Klasen Martin, Wolf Dhana, Eisner Patrick D, Eggermann Thomas, Zerres Klaus, Zepf Florian D, Weber René, Mathiak Klaus
Department of Psychiatry, Psychotherapy and Psychosomatics, Faculty of Medicine, RWTH Aachen, Aachen, Germany.
JARA - Translational Brain Medicine, Aachen, Germany.
Front Neurosci. 2019 Feb 22;13:42. doi: 10.3389/fnins.2019.00042. eCollection 2019.
Aggressive behavior is associated with dysfunctional frontolimbic emotion regulation circuits. Recent findings suggest serotonin as a primary transmitter for prefrontal amygdala control. However, the association between serotonin levels, amygdala regulation, and aggression is still a matter of debate. Neurobehavioral models furthermore suggest a possible mediating influence of the monoamine oxidase A gene () on this brain-behavior relationship, with carriers of low expressing allele varieties being a risk group for aggression. In the present study, we investigated the influence of brain serotonin modulation and genotype on functional amygdala connectivity during aggressive behavior. Modulation of serotonergic neurotransmission with acute tryptophan depletion (ATD) and placebo were administered in a double-blind, cross-over design in 38 healthy male participants. Aggressive behavior was modeled in a violent video game during simultaneous assessment of brain activation with functional magnetic resonance imaging (fMRI). Trait aggression was measured with the Buss-Perry Aggression Questionnaire (BP-AQ), and genotypes were assessed from blood samples. Voxel-wise functional connectivity with anatomically defined amygdala was calculated from the functional data. Tryptophan depletion with ATD reduced aggression-specific amygdala connectivity with bilateral supramarginal gyrus. Moreover, ATD impact was associated with trait aggression and genotype in prefrontal cortex regions. In summary, serotonergic corticolimbic projections contribute to aggressive behavior. Genotype-specific vulnerability of frontolimbic projections may underlie the elevated risk in low expressing allele carriers.
攻击性行为与额叶边缘情绪调节回路功能失调有关。最近的研究结果表明，血清素是前额叶杏仁核控制的主要神经递质。然而，血清素水平、杏仁核调节与攻击性行为之间的关联仍存在争议。神经行为模型进一步表明，单胺氧化酶A基因（）可能在此脑-行为关系中起中介作用，低表达等位基因变体的携带者是攻击性行为的风险群体。在本研究中，我们调查了大脑血清素调节和基因型对攻击性行为期间功能性杏仁核连接性的影响。对38名健康男性参与者采用双盲、交叉设计，通过急性色氨酸耗竭（ATD）和安慰剂对血清素能神经传递进行调节。在通过功能磁共振成像（fMRI）同步评估大脑激活的过程中，在暴力视频游戏中模拟攻击性行为。用Buss-Perry攻击问卷（BP-AQ）测量特质攻击性，并从血样中评估基因型。根据功能数据计算与解剖学定义的杏仁核的体素级功能连接性。ATD导致的色氨酸耗竭降低了杏仁核与双侧缘上回的攻击特异性连接性。此外，ATD的影响与前额叶皮质区域的特质攻击性和基因型有关。总之，血清素能皮质边缘投射有助于攻击性行为。额叶边缘投射的基因型特异性易感性可能是低表达等位基因携带者风险升高的基础。
