The Neural Mechanism Of Negative Self-bias In Depression

Depression accounts for the biggest share of the world’s burden of disease, measured by years to disability. Even though the antidepressant drugs are partly effective, due to the long treatment and limited effect, it is still a big burden to patients, families and society. Depressive disorder is an important public health problem, which needs focus.In the cognitive model of depression, negative self-bias is a stable factor of depression,one of crucial cognitive factors which leading to depression.Many studies indicated that the deficits in the dorsolateral prefrontal cortex(dl PFC) and plethora in the ventromedial prefrontal cortex(vm PFC) might be key roles in the negative self-bias of depression. However, the evidence was limited.In this research, functional magnetic resonance imaging(f MRI), event-related potentials(ERP), and behavioral studies of major depressive disorder(MDD) patients and healthy controls are involved in implicit and explicit self-referential task to better understand the possibility of functional abnormality of vm PFC and dl PFC in negative self-bias in depression.The outcomes and conclusions as following:1. Viewed from valance, in explicit self referential task, the major depressive disorder patients(MDD) had higher score(F=472.170, P=0.000) and longer reaction time(RT)(F=400.908,P=0.000) for negative personality traits compared to never-depressed controls(NC). Besides, MDD had higher score for negative personality traits compared to positive personality traits(P=0.000) as well. The characteristics of ERP were that MDD had larger P2(F=5.647,P=0.023), N2(F=4.731-9.324,P=0.005-0.038) amplitude and had smaller P3(F=4.175-10.856,P=0.003-0.050) amplitude for negative personality traits compared to NC. Compared to positive personality traits, MDD had a longer P2 latency for negative personality traits(F=4.191, P=0.024). Under f MRI condition, MDD showed higher activation in right dl PFC for negative personality traits(t=5.43,k=70,P<0.001) and showed lower activation in left dl PFC for positive personality traits(t=-3.28,k=45,P<0.001) compared to NC. The resulted indicated that MDD showed the negative self-bias in explicit self referential processing, and the difference in ERP mainly existed in the late components, and the abnormal function of dl PFC is vital to negative self-bias in MDD. in implicit self referential task, this no difference in behavioral data. But the characteristics of ERP were that MDD had larger P2(F=4.386, P=0.045) amplitude and had longer N1 latency(F=4.801,P=0.037) for negative personality traits compared to NC. Besides, MDD had larger N2(F=4.876-5.389,P=0.027-0.035), P3(F=4.919-5.180,P=0.030-0.035) amplitude for positive personality traits compared to NC. Under f MRI condition, MDD showed higher activation in Middle occipital gyrus for negative personality traits(t=3.93,k=35,P<0.001) and showed lower activation in left dl PFC for positive personality traits(t=-3.25,k=47,P<0.001) compared to NC. The results indicated that the implicit negative self-bias exist in the early component of ERP, the abnormal function of Middle occipital gyrus is vital to negative self-bias in MDD. The results indicated that negative self-bias exist is a stable characteristics in MDD.2. Viewed from self-relatedness, in explicit self referential task, the characteristics of ERP were that MDD had larger P2(F=5.548,P=0.025), N2(F=5.723,P=0.023), P3(F=5.688,P=0.024) amplitude for high self-related personality traits compared to NC. Under f MRI condition, MDD showed lower activation in right dl PFC for high self-related personality traits(t=-3.32,k=35,P<0.001) and showed higher activation in right dl PFC for low self-related personality traits(t=-3.28,k=45,P<0.001) compared to NC. The results indicated that there is a characteristics of over-focus on self in MDD, which showed in the middle and late components in ERP, and the abnormal function of dl PFC is correlated to the characteristics of over-focus on self in MDD. In implicit self referential task, MDD had higher accuracy rate(F=8.548,P=0.003) and longer RT(F=11.788,P=0.001) for high self-related personality traits compared to low self-related personality traits. The characteristics of ERP were that MDD had larger P2(F=8.565,P=0.010), N2(F=6.060,P=0.020), P3(F=5.639,P=0.024) amplitude and had longer P3(F=6.748,P=0.015) latency for negative personality traits compared to NC. Besides, MDD had longer N2(F=5.035,P=0.033), P3(F=4.438-4.669,P=0.039-0.044) latency for high self-related personality traits compared to NC. Under f MRI condition, MDD showed lower activation in right dl PFC for low self-related personality traits(t=-2.43,k=54,P<0.001) compared to NC and showed higher activation in left cingulate gyrus for positive personality traits(t=2.34,k=34,P<0.05) compared to high self-related personality traits. The results also emphasize the characteristics of over-focus on self in MDD, which showed changes in the middle and late components in ERP, and the abnormal function of dl PFC and cingulate gyrus is correlated to the characteristics of over-focus on self in MDD.3. Viewed from self-certainty, in explicit self referential task, MDD had lower score for low certainty personality traits compared to NC(F=12.142,P=0.001), and compared to low certainty personality traits(F=17.209,P=0.000). Under f MRI condition, MDD showed lower activation in left dl PFC for low certainty personality traits(t=-3.32,k=91,P<0.001) compared to NC. The results indicated that there is a difference between MDD and NC in epistemic investment, and the abnormal function of dl PFC is important to cognitive self processing bias. In implicit self referential task, MDD showed higher activation in vm PFC for low certainty personality traits compared to NC(t=3.52,k=73,P<0.01). The results indicated that the abnormal function of vm PFC is correlated to over-epistemic investment in implicit self processing in MDD.4. Viewed from self-importance, in explicit self referential task, MDD had lower score(F=5.449,P=0.020) for high importance personality traits compared to NC and had longer RT(F=135.449, P=0.020) for high importance personality traits compared to low importance personality traits. Under f MRI condition, MDD showed lower activation in left dl PFC for low importance personality traits(t=-3.34,k=64,P<0.001) compared to NC, and showed higher activation in left dl PFC for high importance personality traits(t=3.16,k=25,P<0.05) compared to low importance personality traits. The results indicated that there is a difference between MDD and NC in emotive investment, and the abnormal function of dl PFC and vm PFC is related to emotive self processing bias. In implicit self referential task, MDD had higher accuracy rate(F=16.356,P=0.000) for high importance personality traits compared to low importance personality traits. Under f MRI condition, MDD showed lower activation in left dl PFC for high importance personality traits(t=-3.32,k=20,P<0.01) compared to NC. The results indicated that self-importance is vital to self processing, which correlated to the abnormal function of dl PFC in MDD.5. Viewed from cognitive load, only in implicit self referential task, the characteristics of ERP were that MDD had larger N2(F=4.931,P=0.034), P3(F=5.516,P=0.026) amplitude and had shorter P3(F=27.875,P=0.000) latency for high load personality traits compared to NC. Besides, MDD had longer P3(F=8.933,P=0.006) latency for low load personality traits compared to NC. Under f MRI condition, MDD showed lower activation in right dl PFC for low load personality traits(t=-3.21,k=61,P<0.001) compared to NC, and lower activation in left dl PFC for high load personality traits(t=-3.24,k=50,P<0.001) compared to NC. Besides, MDD showed higher activation in left postcentral gyrus compared to low load(t=7.77,k=391,P<0.001), and NC showed higher activation in right postcentral gyrus compared to low load(t=8.86,k=359,P<0.001). The results indicated that cognitive load is related to the late components of ERP,and correlated to the abnormal function of postcentral gyrus in MDD.Current study observed the negative bias in depression, and combined with functional magnetic resonance imaging(f MRI), event-related potentials(ERP), and behavioral studies, to better understand the possibility of functional abnormality mechanism of negative self-bias. We hope that our study could beneficial to understand the mechanism of depression and to provide new evidence to the target point of clinical antidepression treatment.