Different patterns of dopaminergic and serotonergic dysfunction in manic, depressive and euthymic phases of bipolar disorder

Summary

A variety of alterations in brain neurotransmitter systems has been proposed as the cause of bipolar disorder (BD). We conducted a PUBMED search, which provided a total of 45 in vivo investigations with PET and SPECT, in which binding to serotonin transporter (SERT), 5-HT_1A receptor (R), 5-HT_2AR, dopamine transporter (DAT), vesicular monoamine transporter (VMAT2), D₁R, D₂R, muscarinic M2R and nicotinic ß2-nAChR as well as dopamine synthesis and/or dopamine release were assessed in BD patients in the manic (6 studies, 39 patients, 77 controls), depressive (15 studies, 248 patients, 488 controls) or eu- thymic condition (18 studies, 265 patients, 293 controls) and in mixed collectives of BD patients (6 studies, 55 patients, 80 controls). The retrospective analysis revealed a complex pattern of dysregulations within and between neurotransmitter systems, which is causally linked to the acute and euthymic states of BD. While increased mesencephalic, limbic and parietotemporoccipital serotonin and increased frontal dopamine underlie mania, the depressive state is characterized by decreased frontal and limbic serotonin, increased frontal and limbic acetylcholine and increased frontal dopamine. Also in euthymia, no normalization of receptor and transporter densities was observed. Alterations of regulation states of bindings sites, however, act together to achieve a normalization of mesencephalic, limbic and cortical serotonin.

Zusammenfassung

Verschiedenen Veränderungen in den Neurotransmittersystemen des Gehirns wird eine Rolle bei der bipolaren Störung (BD) zugeschrieben. Eine PUBMED-Recherche ergab insgesamt 45 in vivo Untersuchungen mit PET oder SPECT, in denen die Bindung an den Serotonintransporter (SERT), den 5-HT_1A-Rezeptor (R), den 5-HT_2AR, den Dopamintransporter (DAT), den vesikulären Monoamintransporter (VMAT2), den D₁R, den D₂R, den muskarini- schen M2R und den nikotinischen ß2-nAChR, die Dopaminsynthese und/oder die Dopaminfreisetzung in bipolaren Patienten im manischen (6 Studien, 39 Patienten, 77 Kontrollen), depressiven (15 Studien, 248 Patienten, 488 Kontrollen) oder euthymen Zustand (18 Studien, 265 Patienten, 293 Kontrollen) und in gemischen Kollektiven (6 Studien, 55 Patienten, 80 Kontrollen) untersucht wurden. Die retrospektive Analyse ergab ein komplexes Muster von Fehlregulationen innerhalb und zwischen den Neurotransmittersystemen, die in kausalem Zusammenhang mit den akuten und euthymen Zuständen stehen. Während der Manie erhöhte mesenzephale, limbische und parietotemporookzipitale Serotoninkonzentrationen sowie eine erhöhte frontale Dopaminkonzentration zu Grunde liegen, ist der depressive Zustand durch eine Erniedrigung der frontalen und limbischen Serotoninkonzentration, erhöhte frontale und limbische Azetylcholinkonzentrationen sowie eine erhöhte frontale Dopaminkonzentration gekennzeichnet. Auch im euthymen Zustand wurde keine Normalisierung der Rezeptor- und Transporterdichten gefunden. Veränderungen im Regulationszustand der Bindungsstellen wirken jedoch zusammen, um eine Normalisierung der mesenzephalen, limbischen und kortikalen Serotoninkonzentrationen zu erreichen.

Keywords

bipolar disorder - mania - depression - euthymia

Schlüsselwörter

Bipolare Störung - Manie - Depression - Euthymie

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