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Το Γονιδιακό Προφίλ Της Κατάθλιψης the Genetic Profile of Depression

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Το Γονιδιακό Προφίλ Της Κατάθλιψης the Genetic Profile of Depression Πανεπιστήμιο Μακεδονίας Σχολή Κοινωνικών, Ανθρωπιστικών Επιστημών και Τεχνών Τμήμα Εκπαιδευτικής και Κοινωνικής Πολιτικής Μεταπτυχιακό Πρόγραμμα: Νευροεπιστήμη της Εκπαίδευσης Το γονιδιακό προφίλ της κατάθλιψης The genetic profile of depression Φοιτήτρια: Πηλίδου Μαργαρίτα Επιβλέπων: Κοσμίδης Ευστράτιος Μέλη της Επιτροπής: Λαγουδάκη Ρόζα, Μασούρα Ελβίρα Ακαδημαϊκό Έτος: 2019 - 2020 Ευχαριστίες Αρχικά, θα ήθελα να ευχαριστήσω τον υπεύθυνο του Μεταπτυχιακού Προγράμματος, καθηγητή Λάζαρο Τριάρχου, χάρις στον οποίο μου δόθηκε η ευκαιρία να έρθω σε επαφή με ένα επιστημονικό πεδίο αρκετά διαφορετικό, από αυτό στο οποίο ειδικεύομαι, αλλά και όλους τους καθηγητές που το κατέστησαν αυτό δυνατό. Ευχαριστώ ιδιαιτέρως την καθηγήτρια Ρόζα Λαγουδάκη για την άμεση και πολύτιμη βοήθεια της στην συγγραφή της εργασίας μου, καθώς και την υπόλοιπη επιτροπή, τον καθηγητή Ευστράτιο Κοσμίδη και την καθηγήτρια Μασούρα Ελβίρα. Το μεγαλύτερο ευχαριστώ το οφείλω στους γονείς μου, οι οποίοι είναι δίπλα μου και με στηρίζουν σε κάθε βήμα της ζωής και της εξέλιξής μου, με αγάπη και υπομονή. Τέλος, θέλω να ευχαριστήσω από καρδιάς την ψυχοθεραπεύτριά μου, Γιούλη Καπούνη, χωρίς την οποία δε θα είχα φτάσει εδώ που βρίσκομαι σήμερα. 2 Πίνακας περιεχομένων Ευχαριστίες .................................................................................................................................. 2 Περίληψη .................................................................................................................................... 5 Abstract ....................................................................................................................................... 6 Μέρος 1ο ..................................................................................................................................... 7 Εισαγωγή ..................................................................................................................................... 7 1. Υπότυποι Κατάθλιψης .............................................................................................................. 8 1.1 Άτυπη Κατάθλιψη - Atypical Depression ....................................................................................... 8 1.2 Διπολική Κατάθλιψη ή Μανιοκατάθλιψη – Bipolar Depression (Manicdepressive Psychosis) .... 9 1.3 Διαταραχή Δυσθυμίας - Dysthymic Disorder ................................................................................ 9 1.4 Ελάσσων Καταθλιπτική Διαταραχή - Minor Depressive Disorder ............................................... 10 1.5 Επιλόχειος Κατάθλιψη – Postpartum Depression ....................................................................... 10 1.6 Εποχιακή Συναισθηματική Διαταραχή - Seasonal Affective Disorder ......................................... 10 1.7 Κατάθλιψη μετά από κάποια απώλεια – Depression after bereavement .................................. 11 1.8 Μείζων Καταθλιπτική Διαταραχή – Major Depressive Disorder ................................................. 11 1.9 Μελαγχολία - Melancholic Depression ........................................................................................ 12 1.10 Μικτή Κατάθλιψη - Μixed depression....................................................................................... 13 1.11 Σύντομη Επαναλαμβανόμενη Κατάθλιψη - Brief Recurrent Depression ................................... 14 1.12 Ψυχωσική Κατάθλιψη - Psychotic Depression .......................................................................... 14 2. Παράγοντες σχετικοί με την κατάθλιψη .................................................................................. 14 2.1 Φύλο ............................................................................................................................................ 14 2.1.1 Προγεννητική και Επιλόχειος Κατάθλιψη ................................................................................ 15 2.1.2 Εμμηνόπαυση ........................................................................................................................... 16 2.2 Οικογενειακό ιστορικό ................................................................................................................ 16 2.3 Άγχος ........................................................................................................................................... 16 2.4 Υποτροπή ..................................................................................................................................... 17 3. Αίτια Κατάθλιψης ................................................................................................................... 18 3.1 Η μονοαμινική υπόθεση .............................................................................................................. 18 3.2 Φλεγμονώδης απόκριση (IRS) ..................................................................................................... 19 3.3 Δυσλειτουργία του άξονα Υποθαλάμου – Υπόφυσης – Επινεφριδίων (HPA) ............................ 20 3.4 Περιβαλλοντικοί Παράγοντες ..................................................................................................... 23 3 3.5 Γενετικοί Παράγοντες .................................................................................................................. 24 4. Θεραπεία ............................................................................................................................... 24 4.1 Ψυχοθεραπεία ............................................................................................................................ 25 4.2 Φαρμακοθεραπεία ...................................................................................................................... 27 Μέρος 2ο .................................................................................................................................... 29 Εισαγωγή ................................................................................................................................... 29 5. Μελέτες ................................................................................................................................. 29 5.1 Μελέτες Σύνδεσης ....................................................................................................................... 29 5.2 Μελέτες συσχέτισης .................................................................................................................... 30 5.3 Μελέτες συσχέτισης ολόκληρου γονιδιώματος - Genome Wide Association Studies (GWAS) .. 30 6. Βάσεις δεδομένων για τις Μελέτες Συσχέτισης ....................................................................... 32 7. Προβλήματα στις Μελέτες Συσχέτισης για την κατάθλιψη ...................................................... 34 8. Έρευνες GWAS για την κατάθλιψη .......................................................................................... 36 9. Πίνακες Αποτελεσμάτων ........................................................................................................ 42 9.1 Συγκεντρωτικός πίνακας όλων των αποτελεσμάτων .................................................................. 42 9.2 Πίνακας συχνά εμφανιζόμενων SNPs ......................................................................................... 61 9.3 Πίνακας συχνά εμπλεκόμενων γονιδίων .................................................................................... 63 10. Συζήτηση αποτελεσμάτων .................................................................................................... 70 11. Συμπεράσματα ..................................................................................................................... 71 12. Προτάσεις για επόμενες έρευνες .......................................................................................... 72 Βιβλιογραφία ............................................................................................................................ 73 4 Περίληψη Η Μείζων Καταθλιπτική Διαταραχή πλήττει ένα σημαντικό και συνεχώς αυξανόμενο ποσοστό του παγκόσμιου πληθυσμού. Τα ερωτήματα που εγείρονται γύρω από αυτήν είναι πολλά. Δεν έχει κατανοηθεί ακόμη πλήρως, γιατί ορισμένοι άνθρωποι είναι πιο ευάλωτοι στο να νοσήσουν, για ποιον ακριβώς λόγο δουλεύουν κάποιες θεραπείες φαρμάκων και γιατί έχουν αποτέλεσμα μόνο στο 50% των ασθενών. Το βασικό, όμως, ζήτημα είναι το γεγονός, ότι δεν έχουν κατανοηθεί πλήρως τα αίτια της διαταραχής και δεν έχουν βρεθεί τα συστήματα και τα γονίδια που εμπλέκονται. Μέσω της παρατήρησης και των ερευνών που έχουν γίνει, είναι πλέον βέβαιο ότι η κατάθλιψη έχει γενετική βάση. Παρόλα αυτά, οι πολυάριθμες και διαφορετικού τύπου έρευνες δεν έχουν δώσει συνεπή αποτελέσματα, τα οποία να μπορούν να αναπαραχθούν. Η αναγνώριση των γονιδίων που σχετίζονται με τη Μείζονα Καταθλιπτική Διαταραχή είναι ένα μεγάλο βήμα, τόσο προς την κατανόηση των μηχανισμών της διαταραχής, όσο και προς τον εντοπισμό των αιτιών και των τρόπων αντιμετώπισής της. H πιο σύγχρονη και πολλά υποσχόμενη μέθοδος έρευνας, στην οποία επικεντρώνεται αυτή η εργασία, είναι οι Μελέτες Ολόκληρου του Γονιδιώματος (Genome Wide Association Studies – GWAS), οι οποίες ήταν επιτυχείς για άλλες ψυχικές διαταραχές, όπως η Σχιζοφρένεια. Στην εργασία αυτή γίνεται, αρχικά στο πρώτο μέρος, μια αναφορά στα όσα γνωρίζουμε για την κατάθλιψη σχετικά με τους τύπους της, τους παράγοντες που την επηρεάζουν, τα γνωστά αίτια και τους τρόπους αντιμετώπισής της. Έπειτα, στο δεύτερο μέρος, θα αναφερθούν οι βασικοί τρόποι έρευνας των εμπλεκόμενων γονιδίων και τα προβλήματα που αντιμετωπίζουν.
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