Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.
Transl Psychiatry. 2012 Apr 3;2(4):e99. doi: 10.1038/tp.2012.29.
Major depressive disorder (MDD) is characterized by affective symptoms and cognitive impairments, which have been associated with changes in limbic and prefrontal activity as well as with monoaminergic neurotransmission. A genome-wide association study implicated the polymorphism rs2522833 in the piccolo (PCLO) gene--involved in monoaminergic neurotransmission--as a risk factor for MDD. However, the role of the PCLO risk allele in emotion processing and executive function or its effect on their neural substrate has never been studied. We used functional magnetic resonance imaging (fMRI) to investigate PCLO risk allele carriers vs noncarriers during an emotional face processing task and a visuospatial planning task in 159 current MDD patients and healthy controls. In PCLO risk allele carriers, we found increased activity in the left amygdala during processing of angry and sad faces compared with noncarriers, independent of psychopathological status. During processing of fearful faces, the PCLO risk allele was associated with increased amygdala activation in MDD patients only. During the visuospatial planning task, we found no genotype effect on performance or on BOLD signal in our predefined areas as a function of increasing task load. The PCLO risk allele was found to be specifically associated with altered emotion processing, but not with executive dysfunction. Moreover, the PCLO risk allele appears to modulate amygdala function during fearful facial processing in MDD and may constitute a possible link between genotype and susceptibility for depression via altered processing of fearful stimuli. The current results may therefore aid in better understanding underlying neurobiological mechanisms in MDD.
重度抑郁症（MDD）的特征是情感症状和认知障碍，这些症状与边缘和前额叶活动的变化以及单胺能神经传递有关。全基因组关联研究表明，涉及单胺能神经传递的 piccolo（PCLO）基因中的多态性 rs2522833 是 MDD 的风险因素。然而，PCLO 风险等位基因在情绪处理和执行功能中的作用或对其神经基质的影响从未被研究过。我们使用功能磁共振成像（fMRI）在 159 名当前 MDD 患者和健康对照组中，在进行情绪面孔处理任务和视觉空间规划任务时，研究了 PCLO 风险等位基因携带者与非携带者之间的差异。在 PCLO 风险等位基因携带者中，我们发现与非携带者相比，在处理愤怒和悲伤面孔时，左杏仁核的活动增加，而与精神病理学状态无关。在处理恐惧面孔时，PCLO 风险等位基因仅与 MDD 患者的杏仁核激活增加有关。在视觉空间规划任务中，我们没有发现基因型对表现或预定义区域的 BOLD 信号有影响，因为任务负荷增加。PCLO 风险等位基因与改变的情绪处理有关，但与执行功能障碍无关。此外，PCLO 风险等位基因似乎在 MDD 患者的恐惧面部处理中调节杏仁核功能，并且可能通过改变对恐惧刺激的处理，构成基因型和抑郁易感性之间的可能联系。因此，目前的结果可能有助于更好地理解 MDD 中的潜在神经生物学机制。
