Breaking the habit – Exploring the potential of peripheral blood mononuclear cells in comparison with plasma as a sample source for biomarker discovery in psychiatry

Jolien Hendrix
Persbericht

Het zit tussen je oren! Of toch in je bloed?

Kennen jullie iemand die een psychische ziekte heeft? Waarschijnlijk wel, want wereldwijd zijn er meer dan 220 miljoen mensen die lijden aan één van de drie belangrijkste psychische ziektes. Dat is 20 keer het aantal inwoners van België! Dit onderzoek draagt bij tot de verbetering van de psychische gezondheidszorg, dit omdat momenteel de kwaliteit hiervan laag is door een gebrek aan biologische testen.

Psychische ziektes zitten niet tussen je oren!

In tegenstelling tot andere ziektes, zijn psychische ziektes nog altijd een mysterie voor wetenschappers over de hele wereld. We weten nog altijd niet hoe mensen psychisch ziek worden of hoe we deze mensen het beste kunnen behandelen. Wat onderzoek naar psychische ziektes verder bemoeilijkt is het feit dat mensen die een psychische ziekte hebben er voor de buitenwereld kerngezond uitzien. Daarom wordt ook vaak gezegd dat het ‘tussen je oren zit’, maar dat is natuurlijk helemaal niet waar!

Naast biologische afwijkingen in de hersenen, zijn bij mensen met een psychische ziekte ook afwijkingen in het bloed gevonden. Wetenschappers proberen momenteel aan de hand van deze biologische afwijkingen een test op te stellen die kan zeggen welke psychische ziekte iemand heeft. Helaas heeft dit tot op de dag van vandaag nog niet veel opgeleverd. Dit is een enorm groot probleem aangezien verschillende psychische ziektes heel hard op elkaar lijken. Daarom krijgen heel veel mensen een foute diagnose en dus ook een foute behandeling. Dit kan ernstige gevolgen hebben aangezien de behandeling van een psychische ziekte vaak zware medicatie omvat om symptomen onder controle te krijgen. Omdat vooral de symptomen van depressie, bipolaire stoornis en schizofrenie hard op elkaar lijken en de nood dus het hoogst is bij deze ziektes, hebben wij deze drie psychische ziektes tijdens dit onderzoek onder de loep genomen.

Vlaamse scriptieprijs

Figuur 1. Visuele voorstelling van de meest voorkomende symptomen bij depressie, bipolaire stoornis en schizofrenie. © @lavelydrawings

Thinking out of the box

Tot nu toe hebben wetenschappers vooral gekeken naar bloedplasma om een biologische test te ontwikkelen, maar aangezien de resultaten van deze onderzoeken zeer teleurstellend zijn, besloten wij om iets anders te gebruiken. Witte bloedcellen leken ons een interessant alternatief, maar er is nog niet veel gekend over het gebruik van witte bloedcellen in vergelijking met bloedplasma voor de ontwikkeling van een biologische test. Daarom heeft deze thesis de technische aspecten van bloedplasma en witte bloedcellen vergeleken om zo te bepalen welke van de twee we het beste zouden gebruiken.

Dit hebben we gedaan door gebruik te maken van een massaspectrometer. Dat is een toestel dat de hoeveelheden van verschillende eiwitten in ons lichaam meet. Eiwitten doen eigenlijk bijna alles in ons lichaam om het goed te laten werken en als er een belangrijk eiwit te veel of te weinig aanwezig is, kan er wel eens iets mislopen. Het is dus niet raar dat er in zieke mensen vaak een bepaald eiwit meer of minder aanwezig is in vergelijking met gezonde mensen. Daarom zijn eiwitten ideaal om als biologische test gebruikt te worden.

In dit geval keken we in het bijzonder naar de eiwitten die we konden vinden in het bloedplasma en in de witte bloedcellen. We vergeleken het aantal verschillende eiwitten die gedetecteerd werden (hoe meer verschillende eiwitten, des te groter de kans dat er eiwitten tussen zitten die gebruikt kunnen worden voor de test) en hoe stabiel de hoeveelheden van deze eiwitten zijn (een test moet accuraat zijn en hiervoor moeten de hoeveelheden van de eiwitten stabiel zijn). Jammer genoeg werden de experimenten vroegtijdig stopgezet om de verspreiding van  COVID-19 tegen te gaan, maar toch kunnen we een voorzichtige conclusie trekken. Uit onze resultaten blijkt dat witte bloedcellen mogelijks betere eigenschappen hebben voor de ontwikkeling van een biologische test dan de zogenaamde ‘gouden standaard’, het bloedplasma. Deze resultaten zullen dus hopelijk andere wetenschappers stimuleren om meer op witte bloedcellen te focussen in plaats van op bloedplasma bij het ontwikkelen van een biologische test voor psychische ziektes.

Wat nu?

Het uiteindelijke doel van dit onderzoek is om eiwitprofielen op te stellen die kenmerkend zijn voor depressie, bipolaire stoornis of schizofrenie. Die eiwitprofielen zijn een soort biologische handtekening uniek voor elke ziekte. Hiermee kunnen witte bloedcellen van patiënten geanalyseerd worden via een biologische test die dan op basis van die handtekening kan zeggen welke psychische ziekte elke patiënt heeft.

spectra

Figuur 2. Een simplistisch voorbeeld van eiwitprofielen die kenmerkend zijn voor depressie, bipolaire stoornis of schizofrenie. Elke kleur stelt één eiwit voor en zoals je kan zien zullen de eiwitprofielen zijn samengesteld uit eiwitten die in verschillende hoeveelheden aanwezig zijn bij patiënten met een depressie, bipolaire stoornis of schizofrenie. © @lavelydrawings

Eens zo’n test is ontwikkeld, zal deze uitgevoerd worden in het laboratorium en zal de patiënt enkele dagen later de resultaten krijgen. In de toekomst wordt het misschien zelfs mogelijk om deze test in de vorm van een ‘lab-on-a-chip’ te maken. Een ‘lab-on-a-chip’ is een klein apparaatje dat de witte bloedcellen van een patiënt kan analyseren. Omdat het zo’n klein en gemakkelijk apparaatje is, kunnen dokters dit op hun bureau zetten waardoor ze de witte bloedcellen van de patiënt dus niet meer moeten opsturen naar laboratorium en gewoon ter plaatse kunnen analyseren. Dat betekent dus dat de dokter en patiënt dan ook meteen het resultaat weten en kunnen starten met een gepaste behandeling, zonder dat er eerst nog een paar dagen gewacht moet worden.

lab on a chip

Figuur 3. Voorbeeld van een ‘lab-on-a-chip’.

Momenteel heeft ons team al enkele kandidaat-eiwitten gevonden die gebruikt zouden kunnen worden voor een biologische test die kan zeggen of een persoon een depressie, bipolaire stoornis of schizofrenie heeft. De volgende stap is om de hoeveelheden van deze eiwitten na te kijken in een grotere groep patiënten. Uiteindelijk zal een programma op de computer dan bepalen hoe goed onze eiwithandtekening kan zeggen welke psychische ziekte iemand heeft. Het uiteindelijke doel van dit onderzoek ligt dus zeker nog niet binnen handbereik, maar toch zijn de eerste stappen gezet om de psychische gezondheidszorg te verbeteren.

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Universiteit of Hogeschool
Master of Biomedical Sciences: Neurosciences
Publicatiejaar
2020
Promotor(en)
Prof dr. Violette Coppens, Prof. dr. Manuel Morrens
Kernwoorden
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