Towards a neurobiological view of depression: Search for diagnostic biomarkers and alterations by electroconvulsive therapy

Erin van Buel

Towards a neurobiological view of depression: Search for diagnostic biomarkers and alterations by electroconvulsive therapy

Vertaalde titel van de bijdrage: Een biologische visie op depressie: Zoektocht naar diagnostische biomarkers en veranderingen door electroconvulsieve therapie

Erin van Buel

Eisel lab - Molecular Neurobiology and Neuroimmunology

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Samenvatting

De ontwikkeling van betere diagnostische methoden en effectievere therapieën kunnen bijdragen aan het verminderen van de ziektelast ten gevolge van depressie.
Biomarkers, zoals bijvoorbeeld eiwitlevels in bloed of urine, kunnen mogelijk bijdragen aan de diagnosticering van depressie. Om te onderzoeken of een combinatie van biomarkers gebruikt kan worden als hulpmiddel bij de diagnosticering van depressie hebben wij de levels van 40 biomarkers bepaald in serum en/of urine van depressieve patiënten en gezonde controles. Vervolgens hebben wij een algoritme ontwikkeld om de resultaten van verschillende biomarkers samen te voegen in een zogenaamde “BioDepression Score”. De resultaten duiden erop dat een combinatie van 17 biomarkers gezamenlijk met voldoende nauwkeurigheid depressieve patiënten van gezonde personen kan onderscheiden.
Electroconvulsieve therapie (ECT) wordt gezien als één van de meest effectieve behandelingen voor depressie. De werkingsmechanismen die ten grondslag liggen aan ECT zijn echter niet volledig duidelijk, maar zijn mogelijk o.a. gerelateerd aan modulatie van de activiteit van het immuunsysteem.
Om meer inzicht te krijgen in het effect van ECT op inflammatie en het immuunsysteem, hebben wij het effect onderzocht van electroconvulsieve shocks (ECS) op de activiteit van microglia (de immuuncellen van de hersenen) in diermodellen voor depressie. De resultaten van deze onderzoeken lopen uiteen: in sommige experimenten wordt een verhoogde activiteit gevonden, terwijl er in andere experimenten geen effect waarneembaar is. Dit wijst erop dat het effect van ECS op de activiteit van microglia afhankelijk is van bepaalde omstandigheden.
Ook hebben wij de mechanismen onderzocht die ten grondslag liggen aan de geheugenproblemen die kunnen optreden als bijwerking van ECT. Wij hebben aanwijzingen gevonden dat inflammatoire mechanismen en veranderingen in het cholinerge neurotransmittersysteem hier waarschijnlijk een rol in spelen.

Vertaalde titel van de bijdrage	Een biologische visie op depressie: Zoektocht naar diagnostische biomarkers en veranderingen door electroconvulsieve therapie
Originele taal-2	English
Kwalificatie	Doctor of Philosophy
Toekennende instantie	Rijksuniversiteit Groningen
Begeleider(s)/adviseur	Eisel, Ulrich, Supervisor Schoevers, Robert, Supervisor Klein, Hans, Co-supervisor Bosker, Fokko, Co-supervisor
Datum van toekenning	30-jun.-2017
Plaats van publicatie	[Groningen]
Uitgever	Rijksuniversiteit Groningen
Gedrukte ISBN's	978-90-367-9861-7
Elektronische ISBN's	978-90-367-9862-4
Status	Published - 2017

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Title and contentsFinal publisher's version, 191 KB
Chapter 1Final publisher's version, 177 KB
Chapter 2Final publisher's version, 517 KB
Chapter 3Final publisher's version, 456 KB
Chapter 4Final publisher's version, 593 KB
Chapter 5Final publisher's version, 1,19 MB
Chapter 6Final publisher's version, 1,17 MB
Chapter 7Final publisher's version, 2,58 MB
Chapter 8Final publisher's version, 173 KB
Nederlandse samenvattingFinal publisher's version, 104 KB
Word of thanksFinal publisher's version, 89,1 KB
Curriculum vitaeFinal publisher's version, 86,6 KB
List of publicationsFinal publisher's version, 89,6 KB
Complete thesisFinal publisher's version, 5,63 MB
PropositionsFinal publisher's version, 444 KB

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title = "Towards a neurobiological view of depression: Search for diagnostic biomarkers and alterations by electroconvulsive therapy",

abstract = "The development of better diagnostic methods and more effective therapies can contribute to the reduction of depression-induced disability.Biomarkers, like for example protein or hormone levels in serum or urine, may potentially serve as an aid for diagnosing depression. To investigate if a combination of biomarkers can contribute to diagnosing depression we determined the levels of 40 potential serum or urine biomarkers in depressed patients and healthy control subjects. We subsequntly developed an algorithm to combine the results of these biomarkers in a so-called “BioDepression Score”. The results suggest that a combination of 17 biomarkers can separate depressed patients from healthy controls with sufficient sensitivity and specificity.Electroconvulsive therapy (ECT) is one of the most effective treatments for depression. The mechanisms behind its antidepressive effects are not entirely clear, but possibly modification of immune system activity plays a role. To gain more insight into the effect of ECT on the immune system, we investigated the effect of electroconvulsive seizures (ECS) on activity of microglia (the immune cells of the brain) in animal models for depression. The results are divergent: while some experiments show increased activity, other experiments fail to demonstrate an effect on microglial activity. This suggests that the effect of ECS on microglial activity is dependent upon certain additional factors.In addition, we studied the mechanisms behind ECT-induced memory deficits, a common side effect of ECT. We found indications that inflammatory mechanisms and changes in the cholinergic neurotransmitter system play a role in the induction of memory deficits by ECT.",

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N2 - The development of better diagnostic methods and more effective therapies can contribute to the reduction of depression-induced disability.Biomarkers, like for example protein or hormone levels in serum or urine, may potentially serve as an aid for diagnosing depression. To investigate if a combination of biomarkers can contribute to diagnosing depression we determined the levels of 40 potential serum or urine biomarkers in depressed patients and healthy control subjects. We subsequntly developed an algorithm to combine the results of these biomarkers in a so-called “BioDepression Score”. The results suggest that a combination of 17 biomarkers can separate depressed patients from healthy controls with sufficient sensitivity and specificity.Electroconvulsive therapy (ECT) is one of the most effective treatments for depression. The mechanisms behind its antidepressive effects are not entirely clear, but possibly modification of immune system activity plays a role. To gain more insight into the effect of ECT on the immune system, we investigated the effect of electroconvulsive seizures (ECS) on activity of microglia (the immune cells of the brain) in animal models for depression. The results are divergent: while some experiments show increased activity, other experiments fail to demonstrate an effect on microglial activity. This suggests that the effect of ECS on microglial activity is dependent upon certain additional factors.In addition, we studied the mechanisms behind ECT-induced memory deficits, a common side effect of ECT. We found indications that inflammatory mechanisms and changes in the cholinergic neurotransmitter system play a role in the induction of memory deficits by ECT.

AB - The development of better diagnostic methods and more effective therapies can contribute to the reduction of depression-induced disability.Biomarkers, like for example protein or hormone levels in serum or urine, may potentially serve as an aid for diagnosing depression. To investigate if a combination of biomarkers can contribute to diagnosing depression we determined the levels of 40 potential serum or urine biomarkers in depressed patients and healthy control subjects. We subsequntly developed an algorithm to combine the results of these biomarkers in a so-called “BioDepression Score”. The results suggest that a combination of 17 biomarkers can separate depressed patients from healthy controls with sufficient sensitivity and specificity.Electroconvulsive therapy (ECT) is one of the most effective treatments for depression. The mechanisms behind its antidepressive effects are not entirely clear, but possibly modification of immune system activity plays a role. To gain more insight into the effect of ECT on the immune system, we investigated the effect of electroconvulsive seizures (ECS) on activity of microglia (the immune cells of the brain) in animal models for depression. The results are divergent: while some experiments show increased activity, other experiments fail to demonstrate an effect on microglial activity. This suggests that the effect of ECS on microglial activity is dependent upon certain additional factors.In addition, we studied the mechanisms behind ECT-induced memory deficits, a common side effect of ECT. We found indications that inflammatory mechanisms and changes in the cholinergic neurotransmitter system play a role in the induction of memory deficits by ECT.

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