key: cord-0693000-aup48w3l
authors: Zhang, Pengyu; Piao, Yi; Chen, Ying; Ren, Jiecheng; Zhang, Longhua; Qiu, Bensheng; Wei, Zhengde; Zhang, Xiaochu
title: The outbreak of COVID-19 altered the relationship between current negative memory biases and future depressive degree in nonclinical depression
date: 2021-01-20
journal: iScience
DOI: 10.1016/j.isci.2021.102081
sha: 97f78cff768d8f04dd7f8ffbc3ab0ac76cb0272f
doc_id: 693000
cord_uid: aup48w3l

The outbreak of the novel coronavirus disease 2019 (COVID-19) has increased concern about people’s mental health under such serious stressful situation, especially depressive symptoms. Cognitive biases have been related to depression degree in previous studies. Here, we used behavioral and brain imaging analysis, to determine if and how the COVID-19 pandemic affects the relationship between current cognitive biases and future depression degree and the underlying neural basis in a nonclinical depressed population. An out-expectation result showed that a more negative memory bias was associated with a greater decrease in future depressive indices in nonclinical depressed participants during the COVID-19 pandemic, which might be due to decreased social stress. These data enhance our understanding of how the depressive degree of nonclinical depressed populations will change during the COVID-19 pandemic and also provide support for social distancing policies from a psychological perspective.

The outbreak of the novel coronavirus disease 2019 (COVID-19) is a major emergency that 30 J o u r n a l P r e -p r o o f as during the pandemic group (DG, n = 30). For detailed experimental design and analysis method, 1 see Transparent Methods. 2

There were no significant differences among the three groups in regard to age, gender or years 4 of education (p > 0.1, Table 1 ). Moreover, the present BDI of the HG was significantly lower than 5 that of the BG and DG (F(2, 92) = 69.48, p < 0.001, Table 1 ), but there was no significant 6 difference between the BG and DG (t(59) = 1.31, p = 0. 19 ). In addition, the future BDI of the HG 7 was also significantly lower than that of the BG and DG (F(2, 92) = 12.32, p < 0.001, Table 1 ), 8

and there was no significant difference between the BG and DG (t(59) = 0.84, p = 0.40). 9

For memory biases, no significant difference was found among the three groups in regard to the 11 percentage of negative (F(2, 88) = 2.17, p = 0.12) or positive (F(2, 88) = 1.63, p = 0.20) words 12 recalled. However, for interpretation biases, the pleasantness ratings in the HG were significantly 13 higher than those in the other two groups (F(2, 92) = 9.12, p < 0.001; compared with the BG, t(63) 14 = 3.74, p < 0.001; compared with the DG, t(62) = 3.67, p < 0.001), with no significant difference 15 found between the BG and DG (t(59) = 0.60, p = 0.55). For attention biases, the accuracy and 16 reaction time (RT) of the sad targets among the neutral distractors condition in the VST were 17 analyzed, and no significant differences were found among the three groups (accuracy: F(2, 92) = 18 1.09, p=0.34; RT: F(2, 92) = 0.18, p=0.84). 19

There was no significant change in future BDI in the HG (t(33) = 0.73, p = 0.47). A significant 21 decrease in the future BDI was found in both BG (t(30) = -3.03, p < 0.01) and DG (t(29) = -4.70, p 22 J o u r n a l P r e -p r o o f < 0.0001). However, there was no significant difference in the change in future BDI between the 1 BG and DG (t(59) = 0.20, p = 0.84). 2

The COVID-19 pandemic altered the ability of negative memory biases to predict future 3 BDI scores. 4

Regarding memory biases, there was no significant difference among the three groups in the 5 correlation between the percentage of negative (for the HG and BG, z = 0.80, p = 0.42; for the HG 6 and DG, z = 0.93, p = 0.35; for the BG and DG, z = 0.13, p = 0.89) or positive (for the HG and 7 BG, z = 0.0077, p = 0.99; for the HG and DG, z = 1.22, p = 0.22; for the BG and DG, z = 1.18, p = 8 0.24) words recalled and present depressive indices. However, the correlation coefficients between 9 the percentage of negative words recalled and future depressive indices in the DG were 10 significantly different than those in the HG (z = 2.58, p < 0.01) and BG (z = 2.87, p < 0.005), with 11 the percentage of negative words recalled significantly predicting future depressive indices in the 12 DG (r = -0.63, p < 0.001, Figure 2A ) but not in the BG (r = 0.057, p = 0.77, Figure 2A ) or the HG 13 (r = -0.052, p = 0.77, Figure 2A ). The correlation coefficients were not significantly different 14 between the HG and BG (z = 0.41, p = 0.68). Moreover, the correlation coefficients between the 15 negative words recalled and future or present depressive indices in the DG were also significantly 16 different (z = 2.74, p < 0.01), and no significant correlation was found between the negative words 17 recalled and present depressive indices (r = -0.076, p = 0.70). In addition, we also found that the 18 percentage of negative words recalled also significantly predicted changes in depressive indices in 19 the DG (r = -0.50, p < 0.01, Figure 2B ) but not in the BG (r = 0.081, p = 0.68, Figure 2B ) or HG (r 20 = -0.21, p = 0.24, Figure 2B ). The results of the comparisons of correlations were consistent when 21 using ANOVA (Table S1 ). No significant differences were found among the three groups in the 22 J o u r n a l P r e -p r o o f correlation between the percentage of positive words recalled and future depressive indices (for 1 the HG and BG, z = 0.73, p = 0.47; for the HG and DG, z = 0.14, p = 0.89; for the BG and DG, z 2 = 0.82, p = 0.41). 3

Regarding interpretation biases, there were no significant differences among the three groups in 4 the correlation coefficients between the pleasantness ratings and the present depressive indices 5 (for the HG and BG, z = 0.067, p = 0.95; for the HG and DG, z = 0.37, p = 0.71; for the BG and 6 DG, z = 0.43, p = 0.67), with the pleasantness ratings significantly or nearly significantly 7 correlated with the present BDI in the DG (r = -0.32, p = 0.083), BG (r =-0.42, p = 0.019), and HG 8 (r = -0.41, p = 0.017). Moreover, the pleasantness ratings also significantly predicted future 9

depressive indices in all three groups (for the DG, r = -0.53, p < 0.005; for the BG, r = -0.37, p = 10 0.038; for the HG, r = -0.43, p = 0.011). 11

Regarding attention biases, there were no significant correlations between the present 12 depressive indices and accuracy (for the DG, r = -0.15, p = 0.41; for the BG, r = 0.26, p = 0.16; for 13 the HG, r = -0.23, p = 0.19) or the average RT for correct responses (for the DG, r = 0.17, p = 0.38; 14 for the BG, r = -0.0094, p = 0.96; for the HG, r = -0.15, p = 0.41) in the sad target condition. 15

Moreover, no significant differences were found among the three groups for the correlation 16 coefficients between future depressive indices and accuracy (for the HG and BG, z = 0.72, p = 17 0.47; for the HG and DG, z = 1.67, p = 0.10; for the BG and DG, z = 0.94, p = 0.35) or the 18 average RT for correct responses (for the HG and BG, z = 0.44, p = 0.66; for the HG and DG, z = 19

1.06, p = 0.29; for the BG and DG, z = 0.61, p = 0.54) in the sad target condition. 20

Correlations between the brain response to sad faces and negative memory biases. 21

Regions of interest were defined as the areas proposed in the introduction section (see Figure  22 J o u r n a l P r e -p r o o f 3A). We calculated the correlations between the responses of those areas to sad faces and negative 1 memory biases. The results showed that the response to sad faces was significantly correlated with 2 negative memory biases in the bilateral DCC (left: r = 0.29, p = 0.049, FDR adjusted, Figure 3B ; 3 right: r = 0.33, p = 0.045, FDR adjusted, Figure 3B ), and right vlPFC (right: r = 0.31, p = 0.049, 4 FDR adjusted, Figure 3B ). No significant correlation was found in the other areas after the 5 correction for multiple comparisons (all p > 0.1, FDR adjusted). The areas (left insula, left STG, 6 left thalamus, left vlPFC, right cuneus, right dlPFC, right insula) in which the response to sad 7 faces was significant (p < 0.05) or nearly significant (p < 0.1) correlated with negative memory 8 biases but didn't survive the correction for multiple comparisons were shown in Table S2 . 9

The COVID-19 pandemic altered the ability of the brain response to sad faces to predict 10 future BDI scores. 11

We further investigated whether the COVID-19 pandemic altered the ability of the response to 12 sad faces in the bilateral DCC, and right vlPFC to predict future depressive indices. The response 13 to sad faces in the left DCC significantly predicted future depressive indices in the DG (r = -0.41, 14 p = 0.026, Figure 4A ) but not in the BG (r = 0.035, p = 0.86) or the HG (r = 0.10, p = 0.60). The 15 correlation coefficients in the DG were also significantly more negative than those in the BG (z = 16 1.68, p = 0.047, one side) and the HG (z = 1.97, p = 0.025, one side). Although the correlations 17 between the future BDI and response to sad faces in the right DCC were not significant in the DG, 18 the trend was the same as that in the contralateral region (r = -0.31, p = 0.10, Figure 4A ). right cuneus, although their correlation with negative memory biases didn't survive the correction 7 for multiple comparisons, the correlation between their responses to sad faces and future BDI 8 scores were also significantly (or nearly significantly) changed during the pandemic compared 9

with the correlation between their responses to sad faces and present BDI scores, with their 10 responses to sad faces more negatively correlated with future BDI scores (see Table S1 ). 11

Comparison of changes in future BDI scores in high or low memory biases subgroups. 12 We further compared the changes in future BDI scores between the BG and DG in the higher 13 and lower negative memory biases subgroups separately. We calculated the quartiles of the 14 percentage of negative words recalled in the IFR in the SDG and defined those with a memory 15 bias higher than the 75% quantile or lower than the 25% quantile as the high bias group and the 16 low bias group, respectively. Two-way ANOVA was carried out, with changes in future BDI as the 17 response variable and pandemic (the BG or DG) and memory bias (high or low bias) as two 18 factors. Significant interactions were found between pandemic and memory bias factors (F(1, 25) 19 = 8.62, p < 0.01, Figure 5 ), with changes in future BDI in the high bias subgroup of the DG being 20 significantly lower than those in the high bias subgroup of the BG (t(13) = 3.37, p < 0.005, Figure  21 5). No significant difference was found between the low bias subgroups of the DG and BG (t(12) 22 = 0.94, p = 0.37, Figure 5 ). 1

To explore the reason underlying the fact that a more negative memory bias was associated with 4 a greater decrease in future depressive degree in nonclinical depressed participants during the 5 COVID-19 pandemic, we further investigated the change in socializing during the COVID-19 6 pandemic and its effect on the relationship between negative memory biases and future BDI scores. 7

We found that social distance significantly increased in all three groups (for the HG, t(32) = 2.55, 8 p = 0.016; for the BG, t(27) = 2.59, p = 0.015; for the DG, t(29) = 3.47, p < 0.005, Figure 6A ). 9

Social frequency (for the HG, t(32) = -7.13, p < 0.001; for the BG, t(27) = -3.20, p < 0.005; for the 10 DG, t(29) = -5.67, p < 0.001, Figure 6A ) and time spent on socializing (for the HG, t(32) = -6.18, 11 p < 0.001; for the BG, t(27) = -4.79, p < 0.001; for the DG, t(29) = -10.00, p < 0.001, Figure 6A ) 12 significantly decreased. Moreover, we also found that degree of stress from socializing 13 significantly or nearly significantly decreased during the COVID-19 pandemic in the BG (t(27) = 14 -1.77, p = 0.088) and DG (t(29) = -3.75, p < 0.001, Figure 6A ) but not in the HG (t(32) = -1.22, p 15 = 0.23). A significant correlation was also found between the degree of change in social frequency 16 and future BDI scores in the DG (r = 0.94, p = 0.016, Figure S2 ). However, the correlation 17 between the degree of change in the stress from socializing and future BDI scores was not 18 significant (r = 0.04, p = 0.96). The lack of significance might be due to the narrow range and 19 unbalanced distribution of the degree of change in the stress from socializing (see Figure S2 ). 20

We further divided the DG into subgroups according to their degree of change in socializing. 21

The subgroup with a higher decrease of socializing always shows a more negative correlation 22 between the negative memory biases and future BDI scores ( Figure 6B ). 1 2

In the present study, we found that a more negative memory bias was associated with a greater 4 decrease in future depressive indices in nonclinical depressed participants during the COVID-19 5 pandemic but not before the pandemic. The result of the lack of a significant difference between 6 the HG and BG in the correlation between current negative memory biases and future depressive 7

indices provides further evidence that this finding is specific to the effect of the pandemic. We 8 further showed that the responses to sad faces in the DCC, which were significantly correlated 9

with negative memory biases, were also negatively correlated with future depressive indices 10 during the COVID-19 pandemic. A comparison of the change in future depressive indices revealed 11 that the change in future BDI in the high bias subgroup of the DG was significantly lower than 12 that in the high bias subgroup of the BG. Investigation of socializing showed that social stress 13 decreased significantly during the pandemic in the nonclinical depressive population and the 14 subgroup of the DG with a higher decrease of socializing showed a more significant and more 15 negative correlation between the negative memory biases and future BDI scores. 16

As we explained in the introduction section, the COVID-19 pandemic may have two possible 17 effects on the relationship between current cognitive biases and future depressive indices in the 18 nonclinical depressed population. One is an increased stress effect considering that the COVID- 19 19 pandemic is a threat to life. The other one is a decreased stress effect considering that social 20 distancing may reduce social stress during the COVID-19 pandemic. Our results support the latter 21 effect. We have provided behavioral evidence that the COVID-19 pandemic promotes a negative 22 correlation between negative memory biases and future depressive indices in the nonclinical 23 J o u r n a l P r e -p r o o f depressive population, which means that a more negative memory bias was associated with a 1 greater decrease in future depressive indices during the pandemic. This effect might be due to the 2 low degree of social stress during the COVID-19 pandemic. The investigation of the socializing of 3 participants also corroborated this explanation. Decreased social frequency, increased social 4 distance and decreased social stress were all found in the nonclinical depressed population during 5 the pandemic. Social stress has been reported to be a crucial risk factor of depression (Paykel, 6 2003; Slavich et al., 2009). Thus, reduced social stress during the COVID-19 pandemic may lead 7 to decreased depressive indices. Our finding that the subgroup of the DG with a higher decrease of 8 socializing showed a more significant and more negative correlation between the negative 9 memory biases and future BDI scores provided further evidence for this explanation. However, it 10 is worth noting that although future depressive indices were negatively correlated with negative 11 memory biases in the DG, no significant difference was found in the future depressive indices 12 between the BG and DG. A possible explanation for this result is that reduced social stress only 13 had a significant effect on individuals with a greater negative memory bias. For those with a less 14 negative memory bias, the development of their depressive mood may be due to other events but 15 not social stress. Thus, their depressive indices did not decrease with social stress during the 16 pandemic. As a result, the depressive indices in the DG were not significantly lower than those in The other possible effect, that the COVID-19 pandemic may increase survival stress and thus 1 promote a greater increase in future depressive indices in participants with a more negative 2 cognitive bias, was not supported by our data (although a positive correlation was found between 3 negative interpretation biases and future depressive indices in the DG, the correlation coefficient 4

was not significant different from that in the BG). The reason for this finding may be that the most 5 severely affected region in China was Wuhan during the COVID-19 pandemic, and the 6 participants in this study mainly lived in other cities and might not have experienced much 7 survival stress. However, the social distancing policy was carried out all over China, thus a 8 reduced social stress effect was found in our data. 9

Brain imaging analysis further corroborated the findings of the behavioral data. We tested ten 10

ROIs highlighted by a previous meta-analysis and found that the responses to sad faces in the 11 bilateral DCC, which were found to be correlated with negative memory biases, were also 12 negatively correlated with future depressive indices during the COVID-19 pandemic. The Although the response to sad faces in the right vlPFC was also correlated with negative memory 20 biases in our results, their correlation with future depressive indices did not show the same pattern 21 as in the behavioral data. A possible explanation for this finding is that the activity in this area 22 might be related to many kinds of depressive symptoms, not only memory biases. Thus, their 1 relationship with future depressive indices was not altered as in the relationship between memory 2 bias and future depressive indices. 3

In the present study, only the relationship between current memory biases and future depression Our results also support social distancing policies that carried out during the pandemic from a 18 psychological perspective. Increasing social distance can not only prevent the spread of 19 COVID-19, but may also reduce social stress and thereby decrease depressive indices in the 20 nonclinical depressed population, especially in those with a more negative memory bias. 21

Moreover, considering that social stress may re-emerge when social distancing goes back to 22 normal, the resumption of work and school should be carried out gradually, not only to prevent the 1 recurrence of the pandemic but also to provide time for people to adapt to re-emerging social 2 stress in case they experience an increased degree of depression. Previous studies have linked too In summary, this study revealed that a more negative memory bias was associated with a greater 6 decrease in future depressive indices during the COVID-19 pandemic in the nonclinical depressive 7 population, which might be due to decreased social stress. The responses of the bilateral DCC to 8 sad faces were found to be correlated with negative memory biases, and their negative correlation 9

with future depressive indices converged with the results from the behavioral data. Our findings 10 also support social distancing policies from a psychological perspective. Increasing social distance 11 not only prevents the spread of COVID-19 but may also reduce social stress and thereby decrease 12 depressive indices in the nonclinical depressed population, especially in those with a more 13 negative memory biases. 14 15

Some limitations of this study must be acknowledged. For the VST, only sad and neutral faces 17 were used. Thus, the reason why no significant correlation between attention biases and future 18 depressive indices was found might be that the nonclinical depressive population may not pay 19 more attention to negative stimuli but may instead pay less attention to positive stimuli. Moreover, 20 all of the nondepressed participants' future BDI were assessed before the pandemic. Thus, our 21 results might not generalize to nondepressed populations. Zhang (zxcustc@ustc.edu.cn). 5

The sources of stimulus materials are provided in the Supplemental Information file. 7

The datasets supporting the current study have not been deposited in a public repository but are 9

available from the lead contact on request. The statistics were performed on R version 3.6.1 10 (64-bit) platform. The code for statistical analysis is available from the Lead Contact on request. 

The authors declare no competing interests. identification task (WI) plus incidental free recall task (IFR) was used to assess memory biases. 11

Interpretation biases were evaluated using the ambiguous scenarios test for depressed mood 12 (AST-D). A visual search task (VST) was used to investigate attentional biases to sad faces. The 13 fMRI experiment was a face viewing task composed of 2 runs, each with 6 blocks. The facial 14 stimuli in each run consisted of grayscale normalized sad, happy, and neutral expressions of 30 15 men and 30 women. In each block, 5 trials of male faces and 5 trials of female faces were shown. 16

In each trial, a face was shown in the center of the screen for 200 ms, followed by a black screen. 17

Each trial lasted for 2 seconds. Then, the next face appeared. A fixation cross was presented for 20 18 seconds between two blocks and for 10 seconds before the first block and after the last block of 19 each session. Prior to the experiment, the subjects were instructed to attentively watch the faces 20 and recognize the corresponding expressions. Correlations between negative memory biases and future BDI in the DG, BG and HG. Future BDI 24 scores were plotted against the percentage of negative words recalled in the IFR task. (B) 1

Changes in the BDI scores were plotted against the percentage of negative words recalled in the 3 IFR task. as mean +/-standard error. * represents p < 0.05, ** represents p < 0.01, *** represents p < 0.001, 8 (*) represents p < 0.1, N.S. represents no significance. One sample t-tests were carried out. (B) 9

Correlations between negative memory biases and future BDI in the higher and lower decrease of 10 socializing subgroups of the DG. The median of change in socializing in the DG was used as the 11 grouping criterion to ensure the balance of sample size in two subgroups. For the stress from 12 socializing, social frequency, and time spent on socializing, subjects with a degree of change in 13 socializing lower (or not higher, depends on the balance of sample size in the two subgroups) than 14 the median was grouped into the high decrease subgroup. For social distance, subjects with a 15 degree of change in social distance higher than the median was grouped into the high decrease 16 subgroup. The subgroup with a higher decrease of socializing always shows a more negative 17 correlation between the negative memory biases and future BDI scores. 18

Tables 20 Table 1 Sample 

Addressing mental health needs: an integral part of COVID-19 12 response

Spatial proximity amplifies 14 valence in emotional memory and defensive approach-avoidance

From depressive 16 symptoms to depressive disorders: the relevance of thresholds

Increased generalized anxiety, depression and distress 19 during the COVID-19 pandemic: a cross-sectional study in Germany

The evolution of the cognitive model of depression and its neurobiological 21 correlates

Comparison of Beck Depression 23 Inventories -1A and -11 in Psychiatric Outpatients

Cognitive and emotional influences in anterior 26 cingulate cortex

Prevalence of self-reported depression and 28 anxiety among pediatric medical staff members during the COVID-19 outbreak in Guiyang

Depression and Anxiety in Hong Kong during 31 COVID-19

Information processing in social phobia

The effects of social deprivation on 2 adolescent development and mental health

Life events and affective disorders

Associations of stressors and uplifts of caregiving with 5 caregiver burden and depressive mood: a meta-analysis

Social anxiety is associated with impaired 8 memory for imagined social events with positive outcomes

Memory biases in remitted depression: The role 10 of negative cognitions at explicit and automatic processing levels

Prevalence, 13 correlates, and course of minor depression and major depression in the national comorbidity 14 survey -Discussion

Stress, memory and the amygdala

Negative cognitive biases predict 18 subsequent depression

Neural correlates of cognitive bias 20 modification for interpretation

Supportive interactions, negative