrants have higher rates of suicidal behaviour in comparison to the indigenous population. Aims: To describe the characteristics of foreign nationality suicide completers and search for differences between them and native Greeks. This is the first study focused on immigrant suicide victims in Greece. Methods: Data were collected for all recorded cases of completed suicide for the two-year period November 2007 to October 2009 at the Athens Department of Forensic Medicine, the largest, by far, of its kind in Greece covering approximately 35% of the country’s population. The material was collected using the method of psychological autopsy as well as from the victims’ forensic records. Results: Nearly 10% of Greece’s 11 million population are of foreign nationality. Approximately half of them live in Athens and its suburbs, an area where 35% of Greece’s population lives. In our sample, 15.8% of the suicide victims were of foreign nationality (53 cases): 41 men (77.4%) and 12 women (22.6%). Higher suicide rates were found for citizens of Kuwaiti (9.1%), Somali (6.7%) and Afghan (0.9%) nationality (immigrant communities with very few members); the lower suicide rates were for individuals of Egyptian (0.01%), Ukrainian (0.01%) and Albanian (0.006%) nationality (the Albanian immigrant community is the largest in Greece). In comparison to their Greek counterparts, immigrant victims were younger (mean age 38.7 vs 54.9 years, p &lt; .001) more often unemployed (p = .007) and with a history of alcohol abuse (p &lt; .001). The main suicide method used by immigrants was hanging (p &lt;.001) while for Greeks it was jumping from a height. Conclusions: Individuals who belong to small national communities seem to have the highest risk of dying by suicide. Immigrant suicide victims differ from the indigenous population in several parameters. Our data could help define the most vulnerable of them and apply more effective suicide prevention strategies

A 2-Year Psychological Autopsy Study of Completed Suicides in the Athens Greater Area, Greece

Objective To study the characteristics of a sample of suicide victims from the Athens Greater Area using the psychological autopsy method for the first time in Greece. Methods We studied all recorded cases of completed suicide for the 2-year time period November 2007 October 2009 collecting data from the victims’ forensic records as well as from the completion of a psychological autopsy questionnaire. Results 335 persons were recorded as suicide victims. We contacted relatives of 256 victims interviewing those of 248 of them (96.9%). The differences regarding sex, marital and employment status between our sample and the general population were statistically significant (p&lt;0.001). The male/female ratio was 3:1. Comparatively more victims were divorced, separated or single and a greater proportion were pensioners or unemployed. 26.0% of the victims had history of prior attempts (64.4% once, 20.3% twice and 15.3% more times). 42.6% were taking psychiatric medication-significantly more women than men according to blood tests; 14.2% had been hospitalized in a psychiatric clinic the year prior to their death. 84.8% have deceased at the place of suicide and 15.2% died in the hospital; 80.3% died indoors and 19.7% outdoors. Men died primarily by hanging or shooting by a firearm while women preferred jumping from height instead (p&lt;0.001). As many as 48.8% had expressed their intention to die to their relatives; 26.6% left a suicide note. Conclusion Our study has shown that the psychological autopsy method is applicable and widely accepted yielding results comparable to the international literature. Specific parameters associated with suicide have been studied for the first time in Greece

Switching Suicide Methods in Order to Achieve Lethality: A Study of Greek Suicide Victims

This article focused on the relation between the method of last attempted suicide and the method used during the subsequent completed suicide. Using the method of psychological autopsy, the authors studied all suicide cases from the Athens Greater Area during a 2-year period. Twenty-four percent of the victims had history of previous suicide attempts. The majority of the suicide attempters switched to a different method (p&lt;0.001) for their final act. This difference is primarily due to the individuals who had chosen self-poisoning or wrist cutting in their last attempted suicide. Both of these groups switched to hanging or jumping from a height for their final attempt. Individuals who attempted suicide by hanging or jumping became completers using mainly the same methods