Zusammenhang zwischen der Einnahme von Lithium und neuroradiologischen Veränderungen bei der bipolar affektiven Störung: Gibt es Hinweise auf ein klinisches Ansprechen?

Zusammenfassung

Zur Vermeidung affektiver Krankheitsphasen im Rahmen der bipolar affektiven Störung erfolgt die psychopharmakologische Behandlung mittels sogenannter Phasenprophylaktika. Traditionell werden unter diesem Begriff die Wirkstoffe Lithium, Valproat, Lamotrigin und Carbamazepin zusammengefasst. Moderne Therapiekonzepte zur Phasenprophylaxe berücksichtigen ebenfalls Antipsychotika der zweiten Generation. In dieser Literaturrecherche sollen die Zusammenhänge zwischen den biologischen Veränderungen des Gehirns und der Einnahme von Lithium dargestellt werden. Hierbei werden Daten aus makrostruktureller, mikrostruktureller und spektroskopischer Bildgebung angeführt.

Daten zu Veränderungen der Makrostruktur unter Lithiumtherapie sind quantitativ am stärksten untersucht. So scheint Lithium im Zusammenhang mit einer Vergrößerung des Volumens von kortikaler und subkortikaler grauer Substanz zu stehen. Des Weiteren zeigt sich unter Lithiumtherapie eine geringradigere mikrosturkurelle Veränderung in Marklageralrealen was auf einen möglichen neuroprotektiven Effekt von Lithium zurückzuführen sein könnte. An Hand der 7-Lithium-MR-Spektroskopie konnte gezeigt werden, dass remittierte und nicht-remittierte Patientinnen und Patienten signifikante intrazerebrale Konzentrationsunterschiede aufzeigen.

Präklinische Daten weisen auf lithiuminduzierte promitotische, als auch antiapoptotische Mechanismen hin und stützen somit die Hypothese eines volumenerhaltenden Effektes mittels Neurogenese. Jedoch könnten hinsichtlich des Lithiums auch osmotische und physikalische Effekte maßgebliche Ursachen für die Volumenzunahme in der makrostrukturellen Bildgebung bilden.

Das mehrheitliche Vorhandensein von Querschnittsstudien zu dieser Thematik und kleine Kohortengrößen stellen typische Limitationen der untersuchten Studien dar.

Hinsichtlich der Forschung zum Lithiummetabolismus könnte insbesondere die 7-Lithium-Spektroskopie zukünftig eine Methode darstellen, um diesbezügliche pharmakokinetische Unterschiede zwischen remittierten und nicht-remittierten Patienten aufzuklären.

Abstract

For avoiding affective episodes, patients with bipolar disorders are treated with mood stabilizers. Under that term, the substances lithium, valproic acid, lamotrigine and carbamazepine are included. In the light of upcoming new psychiatric concepts, the use of second generation antipsychotics is also taken into consideration in pharmacological treatment. In this review, the relation between brain structure and the use of lithium in bipolar disorders is examined. Therefore, results from MRI-, DTI-, SPECT-studies assessing this relation, were included.

Most of the studies are cross-sectional and examined the effects of lithium. The latter is associated with increased cortical and sub-cortical gray matter volume and ameliorative white matter microstructure. 7-lithium spectroscopy showed a significant difference in brain-lithium concentrations between remitted and non-remitted patients.

There are preclinical studies reporting induction of promitotic and antiapoptotic effects by lithium. This literature underpins the hypothesis of lithium-induced neurogenesis. However, osmotic and physical effects of lithium could also explain the demonstrated volume gain in bipolar human brain.

Cross-sectional design and small patient groups are typical limitations of numerous studies included in this review.

Notably, with the 7-lithium spectroscopy of the central nervous system, new perspectives in clinical research to clarify pharmacokinetic differences between remitted and non-remitted bipolar patients can be established in future.

Schlüsselwörter

Bipolar affektive Störung - Lithium - MRT - DTI - MR-Spektroskopie

Key words

Bipolar disorders - Lithium - MRI - DTI - MR-Spectroscopy

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