Dannlowski Udo, Ohrmann Patricia, Konrad Carsten, Domschke Katharina, Bauer Jochen, Kugel Harald, Hohoff Christa, Schöning Sonja, Kersting Anette, Baune Bernhard T, Mortensen Lena S, Arolt Volker, Zwitserlood Pienie, Deckert Jürgen, Heindel Walter, Suslow Thomas
Department of Psychiatry, University of Münster, Germany.
Int J Neuropsychopharmacol. 2009 Feb;12(1):11-22. doi: 10.1017/S1461145708008973. Epub 2008 Jun 11.
The amygdala plays a pivotal role in a cortico-limbic circuitry implicated in emotion processing and regulation. In the present study, functional connectivity of the amygdala with prefrontal areas involved in emotion regulation was investigated during a facial expression processing task in a sample of 34 depressed inpatients and 31 healthy controls. All patients were genotyped for a common functional variable number tandem repeat (VNTR) polymorphism in the promoter region of the monoamine oxidase A gene (MAOA u-VNTR) which has been previously associated with major depression as well as reduced cortico-limbic connectivity in healthy subjects. In our control group, we observed tight coupling of the amygdala and dorsal prefrontal areas comprising the dorsolateral prefrontal cortex (DLPFC), dorsal parts of the anterior cingulate cortex (dACC), and lateral orbitofrontal cortex. Amygdala-prefrontal connectivity was significantly reduced in depressed patients and carriers of the higher active MAOA risk alleles (MAOA-H). Hence, depressed MAOA-H carriers showed the weakest amygdala-prefrontal coupling of the investigated subgroups. Furthermore, reduced coupling of this circuitry predicted more than 40% variance of clinical variables characterizing a longer and more severe course of disease. We conclude that genetic variation in the MAOA gene may affect the course of major depression by disrupting cortico-limbic connectivity.
杏仁核在涉及情绪处理和调节的皮质-边缘回路中起关键作用。在本研究中，对34名抑郁症住院患者和31名健康对照者进行了面部表情处理任务，期间研究了杏仁核与参与情绪调节的前额叶区域之间的功能连接。对所有患者进行基因分型，检测单胺氧化酶A基因（MAOA u-VNTR）启动子区域常见的功能性可变数目串联重复（VNTR）多态性，该多态性先前已与重度抑郁症以及健康受试者皮质-边缘连接性降低相关。在我们的对照组中，观察到杏仁核与包括背外侧前额叶皮质（DLPFC）、前扣带回皮质背侧部分（dACC）和外侧眶额皮质在内的背侧前额叶区域紧密耦合。抑郁症患者和高活性MAOA风险等位基因（MAOA-H）携带者的杏仁核-前额叶连接性显著降低。因此，抑郁的MAOA-H携带者在所研究的亚组中表现出最弱的杏仁核-前额叶耦合。此外，该回路耦合的降低预测了超过40%的临床变量方差，这些变量表征了更长、更严重的病程。我们得出结论，MAOA基因的遗传变异可能通过破坏皮质-边缘连接性来影响重度抑郁症的病程。
