Genetische und neurobiologische Befunde besitzen für die aktuelle Forschung einen besonderen Stellenwert für das Verständnis der bipolaren (manisch-depressiven) Störung. Einige epidemiologische Daten (gleiche Prävalenz in verschiedenen Kulturen, familiäre Häufung, früher durchschnittlicher Krankheitsbeginn) führen zu der Annahme, dass die bipolare Störung stärker als die Depression von genetischen Faktoren bestimmt wird und der Einfluss äusserer Faktoren entsprechend geringer ist. Man vermutet einen komplexen Erbgang mit Veränderungen mehrerer verschiedener Gene bei ein und derselben Person. Erst die Wechselwirkung zwischen ihnen führen dazu, dass ein Mensch für die bipolare Erkrankung prädisponiert ist. Damit es tatsächlich zum Ausbruch kommt, müssen wahrscheinlich nicht-genetische, äussere Faktoren hinzukommen.
Genetische Faktoren
Familienstudien, Zwillingsstudien und Adoptivstudien
Es fanden sich wiederholt
- familiäre Häufungen bipolarer Störungen mit eindeutigen manischen Phasen. Die Bedeutung genetischer Faktoren bei der bipolaren Störung ist dabei höher als bei der Depressionen.
- Für bipolare Störungen fand sich eine Konkordanzrate von 72% bei eineiigen Zwillingen und von 14% bei zweieiigen Zwillingen
- Für unipolare manische Störungen betragen die Konkordanzraten 40% (eineiige) und 14% (zweieiige)
- Kinder, deren einer Elternteil an einer bipolaren Störung leidet, erkranken mit 24% Wahrscheinlichkeit an derselben oder einer anderen affektiven Störung
- Wenn beide Eltern erkrankt sind, beträgt die Erkrankungswahrscheinlichkeit für die Kinder > 55%
- Biologische Verwandte von Adoptivkindern, die an einer affektiven Störung leiden, haben ein deutlich höheres Risiko, ebenfalls an einer uni- oder bipolaren Störung zu erkranken/erkrankt zu sein als die Mitglieder der Gastfamilie
Auch bei den monopolar manischen und bipolaren Störungen ließ sich bislang keine direkte Verantwortlichkeit bestimmter Gene nachweisen. In sogenannten genetischen „Kopplungsanalysen“ konnten jedoch inzwischen einzelne Gene lokalisiert werden, die mit ziemlicher Wahrscheinlichkeit für die Disposition zur Krankheit mitverantwortlich sind. Es handelt sich um folgende „Dispositionsgene“:
- das G72-Gen auf Chromosom 13, wichtig für die glutamaterge Transmission an den Synapsen
- das BDNF (brain-derived neurotrophic factor) – Gen auf Chromosom 11, beteiligt an der Neubildung und am Wachstum von Nervenzellen
- das GRK 3 (G-Protein-Rezeptorkinase) – Gen auf Chromosom 22, beteiligt an dem wichtigen Prozess der Signaltransduktion und v. a. auch im limbischen System verbreitet, welches für das Gefühlserleben und Stimmungen eine besondere Bedeutung hat
Neurobiologische Faktoren
Im Verlauf affektiver Störungen kommt es auch zu funktionellen und strukturellen Veränderungen des Gehirns. Dabei finden sich bei bipolaren Störungen Auffälligkeiten in der gesamten Kette der neuronalen Transmission von der Genexpression bis zum Neurotransmitter (Baumann et al, 2003). Bei den verfügbaren Befunden handelt es sich bislang jedoch erst um einzelne Nachweise signifikanter Veränderungen, die in bestimmte Richtungen weisen. Von einer zusammenhängenden neurobiologischen Theorie der bipolaren Störung scheint die Forschung noch weit entfernt. Es verdichten sich aber die Hinweise, dass die gemeinsame Grundstörung bei affektiven Erkrankungen in einer fehlerhaften postsynaptischen Signaltransduktion zu suchen ist.
- Nachweis funktioneller metabolischer Abweichungen in bildgebenden Verfahren:
- PET- und SPECT-Untersuchungen zeigen inkonsistent aber signifikant eine verringerte (v. a. frontale) kortikale Aktivität des Glucosestoffwechsels während (bipolar oder unipolar) depressiver Phasen (im Vergleich zu gesunden Probanden oder Phasen euthymer oder manischer Stimmung). Die Stimmung scheint also mit der Glucoseaktivität bzw. metabolischen Veränderungen im Gehirn assoziiert zu sein.
- Stukturelle hirnmorphologische Befunde:
- Die in PET- und SPECT-Untersuchungen gefundene Verringerung des Glucosestoffwechsels im präfrontalen Kortex in monopolar oder bipolare depressiven Phasen scheint auch strukturell bedingt zu sein. Im MRT fand sich im Vergleich zu Gesunden in dieser Hirnregion eine Volumenreduktion von 39% bei bipolaren Patienten und von 48% bei monopolar depressiven Patienten.
- Die beobachteten Störungen der chonobiologischen Rhythmen bei affektiven Störungen und insbesondere der bipolaren Störung scheinen auf Störungen im Nucleus suprachiasmaticus („Zeitgeber“), Gewebsuntergänge im Nucleus paraventricularis des Thalamus (PVN) und eine Verminderung der Melatonin-Sekretion zurückzuführen zu sein.
- Relativ spazifisch für bipolare Störungen scheinen zu sein eine Vergrößerung des 3. Ventrikels, Veränderungen der Basalganglien und eine Verkleinerung des Temporallappens.
- Wie unipolare manische oder depressive Störungen gehen auch bipolare Störungen oft mit einer Verkleinerung des Cerebellums (Kleinhirns) einher.
- Nach Verletzungen der rechten Hirnhemisphäre treten häufiger manische Symptome auf.
- neurochemische und neuroendokrine Befunde:
- Es konnte in einigen Studien bei manischen Episoden gleichzeitig erniedrigte Serotoninspiegel und erhöhte Noradrenalinspiegel gefunden werden. Es fand sich bei bipolaren Störungen auch eine Verminderung von MHPG (Noradreanlinmetabolit) im Urin
- Es finden sich Hinweise auf eine erhöhte zentrale cholinerge Aktivität bei bipolaren Störungen
- Depressive Störungen, auch solche bei bipolaren Störungen, gehen mit einem Hyperkortisolismus einher (erhöhtes 24-Stunden-Kortisol und pathologischer Dexamethason-Test)
Detailliertere Informationen über Transmittersysteme und Modellvorstellungen zur Entstehung affektiver Störungen inkl. einer zusammenfassenden Bewertung der Erkenntnislage finden Sie bei den Informationen zur Depression
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